tag:theconversation.com,2011:/au/topics/medical-research-15/articlesMedical research – The Conversation2023-12-21T21:37:49Ztag:theconversation.com,2011:article/2169802023-12-21T21:37:49Z2023-12-21T21:37:49ZThe Douglas-Bell Canada Brain Bank: a goldmine for research on brain diseases<figure><img src="https://images.theconversation.com/files/557356/original/file-20231005-26-rmh9lm.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C4000%2C1508&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The experimental methods available today allow us to break the brain down into its elementary components in order to understand its functions and dysfunctions.</span> <span class="attribution"><span class="source">(Shutterstock)</span></span></figcaption></figure><p>Human beings have always been fascinated by the brain. </p>
<p>Although scientific knowledge about this 1.3 kg of fragile substance embedded in our cranium has long been incomplete, dazzling technical breakthroughs made in recent years are now ushering in a Golden Age of molecular neuroscience. </p>
<p>These breakthroughs have been made possible partly thanks to brain banks, which preserve human brains in the best possible conditions for scientific research. Here in Montréal, we have one of the world’s largest such banks, the Douglas-Bell Canada Brain Bank (DBCBB), <a href="https://douglasbrainbank.ca">founded in 1980 at the Douglas Hospital</a>. </p>
<p>The DBCBB, which receives several brains each month, has collected over 3,600 specimens to date. Every year, its team processes dozens of tissue requests from scientists in Québec, Canada and abroad, preparing some 2,000 samples for research. </p>
<p>Over the past 40 years, these efforts have led to a considerable number of discoveries about different neurological and psychiatric diseases. </p>
<p>As a full professor in the department of psychiatry at McGill University, researcher at the Douglas Research Centre and director of the DBCBB since 2007, I work in close collaboration with <a href="https://www.mcgill.ca/psychiatry/gustavo-turecki">Dr. Gustavo Turecki</a>, co-director of the DBCBB and responsible for the component devoted to psychiatric illnesses and suicide.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/552153/original/file-20231004-17-mdh992.jpg?ixlib=rb-1.1.0&rect=14%2C2%2C1535%2C1231&q=45&auto=format&w=1000&fit=clip"><img alt="cerebral hemisphere" src="https://images.theconversation.com/files/552153/original/file-20231004-17-mdh992.jpg?ixlib=rb-1.1.0&rect=14%2C2%2C1535%2C1231&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/552153/original/file-20231004-17-mdh992.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=475&fit=crop&dpr=1 600w, https://images.theconversation.com/files/552153/original/file-20231004-17-mdh992.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=475&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/552153/original/file-20231004-17-mdh992.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=475&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/552153/original/file-20231004-17-mdh992.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=596&fit=crop&dpr=1 754w, https://images.theconversation.com/files/552153/original/file-20231004-17-mdh992.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=596&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/552153/original/file-20231004-17-mdh992.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=596&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 Douglas-Bell Canada Brain Bank, which receives several brains each month, has collected over 3,600 specimens to date.</span>
<span class="attribution"><span class="source">(Naguib Mechawar)</span>, <span class="license">Fourni par l'auteur</span></span>
</figcaption>
</figure>
<h2>A brief history of research on the human brain</h2>
<p>Scientists only began to identify the microscopic elements that make up the human brain in the second half of the 19th century. </p>
<p>That was when brains were preserved for the first time in formalin, a solution that preserves biological tissue so that it can be handled more easily and stored over a longer term.</p>
<p>At the same time, precision instruments and protocols were being developed that made it possible to examine the microscopic characteristics of nervous tissue.</p>
<p>Until the middle of the 20th century, researchers were mainly satisfied with preserving the brains of patients, taken during autopsies, so they could use them to identify possible macroscopic or microscopic changes linked to either neurological or psychiatric symptoms.</p>
<p>This is in fact what the German neurologist Alois Alzheimer did when he analyzed the brain of one of his patients suffering from dementia. In 1906, he described, for the first time, the microscopic lesions which characterize the disease that now bears his name.</p>
<p>Until the end of the 1970s, numerous collections of brain specimens preserved in formalin were built in hospital environments, a bit like the cabinets of curiosities of olden days.</p>
<p>Towards the end of the 20th century, new experimental approaches were developed allowing the high-resolution analysis of cells and molecules within biological tissues.</p>
<p>It then became necessary to collect and preserve human brains, obtained with the consent of the individual or his or her family, in conditions compatible with modern scientific techniques.</p>
<p>Researchers began freezing one of the cerebral hemispheres in order to measure its various molecular components. The other hemisphere was preserved in formalin to be used for macroscopic and microscopic anatomical studies.</p>
<p>This was the context in which the Douglas-Bell Canada Brain Bank was created.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/552154/original/file-20231004-25-z5k7jp.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="The DBCBB premises" src="https://images.theconversation.com/files/552154/original/file-20231004-25-z5k7jp.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/552154/original/file-20231004-25-z5k7jp.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=399&fit=crop&dpr=1 600w, https://images.theconversation.com/files/552154/original/file-20231004-25-z5k7jp.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=399&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/552154/original/file-20231004-25-z5k7jp.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=399&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/552154/original/file-20231004-25-z5k7jp.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=501&fit=crop&dpr=1 754w, https://images.theconversation.com/files/552154/original/file-20231004-25-z5k7jp.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=501&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/552154/original/file-20231004-25-z5k7jp.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=501&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Montréal is home to one of the world’s largest brain banks, the Douglas-Bell Canada Brain Bank, which was founded in 1980 at the Douglas Hospital.</span>
<span class="attribution"><span class="source">(Naguib Mechawar)</span>, <span class="license">Fourni par l'auteur</span></span>
</figcaption>
</figure>
<h2>New experimental approaches are yielding results</h2>
<p>Leading researchers from many universities around the world now use DBCBB samples to advance their research. This, of course, includes a number of teams in Québec.</p>
<p>For example, with his team from the Douglas Research Centre, which is affiliated with McGill University, <a href="https://douglas.research.mcgill.ca/judes-poirier/">Judes Poirier</a> discovered that the APOE4 gene is a <a href="https://doi.org/10.1016/0140-6736(93)91705-Q">risk factor for Alzheimer’s disease</a>. More recently, the team of <a href="https://crhmr.ciusss-estmtl.gouv.qc.ca/en/researcher/gilbert-bernier">Gilbert Bernier</a>, professor in the department of neuroscience at Université de Montréal, discovered that the lesions characteristic of this disease are associated with <a href="https://doi.org/10.1038/s41598-018-37444-3">abnormal expression of the BMI1 gene</a>.</p>
<p>With regard to psychiatric illnesses, and more specifically depression, major progress has been made recently by the <a href="https://douglas.research.mcgill.ca/mcgill-group-suicide-studies-mgss/">McGill Group for Suicide Studies</a>. </p>
<p>Using cutting-edge methods to isolate and analyze human brain cells, Turecki’s team has succeeded in precisely identifying the cell types whose function is affected in men <a href="https://doi.org/10.1038/s41593-020-0621-y">who have suffered from major depression</a>, and then discovering that the cell types involved in this illness differ <a href="https://doi.org/10.1038/s41467-023-38530-5">between men and women</a>. </p>
<p>These experimental approaches generate huge data sets that can be examined in subsequent studies. This is the case, for example, of work carried out in my laboratory, which identified signs of persistent changes in neuroplasticity within the prefrontal cortex of people with a history of <a href="https://doi.org/10.1038/s41380-021-01372-y">child abuse</a>. In fact, the studies mentioned above enabled us to discover at least one of the cell types involved in this phenomenon. </p>
<p>In short, the experimental methods we have today allow us to break the brain down into its elementary components in order to understand its functions and dysfunctions.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/552155/original/file-20231004-27-62uc6y.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Cerebral hemispheres preserved in formalin" src="https://images.theconversation.com/files/552155/original/file-20231004-27-62uc6y.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/552155/original/file-20231004-27-62uc6y.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=401&fit=crop&dpr=1 600w, https://images.theconversation.com/files/552155/original/file-20231004-27-62uc6y.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=401&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/552155/original/file-20231004-27-62uc6y.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=401&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/552155/original/file-20231004-27-62uc6y.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=504&fit=crop&dpr=1 754w, https://images.theconversation.com/files/552155/original/file-20231004-27-62uc6y.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=504&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/552155/original/file-20231004-27-62uc6y.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=504&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Leading researchers from many universities around the world benefit from Douglas-Bell Canada Brain Bank samples to advance their research.</span>
<span class="attribution"><span class="source">(Naguib Mechawar)</span>, <span class="license">Fourni par l'auteur</span></span>
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</figure>
<h2>Identify, prevent, screen and treat</h2>
<p>Thanks to the hard work and dedication of the entire DBCBB team, as well as the unfailing support of all its partners, patrons (often anonymous) and funding bodies — particularly the FRQS research fund and Québec’s suicide research network, the <a href="https://reseausuicide.qc.ca">Réseau québécois sur le suicide, les troubles de l'humeur et les troubles associés</a> — this invaluable resource has not only managed to survive, but to grow and become one of the largest brain banks in the world. </p>
<p>There is every reason to believe that, in the years to come, the DBCBB will play an important role in the increasingly precise identification of the biological causes of brain diseases, and, as a result, will contribute to the identification of new targets for better approaches to prevention, screening and treatment.</p><img src="https://counter.theconversation.com/content/216980/count.gif" alt="La Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Naguib Mechawar has received funding from CIHR, NSERC, HBHL (CFREF) and FQRS (NEURON ERA-NET and RQSHA).</span></em></p>Montréal is home to one of the world’s largest brain banks, the Douglas-Bell Canada Brain Bank, where discoveries about different neurological and psychiatric diseases are made.Naguib Mechawar, Neurobiologiste, Institut Douglas; Professeur titulaire, Département de psychiatrie, McGill UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2159802023-11-29T20:06:32Z2023-11-29T20:06:32ZMiniature organs on chips could revolutionize health-care research<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/miniature-organs-on-chips-could-revolutionize-health-care-research" width="100%" height="400"></iframe>
