tag:theconversation.com,2011:/global/topics/biomedical-research-1637/articlesBiomedical research – The Conversation2023-02-16T22:48:25Ztag:theconversation.com,2011:article/1993702023-02-16T22:48:25Z2023-02-16T22:48:25ZTwo decades of stagnant funding have rendered Canada uncompetitive in biomedical research. Here’s why it matters, and how to fix it.<figure><img src="https://images.theconversation.com/files/510657/original/file-20230216-28-ouv28s.jpg?ixlib=rb-1.1.0&rect=30%2C45%2C4805%2C2828&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Canada needs to revitalize its scientific mojo, and to do so must improve research funding.</span> <span class="attribution"><span class="source">(Shutterstock)</span></span></figcaption></figure><p>You may imagine that the hard part of being a Canadian scientist is having a bright idea. However, while curiosity, persistence and inventiveness are prerequisites for scientific success, the major obstacle to being a biomedical scientist in Canada is obtaining research funding. </p>
<p>Canadian biomedical scientists receive funding to hire scientific staff and buy experimental materials by applying for federally funded grants from the <a href="https://cihr-irsc.gc.ca/e/193.html">Canadian Institutes of Health Research</a> (CIHR). </p>
<p>To purchase their high-tech tools (infrastructure), researchers apply for grants from the <a href="https://www.innovation.ca/">Canada Foundation for Innovation</a> (CFI). These <a href="https://ised-isde.canada.ca/site/canada-fundamental-science-review/en">grant agencies are underfunded</a>, and some of their programs are poorly designed, with <a href="https://cihr-irsc.gc.ca/e/53379.html">funding success rates so low</a> scientists must apply repeatedly to obtain funding that is financially inadequate. </p>
<p>As a result, Canadian scientists may feel like they spend more time writing grant applications than doing research. The reality is that <a href="https://doi.org/10.1126/science.adg0899">stagnant funding is holding back Canadian science</a>.</p>
<p>Securing CIHR grants has become impractically competitive. Most applications require multiple revisions and resubmissions, often imposing an interval of one to two years between first submission and funding. Since funding from a CIHR project grant only lasts five years, the life of the lab — and the jobs of Canadian scientists — are recurrently in jeopardy. </p>
<h2>Core funding issues</h2>
<p>Let’s review the core problems with the funding of Canadian science. Stagnation in Canada’s biomedical grant funding reflects the fact CIHR’s funding from the Government of Canada <a href="https://can-acn.org/science-funding-in-canada-statistics/#CIHR_Grant_application_success_rates_2000-2021">has not increased since 2006 (in constant dollars, year 2000) and is not predicted to increase by 2025</a>. </p>
<figure class="align-center ">
<img alt="Bar graph showing static spending levels over six years" src="https://images.theconversation.com/files/510677/original/file-20230216-20-ms9knt.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/510677/original/file-20230216-20-ms9knt.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=350&fit=crop&dpr=1 600w, https://images.theconversation.com/files/510677/original/file-20230216-20-ms9knt.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=350&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/510677/original/file-20230216-20-ms9knt.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=350&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/510677/original/file-20230216-20-ms9knt.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=440&fit=crop&dpr=1 754w, https://images.theconversation.com/files/510677/original/file-20230216-20-ms9knt.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=440&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/510677/original/file-20230216-20-ms9knt.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=440&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Graph of planned spending over time illustrates that CIHR funding is flat.</span>
<span class="attribution"><a class="source" href="https://cihr-irsc.gc.ca/e/52738.html#5.1">(CIHR data)</a></span>
</figcaption>
</figure>
<p>The United States is a relevant comparator because it is home to many of the world’s leading scientists. Canadian scientists, if not funded, often relocate to the U.S. Compare America’s National Institutes of Health (NIH) 2020-21 budget of <a href="https://www.nih.gov/about-nih/what-we-do/budget#:%7E:text=The%20NIH%20invests%20most%20of,research%20for%20the%20American%20people.">US$45 billion</a> (roughly C$60 billion) to CIHR’s C$1.2 billion. America’s NIH budget is 50-fold that of Canada’s CIHR budget, but the U.S. population is only nine-fold greater than ours. </p>
<p><a href="https://data.oecd.org/rd/gross-domestic-spending-on-r-d.htm">Canada’s spending on research and development</a>, as a percentage of gross domestic spending, is also smaller than the U.S.’s. </p>
<h2>Grant competition success rates</h2>
<p>The success rate in CIHR grant competitions has declined from 31 per cent in 2005 to <a href="https://can-acn.org/science-funding-in-canada-statistics/">around 15 per cent in 2020</a>. </p>
<p>CIHR evaluates applications on a <a href="https://cihr-irsc.gc.ca/e/4656.html#2.5">scale of zero to 4.9</a>, corresponding to categories of poor, fair, very good, excellent and outstanding. Currently, CIHR grants are rarely funded unless the voted score is outstanding (rated 4.4 to 4.9). Usually only the top 18 per cent of all grants — <a href="https://cihr-irsc.gc.ca/e/53379.html">fewer than one in five</a> — are funded, and virtually all grants rated excellent are rejected. </p>
<p>This low-success endeavor is a demoralizing waste of time for the 82 per cent of scientists who are rejected and for the peer-review volunteers — unpaid colleagues who spent weeks reviewing the applications.</p>
<figure class="align-center ">
<img alt="chart showing CIHR grant rating categories" src="https://images.theconversation.com/files/510643/original/file-20230216-16-vhukiy.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/510643/original/file-20230216-16-vhukiy.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=350&fit=crop&dpr=1 600w, https://images.theconversation.com/files/510643/original/file-20230216-16-vhukiy.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=350&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/510643/original/file-20230216-16-vhukiy.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=350&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/510643/original/file-20230216-16-vhukiy.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=440&fit=crop&dpr=1 754w, https://images.theconversation.com/files/510643/original/file-20230216-16-vhukiy.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=440&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/510643/original/file-20230216-16-vhukiy.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=440&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Almost all grants scored by CIHR as excellent go unfunded.</span>
<span class="attribution"><a class="source" href="https://cihr-irsc.gc.ca/e/4656.html#2.5">(CIHR data)</a></span>
</figcaption>
</figure>
<p>Once funded, challenges remain. All CIHR awarded project grants are now subject to a <a href="https://cihr-irsc.gc.ca/e/52564.html">23.5 per cent across-the-board funding cut</a>. This cut allowed CIHR to fund 87 additional grants per competition from 2018 to 2020, however the value of a five-year project grant shrank from $950,000 to $725,000. </p>
<p>These cuts mean scientific staff must take pay cuts or be terminated, and the approved research can only be partially completed.</p>
<h2>Fixing funding</h2>
<p>Canada needs to revitalize its scientific mojo and <a href="https://www.tvo.org/video/has-canada-lost-its-science-game">to do so must improve research funding</a>. There are several steps that would improve science funding in Canada.</p>
<p><strong>1. Implement the Fundamental Science Review recommendations</strong></p>
<p>The fix for Canadian science was well enunciated by the <a href="https://ised-isde.canada.ca/site/canada-fundamental-science-review/en">Fundamental Science Review, also known as the Naylor Report, in 2017</a>. This report recognized that underfunded Canadian science was falling behind. </p>
<p>It noted that federal underfunding is exacerbated by CIHR’s practice of earmarking substantial portions of its limited funds to targeted proposals that address governmental priorities, rather than funding research and discovery science. </p>
<p>The report made simple recommendations to improve Canadian research: “Rapidly increase its investment in independent, investigator-led, research to redress the imbalance caused by differential investments favouring priority-driven, targeted research.” </p>
<figure class="align-center ">
<img alt="A group of people sitting on blue storage drawer units in a V formation." src="https://images.theconversation.com/files/509333/original/file-20230210-28-7wuu5.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/509333/original/file-20230210-28-7wuu5.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=316&fit=crop&dpr=1 600w, https://images.theconversation.com/files/509333/original/file-20230210-28-7wuu5.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=316&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/509333/original/file-20230210-28-7wuu5.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=316&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/509333/original/file-20230210-28-7wuu5.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=397&fit=crop&dpr=1 754w, https://images.theconversation.com/files/509333/original/file-20230210-28-7wuu5.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=397&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/509333/original/file-20230210-28-7wuu5.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=397&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Members of the author’s research team at the Archer laboratory at Queen’s University.</span>
<span class="attribution"><a class="source" href="https://deptmed.queensu.ca/research/teams/dr-archers-lab">(Author provided)</a>, <span class="license">Author provided</span></span>
</figcaption>
</figure>
<p>It also recommended “formation of an independent advisory committee on basic research and industrial innovation, comprised of leaders in research and industry” (not government employees). Our government currently makes many top-down science funding decisions without a strategic scientific plan or an external scientific committee to advise them. An independent advisory committee would reduce political interference in science. </p>
<p>The Naylor report’s recommendations have not been fully implemented, but would transform Canadian research. This would require commitment of an additional 0.4 per cent of the Government of Canada’s annual budget to our science sector. </p>
<p><strong>2. Fund salaries for scientists who run infrastructure</strong></p>
<p>In the meantime, CFI and CIHR could each implement “researcher-centric” changes. </p>
<p>CFI could accompany its infrastructure grants with funding for the scientists who are needed to operate these complex research platforms. </p>
<p>CFI grants are used to purchase the multi-million-dollar tools needed to conduct research at the cutting-edge, such as <a href="http://dx.doi.org/10.1136/archdischild-2013-304340">NextGen gene sequencers</a> and <a href="https://doi.org/10.1098/rsta.2021.0110">super resolution confocal microscopes</a>. <a href="https://www.innovation.ca/sites/default/files/2021-10/CFI-IF-2020-By-the-numbers.pdf">CFI has a 30 per cent funding success rate</a>, allowing purchase of infrastructure; but it does not pay for the scientists who run these scientific infrastructure platforms. </p>
<p>This makes it difficult to sustain a CFI scientific platform. </p>
<p><strong>3. Bring back the foundation grant program</strong></p>
<p>CIHR could resurrect its very successful foundation grant program. </p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/510660/original/file-20230216-30-iobgib.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A woman in a white coat in a lab" src="https://images.theconversation.com/files/510660/original/file-20230216-30-iobgib.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/510660/original/file-20230216-30-iobgib.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=900&fit=crop&dpr=1 600w, https://images.theconversation.com/files/510660/original/file-20230216-30-iobgib.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=900&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/510660/original/file-20230216-30-iobgib.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=900&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/510660/original/file-20230216-30-iobgib.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1131&fit=crop&dpr=1 754w, https://images.theconversation.com/files/510660/original/file-20230216-30-iobgib.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1131&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/510660/original/file-20230216-30-iobgib.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1131&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Foundation grants allowed scientists to bundle all their research into a single, comprehensive application.</span>
<span class="attribution"><span class="source">(Shutterstock)</span></span>
</figcaption>
</figure>
<p>CIHR understood that its most successful scientists usually required two to three project grants, and recognized the time drag that acquiring multiple project grants required. </p>
<p>They responded in 2014 with the foundation grant program. Foundation grants allowed scientists to bundle all their research into a single, comprehensive application which offered more funding (equivalent to two to three project grants) for a longer duration (seven years instead of five years for project grants). </p>
<p>This allowed researchers to spend more time on doing science and less on writing and reviewing grants. My foundation grant gave me the stability and flexibility to simultaneously study oxygen sensing, mitochondrial dynamics and to develop drugs to treat pulmonary hypertension, cancer and <a href="https://www.queensu.ca/gazette/stories/how-covid-19-damages-lungs">COVID-19</a>.</p>
<p>However, the <a href="https://cihr-irsc.gc.ca/e/51431.html">foundation grant program was unceremoniously terminated</a>, forcing grant holders to once again, apply for two to three simultaneous project grants. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/how-covid-19-damages-lungs-the-virus-attacks-mitochondria-continuing-an-ancient-battle-that-began-in-the-primordial-soup-192597">How COVID-19 damages lungs: The virus attacks mitochondria, continuing an ancient battle that began in the primordial soup</a>
</strong>
</em>
</p>
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<h2>Funding research pays off</h2>
<p>Researchers are key to Canada’s capacity to create a high-tech economy, build the biomedical sector and seed entrepreneurial activity. Researchers also support our academic health sciences centres and universities, making them internationally competitive. </p>
<p>Research has a great return on investment, with an estimated <a href="https://www.americanprogress.org/article/the-high-return-on-investment-for-publicly-funded-research/">30 to 100 per cent of the expenditure on publicly funded research being returned to society</a>. Each research laboratory is a small business creating well-paying jobs, knowledge and intellectual property, which many commercialize. </p>
<p>In addition to launching medical innovations, patents and spin-off companies, Canada’s researchers teach university students, and many CIHR-funded clinician-scientists provide patient care in our hospitals. In all of these ways, investment in research is critical to making Canada healthy, wealthy and wise.</p><img src="https://counter.theconversation.com/content/199370/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Stephen L Archer receives funding from CIHR and CFI. He previously received funding from NIH.</span></em></p>Researchers are key to Canada’s capacity to create a high-tech economy, build the biomedical sector and seed entrepreneurial activity, but they can’t do it without research funding.Stephen L Archer, Professor, Head of Department of Medicine, Queen's University, OntarioLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1961002023-01-10T13:30:06Z2023-01-10T13:30:06ZOrgan-on-a-chip models allow researchers to conduct studies closer to real-life conditions – and possibly grease the drug development pipeline<figure><img src="https://images.theconversation.com/files/501906/original/file-20221219-18-6xab1c.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2044%2C1581&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The lung-on-a-chip can mimic both the physical and mechanical qualities of a human lung.</span> <span class="attribution"><a class="source" href="https://flic.kr/p/HQBa1g">Wyss Institute for Biologically Inspired Engineering, Harvard University/Flickr</a></span></figcaption></figure><p><a href="https://doi.org/10.1007/s40273-021-01065-y">Bringing a new drug to market</a> costs billions of dollars and can take over a decade. These high monetary and time investments are both strong contributors to today’s skyrocketing health care costs and significant obstacles to delivering new therapies to patients. One big reason behind these barriers is the lab models researchers use to develop drugs in the first place.</p>
<p><a href="https://www.fda.gov/patients/drug-development-process/step-2-preclinical-research">Preclinical trials</a>, or studies that test a drug’s efficacy and toxicity before it enters clinical trials in people, are mainly conducted on cell cultures and animals. Both are limited by their poor ability to mimic the conditions of the human body. <a href="https://doi.org/10.1016%2FB978-0-12-803077-6.00009-6">Cell cultures</a> in a petri dish are unable to replicate every aspect of tissue function, such as how cells interact in the body or the dynamics of living organs. And <a href="https://doi.org/10.1093/bioinformatics/btu611">animals</a> are not humans – even small genetic differences between species can be amplified to major physiological differences. </p>
<p><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3902221/">Fewer than 8%</a> of successful animal studies for cancer therapies make it to human clinical trials. Because animal models often fail to predict drug effects in human clinical trials, these late-stage failures can significantly drive up both costs and patient health risks. </p>
<p>To address this translation problem, researchers have been developing a promising model that can more closely mimic the human body – organ-on-a-chip. </p>
<p>As an <a href="https://scholar.google.com/citations?user=FppSA-0AAAAJ&hl=en">analytical chemist</a>, I have been working to develop organ and tissue models that avoid the simplicity of common cell cultures and the discrepancies of animal models. I believe that, with further development, organs-on-chips can help researchers study diseases and test drugs in conditions that are closer to real life.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/CpkXmtJOH84?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Organs-on-chips offer an alternative model for early-phase biomedical research.</span></figcaption>
</figure>
<h2>What are organs-on-chips?</h2>
<p>In the late 1990s, researchers figured out a way to <a href="https://gmwgroup.harvard.edu/files/gmwgroup/files/1073.pdf">layer elastic polymers</a> to control and examine fluids at a microscopic level. This launched the field of <a href="https://doi.org/10.1016/j.mne.2019.01.003">microfluidics</a>, which for the biomedical sciences involves the use of devices that can mimic the dynamic flow of fluids in the body, such as blood.</p>
<p>Advances in microfluidics have provided researchers a platform to culture cells that function more closely to how they would in the human body, specifically with <a href="https://doi.org/10.1038/s41578-018-0034-7">organs-on-chips</a>. The “chip” refers to the microfluidic device that encases the cells. They’re commonly made using the same technology as computer chips. </p>
<p>Not only do organs-on-chips mimic blood flow in the body, these platforms have microchambers that allow researchers to integrate multiple types of cells to mimic the diverse range of cell types normally present in an organ. The fluid flow connects these multiple cell types, allowing researchers to study how they interact with each other.</p>
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<iframe width="440" height="260" src="https://www.youtube.com/embed/M37ZU0Ptkww?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Microfluidics can be used for many applications in biological research.</span></figcaption>
</figure>
<p>This technology can overcome the limitations of both static cell cultures and animal studies in several ways. First, the presence of fluid flowing in the model allows it to mimic both what a cell experiences in the body, such as how it receives nutrients and removes wastes, and how a drug will move in the blood and interact with multiple types of cells. The ability to control fluid flow also enables researchers to fine-tune the optimal dosing for a particular drug.</p>
<p>The <a href="https://doi.org/10.1126/science.1188302">lung-on-a-chip</a> model, for instance, is able to integrate both the mechanical and physical qualities of a living human lung. It’s able to mimic the dilation and contraction, or inhalation and exhalation, of the lung and simulate the interface between the lung and air. The ability to replicate these qualities allows researchers to better study lung impairment across different factors.</p>
<h2>Bringing organs-on-chips to scale</h2>
<p>While organ-on-a-chip pushes the boundaries of early-stage pharmaceutical research, the technology has <a href="https://doi.org/10.1016/j.drudis.2019.03.011">not been widely integrated</a> into drug development pipelines. I believe that a core obstacle for wide adoption of such chips is its high complexity and low practicality.</p>
<p>Current organ-on-a-chip models are difficult for the average scientist to use. Also, because most models are single-use and allow only one input, which limits what researchers can study at a given time, they are both expensive and time- and labor-intensive to implement. The <a href="https://doi.org/10.1039/c6lc01554a">high investments required</a> to use these models might dampen enthusiasm to adopt them. After all, researchers often use the least complex models available for preclinical studies to reduce time and cost.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/501643/original/file-20221216-13-pjt0d0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Close-up of blood-brain barrier on a chip" src="https://images.theconversation.com/files/501643/original/file-20221216-13-pjt0d0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/501643/original/file-20221216-13-pjt0d0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=433&fit=crop&dpr=1 600w, https://images.theconversation.com/files/501643/original/file-20221216-13-pjt0d0.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=433&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/501643/original/file-20221216-13-pjt0d0.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=433&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/501643/original/file-20221216-13-pjt0d0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=544&fit=crop&dpr=1 754w, https://images.theconversation.com/files/501643/original/file-20221216-13-pjt0d0.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=544&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/501643/original/file-20221216-13-pjt0d0.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=544&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">This chip mimics the blood-brain barrier. The blue dye marks where brain cells would go, and the red dye marks the route of blood flow.</span>
<span class="attribution"><a class="source" href="https://flic.kr/p/HRUHqg">Vanderbilt University/Flickr</a></span>
</figcaption>
</figure>
<p>Lowering the technical bar to make and use organs-on-chips is critical to allowing the entire research community to take full advantage of their benefits. But this does not necessarily require simplifying the models. <a href="https://chenresearchlab.umbc.edu">My lab</a>, for example, has designed various <a href="https://doi.org/10.26434/chemrxiv.12964604.v1">“plug-and-play” tissue chips</a> that are standardized and modular, allowing researchers to readily assemble premade parts to run their experiments.</p>
<p>The advent of <a href="https://pubs.acs.org/doi/full/10.1021/ac403397r">3D printing</a> has also significantly facilitated the development of organ-on-a-chip, allowing researchers to directly manufacture entire tissue and organ models on chips. 3D printing is ideal for fast prototyping and design-sharing between users and also makes it easy for mass production of standardized materials.</p>
<p>I believe that organs-on-chips hold the potential to enable breakthroughs in drug discovery and allow researchers to better understand how organs function in health and disease. Increasing this technology’s accessibility could help take the model out of development in the lab and let it make its mark on the biomedical industry.</p><img src="https://counter.theconversation.com/content/196100/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Chengpeng Chen receives funding from the NIH.</span></em></p>Successes in the lab mostly don’t translate to people. Research models that better mimic the human body could close the gap.Chengpeng Chen, Assistant Professor of Chemistry and Biochemistry, University of Maryland, Baltimore CountyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1958732023-01-06T13:30:53Z2023-01-06T13:30:53ZVisualizing the inside of cells at previously impossible resolutions provides vivid insights into how they work<figure><img src="https://images.theconversation.com/files/501408/original/file-20221215-16-mtk39u.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C1078%2C913&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Cryo-electron tomography shows what molecules look like in high-resolution – in this case, the virus that causes COVID-19.</span> <span class="attribution"><a class="source" href="https://nanographics.at/projects/coronavirus-3d/">Nanographics</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span></figcaption></figure><p>All life is <a href="https://www.khanacademy.org/science/biology/intro-to-biology/what-is-biology/a/what-is-life">made up of cells</a> several magnitudes <a href="https://learn.genetics.utah.edu/content/cells/scale/">smaller than a grain of salt</a>. Their seemingly simple-looking structures mask the intricate and complex molecular activity that enables them to carry out the functions that sustain life. Researchers are beginning to be able to visualize this activity to a level of detail they haven’t been able to before.</p>
<p>Biological structures can be visualized by either starting at the level of the whole organism and working down, or starting at the level of single atoms and working up. However, there has been a resolution gap between a cell’s smallest structures, such as the cytoskeleton that supports the cell’s shape, and its largest structures, such as the ribosomes that make proteins in cells.</p>
<p>By analogy of Google Maps, while scientists have been able to see entire cities and individual houses, they did not have the tools to see how the houses came together to make up neighborhoods. Seeing these neighborhood-level details is essential to being able to understand how individual components work together in the environment of a cell.</p>
<p>New tools are steadily bridging this gap. And ongoing development of one particular technique, <a href="https://doi.org/10.1002/1873-3468.13948">cryo-electron tomography, or cryo-ET</a>, has the potential to deepen how researchers study and understand how cells function in health and disease. </p>
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<figcaption><span class="caption">Cryo-EM won the 2017 Nobel Prize in chemistry.</span></figcaption>
</figure>
<p>As the former <a href="https://www.science.org/content/article/jeremy-berg-named-science-editor-chief">editor-in-chief of Science magazine</a> and as a <a href="https://scholar.google.com/citations?user=MZ6qrPUAAAAJ&hl=en">researcher</a> who has studied hard-to-visualize large protein structures for decades, I have witnessed astounding progress in the development of tools that can determine biological structures in detail. Just as it becomes easier to understand how complicated systems work when you know what they look like, understanding how biological structures fit together in a cell is key to understanding how organisms function.</p>
<h2>A brief history of microscopy</h2>
<p>In the 17th century, <a href="https://doi.org/10.1098/rsob.150019">light microscopy</a> first revealed the existence of cells. In the 20th century, electron microscopy offered even greater detail, revealing the <a href="https://www.nobelprize.org/prizes/medicine/1974/summary/">elaborate structures within cells</a>, including organelles like the endoplasmic reticulum, a complex network of membranes that play key roles in protein synthesis and transport.</p>
<p>From the 1940s to 1960s, biochemists worked to separate cells into their molecular components and learn how to determine the 3D structures of proteins and other macromolecules at or near atomic resolution. This was first done using X-ray crystallography to visualize the structure of <a href="https://www.historyofinformation.com/detail.php?entryid=3015">myoglobin</a>, a protein that supplies oxygen to muscles. </p>
<p>Over the past decade, techniques based on <a href="https://www.nobelprize.org/prizes/chemistry/2002/press-release/">nuclear magnetic resonance</a>, which produces images based on how atoms interact in a magnetic field, and <a href="https://doi.org/10.1016/j.molcel.2015.02.019">cryo-electron microscopy</a> have rapidly increased the number and complexity of the structures scientists can visualize.</p>
<h2>What is cryo-EM and cryo-ET?</h2>
<p><a href="https://theconversation.com/scientists-uncovered-the-structure-of-the-key-protein-for-a-future-hepatitis-c-vaccine-heres-how-they-did-it-193705">Cryo-electron microscopy, or cryo-EM</a>, uses a camera to detect how a beam of electrons is deflected as the electrons pass through a sample to visualize structures at the molecular level. Samples are rapidly frozen to protect them from radiation damage. Detailed models of the structure of interest are made by taking multiple images of individual molecules and averaging them into a 3D structure.</p>
<p><a href="https://doi.org/10.1038/nmeth.4115">Cryo-ET</a> shares similar components with cryo-EM but uses different methods. Because most cells are too thick to be imaged clearly, a region of interest in a cell is first thinned by using an ion beam. The sample is then tilted to take multiple pictures of it at different angles, analogous to a CT scan of a body part – although in this case the imaging system itself is tilted, rather than the patient. These images are then combined by a computer to produce a 3D image of a portion of the cell. </p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/501410/original/file-20221215-27-mqhygu.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Cryo-ET image of algal chloroplast" src="https://images.theconversation.com/files/501410/original/file-20221215-27-mqhygu.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/501410/original/file-20221215-27-mqhygu.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=932&fit=crop&dpr=1 600w, https://images.theconversation.com/files/501410/original/file-20221215-27-mqhygu.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=932&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/501410/original/file-20221215-27-mqhygu.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=932&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/501410/original/file-20221215-27-mqhygu.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1172&fit=crop&dpr=1 754w, https://images.theconversation.com/files/501410/original/file-20221215-27-mqhygu.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1172&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/501410/original/file-20221215-27-mqhygu.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1172&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">This is a cryo-ET image of the chloroplast of an algal cell.</span>
<span class="attribution"><a class="source" href="https://dx.doi.org/10.7554/eLife.04889">Engel et al. (2015)</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>The resolution of this image is high enough that researchers – or computer programs – can identify the individual components of different structures in a cell. Researchers have used this approach, for example, to show how proteins move and are degraded inside an <a href="https://doi.org/10.1073/pnas.1905641117">algal cell</a>.</p>
<p>Many of the steps researchers once had to do manually to determine the structures of cells are becoming automated, allowing scientists to identify new structures at vastly higher speeds. For example, combining cryo-EM with artificial intelligence programs like <a href="https://doi.org/10.1038/s41586-021-03819-2">AlphaFold</a> can facilitate image interpretation by predicting protein structures that have not yet been characterized. </p>
<h2>Understanding cell structure and function</h2>
<p>As imaging methods and workflows improve, researchers will be able to tackle some key questions in cell biology with different strategies.</p>
<p>The first step is to decide what cells and which regions within those cells to study. Another visualization technique called <a href="https://doi.org/10.1002/1873-3468.14421">correlated light and electron microscopy, or CLEM</a>, uses fluorescent tags to help locate regions where interesting processes are taking place in living cells.</p>
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<a href="https://images.theconversation.com/files/501414/original/file-20221215-13-dadsmp.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Cryo-EM image of human T-cell leukemia virus type-1 (HTLV-1)" src="https://images.theconversation.com/files/501414/original/file-20221215-13-dadsmp.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/501414/original/file-20221215-13-dadsmp.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=406&fit=crop&dpr=1 600w, https://images.theconversation.com/files/501414/original/file-20221215-13-dadsmp.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=406&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/501414/original/file-20221215-13-dadsmp.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=406&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/501414/original/file-20221215-13-dadsmp.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=510&fit=crop&dpr=1 754w, https://images.theconversation.com/files/501414/original/file-20221215-13-dadsmp.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=510&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/501414/original/file-20221215-13-dadsmp.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=510&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">This is a cryo-EM image of a human T-cell leukemia virus type-1 (HTLV-1).</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/cryo-em-structure-of-human-t-cell-leukemia-virus-royalty-free-image/1300707029">vdvornyk/iStock via Getty Images Plus</a></span>
</figcaption>
</figure>
<p>Comparing the <a href="https://doi.org/10.1016/j.isci.2018.07.014">genetic difference between cells</a> can provide additional insight. Scientists can look at cells that are unable to carry out particular functions and see how this is reflected in their structure. This approach can also help researchers study how cells interact with each other.</p>
<p>Cryo-ET is likely to remain a specialized tool for some time. But further technological developments and increasing accessibility will allow the scientific community to examine the link between cellular structure and function at previously inaccessible levels of detail. I anticipate seeing new theories on how we understand cells, moving from disorganized bags of molecules to intricately organized and dynamic systems.</p><img src="https://counter.theconversation.com/content/195873/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jeremy Berg does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Many microscopy techniques have won Nobel Prizes over the years. Advancements like cryo-ET that allow scientists to see the individual atoms of cells can reveal their biological functions.Jeremy Berg, Professor of Computational and Systems Biology, Associate Senior Vice Chancellor for Science Strategy and Planning, University of PittsburghLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1966522023-01-05T13:26:24Z2023-01-05T13:26:24ZNanomedicines for various diseases are in development – but research facilities produce vastly inconsistent results on how the body will react to them<figure><img src="https://images.theconversation.com/files/502207/original/file-20221220-6047-jjdm3d.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2048%2C1637&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Nanoparticles (white disks) can be used to deliver treatment to cells (blue).</span> <span class="attribution"><a class="source" href="https://flic.kr/p/KjvnhT">Brenda Melendez and Rita Serda/National Cancer Institute, National Institutes of Health</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc/4.0/">CC BY-NC</a></span></figcaption></figure><p><a href="https://doi.org/10.3389/fchem.2018.00360">Nanomedicines</a> took the spotlight during the COVID-19 pandemic. Researchers are using these very small and intricate materials to develop diagnostic tests and treatments. Nanomedicine is already used for various diseases, such as the <a href="https://doi.org/10.1038/s41565-020-0757-7">COVID-19 vaccines</a> and therapies for <a href="https://doi.org/10.1038/nnano.2017.167">cardiovascular disease</a>. The “nano” refers to the use of particles that are only a few hundred nanometers in size, which is <a href="https://www.nano.gov/nanotech-101/what/nano-size">significantly smaller than</a> the width of a human hair.</p>