<p>To understand how bodies work, medical researchers and scientists have created mini models of organs, called organoids. This field of scientific research has had profound impacts on biological discovery and pharmaceutical development.</p>
<p>An organoid is a <a href="https://doi.org/10.1038/s43586-022-00174-y">miniaturized version of an organ</a>. As the name suggests with the Greek suffix <em>oid</em>, meaning “like,” an organoid is designed to mimic the organ it represents. These three-dimensional structures are generated from stem cells and, although only about one millimetre in size, they effectively emulate the morphology or function of the actual organs. </p>
<p>Yet this is only half the narrative. “<a href="https://doi.org/10.1038/s43586-022-00118-6">Organs-on-chips</a>” are a technology that uses intricately carved tunnels (microchannels) on a piece of plastic or polymer that can house cells. These channels facilitate the flow of cell culture media, replicating blood flow in the human body. </p>
<p>Organs-on-chips act like a miniature version of the body’s organs in the lab, making it easier to see if new drugs will work. They act as a dynamic in vitro (artificial) system to better replicate the in vivo (actual living) environment of cells.</p>
<p>These technologies emerged as a solution to the challenges of drug development, which is both time-consuming and exorbitantly expensive.</p>
<h2>Safe drug development</h2>
<p>Developing new drugs has become an arduous and costly process, requiring an average of <a href="https://doi.org/10.1001/jama.2020.1166">14 years and over US$1 billion</a> to bring a drug to market. In addition, developing new drugs includes a high likelihood of failure. </p>
<p>One of the main reasons for the <a href="https://doi.org/10.1038/nrd4539">slow development of new drugs</a> is the inadequate tools for accurately predicting how a drug will work in the human body. To address this, there is a growing recognition of the need for new models, such as organoids and organs-on-chips, which could revolutionize our ability to evaluate drug efficacy more effectively and efficiently.</p>
<h2>Game-changing research</h2>
<p>While both organoids and organs-on-chips hold individual promise, the combination of the two — “organoids-on-chips” — is a game changer. Organoids, despite their excellent biological complexity, lack certain biophysical cues, crucial for a comprehensive representation of human tissues. </p>
<p>On the other hand, organs-on-chips, while incorporating dynamic micro-environments, often incorporate less-than-optimal biological models. Labs often use commercially produced cell lines with genetically altered features.</p>
<p><div data-react-class="InstagramEmbed" data-react-props="{"url":"https://www.instagram.com/p/CwTDM3LRrJJ","accessToken":"127105130696839|b4b75090c9688d81dfd245afe6052f20"}"></div></p>
<p>By combining these technologies, we can leverage the biological accuracy of organoids with the dynamic capabilities of organs-on-chips. This synergy offers a platform that mirrors in vivo physiology, enabling a more accurate study of disease traits and responses to drugs.</p>
<p>In <a href="https://medgen.med.ubc.ca/josef-penninger/">our lab</a>, our primary focus is on incorporating a functional vascular system to organoids. A major breakthrough came in 2019 when we generated <a href="https://doi.org/10.1038/s41586-018-0858-8">blood vessel organoids from human stem cells</a>, providing an unprecedented model for vascular structures. </p>
<p>By integrating these blood vessel models into microfluidic chips and supplying them with blood, immune cells or drugs, we are paving the way for advanced organoids-on-chips that embody the necessary complexity. This enhanced vascular model enables us to vascularize a variety of biological tissues, improving their lifespan, function, growth and maturation.</p>
<h2>Merging physics and biology</h2>
<p>The interdisciplinary foundation of organoids-on-chips combines biology and physics to reflect the intricate interplay of physiological and physical processes in the human body. By integrating principles from both fields, we can develop more sophisticated and accurate physiological models that encompass this inherent complexity.</p>
<p>The pioneering work of researchers at the <a href="https://wyss.harvard.edu/">Wyss Institute at Harvard University</a> is a striking example of the potential of this interdisciplinary approach. In 2010, they developed a “<a href="https://doi.org/10.1126/science.1188302">lung-on-chip</a>” model that not only mimics the biological structure of lung cells, but also replicates the mechanical function of human breathing. </p>
<p>In a remarkable display of innovation, they also created a <a href="https://www.youtube.com/watch?v=VewOqUnwXG0">smoking robot to simulate the effects of cigarette smoke on this lung-on-chip device</a>, and <a href="https://wyss.harvard.edu/news/human-organ-chips-enable-rapid-drug-repurposing-for-covid-19/">tested COVID-19 drugs</a> during the pandemic.</p>
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<figcaption><span class="caption">Researchers at Harvard University look at the impact of smoking on lung cells.</span></figcaption>
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<p>From its initial conception, the field of organs-on-chips has grown exponentially. Highlighting this trend, the geneticist and microbiologist Hans Clevers now leads <a href="https://www.roche.com/about/leadership/hans-clevers">the pharmaceutical giant Roche’s research division</a>. “In 20 years,” Clevers said, “I think organoids will have <a href="https://doi.org/10.1007/s00109-020-02025-3">replaced animal experimentation in toxicology testing</a>.”</p>
<p>In a parallel move, Roche set up <a href="https://institutehumanbiology.com/">the Institute of Human Biology</a>, under the direction of bioengineer <a href="https://doi.org/10.1016/j.stemcr.2021.08.012">Matthias Lutolf</a>. The institute merges the study of organoids with microfluidic technology. </p>
<h2>Future of organoids</h2>
<p>A pivotal development in 2023 was the U.S. <a href="https://doi.org/10.1126/science.adg6264">Food and Drug Administration’s decision to no longer mandate animal testing for new drugs</a> before advancing to human trials. This change underscores the potential of alternatives like organoids and organs-on-chips in early drug testing, and marks a significant milestone for the field.</p>
<p>The <a href="https://doi.org/10.1126/science.aaw7894">potential of organoids-on-chips</a> extends beyond drug screening and toxicity tests. The technology holds promise for a range of exciting applications, including unravelling the fundamental biological principles underlying development and disease. Their applications extend to <a href="https://doi.org/10.1038/s41576-018-0051-9">regenerative medicine</a>, where organs grown from a patient’s own stem cells could be used to replace damaged ones.</p><img src="https://counter.theconversation.com/content/215980/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Clément Quintard 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>Organoids — clusters of specialized cells designed to mimic organs — enable researchers to study biological processes and the effects of drugs.Clément Quintard, Postdoctoral fellow, Penninger Lab, University of British ColumbiaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2146222023-10-12T12:31:00Z2023-10-12T12:31:00ZHorseshoe crab blood is vital for testing intravenous drugs, but new synthetic alternatives could mean pharma won’t bleed this unique species dry<figure><img src="https://images.theconversation.com/files/552874/original/file-20231010-19-onfdw4.jpg?ixlib=rb-1.1.0&rect=33%2C8%2C5579%2C3728&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Horseshoe crabs in spawning season at Reeds Beach, N.J., on June 13, 2023.</span> <span class="attribution"><a class="source" href="https://newsroom.ap.org/detail/HorseshoeCrabHarvest/053d4f924f9c453f808a4d3724a87e73/photo">AP Photo/Matt Rourke</a></span></figcaption></figure><p>If you have ever gotten a vaccine or received an intravenous drug and did not come down with a potentially life-threatening fever, you can thank a horseshoe crab (<em>Limulus polyphemus</em>).</p>
<p>How can animals that are <a href="https://www.britannica.com/animal/horseshoe-crab">often called living fossils</a>, because they have barely changed over millions of years, be so important in modern medicine? Horseshoe crab blood is used to produce a substance called limulus amebocyte lysate, or LAL, which scientists use to test for <a href="https://www.britannica.com/science/endotoxin">toxic substances called endotoxins</a> in intravenous drugs. </p>
<p>These toxins, produced by bacteria, are ubiquitous in the environment and can’t be removed simply through sterilization. They can cause a reaction historically referred to as “<a href="https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/inspection-technical-guides/pyrogens-still-danger">injection fever</a>.” A strong concentration can lead to shock and even death. </p>
<p>Identifying LAL as a highly sensitive detector of endotoxins was a 20th-century medical safety breakthrough. Now, however, critics are raising questions about environmental impacts and the process for reviewing and approving synthetic alternatives to horseshoe crab blood.</p>
<p>We study <a href="https://scholar.google.com/citations?user=Dd_T980AAAAJ&hl=en&authuser=1&oi=ao">science, technology</a> and <a href="https://www.linkedin.com/in/jolie-crunelle/%20student">public policy</a>, and recently published a <a href="https://osf.io/3tm9g/">white paper</a> examining social, political and economic issues associated with using horseshoe crabs to produce LAL. We see this issue as a test case for complicated problems that cut across multiple agencies and require attention to both nature and human health.</p>
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<figcaption><span class="caption">Protecting horseshoe crabs will require persuading the heavily regulated pharmaceutical industry to embrace change.</span></figcaption>
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<h2>An ocean solution</h2>
<p>Doctors began injecting patients with various solutions <a href="https://doi.org/10.1016/j.socscimed.2004.06.044">in the mid-1800s</a>, but it was not until the 1920s that biochemist <a href="https://lemelson.mit.edu/resources/florence-seibert">Florence Seibert</a> discovered that febrile reactions were due to contaminated water in these solutions. She created a method for detecting and removing the substances that caused this reaction, and it became the medical standard in the 1940s.</p>
<p>Known as the <a href="https://www.matresearch.com/pyrogen-testing/">rabbit pyrogen test</a>, it required scientists to inject intravenous drugs into rabbits, then monitor the animals. A feverish rabbit meant that a batch of drugs was contaminated.</p>
<p>The LAL method was discovered by accident. Working with horseshoe crabs at the <a href="https://www.mbl.edu/">Marine Biological Laboratory</a> at Woods Hole, Massachusetts, in the 1950s and ’60s, <a href="https://www.goldengooseaward.org/01awardees/horseshoe-crab-blood">pathobiologist Frederik Bang and medical researcher Jack Levin</a> noticed that the animals’ <a href="https://hub.jhu.edu/magazine/2021/summer/horseshoe-crabs-covid19-medical-uses/">blue blood</a> coagulated in a curious manner. Through a series of experiments, they isolated endotoxin as the coagulant and devised a method for extracting LAL from the blood. This compound would gel or clot nearly instantaneously in the presence of fever-inducing toxins.</p>
<p>Academic researchers, biomedical companies and the U.S. Food and Drug Administration refined LAL production and measured it against the rabbit test. By the 1990s, LAL was the <a href="https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/inspection-technical-guides/bacterial-endotoxinspyrogens">FDA-approved method</a> for testing medicines for endotoxin, largely replacing rabbits.</p>
<p>Producing LAL requires harvesting horseshoe crabs from oceans and beaches, <a href="https://www.theatlantic.com/technology/archive/2014/02/the-blood-harvest/284078/">draining up to 30% of their blood</a> in a laboratory and returning the live crabs to the ocean. There’s dispute about <a href="https://www.scientificamerican.com/article/medical-labs-may-be-killing-horseshoe-crabs/">how many crabs die in the process</a> – estimates range from a few percent to 30% or more – and about possible harmful effects on survivors. </p>