<p>Although researchers have developed <a href="https://doi.org/10.1007/s40820-022-00922-5">several methods</a> to improve the reliability of nanotechnologies, the field still faces one major roadblock: a lack of a standardized way to analyze <a href="https://doi.org/10.1016/j.tibtech.2016.08.011">biological identity</a>, or how the body will react to nanomedicines. This is essential information in evaluating how effective and safe new treatments are. </p>
<p>I’m a researcher studying <a href="https://scholar.google.com/citations?user=D-qg1JwAAAAJ&hl=en">overlooked factors in nanomedicine development</a>. In our <a href="https://doi.org/10.1038/s41467-022-34438-8">recently published research</a>, my colleagues and I found that analyses of biological identity are highly inconsistent across proteomics facilities that specialize in studying proteins.</p>
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<figcaption><span class="caption">Gold is one of the materials used in nanotechnologies.</span></figcaption>
</figure>
<h2>Inconsistent results</h2>
<p>Nanomedicines, just like with all medications, are surrounded by proteins from the body once they come into contact with the bloodstream. This protein coating, known as a <a href="https://doi.org/10.1016/j.ijbiomac.2020.12.108">protein corona</a>, gives nanoparticles a biological identity that determines how the body will recognize and interact with it, like how the immune system has specific reactions against certain pathogens and allergens.</p>
<p>Knowing the precise type, amount and configuration of the proteins and other biomolecules attached to the surface of nanomedicines is critical to determine safe and effective dosages for treatments. However, one of the <a href="https://doi.org/10.1038/s41467-021-27643-4">few available approaches</a> to analyze the composition of protein coronas requires instruments that many nanomedicine laboratories lack. So these labs typically send their samples to separate proteomics facilities to do the analysis for them. Unfortunately, many facilities use <a href="https://doi.org/10.1038/s41587-019-0037-y">different sample preparation methods and instruments</a>, which can lead to differences in results.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/502192/original/file-20221220-20-iflyr8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Cryo-electron microscopy images of protein coronas on nanoparticles" src="https://images.theconversation.com/files/502192/original/file-20221220-20-iflyr8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/502192/original/file-20221220-20-iflyr8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=900&fit=crop&dpr=1 600w, https://images.theconversation.com/files/502192/original/file-20221220-20-iflyr8.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=900&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/502192/original/file-20221220-20-iflyr8.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=900&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/502192/original/file-20221220-20-iflyr8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1131&fit=crop&dpr=1 754w, https://images.theconversation.com/files/502192/original/file-20221220-20-iflyr8.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1131&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/502192/original/file-20221220-20-iflyr8.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1131&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Protein coronas give nanoparticles their biological identities. Images A to C show nanoparticles without protein coronas, while images D to F show proteins (black dots) coating the surface of the particles.</span>
<span class="attribution"><a class="source" href="https://doi.org/10.1038/s41467-022-34438-8">Ashkarran et al. (2022)/Nature Communications</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>We wanted to test how consistently these proteomics facilities analyzed protein corona samples. To do this, my colleagues and I sent biologically identical protein coronas to 17 different labs in the U.S. for analysis. </p>
<p>We had striking results: <a href="https://doi.org/10.1038/s41467-022-34438-8">Less than 2%</a> of the proteins the labs identified were the same. </p>
<p>Our results reveal an extreme lack of consistency in the analyses researchers use to understand how nanomedicines work in the body. This may pose a significant challenge not only to ensuring the accuracy of diagnostics, but also the effectiveness and safety of treatments based on nanomedicines.</p>
<h2>Why standardize nanomedicine?</h2>
<p>Researchers have been working to improve the safety and efficacy of nanomedicine through various approaches. These include modifying study protocols, methodologies and analytical techniques to <a href="https://doi.org/10.1038/s41565-018-0246-4">standardize the field</a> and improve the reliability of nanomedicine data.</p>
<p>Aligned with these efforts, my team and I have identified several critical but often overlooked factors that can influence the performance of a nanomedicine, such as a <a href="https://doi.org/10.1038/s41467-021-23230-9">person’s sex</a>, <a href="https://doi.org/10.1039/C4BM00131A">prior medical conditions</a> and <a href="https://doi.org/10.1039/C9NH00097F">disease type</a>. Taking these factors into account when designing studies and interpreting results could enable researchers to produce more reliable and accurate data and lead to better nanomedicine treatments.</p><img src="https://counter.theconversation.com/content/196652/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Morteza Mahmoudi receives funding from the U.S. National Institute of Diabetes and Digestive and Kidney Diseases (grant DK131417). He is affiliated with PGWC, NanoServ, and Target's Tip. He is a co-founder and director of the Academic Parity Movement (<a href="http://www.paritymovement.org">www.paritymovement.org</a>), a non-profit organization dedicated to addressing academic discrimination, violence and incivility. He receives royalties/honoraria for his published books, plenary lectures, and licensed patents. </span></em></p>The proteins that cover nanoparticles are essential to understanding how they work in the body. Across 17 proteomics facilities in the US, less than 2% of the identified proteins were identical.Morteza Mahmoudi, Assistant Professor of Radiology, Michigan State UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1908762022-11-23T13:19:17Z2022-11-23T13:19:17ZWhat is ethical animal research? A scientist and veterinarian explain<figure><img src="https://images.theconversation.com/files/493593/original/file-20221104-24-tgu2zn.jpg?ixlib=rb-1.1.0&rect=23%2C17%2C1972%2C1478&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Animal research's benefits are clear -- but public awareness of what it involves is not.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/woman-wearing-boiler-suit-and-mask-standing-in-room-royalty-free-image/200399533-001?phrase=%22woman%20wearing%20boiler%20suit%22&adppopup=true">Javier Pierini/DigitalVision via Getty Images</a></span></figcaption></figure><p>A <a href="https://www.reuters.com/world/europe/switzerland-vote-becoming-first-nation-ban-animal-testing-2022-02-13/">proposed measure</a> in Switzerland would have made that country the first to ban medical and scientific experimentation on animals. It failed to pass in February 2022, with only 21% of voters in favor. Yet globally, <a href="https://www.congress.gov/bill/117th-congress/house-bill/8699?s=1&r=8">including in the United States</a>, there is concern about whether animal research is ethical.</p>
<p>We are scientists who support ethical animal research that reduces suffering of humans and animals alike by helping researchers <a href="https://fbresearch.org/medical-advances/animal-research-achievements/">discover the causes of disease and how to treat it</a>. One of us is a <a href="https://scholar.google.com/citations?user=JxIoO1sAAAAJ&hl=en&oi=ao">neuroscientist</a> who studies <a href="https://www.apa.org/ptsd-guideline/treatments/prolonged-exposure">behavioral treatments</a> and <a href="https://doi.org/10.1038/s41398-022-01952-8">medications</a> for people with post-traumatic stress disorder – treatments made possible by <a href="https://doi.org/10.1016%2Fj.nlm.2013.11.014">research with dogs and rodents</a>. The other is a <a href="https://www.enprc.emory.edu/research/divisions/animal_resources/Stammen_Rachelle_L.html">veterinarian</a> who cares for laboratory animals in research studies and trains researchers on how to interact with their subjects. </p>
<p>We both place high importance on ensuring that animal research is conducted ethically and humanely. But what counts as “ethical” animal research in the first place?</p>
<h2>The 4 R’s of animal research</h2>
<p>There is no single standard definition of ethical animal research. However, it broadly means the humane care of research animals – from their acquisition and housing to the study experience itself.</p>
<p>Federal research agencies follow <a href="https://olaw.nih.gov/policies-laws/gov-principles.htm">guiding principles</a> in evaluating the use and care of animals in research. One is that the research must increase knowledge and, either directly or indirectly, have the potential to benefit the health and welfare of humans and other animals. Another is that only the minimum number of animals required to obtain valid results should be included. Researchers must use procedures that minimize pain and distress and maximize the animals’ welfare. They are also asked to consider whether they could use nonanimal alternatives instead, such as mathematical models or computer simulations.</p>
<p>These principles are summarized by the “<a href="https://flexiblelearning.auckland.ac.nz/medsci303/15/1/1/files/overview_of_3rs.pdf">3 R’s” of animal research</a>: reduction, refinement and replacement. The 3 R’s encourage scientists to develop new techniques that allow them to replace animals with appropriate alternatives. </p>
<figure class="align-center ">
<img alt="Two men bend over a microscope in an office with big glass walls overlooking water." src="https://images.theconversation.com/files/493596/original/file-20221104-11-6zdg0h.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/493596/original/file-20221104-11-6zdg0h.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/493596/original/file-20221104-11-6zdg0h.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/493596/original/file-20221104-11-6zdg0h.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/493596/original/file-20221104-11-6zdg0h.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/493596/original/file-20221104-11-6zdg0h.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/493596/original/file-20221104-11-6zdg0h.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="caption">L'Oreal Brazil CEO Marcelo Zimet looks at microscope samples at the Episkin laboratory, which has developed alternative methods to animal testing.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/loreal-brazil-ceo-marcelo-zimet-looks-on-a-microscope-news-photo/1240792707?phrase=%22animal%20testing%22%20brazil&adppopup=true">Mauro Pimentel/AFP via Getty Images</a></span>
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</figure>
<p>Since these guidelines were first disseminated in the <a href="https://caat.jhsph.edu/principles/the-principles-of-humane-experimental-technique">early 1960s</a>, new tools have helped to <a href="https://doi.org/10.1371/journal.pone.0101638">significantly decrease</a> animal research. In fact, since 1985, the number of animals in research has been <a href="https://speakingofresearch.com/facts/statistics/">reduced by half</a>.</p>
<p>A fourth “R” was formalized in the late 1990s: <a href="https://doi.org/10.4103%2F2229-5070.113884">rehabilitation</a>, referring to care for animals after their role in research is complete.</p>
<p>These guidelines are designed to ensure that researchers and regulators consider the costs and benefits of using animals in research, focused on the good it could provide for many more animals and humans. These guidelines also ensure protection of a group – animals – that cannot consent to its own participation in research. There are a number of human groups that cannot consent to research, either, such as infants and young children, but for whom regulated research is still permitted, so that they can <a href="https://philarchive.org/archive/MARART-26">gain the potential benefits from discoveries</a>. </p>
<h2>Enforcing ethics</h2>
<p>Specific <a href="https://www.hopkinsmedicine.org/research/resources/offices-policies/animal-care/">guidelines</a> for ethical animal research are typically established by <a href="https://www.ncbi.nlm.nih.gov/books/NBK24650/">national governments</a>. <a href="https://www.aaalac.org">Independent organizations</a> also provide research standards.</p>
<p>In the U.S., the <a href="http://www.nal.usda.gov/animal-health-and-welfare/animal-welfare-act">Animal Welfare Act</a> protects all warmblooded animals except rats, mice and birds bred for research. Rats, mice and birds are protected – along with fish, reptiles and all other vertebrates – by the <a href="https://olaw.nih.gov/policies-laws/phs-policy.htm">Public Health Service Policy</a>. </p>
<p>Each institution that conducts animal research has an entity called the <a href="https://olaw.nih.gov/resources/tutorial/iacuc.htm">Institutional Animal Care and Use Committee</a>, or IACUC. The IACUC is composed of veterinarians, scientists, nonscientists and members of the public. Before researchers are allowed to start their studies, the IACUC reviews their research protocols to ensure they follow national standards. The IACUC also oversees studies after approval to continually enforce ethical research practices and animal care. It, along with the <a href="https://www.aphis.usda.gov/aphis/ourfocus/animalwelfare/SA_AWA/CT_AWA_Inspections">U.S. Department of Agriculture</a>, accreditation agencies and funding entities, may conduct unannounced inspections.</p>
<p>Laboratories that violate standards may be fined, forced to stop their studies, excluded from research funding, ordered to cease and desist, and have their licenses suspended or revoked. Allegations of misconduct are also investigated by the <a href="https://olaw.nih.gov/home.htm">National Institutes of Health’s Office of Laboratory Animal Welfare</a>.</p>
<p>Above and beyond the basic national standards for humane treatment, research institutions across 47 countries, including the U.S., may seek voluntary accreditation by a nonprofit called the <a href="https://ar.aaalac.org/about/index.cfm">Association for Assessment and Accreditation of Laboratory Animal Care</a>, or AAALAC International. <a href="https://www.unthsc.edu/research/wp-content/uploads/sites/21/Benefits-of-AAALAC-Accreditation.pdf">AAALAC accreditation</a> recognizes the maintenance of high standards of animal care and use. It can also help recruit scientists to accredited institutes, promote scientific validity and demonstrate accountability.</p>
<h2>Principles in practice</h2>
<p>So what impact do these guidelines actually have on research and animals?</p>
<p>First, they have made sure that scientists create protocols that describe the purpose of their research and why animals are necessary to answer a meaningful question that could benefit health or medical care. While computer models and cell cultures can play an important role in some research, others studies, like those on <a href="https://theconversation.com/expanding-alzheimers-research-with-primates-could-overcome-the-problem-with-treatments-that-show-promise-in-mice-but-dont-help-humans-188207">Alzheimer’s disease</a>, need animal models to better capture the complexities of living organisms. The protocol must outline how animals will be housed and cared for, and who will care for and work with the animals, to ensure that they are trained to treat animals humanely. </p>
<p>During continual study oversight, inspectors look for whether animals are provided with housing specifically designed for their species’ behavioral and social needs. For example, mice are given nesting materials to create a <a href="https://med.stanford.edu/animalresearch/animal-care-and-facilities/animal-well-being-at-stanford.html">comfortable environment for living and raising pups</a>. When animals don’t have environmental stimulation, it can alter their <a href="https://doi.org/10.1016/S0166-2236(00)01718-5">brain function</a> – harming not only the animal, but also the science.</p>
<p>Monitoring agencies also consider animals’ distress. If something is known to be painful in humans, it is assumed to be painful in animals as well. Sedation, painkillers or anesthesia must be provided when animals experience more than momentary or slight pain.</p>
<p>For some research that requires assessing organs and tissues, such as the study of heart disease, animals must be euthanized. Veterinary professionals perform or oversee the euthanasia process. Methods must be in compliance with guidelines from the <a href="https://www.avma.org/resources-tools/avma-policies/avma-guidelines-euthanasia-animals">American Veterinary Medical Association</a>, which requires rapid and painless techniques in distress-free conditions. </p>
<p>Fortunately, following their time in research, some animals can be <a href="https://www.hopkinsmedicine.org/research/resources/offices-policies/animal-care/">adopted</a> into <a href="https://homesforanimalheroes.com/">loving homes</a>, and others may be retired to <a href="https://chimphaven.org">havens and sanctuaries</a> equipped with veterinary care, nutrition and enrichment.</p>
<h2>Continuing the conversation</h2>
<p>Animal research benefits both humans and animals. Numerous medical advances exist because they were initially studied in animals – from treatments for <a href="https://www.understandinganimalresearch.org.uk/application/files/7016/4380/3819/medical-advances-and.pdf">cancer</a> and <a href="https://psycnet.apa.org/doi/10.1111/j.1749-6632.1985.tb37592.x">neurodegenerative disease</a> to new techniques for surgery, <a href="https://www.ncbi.nlm.nih.gov/books/NBK218274/">organ transplants</a> and <a href="https://doi.org/10.1093/ilar.49.1.1">noninvasive imaging and diagnostics</a>. </p>
<p>These advances also benefit zoo animals, wildlife and endangered species. Animal research has allowed for the <a href="https://doi.org/10.3201%2Feid1612.100923">eradication of certain diseases in cattle</a>, for example, leading not only to reduced farm cattle deaths and human famine, but also to improved health for wild cattle. <a href="https://nap.nationalacademies.org/read/10089/chapter/7">Health care advances for pets</a> – including <a href="https://doi.org/10.1158/1535-7163.MCT-16-0637">cancer treatments</a>, effective vaccines, nutritional prescription diets and flea and tick treatments – are also available thanks to animal research.</p>
<p>People who work with animals in research have attempted to <a href="https://www.bradglobal.org/">increase public awareness</a> of <a href="https://doi.org/10.1038/s41593-022-01039-z">research standards and the positive effects</a> animal research has had on daily life. However, some have faced harassment and violence from <a href="http://www.sciencedaily.com/releases/2009/09/090915174319.htm">anti-animal research activists</a>. Some of our own colleagues have received death threats.</p>
<p>Those who work in animal research share a deep appreciation for the creatures who make this work possible. For future strides in biomedical care to be possible, we believe that research using animals must be protected, and that animal health and safety must always remain the top priority.</p>
<p><em>Editor’s note: One photo depicting a species that is highly restricted for use in biomedical research has been removed from the article.</em></p><img src="https://counter.theconversation.com/content/190876/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Lana Ruvolo Grasser, Ph.D. is the 2022-2023 American College of Neuropsychopharmacology, Americans for Medical Progress Biomedical Research Awareness Day Fellow. She has previously received funding from the National Institute of Mental Health, Blue Cross Blue Shield Foundation of Michigan, and Wayne State University; none of which has supported the work described herein. She is a member of the Anxiety and Depression Association of America, International Society for Traumatic Stress Studies, International Society for Developmental Psychobiology, and Michigan Society for Neuroscience. Dr. Grasser contributed to this article in her personal capacity. The views expressed are her own and do not necessarily represent the views of the National Institutes of Health or the United States Government. </span></em></p><p class="fine-print"><em><span>Rachelle Stammen works as a Clinical Veterinarian at the Emory National Primate Research Center. She is a member of the American Veterinary Medical Association, American Association of Laboratory Animal Science, Association of Primate Veterinarians, and a Diplomate of the American College of Laboratory Animal Medicine. This work is not affiliated with or reflect the opinions of Emory University or Emory National Primate Research Center. </span></em></p>Guidelines and regulations weigh the medical and health benefits of animal research with researchers’ ability to ensure humane care of their subjects from start to finish.Lana Ruvolo Grasser, Postdoctoral Research Fellow in Neuroscience, National Institutes of HealthRachelle Stammen, Clinical Veterinarian, Emory National Primate Research Center, Emory UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1842872022-08-08T17:23:34Z2022-08-08T17:23:34ZAltruism – but also vulnerability – drive healthy volunteers to take part in clinical research<p>When UK authorities granted permission in October 2020 for the <a href="https://www.biospace.com/article/releases/open-orphan-hvivo-signs-contract-with-uk-government-for-the-development-of-a-Covid-19-human-challenge-study-model/">first controlled infection study</a> to be carried out to test the anti-Covid-19 vaccine Oxford University had just developed, reactions ranged from disbelief to disapproval.</p>
<p>Yet this type of experiment, which exposes healthy volunteers to an infection to assess the efficacy of a vaccine or treatment (it is sometimes called a <a href="https://presse.inserm.fr/infecter-deliberement-les-volontaires-pour-accelerer-la-recherche-vaccinale-Covid-19-vraiment/41183/">‘human infection challenge’</a>), is not just a widespread practice but also an irreplaceable one in clinical research.</p>
<p>But involving healthy people in biomedical research is not risk-free, as recent tragedies have shown. In what context are these healthy volunteers enlisted? What motivates them? And how are they protected?</p>
<h2>The uncertainty of clinical research</h2>
<p>In March 2006, the firm TeGenero sought to assess the tolerance of an antibody designed to fight diseases like rheumatoid arthritis, multiple sclerosis and some leukaemias. Initial results from animal testing had proved relatively safe, so the firm decided to test the new molecule on humans. For this, TeGenero enlisted six healthy volunteers. When the drug was first administered to them, all six quickly suffered multiple organ failure. These unexpected complications were later explained: the antibody that was tested stimulated T-Cells that had previously been activated by other infections. <a href="https://www.apmnews.com/freestory/10/163717/les-graves-complications-de-l-essai-clinique-de-tegenero-seraient-dues-a-un-effet-imprevu-de-l-anticorps-tgn1412-sur-les-lymphocytes-t">These T cells are thought to have migrated to healthy organs and damaged them</a>.</p>
<p>Ten years later, in January 2016, a study commissioned by Portuguese firm Bial to test a molecule designed to relieve pain and anxiety had an even more dramatic outcome: <a href="https://www.lemonde.fr/sante/article/2016/10/11/essai-clinique-de-rennes-un-drame-en-cinq-questions_5011900_1651302.html">one of the six healthy volunteers enlisted was admitted to hospital on the fifth day of receiving daily doses of the experimental drug</a>. His condition worsened, prompting medical authorities to declare him brain dead the next day. He died a few days later.</p>
<p>These two examples are proof that biomedical research, by its very nature, leaves little clue about the benefits participants might gain from it. Yet we cannot deny the considerable scientific and social value of <a href="https://theconversation.com/essais-cliniques-pratiques-et-reglementation-en-france-53331">clinical research</a>: it has helped to develop and greenlight many treatments and operations that have increased the quality and duration of countless patients’ lives.</p>
<p>But therein lies the issue: a patient supposedly knows what the purpose of the research into their own disease is, whereas ‘healthy’ people used in clinical research have different motivations and a different understanding of the research involved.</p>
<h2>In what contexts does clinical research call on healthy volunteers?</h2>
<p>In France, any research conducted on humans is referred to, in the country’s public health code, as <a href="https://www.legifrance.gouv.fr/codes/article_lc/LEGIARTI000032722870/">‘research involving human beings’</a> without prior distinction between an ill volunteer and a healthy one.</p>
<p>Beyond preventive trials and phase-1 clinical research of medical products specific to them, healthy volunteers take part in biomedical studies that can differ wildly from one to the other. Worldwide, most studies involving healthy volunteers assess ‘bioequivalence’. Such studies are carried out to show similarity between blood levels produced by pioneering medicines and their generic versions. They are mostly conducted by specialist firms (‘Contract Research Organisations’) for pharmaceutical companies.</p>
<p>A 2017 survey identified more than <a href="https://www.cambridge.org/core/journals/cambridge-quarterly-of-healthcare-ethics/article/healthy-volunteers-for-clinical-trials-in-resourcepoor-settings-national-registries-can-address-ethical-and-safety-concerns/5D8FA3301ED03122C90DEE3F4B158096">1,000 studies involving molecules being administered to tens of thousands of healthy volunteers</a>, especially in India, China, and North America.</p>
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À lire aussi :
<a href="https://theconversation.com/essais-cliniques-pratiques-et-reglementation-en-france-53331">Essais cliniques : pratiques et réglementation en France</a>
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<p>Healthy volunteers can also be part of a <a href="https://player.vimeo.com/video/59735666">cohort</a> – a group of individuals who accept to be monitored, sometimes over several decades, to provide helpful data in epidemiology and disease evolution. Some cohorts have helped form stores of biological samples (‘biobanks’), which are subsequently used as benchmarks in clinical research.</p>
<p>The Pasteur Institute, for instance, has hosted the <a href="http://www.biobanques.eu/en/nous-connaitre/membres/item/plateforme-icareb-institut-pasteur-paris">ICAReB platform</a> since 2008. ICAReB stores biological samples from around 300 healthy donors. Other biobanks help to assess behavioural mechanisms. For example, the Paris Brain Institute hosts the <a href="https://prismeicm.wixsite.com/prisme-icm">PRISME platform</a>, which lists around 2,000 volunteers available to help develop technological solutions that assess real-life behaviour in a range of settings (waiting room, confined environments, public spaces, etc.), among others.</p>
<p>In a different context, healthy volunteers also serve as ‘comparators’ in research monitoring the victims of the <a href="https://theconversation.com/paris-terror-attacks-france-now-faces-fight-against-fear-and-exclusion-50703">13 November 2015 Paris terrorist attacks</a>.</p>
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À lire aussi :
<a href="https://theconversation.com/13-novembre-et-traumatisme-la-memoire-collective-influence-profondement-la-memoire-individuelle-150005">13 Novembre et traumatisme : « La mémoire collective influence profondément la mémoire individuelle »</a>
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<h2>What are the different “checks” that control clinical research on healthy volunteers in France?</h2>
<p>In line with the country’s public health code, any research conducted on humans in France is subject <a href="https://www.legifrance.gouv.fr/codes/article_lc/LEGIARTI000032722870/">to rulings that ensure participants’ safety and the study’s relevance</a>.</p>
<p>Just as in the case of ill volunteers, healthy individuals have to receive transparent, comprehensible information about how the study will unfold, and the risks involved. This helps formalise their consent. A medical check-up determines whether their participation complies with the criteria of inclusion and exclusion defined in the study’s formal procedure approved by France’s relevant regulatory bodies (research ethics board; ANSM, France’s public agency for assessing health risks from drugs). At any moment, a volunteer can choose to leave the study without having to justify their decision.</p>
<p>In France, healthy volunteers who take part in clinical research are registered in a national database used to track their participation, the amount they have received in compensatory payments, and their waiting period between two studies. A national database entitled <a href="https://vrb.sante.gouv.fr/">VRB</a> (a French acronym meaning ‘volunteers in biomedical research’) lists those who consent to take part in biomedical research. It is worth noting that France and <a href="https://www.hra.nhs.uk/about-us/committees-and-services/the-over-volunteering-prevention-system/">the United Kingdom</a> are the only countries in the world that have set up such a database. The measure is designed to avoid a trend in ‘career’ healthy volunteers, <a href="https://www.newscientist.com/article/mg20327181-500-perils-of-the-professional-lab-rat/">as has arisen in the US</a>.</p>
<h2>What motivates healthy volunteers?</h2>
<p>Being a volunteer in a vaccine trial, a pharmacokinetic study (which examines the fate of a drug in the body) or a cohort gives the participant a sense of belonging to a high-minded community that helps further knowledge.</p>
<p>This kind of approach can be more natural to a volunteer whose everyday activity relates to a particular field of research, like a student in healthcare. Healthy volunteers can also be people with a loved one suffering from a disease – their discovery of clinical research, their awareness of related challenges and their desire to help advance these studies boost participation rates in clinical trials. Whatever a volunteer claims drives them, the importance of their commitment for society is far from trivial.</p>
<p>Some people claim they volunteer for clinical research out of altruism, but others <a href="https://www.anrs.fr/sites/default/files/2018-04/volontaires_etudes_cliniques_prevention.pdf">do so to receive compensatory payments for taking part</a>. Could financial vulnerability be the key factor driving some into volunteering? In France, there is a cap on the yearly amount of compensatory payments a volunteer may receive for the constraints they have to undergo. But for many people, this amount still represents a sizeable sum, especially for those who are in a precarious situation.</p>
<p>Lastly, it is worth noting that not all segments of the population are equally aware of clinical research, which calls into question the ability to make research results relevant to all.</p>
<h2>Ethics and utilitarianism</h2>
<p>It is even trickier to evaluate how financial vulnerability factors in a healthy volunteer’s motivation in countries with weak ethical controls, or even in developed countries with very liberal political systems. Such case-scenarios challenge the very notion of voluntary service, especially as some research conducted <a href="https://www.lexpress.fr/culture/tele/2061-deces-attribues-aux-essais-cliniques-en-inde_1322142.html">outside of adequate regulatory frameworks</a> or on vulnerable <a href="https://www.nature.com/news/human-experiments-first-do-harm-1.9980">populations in developed countries</a> has created a climate of distrust in which healthy volunteers feel exploited.</p>
<p>A volunteer can be led to commit to a clinical study by believing the benefit they gain from taking part – whether it be income or access to primary healthcare in some economic contexts – outweighs any risk they are taking. Yet a volunteer’s vulnerable situation cannot be a criterion of exclusion from any research, as such exclusion would aggravate the volunteer’s vulnerability in two ways: materially, by stripping them of the benefit they expect, and symbolically, by stripping them of their freedom of choice.</p>
<p>Torn between utilitarian guilt and a desire to serve society, researchers are helpless in the face of this dilemma.</p>
<h2>Reducing vulnerable situations</h2>
<p>Though our societies have set standards of arbitration and validation through bodies that regulate research, healthy volunteers should be able to be truly free to decide whether to join the handful of people who take on a risk for the common good.</p>
<p>It is therefore crucial to reduce vulnerable situations so that ethical research can be conducted with respect for healthy volunteers. This can be achieved by helping them <a href="https://www.hal.inserm.fr/inserm-02111121/document">better understand the challenges of the research they will accept to contribute to</a>, and better assess the risks they will be taking. Moreover, information provided to garner <a href="https://www.hal.inserm.fr/inserm-02111121/document#page=5">informed consent</a>, a critical dimension of clinical research, should be tailored to potential cases of vulnerability – especially economic and educational – specific to healthy volunteers. Lastly, widespread global use of national databases, like those used in France and the UK, would help better regulate research that involves healthy volunteers and therefore protect them.</p>
<p>Exposing healthy volunteers to risks that are not always under control routinely calls into question the dilemma between research that can be very useful to many and a risk taken by a few. In the current pandemic, this dilemma has prompted France to give up on infecting healthy volunteers to test anti-Covid-19 vaccines.</p>
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<p><em><a href="https://dndi.org/our-people/bompart/">François Bompart</a>, chair of the access committee at the Drugs for Neglected Diseases Initiative (DNDi), a Swiss non-profit research organisation that develops treatments for neglected diseases, contributed to this article. The authors would also like to thank Mylène Botbol-Baum, Didier Dreyfuss, Christine Lemaitre, Pierre Lombrail, Flavie Mathieu, and Corinne Sebastiani, the other members of the working group <a href="https://www.inserm.fr/en/ethics/ethics-committees-theme-based-think-tanks/">‘Health Research in Resource-Limited Countries’</a>, part of the ethics committee of INSERM, a French public institute for health and medical research.</em></p>
<p><em>This text was published following activities developed as part of the European project <a href="http://www.trust-project.eu">‘Creating and Enhancing TRUSTworthy, Responsible and Equitable Partnerships in International Research’</a>. It was translated from the French by Thomas Young for <a href="http://www.fastforword.fr/en">Fast ForWord</a></em></p><img src="https://counter.theconversation.com/content/184287/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Les auteurs ne travaillent pas, ne conseillent pas, ne possèdent pas de parts, ne reçoivent pas de fonds d'une organisation qui pourrait tirer profit de cet article, et n'ont déclaré aucune autre affiliation que leur organisme de recherche.</span></em></p>What prompts healthy volunteers to take part in clinical research? And how are they protected?Isabelle Remy-Jouet, Ethicienne, Membre du comité Éthique de l'Inserm, Mission DD&RS, Université d'AngersFrançois Eisinger, Professeur associé en santé publique, praticien hospitalier au centre de lutte contre le cancer Institut Paoli-Calmettes, InsermFrançois Hirsch, Membre du comité d'éthique de l'Inserm, InsermLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1821422022-06-20T17:41:45Z2022-06-20T17:41:45ZPeer review: Can this critical step in the publication of science research be kinder?<figure><img src="https://images.theconversation.com/files/469531/original/file-20220617-14-piidla.jpg?ixlib=rb-1.1.0&rect=10%2C107%2C6201%2C4691&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">It can be painful for researchers to read harshly worded criticism of their work from peer reviewers.</span> <span class="attribution"><span class="source">(Shutterstock)</span></span></figcaption></figure><p>Democracy has been called the least worst system of government. Peer review is the least worst system for assessing the merit of scientific work. </p>
<p>Peer review is the written evaluation of a paper by other experts in the field. Though this sounds like assessment by equals, the power imbalance created by the roles of reviewer and reviewed distorts the relationship and affects the tone of the review. Reviews can be patronizing, demanding and unkind. </p>
<p>It is painful to read harshly worded criticism of work that has taken a team hundreds or thousands of hours and been submitted hopefully and in good faith. From our experience, we know that reviews can be accurate, robust and make every scientific point while using language and tone that is helpful and supportive.</p>
<h2>Supportive review</h2>
<p>We are a team of editors of an open-access Canadian kidney journal, the <a href="https://journals.sagepub.com/home/cjk"><em>Canadian Journal of Kidney Health and Disease</em></a>. When we founded our journal in 2014, supportive review was the <a href="https://doi.org/10.1186%2F2054-3581-1-1">first of our guiding principles</a>. Since then, we have written supportively as editors, selected reviewers who write supportively and participated in training <a href="https://kidney.ca/Krescent/Home">the next generation of Canadian kidney scientists</a> to conduct reviews that are complete, rigorous and kind. </p>