<p>Today there are five FDA-licensed <a href="https://asmfc.org/uploads/file/645bf065HSC_Biomedical_BMPs_2023.pdf">LAL producers</a> along the U.S. East Coast. The amount of LAL they produce, and its sales value, are proprietary. </p>
<h2>Bait versus biotech</h2>
<p>As biomedical LAL production ramped up in the 1990s, so did harvesting horseshoe crabs to use as bait for other species, particularly eel and whelk for foreign seafood markets. Over the past 25 years, hundreds of thousands – and in the early years, millions – of horseshoe crabs have been harvested each year for these purposes. Combined, the two fisheries kill <a href="https://asmfc.org/species/horseshoe-crab">over half a million</a> horseshoe crabs every year.</p>
<p>There’s no agreed total population estimate for <em>Limulus</em>, but the most recent <a href="https://asmfc.org/uploads/file/63d2ed62HSCAssessment_PeerReviewReport_May2019.pdf">federal assessment of horseshoe crab fisheries</a> found the population was neither strongly growing nor declining.</p>
<p>Conservationists are worried, and not just about the crabs. Millions of shorebirds <a href="https://atlanticflywayshorebirds.org/">migrate along the Atlantic coast</a>, and many stop in spring, when horseshoe crabs spawn on mid-Atlantic beaches, to feed on the crabs’ eggs. Particularly for <a href="https://www.allaboutbirds.org/guide/Red_Knot/overview">red knots</a> – a species that can migrate up to 9,000 miles between the tip of South America and the Canadian Arctic – gorging on horseshoe crab eggs provides a critical energy-rich boost on their grueling journey.</p>
<p>Red knots were <a href="https://www.federalregister.gov/documents/2014/12/11/2014-28338/endangered-and-threatened-wildlife-and-plants-threatened-species-status-for-the-rufa-red-knot">listed as threatened</a> under the Endangered Species Act in 2015, largely because horseshoe crab fishing threatened this key food source. As biomedical crab harvests came to equal or <a href="https://asmfc.org/species/horseshoe-crab">surpass bait harvests</a>, conservation groups began calling on the LAL industry to find new sources.</p>
<p><div data-react-class="InstagramEmbed" data-react-props="{"url":"https://www.instagram.com/p/Ct2Aji4xcPJ/?utm_source=ig_web_copy_link\u0026igshid=MzRlODBiNWFlZA==","accessToken":"127105130696839|b4b75090c9688d81dfd245afe6052f20"}"></div></p>
<h2>Biomedical alternatives</h2>
<p>Many important medicines are derived from living organisms. Penicillin, the first important antibiotic, was <a href="https://www.sciencemuseum.org.uk/objects-and-stories/how-was-penicillin-developed">originally produced from molds</a>. Other medicines currently in use come from sources including <a href="https://www.goodrx.com/well-being/diet-nutrition/medications-that-contain-animal-byproducts">cows, pigs, chickens and fish</a>. The ocean is a <a href="https://oceanexplorer.noaa.gov/facts/medicinesfromsea.html">promising source</a> for such products.</p>
<p>When possible, synthesizing these substances in laboratories – especially widely used medications like <a href="https://www.cityofhope.org/breakthroughs/art-riggs-tribute">insulin</a> – offers many benefits. It’s typically cheaper and more efficient, and it avoids putting species at risk, as well as addressing <a href="https://www.uspharmacist.com/article/animal-derived-medications-can-be-problematic-for-some-patients">concerns some patients have</a> about using animal-derived medical products.</p>
<p>In the 1990s, researchers at the National University of Singapore <a href="https://patents.google.com/patent/WO1999015676A1/en?inventor=Jeak+Ling+Ding">invented and patented</a> the first process for creating a synthetic, endotoxin-detecting compound using horseshoe crab DNA and <a href="https://www.genome.gov/genetics-glossary/Recombinant-DNA-Technology">recombinant DNA technology</a>. The result, dubbed recombinant Factor C (rFC), mimicked the first step in the three-part cascade reaction that occurs when LAL is exposed to endotoxin. </p>
<p>Later, several biomedical firms <a href="https://www.americanpharmaceuticalreview.com/Featured-Articles/569887-Historical-Milestones-and-Industry-Drivers-in-the-Development-of-Recombinant-Lysate-for-Bacterial-Endotoxin-Testing/">produced their own versions</a> of rFC and compounds called recombinant cascade reagents (rCRs), which reproduce the entire LAL reaction without using horseshoe crab blood. Yet, today, LAL remains the dominant technology for detecting endotoxins in medicine. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/552876/original/file-20231010-22-ilv12l.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A vial partly filled with pale blue fluid" src="https://images.theconversation.com/files/552876/original/file-20231010-22-ilv12l.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/552876/original/file-20231010-22-ilv12l.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/552876/original/file-20231010-22-ilv12l.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/552876/original/file-20231010-22-ilv12l.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/552876/original/file-20231010-22-ilv12l.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/552876/original/file-20231010-22-ilv12l.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/552876/original/file-20231010-22-ilv12l.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">A sample of horseshoe crab blood.</span>
<span class="attribution"><a class="source" href="https://flic.kr/p/riAZsU">Florida Fish and Wildlife Commission</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc-nd/4.0/">CC BY-NC-ND</a></span>
</figcaption>
</figure>
<p>The main reason is that the <a href="https://www.usp.org/">U.S. Pharmacopeia</a>, a quasi-regulatory organization that sets safety standards for medical products, considers rFC and rCR as “alternative” methods for detecting endotoxins, so they require case-by-case validation for use – a potentially lengthy and expensive process. The FDA generally defers to the U.S. Pharmacopeia.</p>
<p>A few large pharmaceutical companies with deep pockets have committed to <a href="https://www.esg.lilly.com/environmental/biodiversity?redirect-referrer=https%3A%2F%2Fwww.google.com%2F#case-studies">switching from LAL to rFC</a>. But most drug producers are sticking with the tried-and-true method. </p>
<p>Conservation groups want the U.S. Pharmacopeia to <a href="https://www.audubon.org/magazine/summer-2018/inside-biomedical-revolution-save-horseshoe-crabs">fully certify rFC</a> for use in industry with no extra testing or validation. In their view, LAL producers are stalling rFC and rCR approval to protect their <a href="https://www.npr.org/2023/06/10/1180761446/coastal-biomedical-labs-are-bleeding-more-horseshoe-crabs-with-little-accountabi">market in endotoxin detection</a>. The U.S. Pharmacopeia and LAL producers counter that they are doing due diligence to <a href="https://hsc.criver.com/#lal-endo">protect public health</a>.</p>
<h2>Change in the offing</h2>
<p>Change may be coming. All major LAL producers now have their own recombinant products – a tacit acknowledgment that markets and regulations are moving toward <em>Limulus</em>-free ways to test for endotoxins. </p>
<p>Atlantic fisheries regulators are currently considering <a href="https://www.asmfc.org/home/2023-annual-meeting">new harvest limits for horseshoe crabs</a>, and the U.S. Pharmacopeia is <a href="https://www.uspnf.com/notices/86-bet-using-recombinant-tests-gen-annc-20230822">weighing guidance</a> on recombinant alternatives to LAL. Public comments will be solicited over the winter of 2024, followed by U.S. Pharmacopeia and FDA review. </p>
<p>Even if rFC and rCR don’t win immediate approval, we believe that collecting more complete data on horseshoe crab populations and requiring more transparency from the LAL industry on <a href="https://asmfc.org/uploads/file/645bf065HSC_Biomedical_BMPs_2023.pdf">how it handles the crabs</a> would represent progress. So would directing medical companies to use recombinant products for testing during the manufacturing process, while saving LAL solely for final product testing. </p>
<p>Making policy on complex scientific issues across diverse agencies is never easy. But in our view, incremental actions that protect both human health and the environment could be important steps forward.</p><img src="https://counter.theconversation.com/content/214622/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>This material is based upon work supported by the National Science Foundation under Award No. 2121146, as well as the Leverhulme Trust through a Leverhulme Trust Research Project Grant. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation or the Leverhulme Trust.</span></em></p><p class="fine-print"><em><span>Jolie Crunelle receives funding from the Aberg Family Fellowship at Rochester Institute of Technology. </span></em></p>Horseshoe crabs play a unique role in medicine, but they’re also ecologically important in their home waters along the Atlantic coast. Can regulators balance the needs of humans and nature?Kristoffer Whitney, Associate Professor of Science, Technology and Society, Rochester Institute of TechnologyJolie Crunelle, Master's Degree Student in Science, Technology, and Public Policy, Rochester Institute of TechnologyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2121822023-08-30T20:35:41Z2023-08-30T20:35:41ZWe won’t always have to use animals for medical research. Here’s what we can do instead<figure><img src="https://images.theconversation.com/files/545212/original/file-20230829-23-6du48r.jpg?ixlib=rb-1.1.0&rect=29%2C266%2C3265%2C2089&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/funny-white-rat-looking-out-cage-592100393">Shutterstock</a></span></figcaption></figure><p>Animals have been used for medical research for thousands of years, dating back to ancient Greece where the <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4495509/">first dissections</a> were performed. </p>
<p>These days, one of the main uses of animals is to ensure the safety of medical products before they’re trialled in humans. </p>
<p>But in addition to the important ethical reasons for minimising animal use, the reality is sometimes animals just aren’t that good at predicting human responses. No animal model, for example, has captured all the human characteristics of complex illnesses like <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3543097/">Alzheimer’s disease</a> or <a href="https://ncats.nih.gov/news/releases/2022/researchers-create-3-D-model-for-rare-neuromuscular-disorders-setting-stage-for-clinical-trial">chronic inflammatory demyelinating polyneuropathy</a> (a neuromuscular disease). This makes is hard to develop effective treatments and cures.</p>
<p>Thankfully, researchers are making progress in developing a collection of alternative approaches, called “non-animal models”. A new <a href="https://www.csiro.au/nonanimalmodels">report</a> from our team at CSIRO Futures examines the potential of non-animal models and the actions Australia will need to take to pursue their use.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/can-we-ethically-justify-harming-animals-for-research-196387">Can we ethically justify harming animals for research?</a>
</strong>
</em>
</p>
<hr>
<h2>What are non-animal models?</h2>
<p>Non-animal models are an alternative set of models that use human cells, tissues and data. </p>
<p>These have the potential to better mimic human responses. In doing so, this can more accurately predict if a medical product is likely to fail, allowing reinvestment in products that are more likely to succeed. </p>
<p>Computer simulations or “in silico models” are one example. These can be used across the medical product development process to complement – and in time potentially replace – other model types. They can be used in drug studies to model a drug’s behaviour within the body, from cellular interactions to processes that involve multiple organs.</p>
<p>Complex three-dimensional biological models are also maturing quickly. Examples include:</p>
<ul>
<li><p><a href="https://hsci.harvard.edu/organoids">organoids</a> – organ “buds” that can be propagated from stem cells or taken from biopsies </p></li>
<li><p><a href="https://www.nature.com/articles/s43586-022-00118-6">organs-on-chips</a> – cells cultured in a miniature engineered chip. These attempt to replicate the physical environment of human organs.</p></li>
</ul>
<p><div data-react-class="Tweet" data-react-props="{"tweetId":"1613253802144026624"}"></div></p>
<h2>What can we use non-animal models for?</h2>
<p>In theory, we can use non-animal models for everything we use animal models for – and more.</p>
<p>Simple non-animal models (human cells cultured over a flat surface) are <a href="https://www.novartis.com/stories/systematically-exposing-vulnerabilities-cancer-cells">already used to help identify drug targets</a> due to their ability to test a large number of compounds and experimental conditions. </p>
<p>In the future, non-animal models will reduce – and eventually replace – animal use across a range of applications:</p>
<ul>
<li>screening potential drugs to see how well they work</li>
<li>toxicology (safety) testing</li>
<li>helping to screen, select and stratify shortlisted participants for clinical trials. This might include an assessment of their unique response to a potential drug.</li>
<li>using patient cells to identify the treatment most likely to help that individual.</li>
</ul>
<p>Outside of medical products designed for humans, non-animal models can also support innovation in veterinary and agricultural medicines, cosmetic testing and eco-toxicology.</p>
<figure class="align-center ">
<img alt="Woman applies lipstick" src="https://images.theconversation.com/files/545213/original/file-20230829-15-sw8ysk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/545213/original/file-20230829-15-sw8ysk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=316&fit=crop&dpr=1 600w, https://images.theconversation.com/files/545213/original/file-20230829-15-sw8ysk.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=316&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/545213/original/file-20230829-15-sw8ysk.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=316&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/545213/original/file-20230829-15-sw8ysk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=398&fit=crop&dpr=1 754w, https://images.theconversation.com/files/545213/original/file-20230829-15-sw8ysk.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=398&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/545213/original/file-20230829-15-sw8ysk.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=398&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Non-animal models can be used to test cosmetics.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/hispanic-latina-putting-lipstick-front-bathroom-2028019892">Shutterstock</a></span>
</figcaption>
</figure>
<h2>An export opportunity for Australia</h2>
<p>Non-animal models present an economic opportunity for Australia, where the models, their components, and surrounding services could be exported to the world.</p>
<p>Our novel economic analysis sized the potential Australian market for two non-animal models: organoids and organs-on-chips. Other models were unable to be sized due to a lack of global market data. </p>
<p>We estimate the Australian organoid market could be worth A$1.3 billion annually by 2040 and create 4,200 new jobs. </p>
<p>The organs-on-chips market could be worth A$300 million annually by 2040 and create 1,000 new jobs. This estimate is lower as this technology is currently less advanced but holds the potential to grow significantly beyond 2040.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/mechanical-forces-in-a-beating-heart-affect-its-cells-dna-with-implications-for-development-and-disease-173484">Mechanical forces in a beating heart affect its cells' DNA, with implications for development and disease</a>
</strong>
</em>
</p>
<hr>
<p>Several Australian entities are already contributing to these opportunities. The Murdoch Children’s Research Institute, for example, provides stem cell and modelling expertise as part of <a href="https://novonordiskfonden.dk/en/projects/novo-nordisk-foundation-center-for-stem-cell-medicine-renew">reNEW</a>, a €300 million international collaboration. </p>
<p>Another example is from <a href="https://schott-minifab.com/">Schott Minifab</a>, an international biotech and medical device company with Australian roots, which has successfully established scaled production of non-animal model components in Australia for domestic and export markets.</p>
<h2>Making it a reality</h2>
<p>Non-animal models have already begun to complement and replace animal use in some areas, such as identifying drug targets. </p>
<p>However, accelerating their development and adoption across a wider range of applications will require further technical advances to lower cost and validate their performance as superior models. </p>
<p>Australia has several research strengths in this field but we need a concentrated effort to help our research make it through to real world impact. </p>
<p>Our report makes ten recommendations for supporting Australia’s pursuit of these opportunities. Critical activities over the next five years include:</p>
<ul>
<li>coordinating local capabilities </li>
<li>investing in upgraded infrastructure</li>
<li>creating and collating data that compares animal and non-animal model performance.</li>
</ul>
<p>Governments, industry and research must collaborate to deliver against these actions. Success will only come from collective efforts.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/is-it-time-for-australia-to-be-more-open-about-research-involving-animals-103439">Is it time for Australia to be more open about research involving animals?</a>
</strong>
</em>
</p>
<hr>
<img src="https://counter.theconversation.com/content/212182/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>As well as the important ethical reasons for minimising animal use in research, the reality is sometimes animals just aren’t that good at predicting human responses.Greg Williams, Associate Director, CSIRO Futures, CSIROLaura Anne Thomas, Strategy Manager, CSIRO Futures, CSIROLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2099772023-07-20T04:28:18Z2023-07-20T04:28:18ZMedical Research Future Fund has $20 billion to spend. Here’s how we prioritise who gets what<figure><img src="https://images.theconversation.com/files/538404/original/file-20230719-15-3n1kch.jpg?ixlib=rb-1.1.0&rect=52%2C276%2C4940%2C3046&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.pexels.com/photo/man-doing-a-sample-test-in-the-laboratory-4033148/">Edward Jenner/Pexels</a></span></figcaption></figure><p>The <a href="https://www.health.gov.au/our-work/medical-research-future-fund">Medical Research Future Fund</a> (MRFF) is a A$20 billion fund to support Australian health and medical research. It was set up in 2015 to deliver practical benefits from medical research and innovation to as many Australians as possible. </p>
<p>Unlike the other research funding agencies, such the National Health and Medical Research Council (NHMRC), most of the MRFF funding is priority-driven. It seeks to fund research in particular areas or topics rather than using open calls when researchers propose their own ideas for funding.</p>
<p>As the <a href="https://www.smh.com.au/politics/federal/not-how-you-run-a-1b-scheme-science-fund-backers-lead-chorus-for-reform-20230619-p5dhni.html">Nine newspapers</a> outlined this week, researchers have criticised the previous Coalition government’s allocation of MRFF funds. There is widespread consensus the former health minister had <a href="https://www.theage.com.au/politics/federal/a-centre-never-built-and-a-hospital-that-missed-out-the-coalition-s-unusual-20b-research-fund-20230619-p5dhng.html">too much influence</a> in the allocation of funds, and there was limited and sometimes no competition when funding was directly allocated to one research group.</p>
<p>The current Health Minister, Mark Butler, has instituted a <a href="https://www.innovationaus.com/billion-dollar-medical-research-grants-process-under-review/">review</a>. So how should the big decisions about how to spend the MRFF be made in the future to maximise its value and achieve its aims? </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/nobel-laureate-brian-schmidts-big-ideas-for-how-australia-funds-and-uses-research-204015">Nobel laureate Brian Schmidt's big ideas for how Australia funds and uses research</a>
</strong>
</em>
</p>
<hr>
<h2>Assess gaps in evidence</h2>
<p>Research priorities for the MRFF are set by the <a href="https://www.health.gov.au/committees-and-groups/australian-medical-research-advisory-board-amrab?language=und">Australian Medical Research Advisory Board</a>, which widely consults with the research sector. </p>
<p>However, most researchers and institutions will simply argue more funding is needed for their own research. If the board seeks to satisfy such lobbying, it will produce fragmented funding that aligns poorly with the health needs of Australians.</p>
<figure class="align-right ">
<img alt="Scientist at a busy bench in a lab" src="https://images.theconversation.com/files/538406/original/file-20230719-17-nbp4qi.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/538406/original/file-20230719-17-nbp4qi.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=900&fit=crop&dpr=1 600w, https://images.theconversation.com/files/538406/original/file-20230719-17-nbp4qi.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=900&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/538406/original/file-20230719-17-nbp4qi.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=900&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/538406/original/file-20230719-17-nbp4qi.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1131&fit=crop&dpr=1 754w, https://images.theconversation.com/files/538406/original/file-20230719-17-nbp4qi.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1131&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/538406/original/file-20230719-17-nbp4qi.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">
<figcaption>
<span class="caption">Most researchers will argue more funding is needed for their research.</span>
<span class="attribution"><a class="source" href="https://www.pexels.com/photo/scientist-in-laboratory-3735736/">Polina Tankilevitch/Pexels</a></span>
</figcaption>
</figure>
<p>A better approach would be to systematically assemble evidence about what is known and the key evidence gaps. Here, the board would benefit from what is known as a “<a href="https://pubmed.ncbi.nlm.nih.gov/15484602/">value of information</a>” framework for decision-making. </p>
<p>This framework systematically attempts to quantify the most valuable information that will reduce the uncertainty for health and medical decision-making. In other words, it would pinpoint which information we need to allow us to better make health and medical decisions.</p>
<p>There have been <a href="https://pubmed.ncbi.nlm.nih.gov/30288400/">attempts</a> to use this method in Australia to help inform how we prioritise hospital-based research. However, we now need to apply such an approach more broadly.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/covid-has-left-australias-biomedical-research-sector-gasping-for-air-145022">COVID has left Australia's biomedical research sector gasping for air</a>
</strong>
</em>
</p>
<hr>
<h2>Seek public input</h2>
<p>A structured framework for engaging with the public is also missing in Australia. The public’s perspective on research prioritisation has often been overlooked, but as the ultimate consumers of research, they need to be heard. </p>
<p>Research is a highly complex and specialised endeavour, so we can’t expect the public to create sensible priorities alone.</p>
<p>One approach used overseas has been developed by the <a href="https://www.jla.nihr.ac.uk/">James Lind Alliance</a>, a group in the United Kingdom that combines the public’s views with researchers to create agreed-on priorities for research. </p>
<p>This is done using an intensive process of question setting and discussion. Priorities are checked for feasibility and novelty, so there is no funding for research that’s impossible or already done.</p>
<figure class="align-left ">
<img alt="Doctor writes on a tablet" src="https://images.theconversation.com/files/538407/original/file-20230719-19-ttgtn1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/538407/original/file-20230719-19-ttgtn1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=900&fit=crop&dpr=1 600w, https://images.theconversation.com/files/538407/original/file-20230719-19-ttgtn1.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=900&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/538407/original/file-20230719-19-ttgtn1.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=900&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/538407/original/file-20230719-19-ttgtn1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1131&fit=crop&dpr=1 754w, https://images.theconversation.com/files/538407/original/file-20230719-19-ttgtn1.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1131&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/538407/original/file-20230719-19-ttgtn1.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">