<p><div data-react-class="Tweet" data-react-props="{"tweetId":"1536639120843362304"}"></div></p>
<p>Supported by a larger group of like-minded people from multiple disciplines, we recently published <a href="https://doi.org/10.1177%2F20543581221080327">an editorial</a> outlining these principles. A dozen other kidney journals expressed their support for the idea, with <a href="https://dx.doi.org/10.1038/s41581-022-00569-w"><em>Nature Reviews Nephrology</em></a>, <a href="https://doi.org/10.1093/ndt/gfac183"><em>NDT</em></a> and <a href="https://doi.org/10.1007/s00467-022-05535-z"><em>Pediatric Nephrology</em></a> publishing co-ordinated editorials recommitting to principles of constructive criticism.</p>
<h2>The long process of research</h2>
<p>Scientific papers condense a large amount of work into a structured format, usually no longer than four to eight times the length of this article. The work of a paper starts with an idea that may be developed by the team for a year or more before it crystallizes into an application for funding, which may go through rounds of revisions. </p>
<p>Once funded, people and budgets are assigned to the project and the work proceeds. The work can involve the time of multiple team members for months and even years.</p>
<p>When the work is complete, they write a paper, detailing what they did, how and why, what they found and what they think it means. This paper itself is often the product of hundreds of hours of work, with multiple authors contributing their specific expertise and working on the messaging of the whole.</p>
<p><div data-react-class="Tweet" data-react-props="{"tweetId":"1171575490760630276"}"></div></p>
<p>The journal receives the manuscript and assigns an editor, who assigns peer reviewers. Peer reviewers are other scientists working on similar topics. They must be totally unconnected with the people writing the paper. With notable exceptions, most journals employ single-masked peer review: the reviewer sees the authorship of the paper but the authors of the paper will not see who wrote the review.</p>
<p>Peer reviewers are not paid or rewarded for their review of the manuscript — they take it on as part of the work of academic life. Essentially, it is an unrewarded activity performed by people who are themselves authors. It varies by discipline, but in biomedicine, they may spend three to six hours on a review.</p>
<h2>Harsh reviews</h2>
<p>How does this altruistic activity, undertaken by a reviewer who is very familiar with the author role, lead to such pain and frustration for other authors? </p>
<p>We think that scientists sometimes confuse harshness with intellectual rigour and that a reviewer’s experience of harshness in reviews of their own work, amplified by the power imbalance between reviewer and reviewed, leads to perpetuation of harsh and unhelpful review. Other reviewers and editors avoid these pitfalls entirely.</p>
<p><div data-react-class="Tweet" data-react-props="{"tweetId":"1506915328705630214"}"></div></p>
<p>“It looks to me like one of your first attempts at scientific publishing, and I can understand that you are also writing in a non-native language” <a href="https://twitter.com/IngridAnell/status/1506915328705630214?s=20&t=2SF4MYOmeNiFo2XW6kNREg">wrote one anonymous reviewer</a> to a mid-career woman scientist with 13 first-author peer-reviewed publications. “I just want to give up today,” she wrote. </p>
<p>But she won’t. Scientists are prepared to receive this kind of feedback and be hurt over and over in the name of science. As editors, we believe there is a better way — that feedback should be rigorous, but will be more readily incorporated if kindly given, to the advancement of science.</p>
<p><div data-react-class="Tweet" data-react-props="{"tweetId":"1498156968778866693"}"></div></p>
<p>These are not new ideas. In 2006, Prof. Mohan Dutta suggested <a href="https://doi.org/10.1207/s15327027hc2002_11">10 commandments for reviewers</a>, all of which focus on the collaborative nature of relationship between reviewer and reviewed. Advice for reviewers often includes a recommendation to write constructively, though sometimes this is phrased as something like “write constructively, and then turn to criticism,” as if those are mutually exclusive. </p>
<p>We can take this principal further and — thanks to our community of reviewers in kidney medicine — we and other kidney journals make a commitment to kindness in review. Dutta’s 10th commandment is “do unto others as you would have them do unto you.” Every branch of science would be improved by implementing this idea.</p><img src="https://counter.theconversation.com/content/182142/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Catherine Clase has received consultation, advisory board membership or research funding from the Ontario Ministry of Health, Sanofi, Pfizer, Leo Pharma, Astellas, Janssen, Amgen, Boehringer-Ingelheim and Baxter. In 2018 she co-chaired a KDIGO potassium controversies conference sponsored at arm's length by Fresenius Medical Care, AstraZeneca, Vifor Fresenius Medical Care, Relypsa, Bayer HealthCare and Boehringer Ingelheim. Catherine is a member of the Cloth Mask Knowledge Exchange, a research and knowledge translation group that includes industry stakeholders. Industry stakeholders contribute to the Cloth Mask Knowledge Exchange by contributing to grant funding, and through in-kind contributions of time and expertise. Industry stakeholders make masks and distribute polypropylene and other fabrics. She is a member of McMaster's Centre of Excellence in Protective Equipment and Materials, and editor-in-chief of clothmasks.org. Catherine Clase receives funding from CIHR, and is a member of the Green Party, the American Society of Nephrology, the Canadian Society of Nephrology, the American Association of Textile Chemists and Colorists and ASTM International.</span></em></p><p class="fine-print"><em><span>Josee Bouchard receives funding from CIHR, Kidney Foundation of Canada and CDTRP. She is affiliated with the Hopital Sacré-Coeur de Montréal, Université de Montréal. She is a member of the Canadian Society of Nephrology and American Society of Nephrology.</span></em></p><p class="fine-print"><em><span>Manish M Sood receives funding from CIHR, the Kidney Foundation of Canada, the Canadian Medical Association and the Heart and stroke foundation. He is supported by the Jindal Research Chair. He has received speaker fees from Astrazeneca. He is affiliated with the Ottawa Hospital Research Institute, uOttawa and the Ottawa Hospital.</span></em></p><p class="fine-print"><em><span>Rachel Holden receives research funding from CIHR, the South Eastern Ontario Medical Organization, and the Translational Institute of Medicine at Queen's University, Kingston, Ontario. She has received investigator initiated research funding from OPKO Renal. She has received consultation or advisory board funding from Sanofi, Bayer and Oksuka. She is a member of the Canadian Society of Nephrology.</span></em></p><p class="fine-print"><em><span>Sunny Hartwig does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Peer review of research sounds like it should be a conversation between equals. Instead, it can be patronizing, demanding and simply unkind. A group of journal editors thinks this should change.Catherine Clase, Professor of Medicine, Epidemiologist, Physician, McMaster UniversityJosee Bouchard, Nephrologist, Professor of Medicine, Université de MontréalManish M Sood, Physician, Professor of Medicine, L’Université d’Ottawa/University of OttawaRachel Holden, Professor of Medicine, Queen's University, OntarioSunny Hartwig, Associate Professor, University of Prince Edward IslandLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1772402022-04-28T17:00:17Z2022-04-28T17:00:17ZSex matters in biomedical research: Many conditions affect men and women differently<figure><img src="https://images.theconversation.com/files/460120/original/file-20220427-14-wpobmy.jpg?ixlib=rb-1.1.0&rect=268%2C391%2C4358%2C2813&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Until recently, most biomedical studies did not consider sex or gender.</span> <span class="attribution"><span class="source">(Pexels/Magda Ehlers)</span></span></figcaption></figure><iframe style="width: 100%; height: 100px; border: none; position: relative; z-index: 1;" allowtransparency="" allow="clipboard-read; clipboard-write" src="https://narrations.ad-auris.com/widget/the-conversation-canada/sex-matters-in-biomedical-research--many-conditions-affect-men-and-women-differently" width="100%" height="400"></iframe>
<p><a href="https://cihr-irsc.gc.ca/e/48804.html">Biomedical research</a> — a broad term covering studies on subjects ranging from cells to experimental animal models — is the starting point for understanding how diseases develop and how we might prevent or treat them. Once such studies have been performed successfully, similar tests can be carried out in humans. These clinical trials form the highest branch of biomedical research. </p>
<p>Biomedical studies have traditionally used <a href="https://cihr-irsc.gc.ca/e/51310.html#a1">male animals and men as research subjects</a>, and the knowledge we have obtained from this research has been applied to both sexes on the assumption that what works for males must also work for females. </p>
<p>Until recently, these studies hardly ever <a href="https://www.canada.ca/en/health-canada/corporate/transparency/corporate-management-reporting/heath-portfolio-sex-gender-based-analysis-policy.html">considered sex — the biological attributes of humans and animals</a> — or gender, the socially constructed characteristics of men, women and gender-diverse people. </p>
<p>That is a problem for everyone, because there are <a href="https://cihr-irsc.gc.ca/e/50833.html">sex differences in how many diseases affect people</a>.</p>
<h2>Sex differences in health conditions</h2>
<p>Pre-menopausal women are <a href="https://doi.org/10.1016/j.jcjd.2020.01.003">less likely to develop diabetes than men or post-menopausal women</a>. Differences like these are critical, given that the elevated levels of blood glucose that define diabetes can lead to life-threatening stroke and heart attacks. </p>
<p>Another significant difference is that women don’t necessarily experience the symptoms of a heart attack that are typical in men — like chest pain — but could <a href="https://www.mayoclinic.org/diseases-conditions/heart-disease/in-depth/heart-disease/art-20046167#:%7E:text=Women%20are%20more%20likely%20than,in%20one%20or%20both%20arms">instead feel nauseated, light-headed or unusually tired</a>. Without studying women and men, we wouldn’t know about these differences and understand what to look for when diagnosing patients. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/460121/original/file-20220427-12-wbxr01.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Nine hands, each presenting a wooden puzzle piece" src="https://images.theconversation.com/files/460121/original/file-20220427-12-wbxr01.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/460121/original/file-20220427-12-wbxr01.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=300&fit=crop&dpr=1 600w, https://images.theconversation.com/files/460121/original/file-20220427-12-wbxr01.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=300&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/460121/original/file-20220427-12-wbxr01.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=300&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/460121/original/file-20220427-12-wbxr01.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=377&fit=crop&dpr=1 754w, https://images.theconversation.com/files/460121/original/file-20220427-12-wbxr01.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=377&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/460121/original/file-20220427-12-wbxr01.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=377&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">Researchers are taking significant steps to ensure biomedical research is more authentic and complete.</span>
<span class="attribution"><span class="source">(Canva)</span></span>
</figcaption>
</figure>
<p>Researchers still haven’t figured out exactly how pre-menopausal women are protected from diabetes and how this illness increases the risk of stroke and heart attacks. This is the main focus of <a href="https://fhs.mcmaster.ca/medsci/faculty/werstuck_geoff.html">research carried out in our lab</a>, where we actively study the mechanisms of this protection and how these diseases develop and progress using male and female animal models. </p>
<p>On average, <a href="https://elifesciences.org/articles/63425">women live longer than men</a>. That seems to suggest women have some kind of health advantage, which is not necessarily accurate.</p>
<p>Although it’s true <a href="https://doi.org/10.1016/j.ajpath.2021.05.011">women are less prone to diabetes, heart attack, stroke and infection</a>, they are likely to face other kinds of illness. Most <a href="https://doi.org/10.7759/cureus.8094">individuals with autoimmune diseases, for example, are women</a>, as we see with arthritis and multiple sclerosis. In these disorders, the immune system, which is supposed to protect us against external invaders such as viruses and bacteria, attacks the body.</p>
<p>It’s clear that research that only looks at male subjects is not telling the whole story. There is a need to evaluate research by how — and on whom — studies are carried out. Can we really generalize a finding when 50 per cent of the population isn’t represented in the study?</p>
<h2>Including both sexes in research</h2>
<figure class="align-right ">
<img alt="A male and female icon against a jigsaw puzzle, with a not equals sign on the missing piece" src="https://images.theconversation.com/files/460122/original/file-20220427-21-amt7q3.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/460122/original/file-20220427-21-amt7q3.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=500&fit=crop&dpr=1 600w, https://images.theconversation.com/files/460122/original/file-20220427-21-amt7q3.jpeg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=500&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/460122/original/file-20220427-21-amt7q3.jpeg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=500&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/460122/original/file-20220427-21-amt7q3.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=628&fit=crop&dpr=1 754w, https://images.theconversation.com/files/460122/original/file-20220427-21-amt7q3.jpeg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=628&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/460122/original/file-20220427-21-amt7q3.jpeg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=628&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Research that only looks at male subjects is not telling the whole story.</span>
<span class="attribution"><span class="source">(Canva)</span></span>
</figcaption>
</figure>
<p>The good news is that in recent years, and in light of the observations of sex differences in the development of diseases, researchers are taking significant steps to ensure biomedical research is more authentic and complete.</p>
<p>In fact, the major research funding agencies in North America now <a href="https://doi.org/10.1210/en.2017-03019">require that studies in humans include female subjects</a>, and that in scientific research using cells and animals, the results should feature both sexes.</p>
<p>Such steps are enormously important because they help researchers better understand the mechanisms and trends they observe and the influence that sex and gender can have on everyone’s health. A more inclusive approach to research will lead to better preventive, diagnostic and therapeutic strategies and fewer health risks.</p>
<p>Though men, women and gender-diverse people share many similarities, understanding how sex differences are expressed through physical health is paramount to improving everyone’s quality of life.</p><img src="https://counter.theconversation.com/content/177240/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Monica De Paoli does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Biomedical studies have traditionally used male animals and men as research subjects. That is a problem for everyone because for many diseases, there are sex differences in how they affect people.Monica De Paoli, Postdoctoral Fellow, Medical Sciences, McMaster UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1761342022-03-20T11:43:17Z2022-03-20T11:43:17ZMajor study shows the need to improve how scientists approach early-stage cancer research<figure><img src="https://images.theconversation.com/files/452401/original/file-20220316-15-1tmf3hp.jpg?ixlib=rb-1.1.0&rect=726%2C0%2C4837%2C2952&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Preclinical research — the kind that takes place before testing on humans — often guides decisions about which potential treatments should continue to clinical trials. But attempts to replicate 50 studies found the odds of getting the same results were only about 50-50.</span> <span class="attribution"><span class="source">(Pexels/Artem Podrez)</span></span></figcaption></figure><iframe style="width: 100%; height: 175px; border: none; position: relative; z-index: 1;" allowtransparency="" src="https://narrations.ad-auris.com/widget/the-conversation-canada/major-study-shows-the-need-to-improve-how-scientists-approach-early-stage-cancer-research" width="100%" height="400"></iframe>
<p>Preclinical studies, the kind that scientists perform before testing in humans, don’t get as much attention as their clinical counterparts. But they are the vital first steps to eventual treatments and cures. It’s important to get preclinical findings right. When they are wrong, scientists waste resources pursuing false leads. Worse, false findings can trigger <a href="https://doi.org/10.1186/s41231-019-0050-7">clinical studies with humans</a>. </p>
<p>Last December, the Center for Open Science (COS) released the worrying results of its eight-year $US 1.5 million <em><a href="https://doi.org/10.7554/eLife.71601">Reproducibility Project: Cancer Biology</a></em> study. Done in collaboration with research marketplace <a href="https://ww2.scienceexchange.com/s/about">Science Exchange</a>, independent scientists found that the odds of replicating results of 50 preclinical experiments from 23 high-profile published studies were no better than a coin toss. </p>
<p>Praise and controversy have followed the project from the beginning. The journal <em>Nature</em> applauded the replication studies as “<a href="https://doi.org/10.1038/541259b">the practice of science at its best</a>.” But the journal <em>Science</em> noted that reactions from some scientists whose studies were chosen ranged from “<a href="https://doi.org/10.1126/science.348.6242.1411">annoyance to anxiety to outrage</a>,” impeding the replications. Although none of the original experiments was described in enough detail to allow scientists to repeat them, <a href="https://doi.org/10.7554/eLife.67995">a third of the original authors were unco-operative</a>, and some were even <a href="https://www.sciencenews.org/article/cancer-biology-studies-research-replication-reproducibility">hostile</a> when asked for assistance.</p>
<figure class="align-center ">
<img alt="A person wearing PPE using a multi-channel pipette in a laboratory" src="https://images.theconversation.com/files/452293/original/file-20220315-15-60adun.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/452293/original/file-20220315-15-60adun.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=231&fit=crop&dpr=1 600w, https://images.theconversation.com/files/452293/original/file-20220315-15-60adun.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=231&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/452293/original/file-20220315-15-60adun.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=231&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/452293/original/file-20220315-15-60adun.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=291&fit=crop&dpr=1 754w, https://images.theconversation.com/files/452293/original/file-20220315-15-60adun.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=291&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/452293/original/file-20220315-15-60adun.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=291&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">It’s important to get preclinical findings right. When they are wrong, scientists waste resources pursuing false leads.</span>
<span class="attribution"><span class="source">(Shutterstock)</span></span>
</figcaption>
</figure>
<p>COS executive director Brian Nosek cautioned that the findings pose “<a href="https://www.science.org/content/article/more-half-high-impact-cancer-lab-studies-could-not-be-replicated-controversial-analysis">challenges for the credibility of preclinical cancer biology</a>.” In a tacit acknowledgement that biomedical research has not been universally rigorous or transparent, the American National Institutes of Health (NIH), the largest funder of biomedical research in the world, has announced that it will <a href="https://www.chemistryworld.com/news/replication-failures-cast-doubt-on-some-cancer-studies/4014881.article">raise requirements for both of these qualities</a>.</p>
<p>I have taught classes and written about good scientific practice in psychology and biomedicine for over 30 years. I’ve reviewed more grant applications and journal manuscripts than I can count, and I’m not surprised.</p>
<figure class="align-right ">
<img alt="A stack of journal articles, with passages highlighted in the top one, with a pen resting on top." src="https://images.theconversation.com/files/452304/original/file-20220315-21-1j5qntp.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/452304/original/file-20220315-21-1j5qntp.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/452304/original/file-20220315-21-1j5qntp.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/452304/original/file-20220315-21-1j5qntp.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/452304/original/file-20220315-21-1j5qntp.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/452304/original/file-20220315-21-1j5qntp.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/452304/original/file-20220315-21-1j5qntp.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Independent scientists found that the odds of replicating results of 50 preclinical experiments from 23 high-profile published studies were no better than a coin toss.</span>
<span class="attribution"><span class="source">(Shutterstock)</span></span>
</figcaption>
</figure>
<p>The twin pillars of trustworthy science — transparency and dispassionate rigour — have wobbled under the stress of <a href="https://royalsocietypublishing.org/doi/10.1098/rsos.160384">incentives that</a> enhance careers at the expense of reliable science. Too often, proposed preclinical studies — and surprisingly, published peer-reviewed ones — <a href="https://doi.org/10.1161/CIRCRESAHA.114.303819">don’t follow the scientific method</a>. Too often, <a href="https://doi.org/10.1089/bio.2020.0037">scientists do not share</a> their government-funded data, even when required by the publishing journal.</p>
<h2>Controlling for bias</h2>
<p>Many preclinical experiments <a href="https://doi.org/10.1007/164_2019_279">lack the rudimentary controls against bias</a> that are taught in the social sciences, though <a href="https://www.cshlpress.com/default.tpl?cart=1646145461247203111&fromlink=T&linkaction=full&linksortby=oop_title&--eqSKUdatarq=1020">rarely in biomedical disciplines</a> such as medicine, cell biology, biochemistry and physiology. Controlling for bias is a key element of the scientific method because it allows scientists to disentangle experimental signal from procedural noise. </p>
<p>Confirmation bias, the tendency to see what we want to see, is one type of bias that good science controls by “blinding.” Think of the “double-blind” procedures in clinical trials in which neither the patient nor the research team knows who is getting the placebo and who is getting the drug. In preclinical research, blinding experimenters to samples’ identities minimizes the chance that they will alter their behaviour, however subtly, in favour of their hypothesis. </p>
<p>Seemingly trivial differences, such as whether a sample is processed in the morning or afternoon or whether an animal is caged in the upper or lower row, can also change results. This is not as unlikely as you might think. Moment-to-moment changes in the micro-environment, such as exposure to light and air ventilation, for example, <a href="https://arriveguidelines.org/arrive-guidelines/randomisation#:%7E:text=Using%20a%20validated%20method%20of,valid%20%5B4%2C5%5D">can change physiological responses</a>. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/452275/original/file-20220315-15-39otqq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A row of clear acrylic animal cages, each housing a white rat." src="https://images.theconversation.com/files/452275/original/file-20220315-15-39otqq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/452275/original/file-20220315-15-39otqq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=420&fit=crop&dpr=1 600w, https://images.theconversation.com/files/452275/original/file-20220315-15-39otqq.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=420&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/452275/original/file-20220315-15-39otqq.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=420&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/452275/original/file-20220315-15-39otqq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=527&fit=crop&dpr=1 754w, https://images.theconversation.com/files/452275/original/file-20220315-15-39otqq.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=527&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/452275/original/file-20220315-15-39otqq.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=527&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Seemingly trivial differences, such as whether an animal is caged in the upper or lower row, can change results.</span>
<span class="attribution"><span class="source">(Shutterstock)</span></span>
</figcaption>
</figure>
<p>If all animals who receive a drug are caged in one row and all animals who do not receive the drug are caged in another row, any difference between the two groups of animals may be due to the drug, to their housing location or to an interaction between the two. You can’t honestly choose between the alternative explanations, and neither can the scientists.</p>
<p>Randomizing sample selection and processing order minimizes these procedural biases, makes the interpretation of the results clearer, and makes them more likely to be replicated. </p>
<p>Many of the replication experiments blinded and randomized, but it’s not known if the original experiments did. All that is known is that for the 15 animal experiments, only <a href="https://doi.org/10.7554/eLife.71601">one of the original studies reported randomization and none reported blinding</a>. But it would not be surprising if many of the studies neither randomized nor blinded.</p>
<h2>Study design and statistics</h2>
<p>According to one estimate, over half of the one million articles published each year <a href="https://doi.org/10.1016/S0140-6736%2809%2960329-9">have biased study designs</a>, contributing to 85 per cent of US$100-billion spent each year on (mostly preclinical) research being wasted. </p>
<p>In a widely reported commentary, industry scientist and former academic Glenn Begley reported being able to reproduce the results of only <a href="https://doi.org/10.1038/483531a">six of 53</a> academic studies (11 per cent). He listed <a href="https://doi.org/10.1038/497433a">six practices</a> of reliable research, including blinding. All six of the studies that replicated followed all six practices. The 47 studies that failed to replicate followed few or, sometimes, none of the practices. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/452283/original/file-20220315-19-vympx.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Three people in white coats with a microscope in the foreground, superimposed with bar graphs and data points." src="https://images.theconversation.com/files/452283/original/file-20220315-19-vympx.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/452283/original/file-20220315-19-vympx.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=372&fit=crop&dpr=1 600w, https://images.theconversation.com/files/452283/original/file-20220315-19-vympx.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=372&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/452283/original/file-20220315-19-vympx.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=372&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/452283/original/file-20220315-19-vympx.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=468&fit=crop&dpr=1 754w, https://images.theconversation.com/files/452283/original/file-20220315-19-vympx.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=468&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/452283/original/file-20220315-19-vympx.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=468&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Misuse of statistics is a common in biomedical research despite calls for better data analysis practices.</span>
<span class="attribution"><span class="source">(Shutterstock)</span></span>
</figcaption>
</figure>
<p>Another way to bias findings is by misusing statistics. As with blinding and randomization, it’s not known which, if any, of the original studies in the reproducibility project misused statistics, because of the studies’ lack of transparency. But that, too, is common practice.</p>
<p>A dictionary of terms describes a slew of poor data analysis practices that can manufacture statistically significant (but false) findings, such as <a href="https://doi.org/10.1207/s15327957pspr0203_4">HARKing</a> (Hypothesizing After the Results are Known), p-hacking (<a href="https://doi.org/10.1177%2F0956797611417632">repeating statistical tests until a desired result is produced</a>) and following a series of data-dependent analysis decisions known as a “<a href="https://doi.org/10.1511/2014.111.460">garden of forking paths</a>” to publishable findings. </p>
<p><a href="https://link.springer.com/chapter/10.1007/164_2019_278#Sec4">These practices</a> are <a href="https://acmedsci.ac.uk/policy/policy-projects/reproducibility-and-reliability-of-biomedical-research">common in biomedical research</a>. <a href="https://doi.org/10.1136/bmj.308.6924.283">Decades of pleas</a> from <a href="https://doi.org/10.1371/journal.pmed.0020124">methodologists</a>, and an <a href="https://magazine.amstat.org/blog/2021/08/01/task-force-statement-p-value/">unprecedented statement</a> from the American Statistical Association to change data analysis practices, however, have <a href="https://doi.org/10.1111/1740-9713.01505">gone unheeded</a>.</p>
<h2>A better future</h2>
<figure class="align-center ">
<img alt="A woman wearing a lab coat and safety glasses and green gloves examining lab samples" src="https://images.theconversation.com/files/452295/original/file-20220315-25-11qxmpb.jpg?ixlib=rb-1.1.0&rect=353%2C0%2C4871%2C3371&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/452295/original/file-20220315-25-11qxmpb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/452295/original/file-20220315-25-11qxmpb.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/452295/original/file-20220315-25-11qxmpb.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/452295/original/file-20220315-25-11qxmpb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/452295/original/file-20220315-25-11qxmpb.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/452295/original/file-20220315-25-11qxmpb.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Incentives and standards should reward practices that produce trustworthy science and censor practices that do not, without killing innovation.</span>
<span class="attribution"><span class="source">(Shutterstock)</span></span>
</figcaption>
</figure>
<p>Those who are anti-science should not take heart in these findings. Preclinical science’s accomplishments are real and impressive. Decades of preclinical research led to the <a href="https://www.nytimes.com/2022/01/15/health/mrna-vaccine.html">development of the COVID-19 mRNA vaccines</a>, for example. And most scientists are doing the best they can within a system that rewards <a href="https://www.theguardian.com/commentisfree/2013/dec/09/how-journals-nature-science-cell-damage-science">quick flashy results</a> over slower reliable ones. </p>
<p>But science is done by humans with all the strengths and weaknesses that go with it. The trick is to reward practices that produce trustworthy science and to censor practices that do not, without killing innovation. </p>
<p>Changing incentives and enforcing standards are the most effective ways to improve scientific practice. The goal is to improve efficiency by ensuring scientists who value transparency and rigour over speed and flash are given a chance to thrive. It’s been <a href="https://doi.org/10.1038/505612a">tried before</a>, with <a href="https://doi.org/10.1080/08989621.2020.1855427">minimal success</a>. This time may be different. The <em>Reproducibility Project: Cancer Biology</em> study and the NIH policy changes it prompted may be just the push needed to make it happen.</p><img src="https://counter.theconversation.com/content/176134/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Robert Nadon does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Preclinical studies are an important part of biomedical research, often guiding future trials in humans. Failure to replicate research results suggests a need to increase the quality of studies.Robert Nadon, Associate Professor, Department of Human Genetics, Faculty of Medicine, McGill UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1733962021-12-09T13:34:54Z2021-12-09T13:34:54ZFiguring out omicron – here’s what scientists are doing right now to understand the new coronavirus variant<figure><img src="https://images.theconversation.com/files/436465/original/file-20211208-137612-ikwh0c.jpg?ixlib=rb-1.1.0&rect=686%2C0%2C7210%2C5150&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A researcher works with COVID-19 samples from patients.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/laboratory-operator-handles-positive-covid-19-samples-to-be-news-photo/1237075524">Thomas Samson/AFP via Getty Images</a></span></figcaption></figure><p><em>Scientists around the world have been racing to learn more about the new omicron strain of SARS-CoV-2, first declared a <a href="https://www.who.int/news/item/26-11-2021-classification-of-omicron-(b.1.1.529)-sars-cov-2-variant-of-concern">“variant of concern” on Nov. 26, 2021</a> by the World Health Organization. Officials cautioned that it would take several weeks before they’d know whether the recently emerged coronavirus variant is more contagious and causes more or less serious COVID-19 than delta and other earlier variants, and whether current vaccines can ward it off.</em></p>
<p><em><a href="https://scholar.google.com/citations?user=OQ7vzu0AAAAJ&hl=en&oi=ao">Peter Kasson is a virologist and biophysicist</a> at the University of Virginia who studies how viruses such as SARS-CoV-2 enter cells and what can be done to stop them. Here he explains what lab-based scientists are doing to help answer the outstanding questions about omicron.</em></p>
<h2>Does prior immunity protect against omicron?</h2>
<p>These are the key lab results everyone is waiting for: How effective are the antibodies people already have at fighting off omicron? If you got the booster shot, are you protected? Or if you had COVID-19 and then were vaccinated?</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/436467/original/file-20211208-25-152atd7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="artist's rendition of a virus with antibodies surrounding it" src="https://images.theconversation.com/files/436467/original/file-20211208-25-152atd7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/436467/original/file-20211208-25-152atd7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=338&fit=crop&dpr=1 600w, https://images.theconversation.com/files/436467/original/file-20211208-25-152atd7.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=338&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/436467/original/file-20211208-25-152atd7.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=338&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/436467/original/file-20211208-25-152atd7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=424&fit=crop&dpr=1 754w, https://images.theconversation.com/files/436467/original/file-20211208-25-152atd7.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=424&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/436467/original/file-20211208-25-152atd7.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=424&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Will the antibodies people already have recognize and thwart omicron?</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/antibodies-attacking-sars-cov-2-virus-corona-virus-royalty-free-image/1328466445">Dr_Microbe/iStock via Getty Images</a></span>
</figcaption>
</figure>
<p>The goal is to see how well antibodies from real people who have had COVID-19 or have been vaccinated against it can hold off omicron in petri dishes in the lab. Scientists expect that antibodies from people exposed to other variants won’t work as well against omicron because of its mutations, but they need to measure how much less well and whether it’s still enough to stop the virus. </p>
<p>To answer these questions, most researchers first make a version of the SARS-CoV-2 virus that can <a href="https://doi.org/10.3390/v12050513">enter cells but not reproduce</a>. A few specialized labs with <a href="https://theconversation.com/we-work-with-dangerous-pathogens-in-a-downtown-boston-biocontainment-lab-heres-why-you-can-feel-safe-about-our-research-163197">extra levels of biosecurity</a> use the actual virus. Scientists add antibodies from the blood of people vaccinated against or recovered from COVID-19 to the virus. They then mix this with human lung cells to see whether the antibodies can stop the virus from infecting the cells.</p>
<p>My laboratory performs this kind of work with <a href="https://doi.org/10.1038/s41541-021-00399-0">SARS-CoV-2</a> and other <a href="https://doi.org/10.1021/acscentsci.8b00494">emerging viruses</a>. Researchers have used these well-established techniques to test out <a href="https://doi.org/10.1038/s41586-021-03696-9">antibodies after COVID-19 recovery</a>, as well as different vaccines and <a href="https://doi.org/10.1056/NEJMc2113468">different variants</a>. </p>
<p>If antibodies people made against prior variants can’t stop omicron from infecting lung cells in the lab, then those antibodies probably won’t protect people out in the world either.</p>
<p>The very first early results are starting to come back, and it looks like <a href="https://www.ahri.org/wp-content/uploads/2021/12/MEDRXIV-2021-267417v1-Sigal.pdf">antibodies against earlier variants are less successful at blocking omicron</a>. Researchers took antibodies from six people who each had two doses of vaccine and from six other people who each had two doses of vaccine and had also recovered from an earlier COVID-19 infection. Antibodies from both groups of people were about 40 times worse at stopping omicron than original SARS-COV-2 strains, based on how much antibody was needed to prevent infection. But the people whose immune systems had seen the virus three times – that is, were doubly vaccinated and had also recovered from COVID-19 – had antibody levels that were high enough to still stop infection.</p>
<p>I’d expect people who have received booster vaccines will have similar or greater levels of immunity and will be at least moderately protected from omicron. But it will need to be tested. <a href="https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-provide-update-omicron-variant">Pfizer has said their early results agree with this prediction</a>, but the data is not yet publicly available. All of this work is not yet peer reviewed and still very preliminary.</p>
<p>Scientists will need to determine how a drop in “neutralization titer,” or how good antibodies are at blocking the virus in the lab, corresponds to a drop in “<a href="https://www.who.int/news-room/feature-stories/detail/vaccine-efficacy-effectiveness-and-protection">vaccine effectiveness</a>” or how likely a vaccinated person is to get COVID-19 compared to an unvaccinated one. Scientists know that <a href="https://doi.org/10.1038/s41591-021-01377-8">better antibodies correspond to more effective vaccines</a>, but the precise numerical relationships need to be determined.</p>
<p><iframe id="ikaxY" class="tc-infographic-datawrapper" src="https://datawrapper.dwcdn.net/ikaxY/1/" height="400px" width="100%" style="border: none" frameborder="0"></iframe></p>
<h2>How contagious is omicron compared to delta?</h2>
<p>The past pandemic year has shown that contagiousness, or transmissibility, has been the key factor in determining whether a coronavirus variant becomes dominant. Delta’s transmissibility has made it the current dominant variant because it simply outran others. But that situation may change with time.</p>
<p>The basic elements of the viral “life” cycle are getting into cells, making more virus, and getting out. Scientists can measure each of these stages in the lab and <a href="https://www.science.org/doi/10.1126/science.abl6184">report what aspects of a variant</a> make it more or less transmissible. In addition to binding to human cells better, some mutations enhance the packaging of new virus and the delivery of its genes once the virus gets into the cell.</p>
<p>While lab-based science can help people understand the biology behind just why a variant is more or less contagious, right now nature is doing a much bigger real-world experiment. Disease surveillance data from the <a href="https://twitter.com/_nickdavies/status/1466204363110633476?s=20">U.K.</a> and <a href="https://files.ssi.dk/covid19/omikron/statusrapport/rapport-omikronvarianten-07122021-1t6o">other countries</a> where delta has been dominant suggest that omicron is gaining share and may eventually displace delta.</p>
<p>Exactly how this plays out may differ from one country to another, depending on factors like the number of vaccinated people and which variants were previously in circulation, but this news about how good omicron is at spreading is concerning.</p>
<h2>Does omicron make people more or less sick?</h2>
<p>This is again a question that will be answered much more quickly by the thousands of people infected with omicron than by work in the lab. It’s important to remember, though, that nature’s experiments are not as carefully controlled as lab experiments. Precise lab work will help explain why omicron might be different, but the first answers here will come from hospitals.</p>
<p>Lab-based scientists will be working with hospitals to analyze what makes some patients more or less sick once they contract omicron. Some early numbers suggest that the <a href="https://www.samrc.ac.za/news/tshwane-district-omicron-variant-patient-profile-early-features">first omicron cases are mostly mild</a>, but public health officials urge caution: Most cases of all COVID-19 variants are mild, and <a href="https://www.samrc.ac.za/news/tshwane-district-omicron-variant-patient-profile-early-features">many of those infected so far with omicron are younger</a>. Hospitalization counts tend to increase somewhat after the initial increase in cases. So this question will take time to answer.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/436468/original/file-20211208-25-5qjw44.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="nurse attends a COVID-19 patient on a hospital ward" src="https://images.theconversation.com/files/436468/original/file-20211208-25-5qjw44.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/436468/original/file-20211208-25-5qjw44.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/436468/original/file-20211208-25-5qjw44.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/436468/original/file-20211208-25-5qjw44.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/436468/original/file-20211208-25-5qjw44.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/436468/original/file-20211208-25-5qjw44.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/436468/original/file-20211208-25-5qjw44.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Epidemiological data about how real patients are faring will fill in the picture.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/registered-nurse-attends-a-patient-with-covid-19-at-the-news-photo/1235025034">Apu Gomes/AFP via Getty Images</a></span>
</figcaption>
</figure>
<h2>How are lab data and public health data complementary?</h2>
<p>Laboratories will provide the first results on immune protection against omicron, although this will be followed up with public health data that will likely confirm the lab results. Public health data will bring the first results on contagiousness and disease severity, which will then be explained by laboratory results.</p>
<p>Once the initial answers from public health data are in, laboratory results are still important to understand why these changes happened and to help predict what future variants will do. How do officials declare a variant of concern in the first place? It’s a combination of public health data and understanding from the lab.</p>
<h2>What do we know already?</h2>
<p>Variants of SARS-CoV-2 don’t change the laws of physics and biology. They cannot leap tall buildings in a single bound. Physical barriers like high-grade masks and good ventilation will still stop the virus. And, very likely, vaccines will continue to provide some amount of protection. The question is how much, and whether the world needs to <a href="https://theconversation.com/how-can-scientists-update-coronavirus-vaccines-for-omicron-a-microbiologist-answers-5-questions-about-how-moderna-and-pfizer-could-rapidly-adjust-mrna-vaccines-172943">change the current vaccines</a> or just provide more of them.</p>
<p>[<em>Research into coronavirus and other news from science</em> <a href="https://theconversation.com/us/newsletters/science-editors-picks-71/?utm_source=TCUS&utm_medium=inline-link&utm_campaign=newsletter-text&utm_content=science-corona-research">Subscribe to The Conversation’s new science newsletter</a>.]</p><img src="https://counter.theconversation.com/content/173396/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Peter Kasson has received funding from the National Institutes of Health, the National Science Foundation, the Knut and Alice Wallenberg Foundation, the Swedish Research Council, and TG Therapeutics. He is affiliated with the University of Virginia and Uppsala University. </span></em></p>Careful lab work will complement public health data as researchers worldwide focus on omicron, asking questions about contagiousness, severity of disease and whether vaccines hold up against it.Peter Kasson, Associate Professor of Molecular Physiology and Biomedical Engineering, University of VirginiaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1619312021-06-10T10:02:16Z2021-06-10T10:02:16ZRemembering Tania Douglas: a brilliant biomedical engineer, academic and friend<figure><img src="https://images.theconversation.com/files/403802/original/file-20210601-23-1rvztpr.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Professor Tania Douglas is warmly remembered as an excellent scientist and a remarkable human being.</span> <span class="attribution"><span class="source">Je'nine May/UCT Health Sciences</span></span></figcaption></figure><p>Tributes from friends, colleagues, collaborators and students have poured in for South African academic Professor Tania Samantha Douglas, an internationally recognised scholar, biomedical engineer and innovator. She passed away on 20 March 2021.</p>
<p>She was admired by many and consulted broadly for her unique insights, in-depth understanding of South Africa’s higher education environment, and open-mindedness. Always vibrant, she was able to fully engage with issues in an unbiased manner – sharing her well-considered thoughts in a friendly and practical way.</p>
<p>Tania obtained the second highest grade in the country in her final school exams in 1987. She went on to read for a BScEng in Electrical and Electronic Engineering at the University of Cape Town (UCT). This was followed by an MS in Biomedical Engineering at Vanderbilt University in Nashville, Tennessee. Then came a PhD in Bioengineering from the University of Strathclyde in Glasgow, and a postdoctoral fellowship in image processing with the Japan Broadcasting Corporation in Tokyo. </p>
<p>In 2000, Tania returned to her alma mater. She took up a lecturer position in the Department of Biomedical Engineering.</p>
<p>In her recent work, she strove to combine biomedical engineering with social context. Her aim was to find novel solutions towards improved health. To this end, she developed a new postgraduate programme in Health Innovation teaching human-centred innovation with an emphasis on end-user engagement. </p>
<p>She believed and advocated that Africa needs to find solutions to its own problems and worked tirelessly to build biomedical engineering capacity across the continent. </p>
<h2>Academic legacy</h2>
<p>During her 21 years at the University of Cape Town, Tania held numerous leadership positions within the department and faculty. These included serving as Divisional Head for a period and serving as Deputy Dean of Research in the Faculty of Health Sciences. She also, for the past decade, led the <a href="http://www.health.uct.ac.za/fhs/research/groupings/miru">Medical Research Council/UCT Medical Imaging Research Unit</a>. </p>
<p>In 2016, Tania was awarded the prestigious South African Research Chair in Biomedical Engineering and Innovation. Two years later she was Founding Director of UCT’s <a href="http://www.bme.uct.ac.za/">Biomedical Engineering Research Centre</a>. </p>
<p>Tania excelled in all spheres of academia. She headed a large research group, and trained and graduated more than 50 master’s and doctoral students. Postdoctoral fellows and junior staff were among those she mentored. She also published extensively in leading international journals, and taught and developed courses. Her scholarly contributions were recognised through numerous awards. These included research fellowships from the <a href="https://www.ictp.it/">International Institute for Theoretical Physics</a> in Trieste, Italy; <a href="https://www.humboldt-foundation.de/">the Alexander von Humboldt Foundation</a> in Germany; and the European Union’s <a href="https://ec.europa.eu/programmes/erasmus-plus/opportunities/individuals/students/erasmus-mundus-joint-masters-scholarships_en">Erasmus Mundus programme</a>. </p>
<p>The Institute of Electrical and Electronics Engineers Women in Engineering’s South Africa Section named her as its female academic/researcher of the year in 2009.</p>
<p>In 2018 she was recognised as a Quartz Africa Innovator. A year later, the South African Women in Science Awards named her as Distinguished Woman Researcher in Research and Innovation. In the past decade, she was elected a Fellow by the South African Academy of Engineering, the International Academy of Medical and Biological Engineering, and the University of Cape Town. She was also a member of the <a href="https://www.assaf.org.za/">Academy of Science of South Africa</a>.</p>
<p>Tania’s <a href="https://scholar.google.co.za/citations?user=BSEwIocAAAAJ&hl=en">research</a> focused on major public health problems in South Africa. She developed novel instruments and computer-assisted techniques. Some of her early work involved <a href="https://www.ajol.info/index.php/cme/article/view/71954">developing image-processing techniques</a> to characterise the facial phenotype associated with foetal alcohol syndrome – a condition of which the incidence in certain communities in South Africa is among the highest in the world. </p>
<p>Tania also made seminal contributions in tuberculosis (TB) diagnosis. One was the development of a ‘smart microscope’ that automated detection of TB bacilli in stained sputum smears. Another was the computer-aided detection of pulmonary pathology in paediatric chest X-rays.</p>
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Read more:
<a href="https://theconversation.com/africa-needs-to-start-creating-its-own-medical-technology-heres-how-84642">Africa needs to start creating its own medical technology. Here's how</a>
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<p>She played a leading role in establishing the African Biomedical Consortium. She also launched and was founding Editor-in-Chief of the open-access electronic journal Global Health Innovation. In addition she edited the open-access eBook <a href="https://openbooks.uct.ac.za/uct/catalog/book/bmeafrica">Biomedical Engineering for Africa</a> (University of Cape Town Libraries; 2019).</p>
<p>Since 2014, Tania had served as Associate Editor of both the South African Journal of Science and Medical Engineering and Physics. In January 2021 she was appointed as Editor-in-Chief of the latter.</p>
<h2>A great void</h2>
<p>Tania was warm and empathetic, and an inspiring mentor to many. As her friend and head of the Department of Human Biology at UCT, Professor Sharon Price, <a href="https://www.caperay.com/blog/in-memoriam-tania-douglas/">wrote</a>:</p>
<blockquote>
<p>We will remember Tania for being an amazing woman – brave, humble and brilliant. She lived her life, and carried her illness, with extraordinary grace and dignity. We will remember her for her astute intellect and her quiet humanity to build others in the process. She was talented and gracious, and we will remember her positive attitude and ever-present beautiful smile.</p>
</blockquote>
<p>Tania is survived by her parents, Rita and Aubrey Douglas.</p>
<p><em>This tribute originally appeared in the <a href="https://sajs.co.za/article/view/11067">South African Journal of Science</a>.</em></p><img src="https://counter.theconversation.com/content/161931/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Ernesta M. Meintjes has received funding from the NRF, DST, TIA, MRC and the National Institutes of Health in the U.S. </span></em></p>She believed and advocated that Africa needs to find solutions to its own problems and worked tirelessly to build biomedical engineering capacity across the continent.Ernesta M. Meintjes, Professor in Biomedical Engineering, University of Cape TownLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1563432021-04-12T19:18:47Z2021-04-12T19:18:47ZWe’re creating ‘humanized pigs’ in our ultraclean lab to study human illnesses and treatments<figure><img src="https://images.theconversation.com/files/391780/original/file-20210325-17-nc2rjy.jpg?ixlib=rb-1.1.0&rect=12%2C6%2C3482%2C1792&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Pigs with human immune systems.</span> <span class="attribution"><span class="source">Ahlea Forster</span>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span></figcaption></figure><p>The U.S. Food and Drug Administration <a href="https://www.federalregister.gov/documents/2002/05/31/02-13583/new-drug-and-biological-drug-products-evidence-needed-to-demonstrate-effectiveness-of-new-drugs-when">requires all new medicines to be tested in animals</a> before use in people. Pigs make better medical research subjects than mice, because they are closer to humans in size, <a href="https://doi.org/10.1016/j.tim.2011.11.002">physiology</a> and <a href="https://doi.org/10.1186/1471-2164-14-332">genetic makeup</a>. </p>
<p>In recent years, <a href="https://faculty.sites.iastate.edu/cktuggle/">our team at Iowa State University</a> has found a way to make pigs an even closer stand-in for humans. We have successfully transferred components of the <a href="https://doi.org/10.3389/fimmu.2020.00100">human immune system into pigs that lack a functional immune system</a>. This breakthrough has the potential to accelerate medical research in many areas, including <a href="https://doi.org/10.1159/000451007">virus</a> and vaccine research, as well as <a href="https://doi.org/10.3389/fonc.2019.00009">cancer</a> and <a href="https://orip.nih.gov/about-orip/research-highlights/severe-combined-immunodeficient-pigs-promising-model-human-stem-cell">stem cell therapeutics</a>. </p>
<h2>Existing biomedical models</h2>
<p>Severe Combined Immunodeficiency, or SCID, is a genetic condition that causes impaired development of the immune system. People can develop SCID, <a href="https://www.cbsnews.com/pictures/bubble-boy-40-years-later-look-back-at-heartbreaking-case/15/">as dramatized in the 1976 movie</a> “<a href="https://wikimili.com/en/The_Boy_in_the_Plastic_Bubble">The Boy in the Plastic Bubble</a>.” Other animals can develop SCID, too, including mice.</p>
<p>Researchers in the 1980s <a href="https://doi.org/10.1126/science.2971269">recognized that SCID mice</a> <a href="https://doi.org/10.1038/335256a0">could be implanted with human immune cells</a> for further study. Such mice are called “humanized” mice and have been optimized over the <a href="https://doi.org/10.1038/cmi.2012.2">past 30 years</a> to study many questions relevant to human health. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/391791/original/file-20210325-17-1vwceuc.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A rack of clear enclosures containing mice in a laboratory setting." src="https://images.theconversation.com/files/391791/original/file-20210325-17-1vwceuc.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/391791/original/file-20210325-17-1vwceuc.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=377&fit=crop&dpr=1 600w, https://images.theconversation.com/files/391791/original/file-20210325-17-1vwceuc.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=377&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/391791/original/file-20210325-17-1vwceuc.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=377&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/391791/original/file-20210325-17-1vwceuc.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=474&fit=crop&dpr=1 754w, https://images.theconversation.com/files/391791/original/file-20210325-17-1vwceuc.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=474&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/391791/original/file-20210325-17-1vwceuc.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=474&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">Mice are valuable models, but they have limitations.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/experimenal-mice-are-raised-in-the-ivc-cages-royalty-free-image/639071964">unoL/iStock via Getty Images</a></span>
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<p>Mice are the most <a href="https://doi.org/10.4103/0975-7406.124301">commonly used animal in biomedical research</a>, but results from <a href="https://sitn.hms.harvard.edu/flash/2020/why-drugs-tested-in-mice-fail-in-human-clinical-trials/">mice often do not translate well to human responses</a>, thanks to <a href="https://doi.org/10.1016/j.ejps.2013.08.018">differences in metabolism</a>, size and <a href="https://doi.org/10.1038/s41586-019-1506-7">divergent cell functions</a> compared with people. </p>
<p>Nonhuman primates are also used for medical research and are certainly closer stand-ins for humans. But using them for this purpose raises <a href="https://doi.org/10.1163/25889567-BJA10002">numerous ethical considerations</a>. With these concerns in mind, the National Institutes of Health <a href="https://www.nature.com/news/nih-to-retire-all-research-chimpanzees-1.18817">retired most of its chimpanzees from biomedical research</a> in 2013. </p>
<p>Alternative animal models are in demand.</p>
<p>Swine are a viable option for medical research because of their similarities to humans. And with their widespread commercial use, pigs are met with fewer ethical dilemmas than primates. Upwards of <a href="https://www.nass.usda.gov/Charts_and_Maps/Livestock_Slaughter/hgheadx3.php">100 million hogs</a> are slaughtered each year for food in the U.S.</p>
<h2>Humanizing pigs</h2>
<p>In 2012, groups at Iowa State University and Kansas State University, including Jack Dekkers, <a href="https://scholar.google.com/citations?hl=en&user=eEspUMQAAAAJ">an expert in animal breeding and genetics</a>, and Raymond Rowland, <a href="https://pubmed.ncbi.nlm.nih.gov/?term=%22Raymond+Rowland%22">a specialist in animal diseases</a>, <a href="https://www.cals.iastate.edu/news/releases/iowa-state-university-seeks-develop-pig-benefit-human-medical-therapies">serendipitously discovered</a> a naturally occurring genetic mutation in pigs that caused SCID. We wondered if we could develop these pigs to create a new biomedical model. </p>
<p>Our group has worked for nearly a decade developing and optimizing SCID pigs for applications in biomedical research. In 2018, we achieved a <a href="https://doi.org/10.3389/fimmu.2020.00100">twofold milestone</a> when working with animal physiologist <a href="https://scholar.google.com/citations?user=iAJav9YAAAAJ&hl=en">Jason Ross</a> and his lab. Together we developed a <a href="https://www.news.iastate.edu/news/2020/05/28/scidpigs2020grant">more immunocompromised pig than the original SCID pig – and successfully humanized it</a>, by transferring cultured human immune stem cells into the livers of developing piglets. </p>
<p>During early fetal development, immune cells develop within the liver, providing an opportunity to introduce human cells. We inject human immune stem cells into fetal pig livers <a href="https://doi.org/10.30802/AALAS-CM-18-000098">using ultrasound imaging as a guide</a>. As the pig fetus develops, the injected human immune stem cells begin to differentiate – or change into other kinds of cells – and spread through the pig’s body. Once SCID piglets are born, we can detect human immune cells in their blood, liver, spleen and thymus gland. This humanization is what makes them so valuable for testing new medical treatments.</p>
<p>We have found that human ovarian tumors <a href="https://doi.org/10.3389/fonc.2019.00009">survive and grow in SCID pigs</a>, giving us an opportunity to study ovarian cancer in a new way. Similarly, because <a href="https://doi.org/10.1111/wrr.12715">human skin survives on SCID pigs</a>, scientists may be able to develop new treatments for skin burns. Other research possibilities are numerous.</p>
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<a href="https://images.theconversation.com/files/388146/original/file-20210306-13-14k76rq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="An indoor space housing pigs, with specialize air vents and plastic sheeting." src="https://images.theconversation.com/files/388146/original/file-20210306-13-14k76rq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/388146/original/file-20210306-13-14k76rq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=173&fit=crop&dpr=1 600w, https://images.theconversation.com/files/388146/original/file-20210306-13-14k76rq.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=173&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/388146/original/file-20210306-13-14k76rq.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=173&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/388146/original/file-20210306-13-14k76rq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=217&fit=crop&dpr=1 754w, https://images.theconversation.com/files/388146/original/file-20210306-13-14k76rq.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=217&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/388146/original/file-20210306-13-14k76rq.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=217&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">The ultraclean SCID pig biocontainment facility in Ames, Iowa.</span>
<span class="attribution"><span class="source">Adeline Boettcher</span>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
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<h2>Pigs in a bubble</h2>
<p>Since our pigs lack essential components of their immune system, they are extremely susceptible to infection and require special housing to help reduce exposure to pathogens. </p>
<p>SCID pigs are <a href="https://doi.org/10.1177/0023677217750691">raised in bubble biocontainment facilities</a>. Positive pressure rooms, which maintain a higher air pressure than the surrounding environment to keep pathogens out, are coupled with highly filtered air and water. All personnel are required to wear full personal protective equipment. We typically have anywhere from two to 15 SCID pigs and breeding animals at a given time. (Our breeding animals do not have SCID, but they are genetic carriers of the mutation, so their offspring may have SCID.) </p>
<p>[<em>Deep knowledge, daily.</em> <a href="https://theconversation.com/us/newsletters/the-daily-3?utm_source=TCUS&utm_medium=inline-link&utm_campaign=newsletter-text&utm_content=deepknowledge">Sign up for The Conversation’s newsletter</a>.]</p>
<p>As with any animal research, ethical considerations are always front and center. All our protocols are approved by Iowa State University’s Institutional Animal Care and Use Committee and are in accordance with <a href="https://grants.nih.gov/grants/olaw/guide-for-the-care-and-use-of-laboratory-animals.pdf">The National Institutes of Health’s Guide for the Care and Use of Laboratory Animals</a>. </p>
<p>Every day, twice a day, our pigs are checked by expert caretakers who monitor their health status and provide engagement. We have veterinarians on call. If any pigs fall ill, and drug or antibiotic intervention does not improve their condition, the animals are humanely euthanized. </p>
<p>Our goal is to continue optimizing our humanized SCID pigs so they can be more readily available for stem cell therapy testing, as well as research in other areas, including cancer. We hope the development of the SCID pig model will pave the way for advancements in therapeutic testing, with the long-term goal of improving human patient outcomes.</p>
<p><em>Adeline Boettcher earned her research-based Ph.D. working on the SCID project in 2019.</em></p><img src="https://counter.theconversation.com/content/156343/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Christopher Tuggle receives funding from the US National Institutes of Health to develop the SCID pig model. The Artemis SCID pig model has been patented by Iowa State University (#9,745,561) and can be licensed for use.</span></em></p><p class="fine-print"><em><span>Adeline Boettcher does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Medical research to benefit people is first conducted in animals. Creating a new biomedical model by inserting human immune cells into pigs may lead to new insights and treatments.Christopher Tuggle, Professor of Animal Science, Iowa State UniversityAdeline Boettcher, Technical Writer II, Iowa State UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1450222020-12-01T19:07:49Z2020-12-01T19:07:49ZCOVID has left Australia’s biomedical research sector gasping for air<figure><img src="https://images.theconversation.com/files/364612/original/file-20201020-23-z6hb5m.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C5162%2C3441&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><span class="source">Shutterstock</span></span></figcaption></figure><p>While COVID-19 has highlighted the value of medical research, it has unfortunately also seriously disrupted it. Lack of funding is driving members of Australia’s once-vibrant virology research community out of the sector, and forcing early-career researchers to turn to fundraising or philanthropy amid intense competition for federal government grants.</p>
<p>This disruption disproportionately affects early- and mid-career researchers (EMCRs) and laboratory-based scientists, especially women (who typically also <a href="https://blogs.lse.ac.uk/covid19/2020/06/05/homeschooling-during-lockdown-will-deepen-inequality/">shoulder the bulk</a> of caring and home-schooling responsibilities).</p>
<p>In Australia, national funding of medical research happens mainly via the <a href="https://www.nhmrc.gov.au/">National Health and Medical Research Council</a>. Over the past ten years there has been <a href="https://www.nhmrc.gov.au/funding/data-research/outcomes-funding-rounds">near stagnant investment</a>, leading to a decline in funding in real terms. In 2019, the average success rates across the main NHMRC Ideas and Investigator Grant schemes was just 11.9%.</p>
<h2>Stagnant investment, plummeting morale</h2>
<p>Morale in the sector has <a href="https://www.afr.com/policy/health-and-education/funding-for-basic-research-disappears-in-a-wave-of-populism-20190620-p51zhj">plummeted</a> and we have lost <a href="https://www.theguardian.com/science/2020/oct/26/one-in-five-australian-scientists-planning-to-leave-survey-shows">talented researchers</a> to the United States, Europe and Asia, prompting leading universities to <a href="https://go8.edu.au/in-the-media-group-of-eight-warns-of-brain-drain-with-7000-jobs-set-to-go">warn of a brain drain</a>.</p>
<p>Eureka Prize-winning cancer biologist <a href="https://www.facebook.com/watch/?v=618261328871953">Darren Saunders</a> and clinical geneticist <a href="https://campusmorningmail.com.au/news/luke-hesson-left-research-and-found-a-better-life">Luke Hesson</a> have both decided to leave academia altogether. The full-time medical research workforce <a href="https://asmr.org.au/wp-content/uploads/2019/04/2019-Factsheet.pdf">declined by 20%</a> between 2012 and 2017.</p>
<h2>How did we get here?</h2>
<p>In 2018, following extensive consultation, the NHMRC funding scheme was overhauled with major objectives to encourage innovation across the sector, reduce the burden on applicants and reviewers, and improve success rates of EMCRs.</p>
<p>In the first two years of this new scheme, the success rates for EMCR Investigator Grants (EL1-2) was <a href="https://www.nhmrc.gov.au/funding/data-research/outcomes-funding-rounds">just 11.7% (250 of 2,133 applications)</a>.</p>
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Read more:
<a href="https://theconversation.com/the-nhmrc-program-grant-overhaul-will-it-change-the-medical-research-landscape-in-australia-78343">The NHMRC program grant overhaul: will it change the medical research landscape in Australia?</a>
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<p>Schemes specifically designed to develop emerging talent are also receiving dwindling support. In 2017 the NHMRC awarded 181 “early career and career development fellowships”; by 2020 that figure had fallen to 122.</p>
<p>The 2019 success rate for <a href="https://www.nhmrc.gov.au/funding/find-funding/ideas-grants">NHMRC Ideas Grants</a> scheme (which sustains fundamental research, including on vaccines) in Australia was <a href="https://www.nhmrc.gov.au/funding/data-research/outcomes-funding-rounds">only 11.1%</a>, despite almost three times as many applications being ranked as “fundable” by expert peer reviewers.</p>
<h2>Onus on universities</h2>
<p>With such low success rates, it has fallen to universities to prop up their research departments and laboratories.</p>
<p>If these trends continue, Australia stands to lose an entire generation of medical researchers. This prompted the <a href="https://www.mtpconnect.org.au/Company?Action=Profile&Company_id=336">Association of Australian Medical Research Institutes</a> in August to <a href="https://www.google.com/url?q=https://aamri.org.au/news-events/media-releases/aamris-budget-priority-secure-the-future-of-australias-next-generation-of-talent/&sa=D&ust=1603167068994000&usg=AOvVaw3XblOaN8f6hXiUz0TPn37Y">call for</a> the government to fund 300 new fellowships for EMCRs through the federal budget. </p>
<p>AAMRI president Jonathan Carapetis said the lack of grants and fellowships has forced EMCRs to rely on philanthropy or fundraising to support their research, adding:</p>
<blockquote>
<p>…due to the economic downturn resulting from COVID-19 the holes in this imperfect system have turned into chasms. These are the researchers who have finished their PhDs, are testing hypotheses on what causes different diseases, developing new treatments and vaccines… Our EMCRs are tomorrow’s scientific leaders, and without action to support them we will lose them.</p>
</blockquote>
<p>This call, however, was not heeded in the recent federal budget, which contained <a href="https://twitter.com/TheASMR1/status/1320889480778108928">no new money for biomedical research</a>.</p>
<h2>Funding the future?</h2>
<p>The federal government’s Medical Research Future Fund (MRFF) was <a href="https://www.health.gov.au/initiatives-and-programs/medical-research-future-fund/about-the-mrff">established in 2015</a> and began dispensing funds in 2017. As the MRFF website <a href="https://www.health.gov.au/initiatives-and-programs/medical-research-future-fund/about-the-mrff">explains</a>, the government uses some of the net interest from the A$20 billion fund to pay for medical research. This year it will disperse around A$650 million.</p>
<p>The MRFF represented a major and very welcome funding boost to Australia’s health and medical research sector.</p>
<p>But the combined NHMRC and MRFF budget still only represents 0.53% of the <a href="https://asmr.org.au/wp-content/uploads/2019/05/ASMRPositionDocument_2019.pdf">total health expenditure in the federal budget</a>.</p>
<p>This is a fraction of the 3% of health expenditure that would bring Australia’s health and medical research spending into line with <a href="https://asmr.org.au/wp-content/uploads/2019/05/ASMRPositionDocument_2019.pdf">other OECD countries</a>. An increase to 3% of health expenditure would generate <a href="https://asmr.org.au/wp-content/uploads/2019/05/ASMRPositionDocument_2019.pdf">A$58 billion in health and economic benefits</a>, according to a Deloitte Access Economics report commissioned by the Australian Society for Medical Research.</p>
<p>The MRFF has recently come under scrutiny as it emerged during Senate estimates that <a href="https://asmr.org.au/wp-content/uploads/2020/08/MRFF-Audit.pdf">up to 65% of funds were distributed without peer review</a>.</p>
<p>What’s more, researchers who narrowly missed out on the incredibly competitive NHMRC Investigator funding cannot apply to the MRFF unless they are a clinical researcher, meaning fundamental biomedical researchers engaged in translational research, but without a medical degree, <a href="https://www.health.gov.au/initiatives-and-programs/clinician-researchers-initiative">miss out</a>.</p>
<h2>Without investment, advances are not possible</h2>
<p>In the post-COVID era, a robust health and medical research sector is essential to lead the discoveries and innovations that will fuel our long-term economic recovery. </p>
<p>The <a href="https://narf.org.au/">National Association of Research Fellows</a> (a peak body representing biomedical researchers; the authors of this article are on the NARF Executive) is calling for:</p>
<ul>
<li><p>at least a doubling of federal funds into the Australian health and medical research sector </p></li>
<li><p>transparent, 360-degree oversight of the targeted calls for expression of interest and allocation of funds from the MRFF with involvement of NHMRC peer review. </p></li>
<li><p>strictly equal support for clinical and fundamental biomedical research.</p></li>
</ul>
<p>This investment would position Australia as an international leader in health and medical research. Without better support for the sector, advances in patient treatment and care are simply not possible.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/more-than-10-000-job-losses-billions-in-lost-revenue-coronavirus-will-hit-australias-research-capacity-harder-than-the-gfc-138210">More than 10,000 job losses, billions in lost revenue: coronavirus will hit Australia's research capacity harder than the GFC</a>
</strong>
</em>
</p>
<hr>
<hr>
<p><em><strong>Editor’s note</strong>: This article references figures tabled in Senate Estimates in March 2020 showing only <a href="https://asmr.org.au/wp-content/uploads/2020/08/MRFF-Audit.pdf">35% of MRFF grants</a> were awarded via a competitive process. It has since been brought to our attention that more recent data are now available, and this figure has now <a href="https://www.health.gov.au/summary-of-mrff-grant-recipients">risen to 73%</a> as of December 2, 2020.</em></p>