<figcaption>
<span class="caption">Research priorities aren’t always obvious.</span>
<span class="attribution"><a class="source" href="https://www.pexels.com/photo/crop-doctor-writing-prescription-on-paper-6098057/">Laura James/Pexels</a></span>
</figcaption>
</figure>
<p>The priorities from the James Lind Alliance process can be surprising. The top priority in the area of <a href="https://www.jla.nihr.ac.uk/priority-setting-partnerships/irritable-bowel-syndrome/top-10-priorities.htm">irritable bowel syndrome</a>, for example, is to discover if it’s one condition or many, while the second priority is to work on bowel urgency (a sudden urgent need to go to the toilet). </p>
<p>While such everyday questions can struggle to get funding in traditional systems that often focus on novelty, funding research in these two priority areas could lead to the most benefits for people with irritable bowel syndrome.</p>
<h2>Consider our comparative advantages</h2>
<p>Australia is a relatively small player globally. To date, the MRFF has allocated around <a href="https://www.health.gov.au/resources/publications/medical-research-future-fund-mrff-grant-recipients?language=und">$2.6 billion</a>, just over 5% of what the United States allocates through the National Institute of Health funding in a <a href="https://www.who.int/observatories/global-observatory-on-health-research-and-development/monitoring/investments-on-grants-for-biomedical-research-by-funder-type-of-grant-health-category-and-recipient">single year</a>.</p>
<p>A single research grant, even if it involves a few million dollars of funding, is unlikely to lead to a medical breakthrough. Instead, the MRFF should prioritise areas where Australia has a comparative advantage. </p>
<p>This could involve building on past success (such as the research that led to the HPV, or human papillomavirus, vaccine to prevent cervical cancer), or where Australian researchers can play a critical role globally.</p>
<p>However, there is an area where Australian researchers have an absolute advantage: using research to improve our own health system. </p>
<p>A prime example would be finding ways to improve dental care access in Australia. For example, a randomised trial of different ways of providing insurance and dental services, similar to the <a href="https://www.rand.org/health-care/projects/hie.html">RAND Health Insurance Experiment</a> conducted in the United States in the 1970s. </p>
<p>This could provide the evidence needed to design a sustainable dental scheme to complement Medicare. Now that is something the MRFF should consider as a funding priority.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/expensive-dental-care-worsens-inequality-is-it-time-for-a-medicare-style-denticare-scheme-207910">Expensive dental care worsens inequality. Is it time for a Medicare-style 'Denticare' scheme?</a>
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</em>
</p>
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<img src="https://counter.theconversation.com/content/209977/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Adrian Barnett receives funding from the Medical Research Future Fund and the National Health and Medical Research Council. He is a member of the NHMRC Research Committee; this article represents his own views.</span></em></p><p class="fine-print"><em><span>Philip Clarke receives funding from the Medical Research Future Fund via grants held at the University of Melbourne.</span></em></p>The Medical Research Future Fund should prioritise areas where Australia has a comparative advantage.Adrian Barnett, Professor of Statistics, Queensland University of TechnologyPhilip Clarke, Professor of Health Economics, University of OxfordLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2099702023-07-19T04:03:59Z2023-07-19T04:03:59ZAlzheimer’s drug donanemab has been hailed as a ‘turning point’ for treatment. But what does it mean for people with the disease?<figure><img src="https://images.theconversation.com/files/538167/original/file-20230719-29-ns8anb.jpg?ixlib=rb-1.1.0&rect=97%2C67%2C4895%2C2739&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/amyloid-plaques-forming-between-neurons-3d-2271276029">Shutterstock</a></span></figcaption></figure><p>Trial results of a new drug to treat Alzheimer’s disease, donanemab, shows it can <a href="https://jamanetwork.com/journals/jama/fullarticle/2807533">slow cognitive decline</a> by 35%. The drug has been hailed as a “turning point” in Alzheimer’s treatment.</p>
<p><div data-react-class="Tweet" data-react-props="{"tweetId":"1680945583383539713"}"></div></p>
<p>But as usual, there’s <a href="https://www.nature.com/articles/d41586-023-02321-1">more to the story</a>. The study only included people with early or mild disease, not more advanced symptoms. Donanemab is not a cure for Alzheimer’s. Nor is it 100% safe. </p>
<p>So what did the trial actually find? And how might this drug affect the lives of people with Alzheimer’s disease? </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/new-alzheimers-drug-what-you-need-to-know-about-donanemabs-promising-trial-results-205156">New Alzheimer’s drug: what you need to know about donanemab’s promising trial results</a>
</strong>
</em>
</p>
<hr>
<h2>What is Alzheimer’s disease?</h2>
<p>There are more than 100 types of dementia, but Alzheimer’s disease is the most common, accounting for <a href="https://alz-journals.onlinelibrary.wiley.com/doi/full/10.1002/alz.12068">around 70%</a> of cases. </p>
<p>The disease is caused by the accumulation of two proteins: amyloid and tau. Amyloid can accumulate for at least 20 years prior to the onset of symptoms, forming clumps in the brain. </p>
<p>Once symptoms have started and are progressing, tau, a marker of cell damage, also begins to accumulate.</p>
<p>Clinical symptoms progress, on average, over <a href="https://jamanetwork.com/journals/jamaneurology/fullarticle/783112">seven to ten years</a> after diagnosis. But in Australia, there is a lag of <a href="https://www.dementia.org.au/sites/default/files/2022-12/Dementia-Australia-annual-report-2021-2022.pdf">up to three years</a> from the point at which people first develop symptoms before a diagnosis is typically made.</p>
<h2>What have drug treatments aimed to do?</h2>
<p>The “<a href="https://www.embopress.org/doi/pdf/10.15252/emmm.201606210">amyloid hypothesis</a>”, which suggests amyloid is the key cause of the disease, has driven Alzheimer’s research for more than 25 years. </p>
<p>Multiple drugs targeting amyloid have, however, failed in clinical trials over most of that period, casting doubt on the validity of amyloid as a target – until recently.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/what-allegations-of-alzheimers-research-fraud-mean-for-patients-187911">What allegations of Alzheimer's research fraud mean for patients</a>
</strong>
</em>
</p>
<hr>
<p>Our bodies produce antibodies in response to the presence of a foreign invader such as a bacteria or virus. Mimicking the approach taken by our immune systems, scientists have developed antibodies in the lab that recognise amyloid as such an invader. </p>
<p>Specifically targeting amyloid, these drugs are known as monoclonal antibodies. Donanemab is one of three monoclonal antibodies targeting amyloid that have shown various degrees of success in clinical trials in slowing decline in people with early stage disease.</p>
<h2>OK so what did the donanemab trial find?</h2>
<p>The manufacturer’s clinical trial included 1,736 patients with very mild memory loss due to Alzheimer’s disease, and with early clinical Alzheimer’s disease. </p>
<p>Half received donanemab by intravenous infusion over an 18-month study, the remainder were treated with a placebo (a “dummy” version). </p>
<p>The results were analysed by dividing the study population into two further groups: those with low to intermediate levels of tau; and those with high tau levels (high tau correlates with the presence of more advanced brain cell damage).</p>
<p>Those with low and intermediate tau declined by 35% less than those treated with placebo. About half of the treatment group cleared amyloid from their brains below the threshold used to diagnose the disease, over 12 months of treatment. </p>
<p>The high tau group did far less well.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/538163/original/file-20230719-27-f0bjsy.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="older couple holding hands with man looking confused" src="https://images.theconversation.com/files/538163/original/file-20230719-27-f0bjsy.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/538163/original/file-20230719-27-f0bjsy.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/538163/original/file-20230719-27-f0bjsy.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/538163/original/file-20230719-27-f0bjsy.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/538163/original/file-20230719-27-f0bjsy.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/538163/original/file-20230719-27-f0bjsy.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/538163/original/file-20230719-27-f0bjsy.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">People may be delaying diagnosis because they think nothing can be done.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/retired-couple-holding-hands-looking-each-1272275779">Shutterstock</a></span>
</figcaption>
</figure>
<p>Participants aged under 75 and those showing only mild cognitive impairment (rather than the full clinical picture of Alzheimer’s disease) had their progression slowed by around 50% over the same period.</p>
<p>Patients were assessed using both cognitive measures and measures of daily function, such as the ability to do personal and household tasks. The results translated into the treatment group showing levels of decline at 18 months that were experienced by the placebo group at 10.5 to 13.6 months, depending on the participant subgroup studied.</p>
<p>Important examples may be that they continue to be able to drive, pay bills, or attend activities outside of the home independently.</p>
<p>But both the treatment and the placebo groups declined overall. In other words, it doesn’t stop the decline, it slows it, in people with mild or early disease. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/lots-of-breakthroughs-still-no-cure-do-the-new-dementia-drugs-bring-us-any-closer-195095">Lots of 'breakthroughs', still no cure. Do the new dementia drugs bring us any closer?</a>
</strong>
</em>
</p>
<hr>
<h2>What are the downsides?</h2>
<p>At least two patients in the trial died from complications of brain swelling caused by donanemab. Around one-quarter of the treatment group showed some degree of swelling, most of which didn’t cause symptoms. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/538165/original/file-20230719-15-c6fftb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="CT scan films displayed" src="https://images.theconversation.com/files/538165/original/file-20230719-15-c6fftb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/538165/original/file-20230719-15-c6fftb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/538165/original/file-20230719-15-c6fftb.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/538165/original/file-20230719-15-c6fftb.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/538165/original/file-20230719-15-c6fftb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/538165/original/file-20230719-15-c6fftb.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/538165/original/file-20230719-15-c6fftb.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">Two patients in the study died from complications from brain swelling.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/alzheimers-disease-on-mri-2-664361179">Shutterstock</a></span>
</figcaption>
</figure>
<p>The cost of donanemab will be significant, at <a href="https://www.washingtonpost.com/health/2023/07/17/alzheimers-drug-lilly-donanemab/">US$26,500</a> or around A$39,000 per year. </p>
<p>Donanemab has already been approved by the US Food and Drug Administration.
Eli Lilly, the drug’s manufacturer, has applied to the Therapeutic Goods Administration (TGA) for approval for use in Australia. </p>
<p>But TGA approval is only the first step to making the drug available here. A further assessment will determine whether the Pharmaceutical Benefits Scheme subsidises the drug to make it affordable.</p>
<p>It’s likely any PBS listing would restrict the drug’s use to people whose disease state mirrors that of those included in the clinical trial population – people with early symptoms, who have had PET scans showing the presence of amyloid (and low and intermediate tau). </p>
<p>This is not a drug for everyone with Alzheimer’s disease.</p>
<h2>Preparing for early detection and treatment</h2>
<p>People have tended to delay seeking assessment of their memory symptoms because “nothing can be done anyway”. GPs may have been reluctant to refer to other specialists for assessment for the same reason. </p>
<p>The potential for early treatment means this needs to change. We also need to develop our diagnostic and treatment infrastructure (building the necessary PET scanners and infusion centres) that will be necessary to facilitate timely diagnosis and treatment when the drug does become available locally.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/what-is-sundowning-and-why-does-it-happen-to-many-people-with-dementia-208005">What is 'sundowning' and why does it happen to many people with dementia?</a>
</strong>
</em>
</p>
<hr>
<img src="https://counter.theconversation.com/content/209970/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Steve Macfarlane has been paid to attend a number of Australian medical advisory board meetings for Eli Lilly, the manufacturer of donanemab, most recently last year. He receives funding from a number of drug companies for conducting pharmaceutical trials. He is affiliated with the RANZCP.</span></em></p>The drug has been hailed as a ‘turning point’ in Alzheimer’s treatment. But keep in mind the trial only included participants with early or mild disease. And while it slowed decline, it’s not a cure.Steve Macfarlane, Head of Clinical Services, Dementia Support Australia, & Associate Professor of Psychiatry, Monash UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2095912023-07-14T02:06:30Z2023-07-14T02:06:30ZKetamine injections for depression? A new study shows promise, but it’s one of many options<figure><img src="https://images.theconversation.com/files/537183/original/file-20230712-29-dtpug1.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C1000%2C666&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Psychedelics like ketamine affect chemical messengers in the brain.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/abstract-brain-fractal-background-digital-illustration-2212346843">Shutterstock</a></span></figcaption></figure><p>Ketamine might be better known as a recreational drug or anaesthetic. But there’s growing evidence for its use for people with hard-to-treat depression.</p>
<p>An Australasian study <a href="https://www.cambridge.org/core/journals/the-british-journal-of-psychiatry/article/efficacy-and-safety-of-a-4week-course-of-repeated-subcutaneous-ketamine-injections-for-treatmentresistant-depression-kads-study-randomised-doubleblind-activecontrolled-trial/FDBAEC51F0891B57F5B04C572D13DA17">out today</a> showed some positive results for people with treatment-resistant depression when they had ketamine injections.</p>
<p>But we don’t know if these effects are sustained in the long term, and there are other ways of delivering ketamine. There are also other treatment options for this type of depression.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/weekly-dose-anaesthetic-and-recreational-drug-ketamine-could-be-used-to-treat-depression-81468">Weekly Dose: anaesthetic and recreational drug ketamine could be used to treat depression</a>
</strong>
</em>
</p>
<hr>
<h2>What is ketamine?</h2>
<p>Ketamine has been used as a powerful <a href="https://www.nature.com/articles/s41593-022-01203-5">general anaesthetic</a> for more than 50 years.</p>
<p>It’s also an <a href="https://www.ncbi.nlm.nih.gov/books/NBK470357/">illicit drug</a> of abuse and is considered a psychedelic. Psychedelics dramatically alter some neurotransmitters (chemical messengers) in the brain <a href="https://pubmed.ncbi.nlm.nih.gov/36280799/">to create</a> a profound change in perception, mood and anxiety.</p>
<p>In early animal studies, ketamine led to increase in levels of certain brain chemicals, such as dopamine, by <a href="https://www.nature.com/articles/mp2017190">up to 400%</a>. This led researchers to trial ketamine in humans to see what would happen in our brains.</p>
<p>Now, doses of ketamine (at those lower than used as an anaesthetic) are being used to help treatment-resistant depression. That’s when someone has tried at least two antidepressants and shows no improvement.</p>
<p>It is usually prescribed under strict conditions and observation that mitigate some <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6322816/">serious risks</a>, such as increased feelings about suicide in some people. So people need to be assessed and monitored not only during treatment, but afterwards.</p>
<p>But some clinicians have resisted using ketamine due to its potential to become a <a href="https://www.ranzcp.org/getmedia/75baa529-2b71-419f-993a-2ff64ede50fe/cm-use-of-ketamine-in-psychiatric-practice.pdf">drug of abuse</a>.</p>
<p>Ketamine is also used to treat other mental health disorders such as <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8959757/">PTSD</a> (post-traumatic stress disorder).</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/hallucinations-in-the-movies-tend-to-be-about-chaos-violence-and-mental-distress-but-they-can-be-positive-too-204547">Hallucinations in the movies tend to be about chaos, violence and mental distress. But they can be positive too</a>
</strong>
</em>
</p>
<hr>
<h2>How about this new study?</h2>
<p>The research involved <a href="https://www.australianclinicaltrials.gov.au/anzctr/trial/ACTRN12616001096448">multiple centres</a> across Australia and New Zealand and compared how well ketamine injected <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193034/">under the skin</a> compared with taking another drug in treating people with treatment-resistant depression.</p>
<p>The trial randomised the 184 study participants into different groups – some receiving ketamine, the rest the drug <a href="https://pubmed.ncbi.nlm.nih.gov/9258787/">midazolam</a>, twice a week over four weeks. Neither the study participants nor those assessing the results knew who had ketamine and who didn’t.</p>
<p>At the start of the study, all participants had a clinical depression score of at least 20 (moderate depression) using a particular scale known as the Montgomery-Asberg Depression Rating Scale.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/537220/original/file-20230713-25-gs9tri.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Doctor in white coat putting hand on shoulder of patient" src="https://images.theconversation.com/files/537220/original/file-20230713-25-gs9tri.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/537220/original/file-20230713-25-gs9tri.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/537220/original/file-20230713-25-gs9tri.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/537220/original/file-20230713-25-gs9tri.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/537220/original/file-20230713-25-gs9tri.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/537220/original/file-20230713-25-gs9tri.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/537220/original/file-20230713-25-gs9tri.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">The study participants had moderate depression.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/doctor-psychiatrist-shakes-hands-encouragement-patient-2188082723">Shutterstock</a></span>
</figcaption>
</figure>
<p>The researchers then looked for a score of less than 11, indicating a shift from a depression to remission.</p>
<p>After four weeks, there was a big difference between people treated with ketamine (19.6% in remission) compared with midazolam (2%). Another, less-strict way of measuring outcomes is to look for a halving of the depression score. This had an even bigger difference (29% compared with 4%). </p>
<p>However, four weeks after the treatment had ended, there was only limited sustained improvement in symptoms in the ketamine group. This suggests treatment may be needed over a longer period.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/do-psychedelics-really-work-to-treat-depression-and-ptsd-heres-what-the-evidence-says-208857">Do psychedelics really work to treat depression and PTSD? Here's what the evidence says</a>
</strong>
</em>
</p>
<hr>
<h2>There are other options</h2>
<p>In the trial, ketamine was given via an injection under the skin, which is a low-cost and efficient option. But ketamine can also be delivered directly into the bloodstream via an intravenous drip. Neither of these two options are routinely available in Australia and New Zealand outside clinical trials.</p>
<p>A third option uses a <a href="https://www.nps.org.au/australian-prescriber/articles/esketamine-hydrochloride-for-treatment-resistant-depression">different form</a> of ketamine and comes in a <a href="https://www.spravato.com/">nasal spray</a> (approved for use in <a href="https://www.tga.gov.au/resources/auspmd/spravato">Australia</a> and New Zealand). </p>
<p>Each option delivers ketamine in different amounts, and research into how these work in practice, and how they compare, is <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193034/">ongoing</a>.</p>
<p>There are also other drug and non-drug options for treatment-resistant depression. These include:</p>
<ul>
<li><p><a href="https://pubmed.ncbi.nlm.nih.gov/33834408/">transcranial magnetic stimulation</a>, which stimulates parts of the brain to improve mood</p></li>
<li><p><a href="https://www.ranzcp.org/events-learning/psychedelic-assisted-therapy">psilocybin</a>, another psychedelic drug that has just been given the go-ahead for use in Australia under strict conditions as part of <a href="https://theconversation.com/psychedelic-medicine-is-on-its-way-but-its-not-doing-shrooms-with-your-shrink-heres-what-you-need-to-know-208568">psychedelic-assisted therapy</a></p></li>
<li><p><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8429332/">psychotherapy</a> (talking therapy) such as cognitive behavioural therapy, <a href="https://www.psychologytoday.com/au/therapy-types/acceptance-and-commitment-therapy">acceptance and commitment therapy</a> and <a href="https://pubmed.ncbi.nlm.nih.gov/29761488/">dialectical behaviour therapy</a></p></li>
<li><p>changing some lifestyle factors, <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7164235/">such as diet</a> and <a href="https://pubmed.ncbi.nlm.nih.gov/28110494/">exercise</a>, or <a href="https://pubmed.ncbi.nlm.nih.gov/32985916/">practising mindfulness</a> meditation.</p></li>
</ul>
<h2>In a nutshell</h2>
<p>Serious consequences of depression include <a href="https://theconversation.com/suicide-rates-are-rising-with-or-without-13-reasons-why-lets-use-it-as-a-chance-to-talk-116434">suicide</a> or a lifetime of anguish. This latest research shows promising outcomes for people whose symptoms are harder to treat. But this option is not yet widely available outside a clinical trial. Only the ketamine nasal spray has been approved for use in Australia and New Zealand.</p>
<p>There are also other treatments. So if your existing treatment is not working for you, discuss this with your doctor who will explain what else is available.</p>
<hr>
<p><em>If this article has raised issues for you, or if you’re concerned about someone you know, call Lifeline on 13 11 14. Beyond Blue provides the free resource <a href="https://www.beyondblue.org.au/docs/default-source/resources/bl0556-what-works-for-depression-booklet_acc.pdf?sfvrsn=fe1646eb_2">A guide to what works for depression</a>.</em></p><img src="https://counter.theconversation.com/content/209591/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Michael Musker 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>This latest research provides hope for people whose symptoms are harder to treat.Michael Musker, Enterprise Fellow (Senior Research Fellow/Senior Lecturer), University of South AustraliaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1711922023-06-30T12:37:43Z2023-06-30T12:37:43ZIs it legal to sell human remains?<figure><img src="https://images.theconversation.com/files/534894/original/file-20230629-29-fif855.jpg?ixlib=rb-1.1.0&rect=9%2C15%2C2108%2C1393&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The handling and disposition of human bodies raises all sorts of ethical and legal questions.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/coffin-on-stage-royalty-free-image/85637547?phrase=funeral&adppopup=true">Jupiterimages/The Image Bank via Getty Images</a></span></figcaption></figure><p>Four individuals were <a href="https://media.wbur.org/wp/2023/06/morgue-indictment.pdf">charged with federal crimes</a> in June 2023 related to the “unlawful transport” across state lines of human remains taken from the Harvard Medical School morgue. This indictment was part of a larger effort by the Department of Justice to <a href="https://www.justice.gov/usao-mdpa/pr/six-charged-trafficking-stolen-human-remains">shut down a national network</a> of people trafficking in human remains. </p>
<p>Cedric Lodge, who had been the morgue manager <a href="http://hms.harvard.edu/news-events/anatomical-gift-program-resources/frequently-asked-questions">until his firing in May</a>, was accused of removing human remains that had been donated to the medical school. According to <a href="https://media.wbur.org/wp/2023/06/morgue-indictment.pdf">the indictment</a>, he and his wife, Denise Lodge, shipped those remains to Katrina MacLean, the owner of a store called Kat’s Creepy Creations, and Joshua Taylor, an individual living in Pennsylvania. Taylor transferred nearly US$40,000 to the Lodges via PayPal, with memos that included “head number 7” and “braiiiiiins.”</p>