<p><em>The article also previously stated Darren Saunders and Luke Hesson have left science altogether. They have in fact decided to continue their scientific research careers outside academia.</em></p><img src="https://counter.theconversation.com/content/145022/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Gina Ravenscroft receives funding from the NHMRC, and is WA representative of the National Association of Research Fellows of NHMRC.</span></em></p><p class="fine-print"><em><span>Elizabeth Gardiner receives funding from the NHMRC and the ARC, and is treasurer of the National Association of Research Fellows of NHMRC. </span></em></p>While COVID-19 has highlighted the invaluable nature of medical research, it has unfortunately also seriously disrupted it. In Australia, the sector now teeters on the brink of collapse.Gina Ravenscroft, Research Fellow, The University of Western AustraliaElizabeth E. Gardiner, Professor, John Curtin School of Medical Research, Australian National UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1499622020-11-13T21:32:07Z2020-11-13T21:32:07ZCOVID-19 vaccine update: Pfizer may be the frontrunner, but Canada has hedged its bets<figure><img src="https://images.theconversation.com/files/368927/original/file-20201111-19-9z36t0.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C1356%2C667&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">People wearing masks walk in front of Pfizer's headquarters in New York City. Pfizer and BioNtech are on track with a vaccine that is 90 per cent effective, say preliminary results, but they are not the only ones in the race. </span> <span class="attribution"><a class="source" href="https://www.cpimages.com/">AP Photo/Bebeto Matthews</a></span></figcaption></figure><p>Pfizer and BioNTech have surprised the world, and given it hope, with the preliminary results of the Phase 3 clinical trial of their coronavirus vaccine.</p>
<p>They <a href="https://www.cbc.ca/news/health/covid-19-vaccine-pfizer-faq-1.5795486">announced on Nov. 9 that the early analysis of the data from the Phase 3 clinical trial, which is still ongoing, showed the vaccine was 90 per cent effective</a>. The unexpectedly high figure still needs to be confirmed in larger numbers and over time. The vaccine is simple to manufacture, but its storage is more complex (the vaccine must be kept at very low temperatures). Large-scale production is expected to begin shortly.</p>
<p>Laboratories around the world are in a race to produce a COVID-19 vaccine. While the finish line is now in sight for Pfizer and BioNTech, the <a href="https://www.who.int/publications/m/item/draft-landscape-of-covid-19-candidate-vaccines">World Health Organization (WHO) lists 202 vaccine candidates</a>, 47 of which are in human trials.</p>
<p>Canada has not put all its eggs in one basket in its plan to protect Canadians from the novel coronavirus. In addition to Pfizer and BioNTech, it has signed six other contracts: Moderna, Sanofi and GlaxoSmithKline, Johnson & Johnson, Novavax, AstraZeneca and Medicago. Canada recently announced <a href="https://www.bnnbloomberg.ca/canada-has-option-for-56m-more-pfizer-vaccine-doses-anand-1.1520535">it had reserved 56 million additional doses of vaccine</a> from Pfizer and BioNTech, on top of the 20 million doses it had already purchased, bringing its order to 76 million.</p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/369366/original/file-20201113-13-ka4r0b.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/369366/original/file-20201113-13-ka4r0b.png?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/369366/original/file-20201113-13-ka4r0b.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=763&fit=crop&dpr=1 600w, https://images.theconversation.com/files/369366/original/file-20201113-13-ka4r0b.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=763&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/369366/original/file-20201113-13-ka4r0b.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=763&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/369366/original/file-20201113-13-ka4r0b.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=958&fit=crop&dpr=1 754w, https://images.theconversation.com/files/369366/original/file-20201113-13-ka4r0b.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=958&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/369366/original/file-20201113-13-ka4r0b.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=958&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Overview of vaccine types in clinical trials, based on WHO Nov. 3 update.</span>
<span class="attribution"><span class="source">(World Health Organization)</span></span>
</figcaption>
</figure>
<p>Canada has secured access to a total of <a href="https://pm.gc.ca/en/news/news-releases/2020/10/23/prime-minister-announces-funding-advance-development-canadian-covid">414 million doses</a> of COVID-19 vaccines from different sources. More importantly, Canada has ensured that it has diversified the types of vaccines it will have.</p>
<p>Scientists are using different platforms to develop COVID-19 vaccines. Some vaccine candidates in clinical trials exploit mechanisms already used in other vaccines. Others are based on innovative approaches that have never been tested before. Here is an overview of the different types of vaccines.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/369370/original/file-20201113-19-h0dqa.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/369370/original/file-20201113-19-h0dqa.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/369370/original/file-20201113-19-h0dqa.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=347&fit=crop&dpr=1 600w, https://images.theconversation.com/files/369370/original/file-20201113-19-h0dqa.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=347&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/369370/original/file-20201113-19-h0dqa.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=347&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/369370/original/file-20201113-19-h0dqa.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=437&fit=crop&dpr=1 754w, https://images.theconversation.com/files/369370/original/file-20201113-19-h0dqa.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=437&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/369370/original/file-20201113-19-h0dqa.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=437&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">The platforms used for COVID-19 vaccine candidates in clinical trials. Strategies already in use are shown in the red box while novel approaches are shown in the green box.</span>
<span class="attribution"><span class="source">Images created using Mol* (Almo and al. (2020) PBD ID 6X6P. Figure created with BioRender.com</span></span>
</figcaption>
</figure>
<h2>Inactivated vaccines</h2>
<p><a href="https://www.sciencedirect.com/topics/immunology-and-microbiology/inactivated-vaccine">Inactivated vaccines have been in use since the 1880s</a>. The viruses in these vaccines have been rendered inactive by chemical treatment, as with SARS-CoV-2 candidate vaccines, or by physical treatment.</p>
<p>With this type of vaccine, the immune system encounters the virus in its entirety. It can mount a defence when it detects the viral spike protein (also called spicule or S-protein), envelope and nucleoprotein.</p>
<p>Currently, seven inactivated vaccine candidates are being tested in humans. Of these, three are in Phase 3 clinical trials. Unlike Phase 1 and Phase 2, which are used to evaluate a vaccine’s tolerability, safety and ability to induce an immune response, a Phase 3 clinical trial allows scientists to test its efficacy.</p>
<h2>Recombinant proteins</h2>
<p><a href="https://dx.doi.org/10.1590%2FS0100-879X2012007500142">Recombinant protein vaccines</a> fall into two categories: subunit and virus-like particle vaccines. </p>
<p>For subunit protein vaccines, a viral protein is produced in large quantities in a living “factory,” such as a bacterium, plant, mammalian or insect cell. When the viral protein is presented to the immune system, it triggers a reaction. </p>
<p>The 13 subunit vaccine candidates currently in Phase 1, 2 or 3 clinical trials are composed of either the entire spike protein or a specific portion of the spike protein called the ‘receptor binding domain’.</p>
<p>Virus-like particle vaccines are composed of a set of viral proteins that mimic the shape of the virus. This particle “pseudo-virus” is an empty shell, devoid of genetic material and non-infectious, but this does not prevent the immune system from recognizing it.</p>
<h2>Viral vector vaccines</h2>
<p>This approach is based on using a virus that is non-pathogenic or of little danger to humans. In the case of the 12 vaccine candidates of this type currently being studied in humans, the viral vectors are mostly <a href="https://www.merckmanuals.com/en-ca/professional/infectious-diseases/respiratory-viruses/adenovirus-infections">adenoviruses</a>. They represent a large group of viruses that can cause colds and conjunctivitis, among other symptoms.</p>
<p>Used as Trojan horses, these viruses are modified to express the SARS-CoV-2 spike protein following vaccination. Viral vector vaccines are a recent strategy, but were used in the development of the <a href="https://dx.doi.org/10.1080%2F21645515.2018.1473698">Ebola virus</a> vaccine.</p>
<h2>RNA and DNA vaccines</h2>
<p>Despite differences in their composition, <a href="http://www.musee-afrappier.qc.ca/en/index.php?pageid=3115a&&switchlang&page=3115a-dna-rna-e">DNA and mRNA (messenger RNA)</a> both contain genetic information for protein production. While an RNA molecule can directly produce that information, DNA requires an intermediate transcription step.</p>
<p>RNA or DNA vaccine candidates differ from other strategies in two ways. First, it is a novel strategy: there is no RNA or DNA vaccine on the market. Second, they are the only vaccine candidates composed solely of genetic material. </p>
<p>In the case of RNA vaccines, messenger RNA molecules are wrapped in lipid nanoparticles. Once the vaccine is injected, the RNA serves as a template for the body’s cells to produce a viral protein — the spike protein, to be precise.</p>
<p>DNA vaccines, on the other hand, are made up of a circular DNA (called a plasmid). This DNA will be transcribed into RNA, which will again serve as a template. </p>
<p>Six RNA vaccine candidates are currently being tested in humans, two of which are in Phase 3. The five DNA vaccine candidates are in Phase 1 and 2 clinical trials.</p>
<h2>Canada in the vaccine race</h2>
<p>The following is an overview of each company that has an agreement with the federal government, the type of vaccine in development and the number of doses reserved by Canada.</p>
<p><strong>Pfizer/BioNTech</strong>: 76 million doses reserved</p>
<p>BioNTech, in Germany, and Pfizer, in the United States, are jointly developing an <a href="https://www.pfizer.ca/rolling-submission-for-COVID-19-vaccine-candidate">RNA vaccine</a>. This candidate encodes for the manufacture of the spike protein.</p>
<p>The Phase 3 clinical study is continuing with more than 43,000 patients in the U.S., Argentina, Brazil, Germany, Turkey and South Africa. The vaccine is reported to be more than <a href="https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-announce-vaccine-candidate-against">90 per cent effective</a> and has not caused any serious side-effects.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/368650/original/file-20201110-15-1tja34k.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/368650/original/file-20201110-15-1tja34k.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=340&fit=crop&dpr=1 600w, https://images.theconversation.com/files/368650/original/file-20201110-15-1tja34k.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=340&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/368650/original/file-20201110-15-1tja34k.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=340&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/368650/original/file-20201110-15-1tja34k.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=427&fit=crop&dpr=1 754w, https://images.theconversation.com/files/368650/original/file-20201110-15-1tja34k.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=427&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/368650/original/file-20201110-15-1tja34k.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=427&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">An overview of Pfizer Manufacturing Belgium in Puurs, Belgium. Pfizer announced that initial results of its COVID-19 vaccine show 90 per cent efficacy.</span>
<span class="attribution"><span class="source">(AP Photo/Virginia Mayo)</span></span>
</figcaption>
</figure>
<p>Despite these encouraging preliminary results, Pfizer and BioNTech <a href="https://www.msn.com/en-us/news/us/cold-storage-challenges-could-hamper-distribution-of-pfizer-moderna-covid-19-vaccines-fauci-says/ar-BB1aUHe9">have not yet crossed the finish line</a>. Detailed data have not been published and questions remain, including the age and risk factors of the vaccinated individuals and the duration of protection. The clinical trial is ongoing and more data will be analyzed.</p>
<p><strong>Moderna</strong>: 56 million doses reserved</p>
<p>The vaccine candidate of Moderna, a U.S.-based biotechnology company, is <a href="https://www.modernatx.com/modernas-work-potential-vaccine-against-covid-19">an RNA vaccine</a>. Once injected, it allows the expression of the spike protein. Currently in Phase 3 clinical trials, the vaccine is being tested in 30,000 individuals in different regions across the United States.</p>
<p><strong>Johnson & Johnson</strong>: 38 million doses reserved</p>
<p>Johnson & Johnson’s candidate is a <a href="https://www.nih.gov/news-events/news-releases/fourth-large-scale-covid-19-vaccine-trial-begins-united-states">viral vector vaccine</a> composed of a human adenovirus that has been modified to render it incapable of multiplying, but capable of expressing the SARS-CoV-2 spike protein. The Phase 3 clinical trial, which began in September 2020, is taking place in several countries and will involve 60,000 participants.</p>
<p><strong>AstraZeneca/University of Oxford</strong>: 20 million doses reserved</p>
<p>Oxford University is partnering with AstraZeneca on a <a href="https://doi.org/10.1016/S0140-6736(20)31604-4">viral vector vaccine</a>. The vaccine candidate is composed of a modified chimpanzee adenovirus that expresses the spike protein. It is in Phase 3 clinical trials.</p>
<p><strong>Novavax</strong>: 76 million doses reserved</p>
<p>The vaccine candidate of Novavax, a U.S. company, is based on the <a href="https://ir.novavax.com/news-releases/news-release-details/novavax-initiates-phase-3-efficacy-trial-covid-19-vaccine-united">recombinant protein</a> strategy. It is composed of the spike protein and an adjuvant, a booster used in vaccines to increase the immune response. The Phase 3 clinical trial began in September 2020 and involves 10,000 participants in the United Kingdom.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/369373/original/file-20201113-13-b7b2uc.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/369373/original/file-20201113-13-b7b2uc.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/369373/original/file-20201113-13-b7b2uc.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=405&fit=crop&dpr=1 600w, https://images.theconversation.com/files/369373/original/file-20201113-13-b7b2uc.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=405&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/369373/original/file-20201113-13-b7b2uc.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=405&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/369373/original/file-20201113-13-b7b2uc.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=509&fit=crop&dpr=1 754w, https://images.theconversation.com/files/369373/original/file-20201113-13-b7b2uc.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=509&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/369373/original/file-20201113-13-b7b2uc.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=509&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Some examples of commercially available vaccines that use the different types of vaccines described.</span>
<span class="attribution"><span class="source">Created from Servier Medical art (http://servier.com/Powerpoint-image-bank). Servier Medical Art by Servier is licensed under a Creative Commons Attribution 3.0-Unported License</span></span>
</figcaption>
</figure>
<p><strong>Sanofi/GSK</strong>: 72 million doses reserved</p>
<p>The candidate from the French company Sanofi and the British giant GlaxoSmithKline (GSK) is composed of an adjuvant and <a href="https://www.sanofi.com/en/media-room/press-releases/2020/2020-09-03-07-00-00">recombinant version</a> of the spike protein, produced in a living factory (baculoviruses). Phase 1 and 2 clinical trials are currently testing its safety, tolerability and ability to induce an immune response.</p>
<p><strong>Medicago</strong>: 76 million doses reserved</p>
<p>Developed by the Québec-based company Medicago, this vaccine candidate is composed of <a href="https://www.medicago.com/en/newsroom/medicago-begins-phase-i-clinical-trials-for-its-covid-19-vaccine-candidate/">virus-like particles</a>. These are produced in plants infected with bacteria that have been genetically modified to produce several SARS-CoV-2 proteins. These plants thus become production plants. </p>
<p>Researchers can extract the particles from the leaves and purify them. Medicago’s vaccine candidate is currently in Phase 1 clinical trials and results are also promising.</p><img src="https://counter.theconversation.com/content/149962/count.gif" alt="La Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Aïssatou Aïcha Sow receives a scholarship financed by the research funds of her research director and by Institut national de la recherche scientifique (INRS). She is a member of the Canadian Virological Society.</span></em></p>Canada has set aside a total of 414 million doses of different types of vaccine. Some exploit known mechanisms, others are based on previously untested approaches.Aïssatou Aïcha Sow, Doctorante en virologie moléculaire, Institut national de la recherche scientifique (INRS)Licensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1481602020-10-22T12:22:55Z2020-10-22T12:22:55ZA tiny circular racetrack for light can rapidly detect single molecules<figure><img src="https://images.theconversation.com/files/364775/original/file-20201021-17-gwtpr6.jpg?ixlib=rb-1.1.0&rect=0%2C14%2C4928%2C3238&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Light is key to ultrasensitive chemical sensors.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/cropped-hand-of-scientist-testing-chemicals-in-royalty-free-image/1029344608?adppopup=true">Kwanchai Lerttanapunyaporn/EyeEm via Getty Images</a></span></figcaption></figure><p><em>The <a href="https://theconversation.com/us/topics/research-brief-83231">Research Brief</a> is a short take about interesting academic work.</em></p>
<h2>The big idea</h2>
<p>My <a href="https://wp.optics.arizona.edu/jsu/">Little Sensor Lab</a> at the University of Arizona develops ultrasensitive optical sensors for medical diagnostics, medical prognostics, environmental monitoring and basic science research. Our sensor technology identifies substances by shining light on samples and measuring the index of refraction, or how much light is slowed down when it passes through a material, which is different from one substance to another – say, water and a DNA molecule. </p>
<p>Our technology lets us detect extremely low concentrations of molecules down to one in a million trillion molecules, and can give results in under 30 seconds.</p>
<p>Ordinarily, index of refraction is too subtle to detect in a single molecule, but using a <a href="https://doi.org/10.1038/lsa.2016.1">technology we developed</a>, we can pass light through a sample thousands of times, which amplifies the change. This makes our sensor among the most sensitive in existence.</p>
<p>The device includes a tiny ring that light races around – 240,000 times in 40 nanoseconds, or billionths of a second. A liquid sample surrounds the sensor. Some of the light extends outside of the ring, where it interacts with the sample thousands of times.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/364603/original/file-20201020-13-1ygjan.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Microscope image of a tapered cylinder with a disc on top of it" src="https://images.theconversation.com/files/364603/original/file-20201020-13-1ygjan.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/364603/original/file-20201020-13-1ygjan.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=515&fit=crop&dpr=1 600w, https://images.theconversation.com/files/364603/original/file-20201020-13-1ygjan.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=515&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/364603/original/file-20201020-13-1ygjan.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=515&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/364603/original/file-20201020-13-1ygjan.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=647&fit=crop&dpr=1 754w, https://images.theconversation.com/files/364603/original/file-20201020-13-1ygjan.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=647&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/364603/original/file-20201020-13-1ygjan.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=647&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">The single-molecule sensor, magnified 1,700 times in this image, is narrower than the diameter of the average human hair. Light races around the ring at the top.</span>
<span class="attribution"><span class="source">Little Sensor Lab, University of Arizona</span>, <a class="license" href="http://creativecommons.org/licenses/by-nc-nd/4.0/">CC BY-NC-ND</a></span>
</figcaption>
</figure>
<p>Unlike other very sensitive detection methods, ours is label-free, meaning that we don’t have to add any radioactive tags or fluorescent labels to identify what we are trying to detect. This means we don’t have to process our samples as much. </p>
<p>Because our sensor is so sensitive, we require only small amounts of a substance, which is useful both for reducing costs and in cases where reagents are difficult to obtain.</p>
<h2>Why it matters</h2>
<p>Some diseases, like cancer, can progress silently, avoiding detection until it’s too late. An ultrasensitive sensor could detect a disease before symptoms appear, letting health care providers treat the disease early, when it’s still curable. The sensor could also be used in a COVID-19 breath test.</p>
<p>Having a rapid and sensitive sensor can also enable monitoring of disease progression and can quantify the effect of different treatments. Our lab, for example, currently works on detecting low concentrations of biomolecules that indicate Alzheimer’s disease or cancer in blood, urine and saliva samples.</p>
<h2>Other research in this field</h2>
<p>Many other approaches require that you either <a href="https://www.scientist.com/2014/06/05/fluorescent-tags-innocent-bystanders/">fluorescently “tag”</a> the thing that you’re trying to detect or amplify DNA using a <a href="https://www.genome.gov/about-genomics/fact-sheets/Polymerase-Chain-Reaction-Fact-Sheet">polymerase chain reaction</a> (PCR). For instance, current COVID-19 testing requires you to choose between a rapid antigen test, which is not as accurate, or a PCR test, which is accurate but expensive and time-consuming. </p>
<p>Active areas of research in this field also include ways to improve sample delivery to the sensor, which can improve the response time and reduce the amount of the target substance needed for detection. Researchers are also working on methods to improve sensor selectivity, which means the sensor can better distinguish the target substance from other substances. This reduces false positives. </p>
<h2>What’s next</h2>
<p>This month, our lab received a $1.8 million grant from the National Institutes of Health to improve the sensor. The next step after demonstrating that our devices work in a research setting would be to move to clinical trials.</p>
<p>[<em>Deep knowledge, daily.</em> <a href="https://theconversation.com/us/newsletters/the-daily-3?utm_source=TCUS&utm_medium=inline-link&utm_campaign=newsletter-text&utm_content=deepknowledge">Sign up for The Conversation’s newsletter</a>.]</p>
<p>In addition, we are continually improving our sensor to make it more sensitive and more selective. We are also working on using the sensor to make a portable, point-of-care medical diagnostic device that could be used for at-home care or given to an EMT in an ambulance or a soldier on a battlefield.</p><img src="https://counter.theconversation.com/content/148160/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Judith Su receives funding from the NIH, the NSF, the Defense Threat Reduction Agency (DTRA), the Gordon & Betty Moore Foundation, the Flinn Foundation, and the Arizona Alzheimer's Consortium. She also owns a financial stake in Femtorays Technologies which develops label-free molecular sensors.</span></em></p>An optical sensor that can detect individual molecules promises early detection of diseases and environmental contamination.Judith Su, Assistant Professor of Biomedical Engineering and Optical Sciences, University of ArizonaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1470872020-10-06T19:18:57Z2020-10-06T19:18:57ZSurgical corsets, respirators: a new exhibition showcases the art hidden in medical devices<figure><img src="https://images.theconversation.com/files/361802/original/file-20201006-22-1b4ajqf.jpeg?ixlib=rb-1.1.0&rect=17%2C0%2C2977%2C1994&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">An artificial respirator made by Both Equipment Ltd, Adelaide, South Australia, 1950-1959.</span> <span class="attribution"><span class="source">Belinda Christi/MAAS</span></span></figcaption></figure><p><em>Review: Design for Life, the Powerhouse Museum, Sydney.</em></p>
<p>Life is messy, yet on the surface it comes neatly packaged. Our skin both enfolds and conceals internal systems that are almost infinite in their complexity. No wonder it’s our largest organ. It also mediates the way we interact with the world, from expressive facial gestures to fine hairs bristling in a cool breeze.</p>
<p>So it is with the technologies that sustain, renovate or enhance our bodies. Their unique shapes and sequences are traced through <a href="https://maas.museum/event/design-for-life/">Design for Life</a>, the latest biomedical exhibition at Sydney’s Powerhouse Museum.</p>
<p>It was a delight to return to the <a href="https://powerhousemuseumalliance.com/">resuscitated Powerhouse</a>. Its collections are extraordinary and this exhibition has drawn thoughtfully on the museum’s diverse artefacts. </p>
<p>The thematic arrangement spans our bodily functions from blood to breathing, as well as the capabilities embodied in therapeutic devices. </p>
<h2>Whimsy in minutiae</h2>
<p>Within the “modification and augmentation” display, visitors can appreciate the extraordinarily delicate stitchwork that underwear manufacturers applied to crafting surgical corsets. Painstakingly laced, these garments both embraced and reshaped the healing bodies beneath.</p>
<p>Design for Life is a very Powerhouse exhibition. Its objects are exquisitely organised, but minimally captioned. We don’t hear the voices of practitioners or patients, nor do we see human bodies or the technology at work. </p>
<p>The atmosphere is archetypically clinical. The staging and lighting are serene and austere, striking in their starkness. Display cases echo the functional, stainless-steel chic of the operating theatre. </p>
<figure class="align-center ">
<img alt="Gallery install shot" src="https://images.theconversation.com/files/361752/original/file-20201005-14-16ffa71.jpg?ixlib=rb-1.1.0&rect=16%2C0%2C5530%2C3700&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/361752/original/file-20201005-14-16ffa71.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/361752/original/file-20201005-14-16ffa71.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/361752/original/file-20201005-14-16ffa71.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/361752/original/file-20201005-14-16ffa71.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/361752/original/file-20201005-14-16ffa71.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/361752/original/file-20201005-14-16ffa71.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">There is a sparse clinical feel to the exhibition.</span>
<span class="attribution"><span class="source">Jessica Maurer/MAAS</span></span>
</figcaption>
</figure>
<p>This sparseness draws attention to whimsical details. </p>
<p><a href="https://www.cochlear.com/au/en/home">Cochlear</a>’s first prototype bionic ear <a href="https://collection.maas.museum/object/416643">from 1979</a> allowed users to optimise what they heard by flicking a switch to choose between “speech” or “music”. </p>
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<em>
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Read more:
<a href="https://theconversation.com/heres-what-music-sounds-like-through-an-auditory-implant-112457">Here's what music sounds like through an auditory implant</a>
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</em>
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<p>We can see that <a href="https://www.eoas.info/biogs/A000347b.htm">Telectronics</a> upgraded their ventricular synchronised pacemaker Model PX2-B, because the code “PX2-C” has been crudely scratched onto the face plate of a prototype. Redolent of 70s-era graffiti, the date “1 – 2 – 75” is also carved roughly into its burnished and stencilled surface. </p>
<p>Such is the untidiness of innovation.</p>
<p>These minutiae matter. In 2020, the display devoted to “breath and resuscitation” is particularly pertinent. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/361792/original/file-20201006-22-cnkkf5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A white, bright gallery space." src="https://images.theconversation.com/files/361792/original/file-20201006-22-cnkkf5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/361792/original/file-20201006-22-cnkkf5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/361792/original/file-20201006-22-cnkkf5.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/361792/original/file-20201006-22-cnkkf5.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/361792/original/file-20201006-22-cnkkf5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/361792/original/file-20201006-22-cnkkf5.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/361792/original/file-20201006-22-cnkkf5.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">A section on breath and resuscitation feels particularly pertinent in 2020.</span>
<span class="attribution"><span class="source">Jessica Maurer/MAAS</span></span>
</figcaption>
</figure>
<p>I relished the opportunity to inspect a 1940s <a href="https://www.australiangasmasks.com/civilian-respirator">civilian respirator</a>. Mass manufactured during the second world war, this rubber mask was intended to protect our domestic populace from a feared <a href="https://collections.museumsvictoria.com.au/items/1553517">gas attack by air</a>. </p>
<p>In theory, its harness could be adjusted to provide an air-tight seal against inhaled poisons. In reality, the straps on the displayed respirator are secured with three homely safety pins.</p>
<h2>Advertising’s hidden messages</h2>
<p>No matter their clinical utility, therapeutic products also require marketing. The cabinet on “medicine and drugs” presents pharmaceutical packaging from the 1940s onwards. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/361793/original/file-20201006-24-zu54lu.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/361793/original/file-20201006-24-zu54lu.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/361793/original/file-20201006-24-zu54lu.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/361793/original/file-20201006-24-zu54lu.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/361793/original/file-20201006-24-zu54lu.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/361793/original/file-20201006-24-zu54lu.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/361793/original/file-20201006-24-zu54lu.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/361793/original/file-20201006-24-zu54lu.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">FLU OIA’, Optical Immuno Assay for the Detection of Influenza A and B, developed and made by Biota, Melbourne, Victoria, Australia and Thermo Electron Corporation, Louisville, Colorado, 2004.</span>
<span class="attribution"><span class="source">Laura Moore/MAAS</span></span>
</figcaption>
</figure>
<p>Most cartons are Spartan, comprising neatly lettered information enlivened by the occasional splash of colour. Within this boxy assemblage, a 1967 packet of <a href="https://collection.maas.museum/object/566000">Bronkephrine</a> stands out. Featuring a cartoonish illustration of a doctor’s bag and syringe, what struck me most was its bold claim.</p>
<p>When used to treat asthma, promised Winthrop Laboratories, Bronkephrine would deliver “rapid, exceptionally safe bronchodilatation without tachycardia”. Clearly <a href="https://www.mydr.com.au/heart-stroke/palpitations">tachycardia</a> – an excessively fast heart rate – had proven problematic with previous asthma remedies. </p>
<p>Reassuring phrases such as “exceptionally safe” have since been <a href="https://www.tga.gov.au/advertising-health-products-rules-about-safety-claims-advertising">banned from pharmaceutical promotions</a>. The more widely we use medical technologies, the more we accept that humans respond to them in idiosyncratic and unanticipated ways, and broad claims about safety are no longer allowed.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/pivot-to-pandemic-how-advertisers-are-using-and-abusing-the-coronavirus-to-sell-135681">Pivot to pandemic: how advertisers are using (and abusing) the coronavirus to sell</a>
</strong>
</em>
</p>
<hr>
<p>This is the fundamental tension undercutting the exhibition: life is not designed. Even in rude health, humans behave in erratic or capricious ways. Our unruly fluids seep onto operating tables and we push the wrong button. We change and adapt devices, and we lose or break objects. </p>
<p>While the emergent design of medical artefacts may represent new technological possibilities, it can also reflect the impact of ignorance, accidents or whimsy.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/361805/original/file-20201006-16-j49tnd.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A line of testing devices." src="https://images.theconversation.com/files/361805/original/file-20201006-16-j49tnd.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/361805/original/file-20201006-16-j49tnd.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/361805/original/file-20201006-16-j49tnd.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/361805/original/file-20201006-16-j49tnd.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/361805/original/file-20201006-16-j49tnd.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/361805/original/file-20201006-16-j49tnd.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/361805/original/file-20201006-16-j49tnd.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">MicroRapid lateral flow blood test device and prototypes, designed and made by Atomo Diagnostics and ide Group, Newington Technology Park, Sydney, New South Wales, Australia, 2013.</span>
<span class="attribution"><span class="source">Laura Moor/MAAS</span></span>
</figcaption>
</figure>
<h2>The medical utility of the hardware store</h2>
<p>This is why my favourite object in Design for Life is a <a href="https://collection.maas.museum/object/148876">carbon surgical laser</a>, introduced by Laser Industries in 1979. The battleship-grey device looks more like an assembly-line robot than a precision incision tool. </p>
<p>Yet it is entirely humanised. Printed operating instructions have been slipped into a cheap plastic sleeve and sticky-taped to its top surface. “If you are uncertain how to look after [the] machine”, they conclude, “please leave it for someone who does”.</p>
<p>The back of the laser unit reminds me of a patient who forgot to lace up their hospital gown, exposing their posterior to an unappreciative ward. </p>
<p>Here we find a chipped gas cylinder plastered with inspection certificates and stickers; a stencilled filter unit; yellowed tubing and electrical leads. Seemingly critical to the laser’s operation is a coiled length of garden hose, complete with an orange Nylex connector as found in backyards across Australia. Struggling to discipline these writhing and disorderly attachments is a length of hardware-store galvanised chain.</p>
<p>This is the reality of healthcare design: much as we might aim for purity of form, function, communication or operation, medical devices are never merely objects. They live with us – or within us – in all of our chaotic unpredictability. Life eludes our designs. </p>
<p>Yet this exhibition confirms the touching endurance of our belief one day – just maybe – we will actually be in control.</p>
<p><em>Design for Life is on at the Powerhouse Museum until January 31, 2021.</em></p><img src="https://counter.theconversation.com/content/147087/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>From 1995 to 2010, Peter Hobbins was a professional medical writer whose clients included some of the manufacturers represented in this exhibition. He has not worked for or received commissions from those sponsors since 2010.</span></em></p>Drawing thoughtfully on the Powerhouse Museum’s collection, this exhibition lovingly exposes the humanity behind biomedical technology.Peter Hobbins, Honorary Associate, Department of History, University of SydneyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1418522020-07-09T12:16:33Z2020-07-09T12:16:33ZCell-like decoys could mop up viruses in humans – including the one that causes COVID-19<figure><img src="https://images.theconversation.com/files/346420/original/file-20200708-3987-kvex63.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2351%2C1025&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Duck decoys lure real ducks within range of hunters. Nanoparticles that look like cells serve as both decoys and hunters to ensnare virus particles.</span> <span class="attribution"><a class="source" href="https://www.flickr.com/photos/clnlnz/12423674924/">Chuck Holland/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span></figcaption></figure><p><em>The Research Brief is a short take about interesting academic work.</em></p>
<h2>The big idea</h2>
<p>Researchers around the world are working frantically to develop COVID-19 vaccines meant to target and attack the SARS-CoV-2 virus. Researchers in my <a href="http://nano.ucsd.edu/%7El7zhang/">nanoengineering lab</a> are taking a different approach toward stopping SARS-CoV-2. Instead of playing offense and stimulating the immune system to attack the SARS-CoV-2 virus, we’re playing defense. We’re working to shield the healthy human cells the virus invades. </p>
<p>Conceptually, the strategy is simple. We create decoys that look like the human cells the SARS-CoV-2 virus invades. So far, we’ve made lung-cell decoys and immune-cell decoys. These cell decoys attract and neutralize the SARS-CoV-2 virus, leaving the real lung or immune cells healthy.</p>
<p>To make the decoys, we collect the outer membranes of the lung or immune cells and wrap them around a core made of biodegradable nanoparticles. From the outside the decoys look the same as the human cells they are impersonating. Our decoys are hundreds of times smaller in diameter than an actual lung or immune cell, but they have all the same cellular hardware sticking out of them. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/346423/original/file-20200708-35-1ahqv9d.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/346423/original/file-20200708-35-1ahqv9d.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=392&fit=crop&dpr=1 600w, https://images.theconversation.com/files/346423/original/file-20200708-35-1ahqv9d.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=392&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/346423/original/file-20200708-35-1ahqv9d.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=392&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/346423/original/file-20200708-35-1ahqv9d.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=492&fit=crop&dpr=1 754w, https://images.theconversation.com/files/346423/original/file-20200708-35-1ahqv9d.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=492&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/346423/original/file-20200708-35-1ahqv9d.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=492&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">In this illustration, six decoys surround a SARS-CoV-2 virus particle before it can reach a human cell.</span>
<span class="attribution"><a class="source" href="https://drive.google.com/drive/folders/1sRBmpQwTTZzqsN3GRWSZwvDqDOSb-_vt">David Baillot, UC San Diego Jacobs School of Engineering</a>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<p>We call them “nanosponges” because they soak up harmful pathogens and toxins that attack the cells they impersonate. My team and I first developed the concept 10 years ago, and since then we’ve shown the nanosponges offer a new approach to fighting viral infections like <a href="https://doi.org/10.1002/adma.201802233">HIV</a>; <a href="https://doi.org/10.1038/nnano.2013.54">bacterial infections</a> like methicillin-resistant <em>Staphylococcus aureus</em>, or MRSA, <em>E. coli</em> and <a href="https://doi.org/10.1073/pnas.1714267114">sepsis</a>; and inflammatory diseases like <a href="https://doi.org/10.1038/s41565-018-0254-4">rheumatoid arthritis</a>.</p>
<p>We recently <a href="https://doi.org/10.1021/acs.nanolett.0c02278">published results</a> showing that the SARS-CoV-2 coronavirus binds to these decoy nanosponges, which were more than 90% effective in causing the virus to lose its ability to infect cells in petri dishes. Once the virus is locked into the decoy, it can’t invade any real cells, and is cleared by the body’s immune system. </p>
<h2>Why it matters</h2>
<p>Vaccines are critical for protecting against viral infections, but as viruses mutate they can render vaccines and treatments ineffective. This is why new flu vaccines are <a href="https://theconversation.com/influenza-the-search-for-a-universal-vaccine-90908">developed each year</a>. Fortunately, SARS-CoV-2 <a href="https://medicalxpress.com/news/2020-06-sars-cov-mutating-slowly-good.html">doesn’t appear to mutate as quickly</a> as influenza viruses, but this highlights the need for alternatives that are unaffected by mutations.</p>
<p>I’m hopeful that other teams of researchers come up with safe and effective treatments for COVID-19 as soon as possible. But for now, my team is working and planning as if the world is counting on us.</p>
<h2>What still isn’t known</h2>
<p>The different types of nanosponges we’ve developed are in various stages of pre-clinical development. So far, the results look promising, but there is more work to do to ensure they’re safe and effective. </p>
<p>Cellular nanosponges are a new kind of drug. We made the first nanosponges <a href="https://doi.org/10.1073/pnas.1106634108">using human red blood cell membranes</a>, and these are the furthest along in the regulatory process, having undergone all stages of pre-clinical testing. </p>
<h2>What’s next</h2>
<p><a href="https://cellics.com/">Cellics Therapeutics</a>, a startup company I co-founded, is in the process of submitting an investigational new drug application to the FDA for the red blood cell nanosponges to treat bacterial pneumonia. If these red blood cell nanosponges get FDA approval and if the pre-clinical data for the COVID-19 nanosponges keep looking good, the COVID-19 nanosponges could have a clearer path to clinical trials in the years ahead.</p>
<p>We are currently testing the nanosponges for SARS-CoV-2 in animals. If the nanosponges do reach the clinical trial stage, there are several ways of delivering the therapy, including direct delivery into the lung for intubated patients via an inhaler like those used by asthmatic patients or through an intravenous injection. </p>
<p>There is also the possibility that our immune-cell nanosponges could soak up the inflammatory cytokine proteins that are triggering the <a href="https://theconversation.com/blocking-the-deadly-cytokine-storm-is-a-vital-weapon-for-treating-covid-19-137690">dangerous immune system overreactions</a> in some people suffering from COVID-19.</p>
<p>[<em>You need to understand the coronavirus pandemic, and we can help.</em> <a href="https://theconversation.com/us/newsletters/the-daily-3?utm_source=TCUS&utm_medium=inline-link&utm_campaign=newsletter-text&utm_content=coronavirus-help">Read The Conversation’s newsletter</a>.]</p><img src="https://counter.theconversation.com/content/141852/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Liangfang Zhang consults to/owns shares in Cellics Therapeutics, Inc. He receives funding from the Defense Threat Reduction
Agency. </span></em></p>Nanoparticles dressed up in cell membranes snag SARS-CoV-2 virus particles before they reach human cells.Liangfang Zhang, Professor of Nanoengineering, University of California, San DiegoLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1148712020-06-18T08:02:59Z2020-06-18T08:02:59ZThis 3D printed ‘bone brick’ could transform how we treat bomb injuries – inside story<figure><img src="https://images.theconversation.com/files/319079/original/file-20200306-118923-1qkzhfy.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption"></span> <span class="attribution"><span class="license">Author provided</span></span></figcaption></figure><p>For thousands of Syrian refugees who have suffered horrific blast injuries after being hit by barrel bombs and other devices of death in their war-torn homeland, the only option is amputation. When you see the damage a blast injury can do it’s a shock to the system and is so very sad and upsetting. </p>
<p><a href="https://www.amnesty.org.uk/circle-hell-barrel-bombs-aleppo-syria">Barrel bombs</a> have been dropped throughout the long conflict that has torn Syria apart and caused untold misery and pain to so many innocent civilians. At the start of 2018, <a href="https://www.amnesty.org.uk/circle-hell-barrel-bombs-aleppo-syria">Amnesty International reported</a> that barrel bombs had killed more than 11,000 civilians in Syria since 2012, injuring many more.</p>
<p>The barrel bomb is a type of improvised explosive device which – <a href="https://www.nytimes.com/interactive/2019/12/31/world/middleeast/syria-united-nations-investigation.html">according to the UN</a> – is used extensively by the Syrian Air Force. They are made from large oil barrels and are typically filled with TNT, oil and even chunks of steel. Due to the large amount of explosives that can be packed into a barrel, the resulting explosion can be devastating.</p>
<p>Even if a person survives such a blast, their limbs are at risk of suffering a large, often jagged break which, even in the best conditions, would be a major challenge to repair. In a fully equipped, state-of-the-art hospital such patients would be able to access expert orthopaedic surgery and a lot of expensive aftercare.</p>
<p>But in a refugee camp, far away from any sophisticated surgical intervention, these types of complex procedures with timely recovery and care implications are just not possible. So at the moment, amputation is unfortunately the most likely outcome in many of these cases.</p>
<hr>
<figure class="align-right ">
<img alt="" src="https://images.theconversation.com/files/288776/original/file-20190820-170910-8bv1s7.png?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/288776/original/file-20190820-170910-8bv1s7.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=600&fit=crop&dpr=1 600w, https://images.theconversation.com/files/288776/original/file-20190820-170910-8bv1s7.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=600&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/288776/original/file-20190820-170910-8bv1s7.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=600&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/288776/original/file-20190820-170910-8bv1s7.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=754&fit=crop&dpr=1 754w, https://images.theconversation.com/files/288776/original/file-20190820-170910-8bv1s7.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=754&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/288776/original/file-20190820-170910-8bv1s7.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=754&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption"></span>
</figcaption>
</figure>
<p><strong><em>This article is part of Conversation Insights</em></strong>
<br><em>The Insights team generates <a href="https://theconversation.com/uk/topics/insights-series-71218">long-form journalism</a> derived from interdisciplinary research. The team is working with academics from different backgrounds who have been engaged in projects aimed at tackling societal and scientific challenges.</em> </p>
<hr>
<p>Many of these bone shattering injuries are untreatable because of the constant risk of infection from procedures carried out in the field and the collapse of the healthcare system. A simpler and cheaper way to help these people needed to be invented and my colleagues and I believe we have done just that. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/311604/original/file-20200123-162232-1cf2sg6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/311604/original/file-20200123-162232-1cf2sg6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=409&fit=crop&dpr=1 600w, https://images.theconversation.com/files/311604/original/file-20200123-162232-1cf2sg6.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=409&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/311604/original/file-20200123-162232-1cf2sg6.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=409&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/311604/original/file-20200123-162232-1cf2sg6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=514&fit=crop&dpr=1 754w, https://images.theconversation.com/files/311604/original/file-20200123-162232-1cf2sg6.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=514&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/311604/original/file-20200123-162232-1cf2sg6.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=514&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Andrew Weightman and Paulo Bartolo in the lab.</span>
<span class="attribution"><span class="source">JillJennings/The University of Manchester</span>, <span class="license">Author provided</span></span>
</figcaption>
</figure>
<p>Our treatment uses a temporary, 3D printed “bone brick” to fill the gap. They are made up of polymer and ceramic materials and can be clicked together just like a Lego brick to fit perfectly into whatever gap has been created by the blast injury. The bricks are degradable and allow new tissue to grow around them. This structure will support the load like a normal bone, induce the formation of new bone and, during this process, the bricks will dissolve. The idea is that the surgeon can open a bag of bricks and piece them together to fit that particular defect and promote the bone growth.</p>
<p>The solution has been a long time coming and it was very much the plight of Syrian refugees that inspired it. It struck a very personal chord. I recognise that misery and pain and see my younger self on the faces of the children. I was born and grew up in Mozambique in South-East Africa in 1968. It was the middle of the war of independence and the country was in turmoil.</p>
<p>My family inevitably became caught up in the <a href="https://www.bbc.co.uk/news/world-africa-13890720">decade-long conflict</a> that involved the Portuguese community that was living and working in Mozambique and the <a href="https://www.britannica.com/topic/Frelimo">Frelimo</a> (The Mozambique Liberation Front) resistance movement that were seeking independence and self-rule. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/310503/original/file-20200116-181598-1skkubv.PNG?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/310503/original/file-20200116-181598-1skkubv.PNG?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=598&fit=crop&dpr=1 600w, https://images.theconversation.com/files/310503/original/file-20200116-181598-1skkubv.PNG?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=598&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/310503/original/file-20200116-181598-1skkubv.PNG?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=598&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/310503/original/file-20200116-181598-1skkubv.PNG?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=751&fit=crop&dpr=1 754w, https://images.theconversation.com/files/310503/original/file-20200116-181598-1skkubv.PNG?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=751&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/310503/original/file-20200116-181598-1skkubv.PNG?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=751&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Paulo Bartolo with his mother and younger brother Jose Manuel in 1973-4 at their home in Manhica, Mozambique.</span>
<span class="attribution"><span class="source">Paulo Bartolo</span>, <span class="license">Author provided</span></span>
</figcaption>
</figure>
<p>It was 1973 and these were dangerous times. I was about five years old and it was a very frightening and disruptive period of my life. We moved up and down the country as my father’s job in civil administration changed and required us to move to the Niassa government base in Vila Cabral (now Lichinga). </p>
<p>One episode sticks out vividly. My one-year-old brother, Jose Manuel, and I were taken from our home in Maragra and moved to a refugee camp in an area of South Africa called Nelspruit, as we tried to escape the escalating violence. We were safe but I was always anxious and scared about the security of our family. </p>
<figure class="align-right ">
<img alt="" src="https://images.theconversation.com/files/310511/original/file-20200116-181598-1ektu8z.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/310511/original/file-20200116-181598-1ektu8z.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=412&fit=crop&dpr=1 600w, https://images.theconversation.com/files/310511/original/file-20200116-181598-1ektu8z.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=412&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/310511/original/file-20200116-181598-1ektu8z.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=412&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/310511/original/file-20200116-181598-1ektu8z.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=517&fit=crop&dpr=1 754w, https://images.theconversation.com/files/310511/original/file-20200116-181598-1ektu8z.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=517&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/310511/original/file-20200116-181598-1ektu8z.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=517&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">The two brothers with their father outside the administrative office where he worked in Vila Cabral.</span>
<span class="attribution"><span class="license">Author provided</span></span>
</figcaption>
</figure>
<p>Although we were only in the camp for around a month before we were transferred to start a new life in Portugal when I was six, that experience stayed with me for life. It gave me a strong sense of empathy for others who are being displaced by war. And it would eventually strengthen my commitment to use my bio-medical expertise to try and do something to help other refugees.</p>
<h2>Blast injuries and amputations</h2>
<p>The first time I was made fully aware of the impact of blast injuries in the Syrian conflict was when <a href="https://mft.nhs.uk/mri/consultants/mr-amer-shoaib/#targetText=Amer%20Shoaib%20is%20a%20Consultant,pain%20and%20Achilles%20tendon%20injuries.">Amer Shoaib</a> – a consultant orthopaedic surgeon at Manchester Royal infirmary – came to my university to discuss his experience and the problems he faced in treating these injuries in Syrian refugees. </p>
<p>Shoaib is a limb-injury expert with experience of working on the frontline of various conflicts and crisis zones as a humanitarian worker. He told us that in Syria the after effects of blast injuries were sometimes untreatable because of the constant risk of infection. The collapse of the healthcare system has also led to many treatments being done by people who are not, in fact, trained medics.</p>
<p>Shoaib was working in refugee camps in Turkey and I, along with my Manchester research colleagues Andy Weightman and Glenn Cooper, decided we needed to help and apply our expertise. We all wanted to make a difference and we continued our discussion late into the evening. This conversation developed into the idea of the “bone bricks”.</p>
<h2>A game-changer</h2>
<p>My own academic interests include biofabrication for tissue engineering. This involves fabricating bone, nerve, cartilage and skin through the use of 3D printing. 3D printing technology can now reproduce biocompatible and biodegradable materials that can be used in the human body. </p>
<p>Current grafting techniques have several limitations, including the risk of infection and disease transmission. They are also quite costly and present a high risk of further injury and serious bleeding. This work is centred on creating orthopaedic devices – or scaffolds – that can enable the regeneration of bone tissues to repair fractures.</p>
<p>I had been busy responding to the calls from clinicians to make these tools more agile, smaller in scale and responsive to more personalised healthcare. But the challenge set by the Syrian situation was a game-changer: we had to consider other new factors, such as making the scaffolds even more cost-effective and useable in demanding environments where it is very difficult to manage infection. </p>
<p>Part of our solution to these challenges was to use relatively low-cost 3D printing technology to create bone bricks with a degradable porous structure into which a special infection-fighting paste can be injected. The bone brick prosthesis and paste will prevent infection, promote bone regeneration and create a mechanically stable bone union during the healing period. </p>
<p>The challenge of creating this pioneering prosthesis led us on a journey to Turkey in 2016 where we met with academics, surgeons and medical companies. We were convinced that our proposed new technique could dramatically improve the medical response to life-changing limb injuries in the challenging conditions of these camps. It was clear that our project should be focused on patients within the Syrian refugee community in Turkey where they have found a safe haven from the horrors of war. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/299448/original/file-20191030-17893-1m9chou.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/299448/original/file-20191030-17893-1m9chou.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=385&fit=crop&dpr=1 600w, https://images.theconversation.com/files/299448/original/file-20191030-17893-1m9chou.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=385&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/299448/original/file-20191030-17893-1m9chou.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=385&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/299448/original/file-20191030-17893-1m9chou.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=484&fit=crop&dpr=1 754w, https://images.theconversation.com/files/299448/original/file-20191030-17893-1m9chou.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=484&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/299448/original/file-20191030-17893-1m9chou.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=484&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption"></span>
<span class="attribution"><span class="license">Author provided</span></span>
</figcaption>
</figure>
<p>Once we secured the backing of <a href="https://www.ukri.org/research/global-challenges-research-fund/">the Global Challenges Research Fund</a> (a £1.5 billion pot provided by the UK government to support cutting edge research that specifically addresses the challenges faced by developing countries) we began to put our project into motion. As a first step Weightman, Cooper and I visited <a href="https://www.sabanciuniv.edu/en">Sabanci University</a> in Istanbul to meet with our lead collaborator there, <a href="http://myweb.sabanciuniv.edu/bahattinkoc/">Bahattin Koç</a>, who introduced us to a group of clinicians who had been dealing with the refugees and their injuries firsthand and were able to share their knowledge. Their experiences gave us insight into the challenges of treating serious bone injuries in the field. </p>
<p>Our collaborators in Turkey helped to ensure we shaped the design and specifications of the bone bricks so they aligned as closely as possible to the needs of the frontline clinicians. During our stay in Istanbul we were constantly reminded of the human cost of the <a href="https://www.bbc.co.uk/news/world-middle-east-39252307">Syrian civil war</a>. We would often witness groups of displaced families, including children, who had fled the conflict and were seeking refuge and the chance to rebuild their lives. What we had seen on TV about Syria, with helicopters dropping bombs, was brought home to us. Some of my colleagues have children the same age as those we want to help and it made us even more determined to do something. </p>
<h2>War in Syria</h2>
<p>The Syrian conflict has displaced around 3 million refugees into Turkey, accounting for around 4% of its population. Turkey provides free healthcare services to Syrians and, as such, the burden on the healthcare system <a href="https://reliefweb.int/report/turkey/turkey-response-syria-crisis-november-30-2016">is significant</a>, with 940,000 patients treated, 780,000 operations and 20.2 million outpatient services taken up between 2011 and 2017 alone.</p>
<p>The Turkish government <a href="https://edition.cnn.com/2019/08/07/middleeast/turkey-syrian-refugees-istanbul-intl/index.html">says</a> it has spent more than US$37 billion hosting Syrian refugees. We hope that our bone bricks innovation can make a contribution to this crisis, helping to mitigate Turkey’s healthcare costs and also significantly improve the human cost of this crisis.</p>
<p>Our project is focused on bone injuries that are often caused by blast explosions, which are powerful enough to throw a person many yards and shatter bodies. Shoaib once said to us:</p>
<blockquote>
<p>If you look at the way people were injured 100 years ago, 90% were the military and 10% were civilians. <a href="https://theconversation.com/modern-conflict-blurs-the-line-between-soldiers-and-civilians-28929">It’s now the other way around</a>.</p>
</blockquote>
<p>This is certainly true for the Syrian crisis where thousands of people are suffering terrible injuries. Given that <a href="https://www.theguardian.com/world/2016/feb/11/report-on-syria-conflict-finds-115-of-population-killed-or-injured">almost 2 million people</a> have been injured in the Syrian civil war, we estimate that 100,000 people have been affected by large bone loss and of those injured since 2013 there have been more than 30,000 amputations – equating to about 7,500 a year. Amputation has associated physical complications including heart attack, slow wound healing and the constant risk of infection.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/modern-conflict-blurs-the-line-between-soldiers-and-civilians-28929">Modern conflict blurs the line between soldiers and civilians</a>
</strong>
</em>
</p>
<hr>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/311580/original/file-20200123-162210-1ipki6g.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/311580/original/file-20200123-162210-1ipki6g.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=403&fit=crop&dpr=1 600w, https://images.theconversation.com/files/311580/original/file-20200123-162210-1ipki6g.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=403&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/311580/original/file-20200123-162210-1ipki6g.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=403&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/311580/original/file-20200123-162210-1ipki6g.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=507&fit=crop&dpr=1 754w, https://images.theconversation.com/files/311580/original/file-20200123-162210-1ipki6g.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=507&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/311580/original/file-20200123-162210-1ipki6g.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=507&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Bone brick under x750 magnification.</span>
<span class="attribution"><span class="source">Paulo Bartolo</span>, <span class="license">Author provided</span></span>
</figcaption>
</figure>
<h2>Catastrophic limb amputation</h2>
<p>Current bone repair techniques are complex. They include: </p>
<ul>
<li><p>The leg or arm being harnessed in a metal fixing device or cage which allows slow-growing bone tissue to reconnect. But this process frequently creates complications caused by metal wires transfixing and cutting through soft tissues as the frame is extended to lengthen the bone. It is a lengthy and meticulous. </p></li>
<li><p>Placing a pin or plate implant to stabilise the bone gap and enable the tissue to reconnect. This procedure requires complex surgery in specialist centres of excellence and can only be considered in extreme and selected cases.</p></li>
<li><p>Bone shortening procedures, where healing is stimulated by removing damaged bone tissue. Or there are forms of bone grafting techniques which use transplanted bone to repair and rebuild damaged bones. </p></li>
</ul>
<p>And it must be remembered, traumatic limb amputation is a catastrophic injury and an irreversible act that has a sudden and emotionally devastating impact on the patient. As a consequence, this not only impacts a person’s ability to earn a living but also brings very serious psychological issues for the patient because of the cultural stigma associated with limb loss.</p>
<p>External prosthetic limbs after amputation provide some with a solution but they are not suitable for all. <a href="https://www.ncbi.nlm.nih.gov/pubmed/30782746">Studies show</a> that the long term healthcare costs of amputation are three times higher than those treated by limb salvage. Clearly, saving a limb offers a better quality of life and functional capacity than amputation and external prosthetics. </p>
<h2>Just like Lego</h2>
<p>With many blast injuries, the bone defects are totally impossible to heal. What we are doing is creating a temporary structure using bone bricks to fill the gap. Our treatment uses medical scaffolds, made up of polymer and ceramic materials, which can be clicked together like a Lego brick, creating a degradable structure which then allows new tissue to grow. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/311657/original/file-20200123-162190-ql0zrz.PNG?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/311657/original/file-20200123-162190-ql0zrz.PNG?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=472&fit=crop&dpr=1 600w, https://images.theconversation.com/files/311657/original/file-20200123-162190-ql0zrz.PNG?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=472&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/311657/original/file-20200123-162190-ql0zrz.PNG?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=472&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/311657/original/file-20200123-162190-ql0zrz.PNG?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=594&fit=crop&dpr=1 754w, https://images.theconversation.com/files/311657/original/file-20200123-162190-ql0zrz.PNG?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=594&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/311657/original/file-20200123-162190-ql0zrz.PNG?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=594&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">A prototype brick just off the 3D printer at the University of Manchester.</span>
<span class="attribution"><span class="source">Paulo Bartolo</span>, <span class="license">Author provided</span></span>
</figcaption>
</figure>
<p>We are also developing software to allow the clinician, based on the information on the bone defect, to select the exact number of bone bricks with the specific shape and size and information on how to assemble – just like Lego instructions. The connection between the bone brick design and the 3D printing system is completed. We’re now in the process of integrating with the software that will link the scanning of information from the wound area with the identification of the correct type of bone bricks and assembly mechanism.</p>
<p>An antibiotic ceramic paste is stored in a hollow in the middle of the brick and is a highly practical way to combat infection while the limb repairs and hugely improves the chances of success. </p>
<p>The bone brick solution is much more cost effective than current methods of treatment. We expect our limb-saving solution will be less than £200 for a typical 100mm fracture injury. This is far cheaper than current solutions, which can cost between £270 and £1,000 for an artificial limb depending on the type needed. </p>
<h2>When will they be used on humans?</h2>
<p>My team and I are entering the final stages of a three-year project. Our team consists of academics and clinicians from Manchester and Turkey, as well as a pool of ten bone injury patients drawn from the UK, Turkey and Syria. We have already evaluated the modular bone bricks system in a computer simulation, created prototypes of the modular bone bricks using 3D printing technologies in the lab, and conducted in-vitro (laboratory) testing of mechanical and biological characterisation of the bricks. This will be followed by in-vivo (animal) testing to prepare the device for regulatory approval and a pathway to implementation by clinicians. Once all these stages are complete the project we will be ready to trial on human patients. </p>
<p>The final stage will then be to translate the research into building a useable, medical device. This will be undertaken by a follow-on clinical trial on about 20 patients with large bone loss, some of which we expect will be drawn from the Syrian refugee community. The project will be subject to strict ethical scrutiny and approval.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/311585/original/file-20200123-162221-mrh1t1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/311585/original/file-20200123-162221-mrh1t1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=600&fit=crop&dpr=1 600w, https://images.theconversation.com/files/311585/original/file-20200123-162221-mrh1t1.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=600&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/311585/original/file-20200123-162221-mrh1t1.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=600&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/311585/original/file-20200123-162221-mrh1t1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=754&fit=crop&dpr=1 754w, https://images.theconversation.com/files/311585/original/file-20200123-162221-mrh1t1.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=754&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/311585/original/file-20200123-162221-mrh1t1.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=754&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">A bone brick under Electron Microscopy scanning.</span>
<span class="attribution"><span class="source">Paolo Bartolo</span>, <span class="license">Author provided</span></span>
</figcaption>
</figure>
<p>We hope this project will lead to further development of emergency healthcare in the developing world and could bring hope to a Syrian refugee community in dire need while their country rebuilds. Our long term hope is that bone bricks will be of use, not only in refugee crises, but also in many other healthcare situations, such as accidents and natural disasters – in both developing and developed nations. For example, in the UK around 2,000 patients a year receive treatment for severe fractures requiring surgical reconstruction for <a href="https://www.nice.org.uk/Media/Default/About/what-we-do/Into-practice/measuring-uptake/NICE-Impact-falls-and-fragility-fractures.pdf">bone loss</a>. </p>
<p>The burden to the health service relating to major traumatic injuries is <a href="https://www.ncbi.nlm.nih.gov/pubmed/27333868">estimated to be in excess of £0.5bn</a>. In addition, the estimated loss of contribution to the economy due to extended periods of rehabilitation is another <a href="https://www.england.nhs.uk/wp-content/uploads/2016/04/rehabilitation-comms-guid-16-17.pdf">£3.5 billion</a>.</p>
<p>We believe the bone brick project could help alleviate some of those economic burdens and drastically improve the patient experience. But it is the plight of the Syrian refugees that continues to inspire and inform this project. We hope that, perhaps in five years’ time, bone bricks will be used in the field on humans, finally giving medics and victims an alternative to catastrophic limb amputation.</p>
<hr>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/313478/original/file-20200204-41481-1n8vco4.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/313478/original/file-20200204-41481-1n8vco4.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=112&fit=crop&dpr=1 600w, https://images.theconversation.com/files/313478/original/file-20200204-41481-1n8vco4.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=112&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/313478/original/file-20200204-41481-1n8vco4.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=112&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/313478/original/file-20200204-41481-1n8vco4.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=140&fit=crop&dpr=1 754w, https://images.theconversation.com/files/313478/original/file-20200204-41481-1n8vco4.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=140&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/313478/original/file-20200204-41481-1n8vco4.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=140&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption"></span>
</figcaption>
</figure>
<p><em>For you: more from our <a href="https://theconversation.com/uk/topics/insights-series-71218?utm_source=TCUK&utm_medium=linkback&utm_campaign=TCUKengagement&utm_content=InsightsUK">Insights series</a>:</em></p>
<ul>
<li><p><em><a href="https://theconversation.com/they-put-a-few-coins-in-your-hands-to-drop-a-baby-in-you-265-stories-of-haitian-children-abandoned-by-un-fathers-114854?utm_source=TCUK&utm_medium=linkback&utm_campaign=TCUKengagement&utm_content=InsightsUK">‘They put a few coins in your hands to drop a baby in you’ – 265 stories of Haitian children abandoned by UN fathers</a></em></p></li>
<li><p><em><a href="https://theconversation.com/the-end-of-the-world-a-history-of-how-a-silent-cosmos-led-humans-to-fear-the-worst-120193?utm_source=TCUK&utm_medium=linkback&utm_campaign=TCUKengagement&utm_content=InsightsUK">The end of the world: a history of how a silent cosmos led humans to fear the worst</a></em></p></li>
<li><p><em><a href="https://theconversation.com/decades-neglecting-an-ancient-disease-has-triggered-a-health-emergency-around-the-world-121282?utm_source=TCUK&utm_medium=linkback&utm_campaign=TCUKengagement&utm_content=InsightsUK">Decades neglecting an ancient disease has triggered a health emergency around the world</a></em></p></li>
</ul>
<p><em>To hear about new Insights articles, join the hundreds of thousands of people who value The Conversation’s evidence-based news. <a href="https://theconversation.com/uk/newsletters/the-daily-newsletter-2?utm_source=TCUK&utm_medium=linkback&utm_campaign=TCUKengagement&utm_content=InsightsUK"><strong>Subscribe to our newsletter</strong></a>.</em></p><img src="https://counter.theconversation.com/content/114871/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>This article was written with the assistance of Shaden Jaradat from The University of Manchester. Bone bricks research credits go to Paulo Bartolo, Glen Cooper and Andrew Weightman from The University of Manchester, Bahattin Koc from Sabanci University in Turkey and Gordon Blunn from the University of Portsmouth, with clinical support from Amer Shoaib.