<p>As a scholar whose research is centered on the <a href="https://law.wfu.edu/faculty/profile/marshtd/">laws regarding the status, treatment and disposition of human remains</a>, I am often asked about the legality and ethics of <a href="https://www.huffpost.com/entry/laws-permitting-human-remains_b_1769082">selling bodies</a>, especially when stories like the <a href="https://www.boston.com/news/crime/2023/06/16/is-it-legal-to-sell-human-remains-harvard-morgue-scandal-raises-questions/">Harvard morgue case</a> or <a href="https://abcnews.go.com/US/tiktok-user-sells-human-bones-ignites-ethical-debate/story?id=80541972">a TikTok user selling human bones</a> begin to circulate.</p>
<p>My answers often surprise people.</p>
<h2>State by state</h2>
<p>It is not illegal to sell human remains under federal law. That’s why the defendants in the Harvard Medical School case were <a href="https://www.justice.gov/usao-mdpa/pr/six-charged-trafficking-stolen-human-remains">charged with interstate transport of stolen goods</a>, rather than “trafficking human remains.” </p>
<p>There is actually very little federal law regarding the dead. The most significant is the Federal Trade Commission’s <a href="https://www.ftc.gov/news-events/topics/truth-advertising/funeral-rule">Funeral Rule</a>, which requires funeral homes to provide certain disclosures to consumers.</p>
<p>Instead, the vast majority of law respecting the dead is state law, which varies significantly.</p>
<p>By my count, the sale of human remains is broadly and expressly illegal in only eight states: <a href="http://www.leg.state.fl.us/Statutes/index.cfm?App_mode=Display_Statute&Search_String=&URL=0800-0899/0872/Sections/0872.01.html#:%7E:text=View%20Entire%20Chapter,775.082%20or%20s.">Florida</a>, <a href="https://codes.findlaw.com/ga/title-31-health/ga-code-sect-31-21-41/">Georgia</a>, <a href="https://malegislature.gov/Laws/GeneralLaws/PartIV/TitleI/Chapter272/Section72">Massachusetts</a>, <a href="https://www.revisor.mo.gov/main/OneSection.aspx?section=194.410&bid=10000&hl=#:%7E:text=194.410.,commits%20a%20class%20E%20felony.">Missouri</a>, <a href="https://www.revisor.mo.gov/main/OneSection.aspx?section=194.410&bid=10000&hl=#:%7E:text=194.410.,commits%20a%20class%20E%20felony.">New Hampshire</a>, <a href="https://www.scstatehouse.gov/code/t44c043.php">South Carolina</a>, <a href="https://casetext.com/statute/texas-codes/penal-code/title-9-offenses-against-public-order-and-decency/chapter-42-disorderly-conduct-and-related-offenses/section-4208-abuse-of-corpse#:%7E:text=Section%2042.08%20%2D%20Abuse%20of%20Corpse%20(a)%20A%20person%20commits,illegally%20disinterred%3B%20(3)%20sells">Texas</a> and <a href="https://law.lis.virginia.gov/vacode/title32.1/chapter8/section32.1-303/">Virginia</a>. </p>
<p>Perhaps one reason the Harvard morgue case is being handled by the Department of Justice is that although selling human remains is illegal in Massachusetts and New Hampshire, it does not violate state law in Pennsylvania, where some of the activity took place.</p>
<p>In more than two dozen other states, <a href="https://www.lawyersandjudges.com/products/the-law-of-human-remains">it is illegal to sell human remains</a> only under certain circumstances. A number of these states make it expressly illegal to sell human remains or organs that were donated for anatomical study, transplantation or medical therapy. </p>
<p>Most commonly, it is illegal to sell human remains that have been unlawfully removed from a place of burial. For example, in <a href="https://www.ncleg.gov/EnactedLegislation/Statutes/PDF/ByArticle/Chapter_70/Article_3.pdf">North Carolina</a>, it is a crime to “knowingly exhibit or sell any human skeletal remains from unmarked burials.” However, this specific phrasing means that the North Carolina law could not be applied to a situation like the Harvard case, where the body was obtained from a morgue. Nor could it be applied to the sale of body parts other than skeletal remains.</p>
<h2>Up for sale</h2>
<p>In fact, it is surprisingly easy to purchase human remains in the United States, even in states where such sales are expressly illegal. There are brick-and-mortar stores, like <a href="https://www.cbsnews.com/boston/news/katrina-maclean-peabody-creepy-dolls-store-charged-harvard-morgue-body-part-theft/">Kat’s Creepy Creations</a> in Massachusetts, which sell skeletal remains. </p>
<p>But increasingly, retail traffic in human remains <a href="https://doi.org/10.1111/1556-4029.13147">takes place online</a>. The sales of human remains have been banned on Etsy and eBay <a href="https://money.cnn.com/2012/08/10/technology/etsy-bans-drugs/index.html">since 2012</a> <a href="https://www.buzzfeednews.com/article/danvergano/skull-sales">and 2016</a>, respectively, but social networks like Facebook are <a href="https://www.livescience.com/human-bone-trade-facebook.html">rife with groups</a> where body parts are sold and traded. One of the defendants in the Harvard Medical School case <a href="https://www.newsweek.com/woman-posted-human-skull-instagram-before-harvard-morgue-indictment-1807078">advertised at least one skull on Instagram</a>.</p>
<p>It is difficult to determine how human remains end up in the retail stream because most body parts for sale have been de-identified. In other words, the seller does not name the deceased person whose remains are being sold and usually does not reveal how the remains were obtained – and there is no law requiring them to do so.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/534901/original/file-20230629-26-9mgo4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A man in a green uniform and cap walks around a tombstone with a small fence around it in a wooded area." src="https://images.theconversation.com/files/534901/original/file-20230629-26-9mgo4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/534901/original/file-20230629-26-9mgo4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=397&fit=crop&dpr=1 600w, https://images.theconversation.com/files/534901/original/file-20230629-26-9mgo4.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=397&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/534901/original/file-20230629-26-9mgo4.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=397&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/534901/original/file-20230629-26-9mgo4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=499&fit=crop&dpr=1 754w, https://images.theconversation.com/files/534901/original/file-20230629-26-9mgo4.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=499&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/534901/original/file-20230629-26-9mgo4.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>
<figcaption>
<span class="caption">A historian inspects a Civil War-era grave dug up by grave robbers on National Park Service property in Maryland.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/wheeler8-date-5-31-06-photographer-katherine-frey-the-news-photo/103800735?adppopup=true">Katherine Frey/The The Washington Post via Getty Images</a></span>
</figcaption>
</figure>
<p>There are a few explicitly illegal methods of obtaining human remains in the U.S. Grave robbery, for example, <a href="https://www.lawyersandjudges.com/products/the-law-of-human-remains?_pos=2&_sid=b1c0b1545&_ss=r&variant=6027975619">is specifically outlawed</a> in nearly every state. Digging up corpses was a <a href="https://www.smithsonianmag.com/history/in-need-cadavers-19th-century-medical-students-raided-baltimores-graves-180970629/">significant problem</a> in the 1800s, when medical schools first began <a href="https://theconversation.com/medical-students-honor-body-donors-through-words-deeds-and-ceremonies-208168">to teach students through anatomical dissection</a>.</p>
<p>When a person dies in the U.S., there are limited legal options for the disposition of their body, which effectively prevents an individual from arranging to sell their own remains. </p>
<p>In every state, remains may be buried, entombed, cremated, donated to science or removed from the state or order to be lawfully disposed of elsewhere. More than half of states have legalized a process called <a href="https://www.cremationassociation.org/page/alkalinehydrolysis">alkaline hydrolysis</a>, also known as <a href="https://www.cremationassociation.org/blogpost/776820/313847/What-do-you-know-about-Alkaline-Hydrolysis">aquamation or water cremation</a>, which dissolves the body in a base solution. In seven states, remains may be disposed of via <a href="https://connectingdirectors.com/65987-nevada-legalizes-nor">natural organic reduction</a>, also called <a href="https://www.popsci.com/environment/composting-body-burial/">human composting</a>.</p>
<h2>Final gift</h2>
<p>If an individual or their family donates remains to science, typically a nonprofit organization or university takes possession of the remains.</p>
<p>The use of those remains varies widely. A medical school like Harvard has an <a href="https://meded.hms.harvard.edu/anatomical-gift-program">anatomical donation program</a> to obtain intact cadavers to be used in gross anatomy labs and other teaching settings. </p>
<p>However, people sometimes donate to a non-transplant tissue bank, often called “body brokers.” Given the high costs of funeral arrangements in the U.S., some families donate a loved one’s remains to body brokers, who dispose of remains without cost to the family. </p>
<p>Bluntly speaking, body brokers carve up human remains and distribute them to be used in medical therapy or research, with little regulation – the subject of a <a href="https://www.reuters.com/investigates/special-report/usa-bodies-brokers/">2017 Reuters investigation</a>. They do charge for processing and transporting human remains, and one such company, Science Care, <a href="https://www.reuters.com/investigates/special-report/usa-bodies-science/">generated $27 million in revenue in 2017</a>.</p>
<p>Body brokers are <a href="https://nfda.org/news/media-center/nfda-news-releases/id/7475/congress-takes-significant-step-to-regulate-body-brokers">more controversial</a> than university anatomical donation programs, but in both cases, remains are used for medical education or research. The ultimate disposition of remains donated to science is typically cremation.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/534896/original/file-20230629-25452-4u7cgg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A body lies covered by a white sheet on a metal table in a white and yellow lab-like room." src="https://images.theconversation.com/files/534896/original/file-20230629-25452-4u7cgg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/534896/original/file-20230629-25452-4u7cgg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=389&fit=crop&dpr=1 600w, https://images.theconversation.com/files/534896/original/file-20230629-25452-4u7cgg.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=389&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/534896/original/file-20230629-25452-4u7cgg.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=389&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/534896/original/file-20230629-25452-4u7cgg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=489&fit=crop&dpr=1 754w, https://images.theconversation.com/files/534896/original/file-20230629-25452-4u7cgg.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=489&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/534896/original/file-20230629-25452-4u7cgg.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">Human remains donated to science are meant to be disposed of with respect.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/pathology-department-in-a-hospital-royalty-free-image/539882937?phrase=morgue&adppopup=true">Team Static/fStop via Getty Images</a></span>
</figcaption>
</figure>
<h2>Seeking justice</h2>
<p>If bodies donated to science are not <a href="https://nfda.org/news/media-center/nfda-news-releases/id/7475/congress-takes-significant-step-to-regulate-body-brokers">treated with the respect and dignity</a> that the donors were promised by the recipient institution, as in the Harvard Medical School case, there are several possible legal options. </p>
<p>First, there could be federal or state criminal charges in the small number of states that broadly outlaw the sale of human remains. </p>
<p>Second, 30 states outlaw the mistreatment or mutilation of human remains. These criminal laws are generally referred to as “<a href="https://funerallaw.typepad.com/blog/2015/10/does-the-law-limit-what-you-can-do-with-human-remains-yes-understanding-abuse-of-corpse-laws.html">abuse of corpse” statutes</a>.</p>
<p>Finally, the families of the donors may have a private cause of action against the recipient institution or against people who took the remains without permission. There are <a href="https://www.ali.org/projects/show/torts-miscellaneous-provisions/">two possible tort claims</a> that families could bring: interference with the family’s right to respectfully dispose of the remains, known formally as “interference with the right of sepulcher,” and infliction of emotional harm based on mistreatment of human remains.</p>
<p>I have yet to encounter a person who is not horrified by the treatment of the bodies donated to Harvard Medical School and then diverted into curiosity shops and private collections, especially when I explain that such activities are not clearly illegal in every state. </p>
<p>Respectful treatment of human remains, and of the loved ones they leave behind, appears to be a universal value. Yet there is a clear mismatch between these social norms and the law – for now.</p><img src="https://counter.theconversation.com/content/171192/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Tanya D. Marsh 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>The short answer: It’s complicated – and depends, in part, where you live.Tanya D. Marsh, Professor of Law, Wake Forest UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2081682023-06-28T12:34:48Z2023-06-28T12:34:48ZMedical students honor body donors through words, deeds and ceremonies<figure><img src="https://images.theconversation.com/files/534396/original/file-20230627-27-sd4cd.jpg?ixlib=rb-1.1.0&rect=0%2C4%2C1024%2C677&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Donors' bodies lie covered in an anatomy lab at the Justus Liebig University in Giessen, Germany.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/march-2023-hesse-gie%C3%9Fen-couch-with-covered-body-donations-news-photo/1249666093?adppopup=true">Sebastian Gollnow/picture alliance via Getty Images</a></span></figcaption></figure><p><a href="https://www.justice.gov/usao-mdpa/pr/six-charged-trafficking-stolen-human-remains">Six people were charged</a> on June 14, 2023, with buying and selling human remains stolen from the Harvard Medical School morgue and from an Arkansas mortuary. The macabre story <a href="https://apnews.com/article/stolen-human-body-parts-harvard-medical-school-a33afcd82908dda340f4c1df18e7b43f">made national headlines</a>, particularly the indictment of Cedric Lodge: a morgue manager at Harvard from 1995 until earlier this year.</p>