The research is funded by the Engineering and Physical Sciences Research Council.
The research team is grateful for the excellent work conducted by a large number of post-doctoral research associates, PhD and MSc students.</span></em></p>A cutting edge new research project is developing Lego-like bricks made from biomaterials to replace bone fragments in shattered limbs.Paulo Bartolo, Chair Professor on Advanced Manufacturing, University of ManchesterLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1377562020-05-12T12:35:06Z2020-05-12T12:35:06ZAI tool searches thousands of scientific papers to guide researchers to coronavirus insights<figure><img src="https://images.theconversation.com/files/332869/original/file-20200505-83757-1nuyewy.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C8000%2C4491&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Artificial intelligence can do what humans can't – connect the dots across the majority of coronavirus research.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/coronavirus-royalty-free-image/1215382103?adppopup=true">baranozdemir/E+ via Getty Images</a></span></figcaption></figure><p><em>The Research Brief is a short take about interesting academic work.</em></p>
<h2>The big idea</h2>
<p>The scientific community worldwide has mobilized with unprecedented speed to tackle the COVID-19 pandemic, and the emerging research output is staggering. Every day, <a href="https://covid19primer.com/dashboard">hundreds of scientific papers about COVID-19 come out</a>, in both traditional journals and non-peer-reviewed preprints. There’s already far more than any human could possibly keep up with, and more research is constantly emerging.</p>
<p>And it’s not just new research. We estimate that there are as many as 500,000 papers relevant to COVID-19 that were published before the outbreak, including papers related to the outbreaks of SARS in 2002 and MERS in 2012. Any one of these might contain the key information that leads to effective treatment or a vaccine for COVID-19.</p>
<p>Traditional methods of searching through the research literature just don’t cut it anymore. This is why <a href="https://www.covidscholar.org/about">we and our colleagues</a> at Lawrence Berkeley National Lab are using the latest artificial intelligence techniques to build <a href="https://www.covidscholar.org/">COVIDScholar</a>, a search engine dedicated to COVID-19. COVIDScholar includes tools that pick up subtle clues like similar drugs or research methodologies to recommend relevant research to scientists. AI can’t replace scientists, but it can help them gain new insights from more papers than they could read in a lifetime.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/333182/original/file-20200506-49538-ey2oya.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/333182/original/file-20200506-49538-ey2oya.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=395&fit=crop&dpr=1 600w, https://images.theconversation.com/files/333182/original/file-20200506-49538-ey2oya.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=395&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/333182/original/file-20200506-49538-ey2oya.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=395&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/333182/original/file-20200506-49538-ey2oya.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=496&fit=crop&dpr=1 754w, https://images.theconversation.com/files/333182/original/file-20200506-49538-ey2oya.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=496&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/333182/original/file-20200506-49538-ey2oya.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=496&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">COVIDScholar is a search engine with machine learning algorithms under the hood.</span>
<span class="attribution"><span class="source">Screen capture by The Conversation</span></span>
</figcaption>
</figure>
<h2>Why it matters</h2>
<p>When it comes to finding effective treatments for COVID-19, time is of the essence. Scientists spend <a href="https://doi.org/10.1371/journal.pone.0189753">23% of their time searching for and reading papers</a>. Every second our search tools can save them is more time to spend making discoveries in the lab and analyzing data.</p>
<p>AI can do more than just save scientists time. Our group’s previous work showed that AI <a href="https://doi.org/10.1038/s41586-019-1335-8">can capture latent scientific knowledge</a> from text, making connections that humans missed. There, we showed that AI was able to suggest new, cutting-edge functional materials years before their discovery by humans. The information was there all along, but it took combining information from hundreds of thousands of papers to find it.</p>
<p>We are now applying the same techniques to COVID-19, to find existing drugs that could be repurposed, genetic links that might help develop a vaccine or effective treatment regimens. We’re also starting to build in new innovations, like using molecular structures to help find which drugs are similar to each other, including those that are similar in unexpected ways.</p>
<h2>How we do this work</h2>
<p>The most important part of our work is the data. We’ve built web scrapers that collect new papers as they’re published from a wide variety of sources, making them available on our website within 15 minutes of their appearance online. We also clean the data, fixing mistakes in formatting and comparing the same paper from multiple sources to find the best version. Our machine learning algorithms then go to work on the paper, tagging it with subject categories and marking work important to COVID-19.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/333116/original/file-20200506-49550-10it6ws.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/333116/original/file-20200506-49550-10it6ws.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=181&fit=crop&dpr=1 600w, https://images.theconversation.com/files/333116/original/file-20200506-49550-10it6ws.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=181&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/333116/original/file-20200506-49550-10it6ws.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=181&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/333116/original/file-20200506-49550-10it6ws.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=228&fit=crop&dpr=1 754w, https://images.theconversation.com/files/333116/original/file-20200506-49550-10it6ws.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=228&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/333116/original/file-20200506-49550-10it6ws.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=228&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">COVIDScholar labels and categorizes about 250 journal papers a day to help researchers make connections they might otherwise miss.</span>
<span class="attribution"><span class="source">Kevin Cruse and Haoyan Huo</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<p>We’re also continuously seeking out experts in new areas. Their input and annotation of data is what allows us to train new AI models.</p>
<h2>What’s next</h2>
<p>So far, we have assembled a collection of over 60,000 papers on COVID-19, and we’re expanding the collection daily. We’ve also built search tools that group research into categories, suggest related research and allow users to find papers that connect different concepts, such as papers that connect a specific drug to the diseases it’s been used to treat in the past. We’re now building AI algorithms that allow researchers to plug search results into quantitative models for studying topics like protein interactions. We’re also starting to dig through the past literature to find hidden gems.</p>
<p>We hope that very soon, researchers using COVIDScholar will start to identify relationships that they might never have imagined, bringing us closer to treatments and a remedy for COVID-19.</p>
<p>[<em>You’re too busy to read everything. We get it. That’s why we’ve got a weekly newsletter.</em> <a href="https://theconversation.com/us/newsletters/weekly-highlights-61?utm_source=TCUS&utm_medium=inline-link&utm_campaign=newsletter-text&utm_content=weeklybusy">Sign up for good Sunday reading.</a> ]</p><img src="https://counter.theconversation.com/content/137756/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Amalie Trewartha receives funding from the Department of Energy and has previously received funding from the Toyota Research Institute.</span></em></p><p class="fine-print"><em><span>John Dagdelen works for Lawrence Berkeley National Laboratory. He receives funding from Berkeley Lab and previously from the Toyota Research Institute. </span></em></p>The scientific community is churning out vast quantities of research about the coronavirus pandemic – far too much for researchers to absorb. An AI system aims to do the heavy lifting for them.Amalie Trewartha, Post Doctoral Fellow, University of California, BerkeleyJohn Dagdelen, Graduate Student Researcher, Persson Group, University of California, BerkeleyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1379862020-05-06T18:02:54Z2020-05-06T18:02:54ZA mysterious illness is striking children amid the coronavirus pandemic – but is it Kawasaki disease?<figure><img src="https://images.theconversation.com/files/333130/original/file-20200506-49556-14bv10f.jpg?ixlib=rb-1.1.0&rect=2%2C5%2C1979%2C1233&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A number of young COVID-19 patients have developed inflammation in multiple organs.</span> <span class="attribution"><a class="source" href="http://gettyimages.com">Ezra Acayan/Getty Images</a></span></figcaption></figure><p>Critically ill children have been ending up in intensive care units with shock-like symptoms in recent weeks, adding yet another mysterious layer to the coronavirus pandemic. </p>
<p>New York health officials began <a href="https://www1.nyc.gov/assets/doh/downloads/pdf/han/alert/2020/covid-19-pediatric-multi-system-inflammatory-syndrome.pdf">issuing alerts</a> on May 4, describing young patients, ages 2-15, with inflammation in multiple organ systems and features of Kawasaki disease, a childhood illness of unclear origin. They <a href="http://dmna.ny.gov/covid19/docs/all/DOH_COVID19_PediatricInflammatorySyndrome_050620.pdf">raised the count to 64 suspected cases</a> on May 6, and the governor reported over the weekend that <a href="https://www.governor.ny.gov/news/amid-ongoing-covid-19-pandemic-governor-cuomo-announces-new-york-notifying-49-other-states">three children had died</a>. </p>
<p>A few days earlier, officials in the <a href="https://picsociety.uk/wp-content/uploads/2020/04/PICS-statement-re-novel-KD-C19-presentation-v2-27042020.pdf">United Kingdom notified doctors of similar cases</a> there, also describing them as having features similar to Kawasaki disease and toxic shock syndrome. Several of the children had tested positive for COVID-19.</p>
<p>Drawing connections to Kawasaki disease, however, may be premature. Although there are some similarities between the illnesses, there are also many differences.</p>
<p>My clinical practice is as <a href="http://medicine.buffalo.edu/faculty/profile.html?ubit=markhica">a pediatric infectious disease physician</a>. I also do biomedical research using the body’s immune responses, particularly the antibodies produced, to help find the cause of illness and to help design vaccines. Our group has been collecting samples from Kawasaki disease cases for years. With the COVID-19 pandemic, we responded to the call for researchers and began developing tests to assess the antibody response during COVID-19. </p>
<p>When we started on this path, I did not think these interests would overlap so directly. However, with recent reports of certain COVID-19 cases looking like Kawasaki disease, we are now running tests to see if there is a similar immune response between COVID-19 and Kawasaki disease cases. </p>
<h2>Kawasaki versus the new illnesses</h2>
<p>Kawasaki disease is an inflammatory condition in children who develop a prolonged fever, inflammation of the mouth and lips, rash, swelling of the hands and feet, inflamed eyes, and lymph node swelling that typically is only on one side of the neck. There can also be incomplete cases that do not have all these symptoms. </p>
<p>Kawasaki disease can have serious consequences: Roughly one-quarter of children diagnosed with it will have inflammation in the vessels that feed the heart, and rarely children will present with heart attacks or shock and need prolonged intensive care.</p>
<p>Unfortunately, we don’t know what causes Kawasaki disease. A litany of viruses, bacteria, fungi and environmental factors have been proposed in the past, including other members of the coronavirus family. Despite not knowing what causes Kawasaki disease, we have found that timely treatments with pooled human antibody preparations – intravenous immunoglobulin, or IVIG – can significantly reduce the heart vessel inflammation. </p>
<p>For the new COVID-19-associated cases showing a significant inflammatory response, many of the reports <a href="https://www.cnn.com/2020/04/29/health/rare-inflammatory-syndrome-us-covid-19/index.html">reflected in</a> <a href="https://www.nytimes.com/2020/05/05/nyregion/kawasaki-disease-coronavirus.html">the media</a> and public health announcements have not been published in medical journals. Instead, details have been shared among the medical community in conference calls, message boards and online meetings.</p>
<p><a href="https://hosppeds.aappublications.org/content/hosppeds/early/2020/04/06/hpeds.2020-0123.full.pdf">Only one case</a> I know of describing Kawasaki disease associated with COVID-19 has been published. This case, like many of the cases being discussed informally, had no cardiac vessel involvement and lacked a number of clinical symptoms of classic Kawasaki disease. </p>
<h2>Some overlap, but different symptoms</h2>
<p>There are a number of reasons why the new COVID-19-associated inflammatory disorder and Kawasaki disease seem to be different entities. </p>
<p>Although there is some overlap, these COVID-19-associated cases have fairly different laboratory results. There also tends to be more severe abdominal pain, nausea and vomiting in new cases than would be usual for Kawasaki disease. </p>
<p>The impact on the patient’s heart is focused more on the vessels in Kawasaki disease. The COVID-19-associated cases, in comparison, are globally dysfunctional with only a few describing any vessel inflammation. </p>
<p>The ages and locations of the described new cases are also not typical for Kawasaki disease. Many of the children with severe COVID-19-associated shock are outside the typical age range for Kawasaki disease, which primarily targets children under 7. </p>
<p>The annual case count of Kawasaki disease is also much higher in Asian countries, particularly in Japan, where it is roughly 10 times the rate in North America. I would have expected an association to be described during the first reports of the pandemic, but informal reports from Japan and China don’t appear to describe this severe inflammation in children.</p>
<p>That being said, some children with Kawasaki disease will test positive for the new coronavirus. In North America, there are estimated to be <a href="https://doi.org/10.1161/CIR.0000000000000484">5,000-6,000 annual cases of Kawasaki disease</a>. Overlaying <a href="https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/cases-in-us.html">more than 1 million cases of COVID-19</a> throughout the United States, there will be some overlap. </p>
<h2>What we still need to learn</h2>
<p>Reports about these new pediatric COVID-19-associated cases are very preliminary. We will learn more as research and details about ongoing and future cases are compiled by the medical community and published for more complete review.</p>
<p>Perhaps studying these new cases will shed much needed light on the cause of Kawasaki disease, a disorder that has perplexed pediatricians for a half-century. As both conditions appear to incite a large inflammatory response in certain children, continued research is needed to provide the “how” for the new COVID-19-associated cases and the “what causes it” for Kawasaki disease. </p>
<p>States such as New York are making the right move by formally gathering data on severely inflamed children during this pandemic, as proper treatments for these new COVID-19-associated cases need to be found.</p>
<p><em>This article was updated with new numbers from the New York Department of Health.</em></p>
<p>[<em>You’re smart and curious about the world. So are The Conversation’s authors and editors.</em> <a href="https://theconversation.com/us/newsletters/weekly-highlights-61?utm_source=TCUS&utm_medium=inline-link&utm_campaign=newsletter-text&utm_content=weeklysmart">You can get our highlights each weekend</a>.]</p><img src="https://counter.theconversation.com/content/137986/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Mark Hicar does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>A biomedical researcher and pediatrician who works with Kawasaki disease and COVID-19 explains the similarities and differences in the worrisome cases doctors are starting to see.Mark Hicar, Assistant Professor, University at BuffaloLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1351442020-04-02T14:57:21Z2020-04-02T14:57:21ZScale of COVID-19 calls for new approaches – like crowdsourcing – to research<figure><img src="https://images.theconversation.com/files/324334/original/file-20200331-65495-9ecz42.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Traditional approaches to biomedical research and development are costly and time consuming.</span> <span class="attribution"><span class="source">GettyImages</span></span></figcaption></figure><p>COVID-19 is not the world’s first pandemic. Nor is it the only type of big problem that the world faces. Environmental degradation and drug-resistant diseases are other examples. </p>
<p>What’s special about the new coronavirus is the speed with which it has arisen and multiplied. </p>
<p>The current system of scientific and academic research can’t respond fast enough to problems like these, especially when data is still being generated. But there are potentially ways of overcoming this mismatch. </p>
<p>I <a href="https://www.tandfonline.com/doi/full/10.1080/20421338.2017.1341093">propose</a> that crowdsourcing is a promising approach to biomedical research and development (R&D) and could produce solutions to pandemics like this one.</p>
<p>The biomedical research and development industry largely responds to private incentives – even if subsidised by governments. Drugs are more likely to be developed for <a href="https://aeon.co/essays/will-medicine-ever-recover-from-the-perverse-economics-of-drugs">wealthy markets</a> offering opportunities for chronic medicines that need to be taken for the rest of one’s life. This is because drug companies face the challenge of very large initial investments which they might not be able to recoup if a drug is not profitable. There’s less incentive to do R&D that could have wider social benefits. </p>
<p>A large-scale response to the COVID-19 outbreak is under way and there are already <a href="https://www.theguardian.com/world/2020/apr/01/coronavirus-vaccine-when-will-it-be-ready-covid-19">vaccines under development</a>. But there is no indication yet that they will be successful. The current R&D response may simply not be large enough to stop the pandemic quickly enough. </p>
<h2>How do we stop COVID-19?</h2>
<p>To stop this pandemic, it may be necessary to move activities out of already productive (and profitable) research activities. And this may have to happen on a scale that is proportionate to the scale of the cost of the outbreak. A radical restructuring of the incentives of the biomedical research industry may be necessary to shift this activity away from its profitable uses and into (uncertain) vaccine research.</p>
<p>Academic <a href="http://www.scielo.org.za/pdf/sajems/v20n1/34.pdf">research</a> suggests how this might be done. Probabilistic innovation theory suggests that problems such as COVID-19 need to be exposed to processes that radically increase their probability of success. This may require novel technologies and methods to greatly increase the chances of solving the problem such as biomedical crowdsourcing, machine learning and big data science. </p>
<p>These have already demonstrated their effectiveness in <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6110041/pdf/CAS-11-33.pdf">biomedical research</a>, but not yet at the scale required to stop the pandemic. Another useful example of biomedical crowdsourcing is gamification, a process whereby complex biomedical problems are used as the basis for computer games, with the goal of solving them. The site <a href="https://fold.it/">FoldIt</a> is successfully using protein folding games to solve these kinds of problems. </p>
<p>A useful way of thinking about this approach is in terms of a societal benefit ratio. This is the ratio of the research efforts invested in solving a problem to the consequences of the same problem. In other words, many problems with very high human and economic costs don’t receive enough problem solving resources – the scale of the investments in solving these problems should be appropriate to the scale of the problem, or it might not be solved. </p>
<p>Current R&D efforts aimed at tackling the pandemic may produce a societal benefit ratio that is too small. The COVID-19 pandemic potentially affects around <a href="https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200325-sitrep-65-covid-19.pdf?sfvrsn=2b74edd8_2">8 billion</a> people. Estimates of necessary interventions suggest that, if not addressed, the damage to the global economy could be in the <a href="https://unctad.org/en/pages/newsdetails.aspx?OriginalVersionID=2315">trillions of dollars</a>. The problem with current approaches seems to be that they are largely rooted in the profit-driven structure of the biomedical industry. Even with academic collaborators, this restricts the size of the investments in solving the problem. </p>
<p>Existing efforts will surely come up with a solution given enough time. But it might be necessary to consider other scientific approaches that have already demonstrated their success in biomedical research, and try them at a large enough scale.</p>
<h2>How crowdsourcing works</h2>
<p>Advances in technology have made it possible to crowdsource solutions to biomedical problems. Biomedical crowdsourcing is a problem-solving methodology based on putting problems online as an open call for anyone to solve. Sites like <a href="https://www.innocentive.com/">InnoCentive</a> provide platforms for the initiation and administration of scientific crowdsourcing, but a large-scale global project might be administered by the United Nations or the World Health Organisation. </p>
<p>The successes of crowdsourcing in biomedical research are <a href="https://academic.oup.com/bmb/article/115/1/67/260667">well documented</a>. Sites such as <a href="https://www.innocentive.com/resources-overview/case-studies/">InnoCentive</a> have shown that complex scientific problems can often be solved more cheaply and quickly than they would using in-house R&D departments.</p>
<p>It could be argued that the scale of the crowdsourcing efforts to date has been too small to force activity into uncertain avenues of research. If governments across the world were to pledge a portion of their ongoing economic costs of the pandemic, it might be possible to offer a large biomedical crowdsourcing award, for example in excess of a thousand billion dollars. The scale of this award would better match the scale of the <a href="https://unctad.org/en/pages/newsdetails.aspx?OriginalVersionID=2315">consequences</a> of the pandemic. Such countries would not have to pay a cent if a solution were not found. Those seeking to solve the problem (solvers) bear the cost and risk of these efforts. This makes it necessary to offer a very large award. These costs include opportunity costs, such as the costs of not doing other work in the meantime.</p>
<p>If crowdsourcing were to solve this problem, then what of others that we have failed to solve until now? The current pandemic might offer researchers a unique chance to test this methodology at a large scale. If necessity drives invention, then there is no more important time than this to try new ideas.</p><img src="https://counter.theconversation.com/content/135144/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Chris William Callaghan does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Crowdsourcing is a promising approach to biomedical research and development (R&D) and could produce solutions to pandemics like this one.Chris William Callaghan, Professor, University of the WitwatersrandLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1290682020-01-15T19:08:18Z2020-01-15T19:08:18ZDon’t die wondering: apps may soon be able to predict your life expectancy, but do you want to know?<figure><img src="https://images.theconversation.com/files/310160/original/file-20200115-151844-1ole8rh.jpg?ixlib=rb-1.1.0&rect=46%2C23%2C3833%2C2681&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Monaco and Japan have some of the highest life expectancies in the world. But calculating an individual's life expectancy will require taking data analysis several steps further.</span> <span class="attribution"><span class="source">SHUTTERSTOCK</span></span></figcaption></figure><p><em>When will I die?</em></p>
<p>This question has endured across cultures and civilisations. It has given rise to a plethora of religions and spiritual paths over thousands of years, and more recently, <a href="https://apps.apple.com/us/app/when-will-i-die/id1236569653">some highly amusing apps</a>. </p>
<p>But this question now prompts a different response, as technology slowly brings us closer to accurately predicting the answer. </p>
<p>Predicting the lifespan of people, or their “Personal Life Expectancy” (PLE) would greatly alter our lives. </p>
<p>On one hand, it may have benefits for policy making, and help optimise an individual’s health, or the services they receive. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/were-not-just-living-for-longer-were-staying-healthier-for-longer-too-118588">We're not just living for longer – we're staying healthier for longer, too</a>
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<p>But the potential misuse of this information by the government or private sector poses major risks to our rights and privacy.</p>
<p>Although generating an accurate life expectancy is currently difficult, due to the complexity of factors underpinning lifespan, emerging technologies could make this a reality in the future.</p>
<h2>How do you calculate life expectancy?</h2>
<p>Predicting life expectancy is not a new concept. <a href="http://www.bbc.com/travel/story/20170807-living-in-places-where-people-live-the-longest">Experts do this</a> at a population level by classifying people into groups, often based on region or ethnicity. </p>
<p>Also, tools such as <a href="https://www.nature.com/articles/s41598-018-23534-9">deep learning</a> and <a href="https://mipt.ru/english/news/scientists_use_ai_to_predict_biological_age_based_on_smartphone_and_wearables_data">artificial intelligence</a> can be used to consider complex variables, such as biomedical data, to predict someone’s biological age. </p>
<p>Biological age refers to how “old” their body is, rather than when they were born. A 30-year-old who smokes heavily may have a biological age closer to 40.</p>
<p><a href="https://www.mdpi.com/2227-7080/6/3/74/htm">Calculating a life expectancy reliably</a> would require a sophisticated system that considers a breadth of environmental, geographic, genetic and lifestyle factors – <a href="https://www1.health.gov.au/internet/publications/publishing.nsf/Content/oatsih-hpf-2012-toc%7Etier1%7Elife-exp-wellb%7E119">all of which have influence</a>.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/310166/original/file-20200115-151848-pc2cam.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/310166/original/file-20200115-151848-pc2cam.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/310166/original/file-20200115-151848-pc2cam.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=389&fit=crop&dpr=1 600w, https://images.theconversation.com/files/310166/original/file-20200115-151848-pc2cam.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=389&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/310166/original/file-20200115-151848-pc2cam.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=389&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/310166/original/file-20200115-151848-pc2cam.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=489&fit=crop&dpr=1 754w, https://images.theconversation.com/files/310166/original/file-20200115-151848-pc2cam.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=489&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/310166/original/file-20200115-151848-pc2cam.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=489&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">The use of devices such as fitness trackers will become crucial in predicting personal life expectancy in the future.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-vector/healthy-lady-run-away-angel-death-329261456">Shutterstock</a></span>
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<p>With <a href="https://builtin.com/artificial-intelligence/machine-learning-healthcare">machine learning</a> and artificial intelligence, it’s becoming feasible to analyse larger quantities of data. The use of deep learning and cognitive computing, such as with <a href="https://www.ibm.com/watson-health">IBM Watson</a>, helps doctors make more accurate diagnoses than using human judgement alone. </p>
<p>This, coupled with <a href="https://www.cio.com/article/3273114/what-is-predictive-analytics-transforming-data-into-future-insights.html">predictive analytics</a> and increasing computational power, means we may soon have systems, or even apps, that can calculate life expectancy.</p>
<h2>There’s an app for that</h2>
<p>Much like <a href="https://www.mdanderson.org/for-physicians/clinical-tools-resources/clinical-calculators.html">existing tools</a> that predict cancer survival rates, in the coming years we may see apps attempting to analyse data to predict life expectancy.</p>
<p>However, they will not be able to provide a “death date”, or even a year of death.</p>
<p>Human behaviour and activities are so unpredictable, it’s almost impossible to measure, classify and predict lifespan. A personal life expectancy, even a carefully calculated one, would only provide a “natural life expectancy” based on generic data optimised with personal data.</p>
<p>The key to accuracy would be the quality and quantity of data available. Much of this would be taken directly from the user, including gender, age, weight, height and ethnicity.</p>
<p>Access to real-time sensor data through fitness trackers and smart watches could also monitor activity levels, heart rate and blood pressure. This could then be coupled with lifestyle information such as occupation, socioeconomic status, exercise, diet and family medical history. </p>
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<p>
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Read more:
<a href="https://theconversation.com/your-local-train-station-can-predict-health-and-death-54946">Your local train station can predict health and death</a>
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<p>All of the above could be used to classify an individual into a generic group to calculate life expectancy. This result would then be refined over time through the analysis of personal data, updating a user’s life expectancy and letting them monitor it.</p>
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<img alt="" src="https://images.theconversation.com/files/308303/original/file-20191230-11891-nswi58.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/308303/original/file-20191230-11891-nswi58.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=176&fit=crop&dpr=1 600w, https://images.theconversation.com/files/308303/original/file-20191230-11891-nswi58.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=176&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/308303/original/file-20191230-11891-nswi58.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=176&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/308303/original/file-20191230-11891-nswi58.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=221&fit=crop&dpr=1 754w, https://images.theconversation.com/files/308303/original/file-20191230-11891-nswi58.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=221&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/308303/original/file-20191230-11891-nswi58.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=221&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="caption">This figure shows how an individual’s life expectancy might change between two points in time (F and H) following a lifestyle improvement, such as weight loss.</span>
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<h2>Two sides of a coin</h2>
<p>Life expectancy predictions have the potential to be beneficial to individuals, health service providers and governments.</p>
<p>For instance, they would make people more aware of their general health, and its improvement or deterioration over time. This may motivate them to make healthier lifestyle choices.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/faster-more-accurate-diagnoses-healthcare-applications-of-ai-research-114000">Faster, more accurate diagnoses: Healthcare applications of AI research</a>
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<p>They could also be used by insurance companies to provide individualised services, such as how some car insurance companies use <a href="https://www.theguardian.com/money/2017/dec/16/motoring-myths-black-boxes-telematics-insurance">black-box technology</a> to reduce premiums for more cautious drivers.</p>
<p>Governments may be able to use predictions to more efficiently allocate limited resources, such as social welfare assistance and health care funding, to individuals and areas of greater need.</p>
<p>That said, there’s a likely downside. </p>
<p>People <a href="https://www.theatlantic.com/health/archive/2017/11/the-existential-slap/544790/">may become distressed</a> if their life expectancy is unexpectedly low, or at the thought of having one at all. This raises concerns about how such predictions could impact those who experience or are at risk of mental health problems. </p>
<p>Having people’s detailed health data could also let insurance companies more accurately profile applicants, <a href="https://www.abc.net.au/news/2019-07-08/fitness-tracker-used-to-set-health-insurance-premiums/11287126">leading to discrimination against groups or individuals</a>. </p>
<p>Also, pharmaceutical companies could coordinate targeted medical campaigns based on people’s life expectancy. And governments could choose to tax individuals differently, or restrict services for certain people.</p>
<h2>When will it happen?</h2>
<p>Scientists have been working on ways to <a href="https://towardsdatascience.com/what-really-drives-higher-life-expectancy-e1c1ec22f6e1">predict human life expectancy</a> for many years. </p>
<p>The solution would require input from specialists including demographers, health scientists, data scientists, IT specialists, programmers, medical professionals and statisticians.</p>
<p>While the collection of enough data will be challenging, we can likely expect to see advances in this area in the coming years.</p>
<p>If so, issues related to data compliance, as well and collaboration with government and state agencies will need to be carefully managed. Any system predicting life expectancy would handle highly sensitive data, raising ethical and privacy concerns.</p>
<p>It would also attract cybercriminals, and various other security threats.</p>
<p>Moving forward, the words of Jurassic Park’s Dr Ian Malcolm spring to mind:</p>
<blockquote>
<p>Your scientists were so preoccupied with whether or not they could, they didn’t stop to think if they should.</p>
</blockquote><img src="https://counter.theconversation.com/content/129068/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>The authors do not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and have disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Predicting life expectancy remains in the realm of science fiction, but it may soon be possible. Are we prepared for such information? And who else would benefit from this knowledge?James Jin Kang, Lecturer, Edith Cowan UniversityPaul Haskell-Dowland, Associate Dean (Computing and Security), Edith Cowan UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/986962018-08-29T22:54:20Z2018-08-29T22:54:20ZWhy we need academic health science centres<figure><img src="https://images.theconversation.com/files/234004/original/file-20180829-86141-1gi9ah3.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A few woefully underfunded academic health sciences centres are responsible for providing complex care to patients with life-threatening illnesses as well as training future doctors and testing the latest in new surgical techniques.</span> <span class="attribution"><span class="source">(Shutterstock)</span></span></figcaption></figure><p>Academic health science centres (AHSCs) are Canada’s high-performance vehicles for better health. </p>
<p>These are partnerships between a university with a medical school and its teaching hospital. While there are hundreds of hospitals in Canada, there are few AHSCs.</p>
<p>The doctors who work there are called academic physicians and they train Canada’s medical students and residents — providing the seed crop of doctors who will ultimately lead the provision of care to Canadians. They also provide complex care and perform research. </p>
<p>When well maintained, these medical centres propel us safely forward for years to come. However, if neglected and ignored, they may ultimately leave us sick and stranded at the roadside. </p>
<p>After assessing Canada’s AHSC, a national group called the Canadian Association of Professors of Medicine (CAPM) concluded that <a href="http://deptmed.queensu.ca/blog/?p=1724">it’s time to fill the tank, change the oil and provide some tender loving care.</a></p>
<p>I would argue that academic medicine is currently experiencing the best of worlds and the worst of worlds. We possess new and powerful diagnostic and therapeutic tools and are poised to deliver more innovative care. However, our ability to accomplish these goals is challenged by a number of sociological, demographic and governmental factors. </p>
<p>This article aims to highlight these challenges, not as a complaint, rather to identify potholes in the road so that they can be avoided or repaired and we can accelerate our progress forward.</p>
<h2>Research and specialized facilities</h2>
<p>Academic health sciences centres conduct research — in the form of <em>clinical trials</em> (to test new drugs, devices and diagnostics), <em>population health studies</em> (to understand diseases at the population level) and <em>translational research</em> (to move basic science to the bedside and back again). </p>
<p>Research is a form of critical inquiry and discovery that generates the evidence upon which medical practise is based. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/234006/original/file-20180829-86135-1g1o9ql.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/234006/original/file-20180829-86135-1g1o9ql.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/234006/original/file-20180829-86135-1g1o9ql.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/234006/original/file-20180829-86135-1g1o9ql.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/234006/original/file-20180829-86135-1g1o9ql.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/234006/original/file-20180829-86135-1g1o9ql.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/234006/original/file-20180829-86135-1g1o9ql.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Academic health science centres test the latest surgical techniques.</span>
<span class="attribution"><span class="source">(Shutterstock)</span></span>
</figcaption>
</figure>
<p>These doctors are also the experts who provide complex care for patients with life-threatening illnesses — including advanced surgeries, transplantation, catheter-based interventions to treat heart attacks and stroke and so much more. They also test the latest surgical techniques and interventions and evaluate new forms of molecular diagnostics.</p>
<p>The ASHC is also home to specialized and expensive core facilities including clinical laboratories, pharmacies and radiology programs (think PET scanners and MRIs) and interventional rooms (including robotic surgery suites, catheterization laboratories and the like) that support the community. </p>
<h2>Congested hospital wards</h2>
<p>To put into perspective how unique these organizations are, we can look at the numbers. Out of approximately 231 hospital sites in Ontario, only 16 are acute care academic centres and only five are fully-fledged AHSCs with medical schools. </p>
<p>These are located at McMaster University, University of Ottawa, Queen’s University, University of Toronto and Western University. Such classifications are however complicated, because the Northern Ontario School of Medicine also has a school of medicine and many of the features of an AHSC.</p>
<p>A 2010 report from the National Task Force on the Future of Canada’s Academic Health Sciences Centres concluded that <a href="http://www.healthcarecan.ca/wp-content/themes/camyno/assets/document/Reports/2010/External/EN/ThreeMissions_EN.pdf">AHSCs provide the majority of complex care in Canada</a>. </p>
<p>However, one of the problems we face is the influx of Canada’s aging population of baby boomers into hospitals. Many of these people require alternate levels of care (ALC) and social support, rather than acute, tertiary care. But Canada lacks a <a href="https://theconversation.com/how-to-solve-canadas-wait-time-problem-96170">comprehensive senior care network</a> and in many hospitals in Ontario, <a href="http://deptmed.queensu.ca/blog/?p=1326">ALC’s occupy 10 to 20 per cent of acute-care beds.</a> </p>
<p>This, along with challenges such as the opioid crisis and homelessness, is congesting emergency departments and overcrowding inpatient wards. This compromises delivery of quality care and challenges physician wellness.</p>
<h2>‘What makes dollars makes sense’</h2>
<p>Academic health science centres are poorly understood by government. Often, to cater to public opinion, the government focuses on enhancing outpatient care, ignoring the <a href="http://deptmed.queensu.ca/blog/?p=1563">importance of accessing state of the art, innovative care</a>.</p>
<p>Compensation models are also misaligned with services provided. Most doctors in the community are paid on what we call a “fee for service” (FFS) payment plan. This means that they bill for each patient they see, for the service rendered. </p>
<p>This model disproportionately rewards clinical activity, particularly procedural activities, while <a href="http://deptmed.queensu.ca/blog/?p=1563">failing to fund many important and time-consuming consultative services, and not funding research and educational activities at all</a>. </p>
<p>At its worst this can lead to a culture where, “what makes dollars makes sense.” </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/234011/original/file-20180829-86144-5681qd.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/234011/original/file-20180829-86144-5681qd.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=375&fit=crop&dpr=1 600w, https://images.theconversation.com/files/234011/original/file-20180829-86144-5681qd.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=375&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/234011/original/file-20180829-86144-5681qd.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=375&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/234011/original/file-20180829-86144-5681qd.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=471&fit=crop&dpr=1 754w, https://images.theconversation.com/files/234011/original/file-20180829-86144-5681qd.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=471&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/234011/original/file-20180829-86144-5681qd.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=471&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">An anti-fentanyl advertisment is seen on a sidewalk in downtown Vancouver, Tuesday, April, 11, 2017. The opioid crisis is contributing to the congestion of emergency departments.</span>
<span class="attribution"><span class="source">THE CANADIAN PRESS/Jonathan Hayward</span></span>
</figcaption>
</figure>
<p>Training pipeline goals at medical schools are also misaligned. While Canada needs large numbers of general practitioners, AHSCs need highly specialized physicians — cardiologists and cardiac surgeons, neurosurgeons and neurologists, gastroenterologists and general surgeons, nephrologists and transplant surgeons, laboratory medicine specialists, anaesthetists and radiologists. A focus on training more general internists is also important to the sustainability of our health-care system. </p>
<p>Finally, Canada lacks a funding mechanism to support the training of our most advanced learners, who are referred to as “fellows.” These are the doctors that go on to provide complex care such as coronary angioplasty, endovascular therapy for stroke, transplant medicine or catheter-based treatment of heart arrhythmias. </p>
<p>In the absence of fellowship funding, Canadian AHSCs rely increasingly on importing international medicine graduates to staff their hospitals.</p>
<h2>No funding for outstanding research</h2>
<p>Finally, we have inadequate research funding models. The creation of a clinician scientist takes approximately three additional years of postgraduate medical training. This is followed by five years as a junior faculty member, during which substantial time protection and mentorship are required. </p>
<p>This is difficult to provide when the rate of success for research proposals at Canada’s agency for funding biomedical research — the Canadian Institute of Health Research (CIHR) — is below 15 per cent. </p>
<p>Due to lack of funds, CIHR has been rejecting 80 to 90 per cent of funding applications, including those deemed outstanding by peer review. CIHR was intended to have a budget equal to one per cent of public health spending, but this has not kept up with health expenditures or inflation.</p>
<p>The <a href="http://www.sciencereview.ca/eic/site/059.nsf/eng/home">2017 Naylor report</a>, from the expert panel on Canada’s Fundamental Science Review notes: </p>
<blockquote>
<p>“Canada ranks well globally in higher education expenditures on research and development as a percentage of GDP, but is an outlier in that funding from federal government sources accounts for less than 25 per cent of that total, while institutions now underwrite 50 per cent of these costs with adverse effects on both research and education.” </p>
</blockquote>
<p>The report recommended an increase in CIHR funding of, “$485 million, phased in over four years, directed to funding investigator-led research.” However, while some of the report’s recommendations were taken up in the 2018 Federal budget, many outstanding grants will continue to be unfunded.</p>
<h2>The future is a federally-funded network</h2>
<p>Alternate funding plans (AFPs) need to be considered, which reward activities in education, research and clinical care equally. </p>
<p>AHSCs also need more research funding — to enable the next wave of researchers to <a href="https://www.policyschool.ca/wp-content/uploads/2016/03/funding-medical-research-zwicker-emery.pdf">save lives</a>. To achieve this they need an improved budget structure. </p>
<p>We should also create a federally funded network of accredited AHSCs. Although health care is primarily provincially funded, the federal government’s funding via the Canada Health Transfer accounts for approximately a quarter of the health-care budget. </p>
<p>Federal funding is both discretionary and growing (at a rate of around six per cent per year). This funding could be used selectively to develop, advance and unify a national network of AHSCs, in which academic departments of medicine could thrive. </p>
<p>With such investment we would certainly see benefits beyond improved health care.</p><img src="https://counter.theconversation.com/content/98696/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Stephen Archer receives research funding from CIHR, the Canada Foundation for Innovation, the Ontario Ministry of Research Innovation and The William J Henderson Foundation .</span></em></p>Canada’s systems of health funding, medical training and physician compensation need an overhaul – to support vital centres of medical research and complex care.Stephen L Archer, Professor, Head of Department of Medicine, Queen's University, OntarioLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1004352018-08-07T10:40:25Z2018-08-07T10:40:25ZFunding basic research plays the long game for future payoffs<figure><img src="https://images.theconversation.com/files/230804/original/file-20180806-191013-1fnl7ab.jpg?ixlib=rb-1.1.0&rect=429%2C222%2C3660%2C2667&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">It takes time to see which finding might be a golden egg.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/one-gold-egg-lays-among-common-111414110">Neamov/Shutterstock.com</a></span></figcaption></figure><p>The Senate recently proposed to increase the research budgets of the <a href="http://www.sciencemag.org/news/2018/06/senate-panel-proposes-2-billion-54-increase-nih">National Institutes of Health</a>, <a href="http://www.sciencemag.org/news/2018/06/nasa-science-and-nsf-do-well-senate-spending-bill">National Science Foundation and NASA</a>. While this is encouraging to the many scientists whose research is dependent on grants from these agencies, it comes at a time when scientific research is under increased scrutiny.</p>
<p>Questioning the merit of scientific research is certainly not new. In the 1970s and 1980s the <a href="https://www.wisconsinhistory.org/turningpoints/search.asp?id=1742">Golden Fleece Awards</a> were an ignominious honor bestowed by a U.S. senator on what he considered “wasteful” research. The majority of the ire was aimed at research thought to be “useless.” </p>
<p>But having no obvious immediate application <a href="https://theconversation.com/tracing-the-links-between-basic-research-and-real-world-applications-82198">doesn’t mean something will never be of use</a>.</p>
<p>Perhaps the difficultly in justifying basic research is in part a branding problem. The goal of this type of work is to understand the fundamental principles of nature, and it spans the STEM fields (Science, Technology, Engineering and Mathematics). Once these fundamental principles are understood, they can be applied to more translational research that can have direct benefits to patients or consumers. </p>
<p>But the benefits of basic research are often not instantly recognizable. Potential long-term payoffs – perhaps ones that haven’t even been imagined yet – won’t help consumers or patients now.</p>
<p>There are countless discoveries whose eventual impact would have been very difficult to predict when the research was in its infancy. Honors like the <a href="https://www.goldengooseaward.org/">Golden Goose Award</a>, presented every fall since 2012, combat the idea of basic research being “wasteful” or “useless” by underscoring that it’s actually the foundation for further scientific innovation. Given enough time and support, basic research can yield significant real-world benefits that were hard to predict in advance. Here are two examples of scientific curiosity paying substantial dividends decades after the initial discovery.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/230806/original/file-20180806-34489-1u0hpnh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/230806/original/file-20180806-34489-1u0hpnh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/230806/original/file-20180806-34489-1u0hpnh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/230806/original/file-20180806-34489-1u0hpnh.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/230806/original/file-20180806-34489-1u0hpnh.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/230806/original/file-20180806-34489-1u0hpnh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/230806/original/file-20180806-34489-1u0hpnh.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/230806/original/file-20180806-34489-1u0hpnh.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">What could a bioluminescent jellyfish contribute to medical science?</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/crystal-jellyfish-aequorea-victoria-bioluminescent-hydrozoan-671090275">LagunaticPhoto/Shutterstock.com</a></span>
</figcaption>
</figure>
<h2>From glowing jellyfish to biomedical imaging</h2>
<p>It was very unlikely that scientists were thinking of medical applications when in the 1950s they started studying why some <a href="https://doi.org/10.1098/rspb.1955.0066">jellyfish glow</a>. Marine biologists discovered that the jellyfish <em>Aequorea victoria</em> was <a href="https://ocean.si.edu/ocean-life/fish/bioluminescence">bioluminescent</a>. What was unclear at the time was how this jellyfish produces its light, which is a vibrant green color.</p>
<p>Seven years later a group of researchers discovered that the living light from the jellyfish came from a single protein they called <a href="https://doi.org/10.1002/jcp.1030590302">aequorin</a>. Strangely, the light from the purified aequorin protein was blue, not green. After another eight years of work they found that a partner protein to aequorin, which they called green fluorescent protein (<a href="https://doi.org/10.1002/jcp.1040770305">GFP</a>), produced the vibrant green-colored light seen in the living jellyfish.</p>
<p>The question then became how did the two proteins work together to produce this light? It took another 10 years of work to get the answer. A series of papers published in the early 1970s characterized a small molecule called a <a href="https://doi.org/10.2144/000113765">chromophore</a> that integrated into the <a href="https://doi.org/10.1016/0014-5793(79)80818-2">GFP protein structure</a>. The <a href="https://doi.org/10.1126/science.273.5280.1392">structure of GFP</a> was discovered in the early 1990s, which further helped researchers understand how this protein created light in living cells.</p>
<p>The first time the GFP protein was produced in an organism other than a jellyfish was in 1992. Expressing GFP in the small worm <em>C. elegans</em> and the bacterium <em>E. coli</em> <a href="https://doi.org/10.1126/science.8303295">made them both glow</a> a brilliant green color. This breakthrough, nearly 40 years after the initial jellyfish study, opened the door for using GFP as powerful tool for biomedical research. Today researchers use GFP to track protein interactions and movement in living cells, which is useful in the study of cancer and bacterial diseases. A current literature search in PubMed returns over 30,000 peer-reviewed published papers using the search term “<a href="https://www.ncbi.nlm.nih.gov/pubmed/?term=%22green+fluorescent+protein%22">green fluorescent protein</a>.”</p>
<p>The impact of GFP has also been recognized with a <a href="https://www.nobelprize.org/nobel_prizes/chemistry/laureates/2008/advanced-chemistryprize2008.pdf">Nobel Prize</a> in 2008 and an inaugural Golden Goose Award in 2012.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/230807/original/file-20180806-191031-1y0ysvs.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/230807/original/file-20180806-191031-1y0ysvs.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/230807/original/file-20180806-191031-1y0ysvs.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/230807/original/file-20180806-191031-1y0ysvs.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/230807/original/file-20180806-191031-1y0ysvs.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/230807/original/file-20180806-191031-1y0ysvs.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/230807/original/file-20180806-191031-1y0ysvs.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/230807/original/file-20180806-191031-1y0ysvs.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=566&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">What could a bacteria’s immune system add to genetic researchers’ toolkit?</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/3d-illustration-crisprcas13a-system-1029539410">Meletios Verras/Shutterstock.com</a></span>
</figcaption>
</figure>
<h2>From bacterial immunity to genome editing</h2>
<p>A more recent example of how basic research is now driving incredible innovation can be found in the fields of synthetic biology and genome editing, thanks to what actually started out very humbly as the characterization of bacteria. In the late 1980s, researchers found that certain bacteria had <a href="https://doi.org/10.1128/jb.169.12.5429-5433.1987">short repeated regions</a> in their genome, but they didn’t know their purpose. They called these DNA sequences Clustered Regularly Interspaced Short Palindromic Repeats; you’ve probably heard its acronym nickname <a href="https://doi.org/10.1046/j.1365-2958.2002.02839.x">CRISPR</a>. Work characterizing and cataloging bacteria that had these short repeated sequences continued for 20 years before researchers discovered proteins associated with the short DNA repeats. They called them CRISPR associated, or Cas, proteins.</p>
<p>One major advance happened in 2005 when researchers realized that CRISPR sequences found in bacterial genomes <a href="https://doi.org/10.1099/mic.0.28048-0">match DNA in phages</a>, viruses that infect bacteria. A few more years later, scientists showed that the CRISPR-Cas system was a type of <a href="https://doi.org/10.1126/science.1138140">adaptive immunity</a> that bacteria use to remember phage infection and prevent it from happening again. The Cas protein cuts invading phage’s DNA to stop infection. This discovery was groundbreaking; no one had known something as simple as a single-celled bacterium could have a sophisticated immune system.</p>
<p>And then in 2013, researchers realized this type of directed DNA cutting could be used to <a href="https://doi.org/10.1126/science.1231143">edit the genomes of other organisms</a>, not just bacteria. The method was quickly adapted for use in yeast, worm, fruit fly, zebrafish, mouse, plant and human cells. Genome editing in this way will have far-reaching implications for everything from food production to stem cell therapies.</p>
<p>Thirty years after its discovery, the scope of CRISPR research is truly impressive; a current literature search in PubMed returns over 10,000 peer-reviewed published papers using the search term “<a href="https://www.ncbi.nlm.nih.gov/pubmed/?term=CRISPR">CRISPR</a>.” The technologies stemming from CRISPR have not won a Golden Goose Award or Nobel Prize yet, but some speculate it is only a <a href="http://blogs.plos.org/synbio/2017/10/05/when-will-crispr-get-a-nobel-prize/">matter of time</a>.</p>
<h2>Curiosity and patience yield dividends</h2>
<p>Answering fundamental questions – Why do jellyfish glow? Why do bacterial genomes have short repeating DNA sequences? – <a href="https://www.goldengooseaward.org/awardees/">can lead to innovation and tangible benefits</a> in many aspects of everyday life. And a Golden Goose Award or Nobel Prize is not required to show that a discovery has translational application. An entrepreneurship study published in 2017 highlighted that more than 75 percent of research articles published are <a href="https://doi.org/10.1126/science.aam9527">eventually referenced in at least one patent disclosure</a>. This study showed a strong link between patent applications, ostensibly a quantitative metric of innovation, and basic research taking place at universities and government laboratories. </p>
<p>Real-world impacts stemming from basic research can take decades to unfold. If basic science is not supported and funded in the U.S., other countries will take over the innovation leadership role. Much like the goose that laid golden eggs, time and patience are required to get the most out of basic research.</p><img src="https://counter.theconversation.com/content/100435/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jeffrey Gardner receives funding from the US Department of Energy. </span></em></p>Basic research can be easy to mock as pointless and wasteful of resources. But it’s very often the foundation for future innovation – even in ways the original scientists couldn’t have imagined.Jeffrey Gardner, Associate Professor of Biological Sciences, University of Maryland, Baltimore CountyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/840322018-01-03T11:20:41Z2018-01-03T11:20:41ZNovelty in science – real necessity or distracting obsession?<figure><img src="https://images.theconversation.com/files/199939/original/file-20171219-5004-1ecssnn.jpg?ixlib=rb-1.1.0&rect=693%2C5%2C2809%2C1943&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">It may take time for a tiny step forward to show its worth.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/man-grey-suit-hold-light-left-541269598">ellissharp/Shutterstock.com</a></span></figcaption></figure><p>In a <a href="https://www.nature.com/news/1-500-scientists-lift-the-lid-on-reproducibility-1.19970">survey of over 1,500 scientists</a>, more than 70 percent of them reported having been unable to reproduce other scientists’ findings at least once. Roughly half of the surveyed scientists ran into problems trying to reproduce their own results. No wonder people are talking about a “<a href="https://theconversation.com/us/topics/reproducibility-5484">reproducibility crisis</a>” in scientific research – an epidemic of studies that <a href="https://thenextregeneration.wordpress.com/2013/07/23/replicability-of-high-impact-papers-in-stem-cell-research/">don’t hold up</a> when <a href="https://thenextregeneration.wordpress.com/2013/10/26/the-replicability-crisis-in-cancer-research/">run a second time</a>.</p>
<p>Reproducibility of findings is a core foundation of science. If scientific results only hold true in some labs but not in others, then how can researchers feel confident about their discoveries? How can society put evidence-based policies into place if the evidence is unreliable?</p>
<p>Recognition of this “crisis” has prompted calls for reform. Researchers are feeling their way, experimenting with different practices meant to help distinguish solid science from irreproducible results. Some people are even starting to reevaluate how choices are made about what research actually gets tackled. Breaking innovative new ground is flashier than revisiting already published research. Does prioritizing novelty naturally lead to this point?</p>
<h2>Incentivizing the wrong thing?</h2>
<p>One solution to the reproducibility crisis could be simply to conduct lots of replication studies. For instance, the <a href="https://elifesciences.org/collections/9b1e83d1/reproducibility-project-cancer-biology">scientific journal eLife</a> is participating in an initiative to validate and reproduce important recent findings in the field of cancer research. The first set of these “rerun” studies was recently released and <a href="http://www.nature.com/news/cancer-reproducibility-project-releases-first-results-1.21304">yielded mixed results</a>. The results of 2 out of 5 research studies were reproducible, one was not and two additional studies did not provide definitive answers.</p>
<p>There’s no need to restrict these sort of rerun studies to cancer research – reproducibility issues can be spotted across <a href="https://theconversation.com/we-found-only-one-third-of-published-psychology-research-is-reliable-now-what-46596">various fields</a> <a href="https://theconversation.com/half-of-biomedical-research-studies-dont-stand-up-to-scrutiny-and-what-we-need-to-do-about-that-45149">of scientific research</a>.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/199940/original/file-20171219-4995-ddcteg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/199940/original/file-20171219-4995-ddcteg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/199940/original/file-20171219-4995-ddcteg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/199940/original/file-20171219-4995-ddcteg.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/199940/original/file-20171219-4995-ddcteg.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/199940/original/file-20171219-4995-ddcteg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/199940/original/file-20171219-4995-ddcteg.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/199940/original/file-20171219-4995-ddcteg.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">Researchers should be rewarded for carefully shoring up the foundations of the field.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/scientist-working-laboratory-38872966">Alexander Raths/Shutterstock.com</a></span>
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<p>But there’s at least one major obstacle to investing time and effort in this endeavor: the quest for novelty. The <a href="https://doi.org/10.3389/fnhum.2013.00291">prestige of an academic journal</a> depends at least partly on how often the research articles it publishes are cited. Thus, research journals often want to publish novel scientific findings which are more likely to be cited, not necessarily the results of newly rerun older research.</p>
<p>A <a href="https://doi.org/10.1016/j.jclinepi.2012.06.009">study of clinical trials published in medical journals</a> found the most prestigious journals prefer publishing studies considered highly novel and not necessarily those that have the most solid numbers backing up the claims. Funding agencies such as the National Institutes of Health ask scientists who review research grant applications to provide an “innovation” score in order to <a href="https://grants.nih.gov/grants/peer/critiques/rpg_D.htm">prioritize funding for the most innovative work</a>. And scientists of course notice these tendencies – one study found the use of positive words like “novel,” “amazing,” “innovative” and “unprecedented” in paper abstracts and titles <a href="https://doi.org/10.1038/nature.2015.19024">increased almost ninefold between 1974 and 2014</a>.</p>
<p>Genetics researcher <a href="http://dbbs.wustl.edu/faculty/Pages/faculty_bio.aspx?SID=5137">Barak Cohen</a> at Washington University in St. Louis <a href="https://doi.org/10.7554/eLife.28699">recently published a commentary</a> analyzing this growing push for novelty. He suggests that progress in science depends on a delicate balance between novelty and checking the work of other scientists. When rewards such as funding of grants or publication in prestigious journals emphasize novelty at the expense of testing previously published results, science risks developing cracks in its foundation.</p>
<h2>Houses of brick, mansions of straw</h2>
<p>Cancer researcher William Kaelin Jr., a recipient of the <a href="http://www.laskerfoundation.org/awards/show/oxygen-sensing-essential-process-survival/">2016 Albert Lasker Award for Basic Medical Research</a>, <a href="http://www.nature.com/news/publish-houses-of-brick-not-mansions-of-straw-1.22029">recently argued</a> for fewer “mansions of straw” and more “houses of brick” in scientific publications.</p>
<p>One of his main concerns is that scientific papers now inflate their claims in order to emphasize their novelty and the relevance of biomedical research for clinical applications. By exchanging depth of research for breadth of claims, researchers may be at risk of compromising the robustness of the work. By claiming excessive novelty and impact, researchers may undermine its actual significance because they may fail to provide solid evidence for each claim. </p>
<p>Kaelin even suggests that some of his <a href="http://www.pnas.org/content/93/20/10595">own work from the 1990s, which transformed cell biology research</a> by discovering how cells can sense oxygen, may have struggled to get published today.</p>
<p>Prestigious journals often now demand complete scientific stories, from basic molecular mechanisms to proving their relevance in various animal models. Unexplained results or unanswered questions are seen as weaknesses. Instead of publishing one exciting novel finding that is robust, and which could spawn a new direction of research conducted by other groups, researchers now spend years gathering a whole string of findings with broad claims about novelty and impact.</p>
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<a href="https://images.theconversation.com/files/199942/original/file-20171219-4980-14si8bk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/199942/original/file-20171219-4980-14si8bk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/199942/original/file-20171219-4980-14si8bk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=397&fit=crop&dpr=1 600w, https://images.theconversation.com/files/199942/original/file-20171219-4980-14si8bk.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=397&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/199942/original/file-20171219-4980-14si8bk.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=397&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/199942/original/file-20171219-4980-14si8bk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=499&fit=crop&dpr=1 754w, https://images.theconversation.com/files/199942/original/file-20171219-4980-14si8bk.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=499&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/199942/original/file-20171219-4980-14si8bk.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=499&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">There should be more than one path to a valuable journal publication.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/divergence-paths-forest-crossroads-among-many-681313621">Mehaniq/Shutterstock.com</a></span>
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<h2>Balancing fresh findings and robustness</h2>
<p>A challenge for editors and reviewers of scientific manuscripts is assessing the novelty and likely long-term impact of the work they’re assessing. The eventual importance of a new, unique scientific idea is sometimes difficult to recognize even by peers who are grounded in existing knowledge. Many basic research studies form the basis of future practical applications. One recent study found that of basic research articles that received at least one citation, <a href="https://theconversation.com/tracing-the-links-between-basic-research-and-real-world-applications-82198">80 percent were eventually cited by a patent application</a>. But it takes time for practical significance to come to light.</p>
<p>A collaborative team of economics researchers <a href="https://doi.org/10.1016/j.respol.2017.06.006">recently developed an unusual measure of scientific novelty</a> by carefully studying the references of a paper. They ranked a scientific paper as more novel if it cited a diverse combination of journals. For example, a scientific article citing a botany journal, an economics journal and a physics journal would be considered very novel if no other article had cited this combination of varied references before.</p>
<p>This measure of novelty allowed them to identify papers which were more likely to be cited in the long run. But it took roughly four years for these novel papers to start showing their greater impact. One may disagree with this particular indicator of novelty, but the study makes an important point: It takes time to recognize the full impact of novel findings. </p>
<p>Realizing how difficult it is to assess novelty should give funding agencies, journal editors and scientists pause. Progress in science depends on new discoveries and following unexplored paths – but solid, reproducible research requires an equal emphasis on the robustness of the work. By restoring the balance between demands and rewards for novelty and robustness, science will achieve even greater progress.</p><img src="https://counter.theconversation.com/content/84032/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jalees Rehman receives funding from the National Institutes of Health (NIH). </span></em></p>Scientists are rewarded with funding and publications when they come up with innovative findings. But in the midst of a ‘reproducibility crisis,’ being new isn’t the only thing to value about research.Jalees Rehman, Professor of Medicine, Pharmacology and Bioengineering, University of Illinois ChicagoLicensed as Creative Commons – attribution, no derivatives.