<p>As <a href="https://chaplaincyinnovation.org/team/amy-lawton-phd">a scholar in the sociology of religion</a>, <a href="http://hdl.handle.net/11134/20002:860685608">my research</a> explores practices related to whole-body donation in medical schools across the United States. While these accusations against Lodge are deeply troubling, they are an aberration: Medical school communities go to incredible lengths to respect and honor the people who donate their bodies to science.</p>
<p>Much of this happens behind closed doors. The serious scientific work of anatomical study is undergirded by practices that promote the donors’ dignity, including memorial ceremonies to honor their gift. I conducted <a href="http://hdl.handle.net/11134/20002:860685608">a census of allopathic medical schools</a> – schools that grant the M.D. degree – and analyzed recordings of 60 donor memorial ceremonies, as well as other materials.</p>
<h2>Foundation of learning</h2>
<p>Despite advances made in technology, including virtual reality and 3D anatomy software, dissecting a real human body is generally considered irreplaceable in Western medical education. Substitutions result in <a href="https://doi.org/10.1002/ase.1859">less effective instruction</a>, leading to lower scores on practical and written examinations. One benefit is that <a href="https://doi.org/10.1002/ase.1758">students who learn from dissection</a> see normal bodies, with diversity, variations and imperfections that would not be evident on models. Faculty <a href="http://hdl.handle.net/11134/20002:860685608">views donor bodies as essential</a> because they are always accurate and up to date, which cannot always be said about books or software. </p>
<p>In the U.S., medical schools <a href="https://www.statnews.com/2016/08/17/body-donations-medical-school/">accept bodies from donors</a> and next of kin. A minority of institutions <a href="https://doi.org/10.1002/ase.1853">accept unclaimed bodies</a>, but their use is controversial.</p>
<p>Bodies’ importance goes beyond their effectiveness as a teaching tool. Anatomy lab marks the students’ <a href="https://doi.org/10.1002/ar.b.20117">initiation into the medical profession</a>. It teaches not only anatomy but the value of the human person, professionalism, ethics and clinical skills such as diagnosis. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/534397/original/file-20230627-35262-9zpqxh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A young brunette woman wearing gloves rinses a human heart in a sink in an anatomy lab." src="https://images.theconversation.com/files/534397/original/file-20230627-35262-9zpqxh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/534397/original/file-20230627-35262-9zpqxh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=427&fit=crop&dpr=1 600w, https://images.theconversation.com/files/534397/original/file-20230627-35262-9zpqxh.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=427&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/534397/original/file-20230627-35262-9zpqxh.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=427&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/534397/original/file-20230627-35262-9zpqxh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=537&fit=crop&dpr=1 754w, https://images.theconversation.com/files/534397/original/file-20230627-35262-9zpqxh.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=537&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/534397/original/file-20230627-35262-9zpqxh.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=537&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 lessons medical students learn from donor bodies go beyond anatomy.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/liz-harkin-uses-a-running-tap-to-clean-out-a-human-heart-news-photo/145376204?adppopup=true">Bill O'Leary/The Washington Post via Getty Images</a></span>
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<p>From day one, medical students studying gross anatomy are encouraged to think of the donor body as <a href="https://www.nytimes.com/2023/05/31/science/donor-bodies-medical-school-appreciation.html">their “first patient</a>,” someone for whom they will care and from whom they will learn. Medical students are responsible for preserving the body, performing dissections correctly so as not to cause unnecessary mutilation, and speaking of the body and the donor respectfully. </p>
<p>Students work in teams, each of which is usually responsible for dissecting one body. Many also feel a sense of responsibility toward their donors – a duty to learn as much as they can, taking full advantage of the gift they have been given.</p>
<h2>Reflection and respect</h2>
<p>At the end of the semester, students say goodbye to the donors. My research found that more than nine out of 10 allopathic medical schools mark this occasion with a memorial ceremony. <a href="https://thedo.osteopathic.org/2018/03/acom-honors-anatomical-donors-memorial-space-reflection/">Ceremonies also take place</a> at schools for other branches of health care, such as <a href="https://www.liberty.edu/lucom/news/lucom-class-of-2024-hosts-annual-symbolic-memorial-honoring-first-patients/">osteopathy</a> and <a href="https://blogs.chapman.edu/crean/2015/04/08/honoring-those-who-give-life-to-science-donor-memorial-ceremony/">physical therapy</a>. Wherever students learn from body donors, they gather together to express their gratitude for a gift that can never be reciprocated.</p>
<p>Some ceremonies are conducted before an audience that includes the friends and families of all body donors used that year. Some are open to the medical school community, and others are for the students alone. For many, these donors have played a transformative role in their lives. It is common to hear students refer to their donors as a friend or mentor. </p>
<p>At the 2018 University of Iowa ceremony, a student reflected: “I know her hands, her feet, what parts of her may have ached towards the end of life, which organs let her down. I spent countless hours as her pupil. She taught me things about life that no living person ever could. When I was confused and needed time to think, she was patient. My donor entrusted me with the intimate gift of her body to learn about the topics that make my heart race.” </p>
<p>Learning in the anatomy lab and participating in a donor memorial ceremony have something important in common. Both experiences <a href="https://www.britannica.com/topic/sacred">stand apart from everyday life</a>, making them, in a sense, sacred. These ceremonies set aside a special time and space for <a href="https://doi.org/10.1002/ar.10188">reflection and remembrance</a> – time and space that busy medical students do not usually have.</p>
<p>Unlike most memorial services, these students have no personal memories of the deceased. In fact, some are not even told their donor’s first name, which is often concealed to preserve privacy.</p>
<p>Yet they know at least one fact: This person cared about medicine and other people’s health. Students reflect on how generous and principled the donors must have been – as well as their families, who were willing to carry out loved ones’ wishes in their time of grief. Though students did not witness donors’ lives, they can still <a href="http://hdl.handle.net/11134/20002:860685608">celebrate and honor them</a>. </p>
<p>A student at the University of Cincinnati’s 2019 service shared: “I am overwhelmed with respect and gratitude for all our donors. … As we gather here today, let’s remember the legacy that all of these donors and family members have left in all of us, and celebrate the legacy that they continue to forge even after death.” </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/534452/original/file-20230627-27-jgyme6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Rows of young people in white medical coats stand respectfully outside at a ceremony." src="https://images.theconversation.com/files/534452/original/file-20230627-27-jgyme6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/534452/original/file-20230627-27-jgyme6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=356&fit=crop&dpr=1 600w, https://images.theconversation.com/files/534452/original/file-20230627-27-jgyme6.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=356&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/534452/original/file-20230627-27-jgyme6.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=356&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/534452/original/file-20230627-27-jgyme6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=448&fit=crop&dpr=1 754w, https://images.theconversation.com/files/534452/original/file-20230627-27-jgyme6.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=448&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/534452/original/file-20230627-27-jgyme6.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=448&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Medical students at the University of Mississippi Medical Center attend the Ceremony of Thanksgiving in Memory of Anatomical Donors in 2018.</span>
<span class="attribution"><a class="source" href="https://newsroom.ap.org/detail/HonoringTheirGifts/57639ee975e143e6b8acc8d0048f069b/photo?Query=donor%20body%20ceremony&mediaType=photo&sortBy=arrivaldatetime:desc&dateRange=Anytime&totalCount=41&currentItemNo=7">AP Photo/Rogelio V. Solis</a></span>
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<p>A donor body’s gift cannot be “paid back,” but medical students can try to pay it forward. Many describe ways they will try to serve others, as the donor did. Some doctors-to-be express a sense that the donors will forever guide their hands.</p>
<p>There is no foolproof way to prevent bad actors in any institution. Yet research into donor memorial ceremonies shows that no one takes the gift of body donation more seriously than the recipients.</p><img src="https://counter.theconversation.com/content/208168/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Amy Lawton received funding from the Templeton Religion Trust administered through the Issachar Fund.</span></em></p>The lessons students learn from dissecting donor bodies go beyond anatomy – and they try to pay that gift forward.Amy Lawton, Research Manager, Chaplaincy Innovation Lab, Brandeis UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2004962023-03-31T12:23:01Z2023-03-31T12:23:01ZUnconscious biases continue to hold back women in medicine, but research shows how to fight them and get closer to true equity and inclusion<figure><img src="https://images.theconversation.com/files/518544/original/file-20230330-1798-cyxmdb.jpg?ixlib=rb-1.1.0&rect=1155%2C396%2C4595%2C3190&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Women face much higher levels of discrimination in hiring and promotions compared to male medical professionals.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/female-doctors-discussing-while-walking-in-hospital-royalty-free-image/961012938?phrase=medical%20team%20diverse&adppopup=true">Cavan Images/Getty Images</a></span></figcaption></figure><p>If you work at a company, university or large organization, you’ve probably sat through a required training session meant to fight gender and racial discrimination in the workplace. Employers increasingly invest in efforts to promote diversity, equity and inclusion – commonly referred to as DEI policies. Yet research shows these efforts often <a href="https://doi.org/10.1037/pspa0000160">fail to address the implicit biases</a> that often lead to discrimination.</p>
<p><a href="https://scholar.google.com/citations?user=10vXfYgAAAAJ&hl=en&oi=ao">I am a professor and a physician</a> who has been working in university settings for over 30 years. I also study and speak about discrimination in medicine and science. Like <a href="https://nap.nationalacademies.org/catalog/24994/sexual-harassment-of-women-climate-culture-and-consequences-in-academic">most of my female colleagues</a>, I have personally seen and experienced gender discrimination on many occasions throughout my career.</p>
<p>However, two things seem to have changed in recent years. First, modern training programs are <a href="https://pubmed.ncbi.nlm.nih.gov/36937456/">starting to reflect decades of research</a> on effective interventions. Second, I am noticing a gradual shift with people now more interested in actively addressing discrimination and harassment than ever before. Taken together, these changes give me hope that the medical profession is finally making progress on efforts to fight discrimination.</p>
<h2>Existing policies haven’t worked</h2>
<p>Many institutional policies <a href="https://ss-usa.s3.amazonaws.com/c/308463326/media/27436024f0b84dfd274918375735238/202102%20-%20DEI%20Report.pdf">outline anti-racist and anti-sexist goals</a>, but research shows results have <a href="https://doi.org/10.1073/pnas.1706255114">been slow in coming</a>.</p>
<p>In a study I conducted to understand what continues to <a href="https://doi.org/10.1001/jamanetworkopen.2021.25843">hold women back in their careers</a>, I interviewed more than 100 men and women in academic medicine, including many in high-powered positions. In my study, dozens of interviewees told me stories of DEI policies that, even with the right intentions, failed to produce good results.</p>
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<a href="https://images.theconversation.com/files/518545/original/file-20230330-26-u00thy.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A man sitting at the head of a table." src="https://images.theconversation.com/files/518545/original/file-20230330-26-u00thy.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/518545/original/file-20230330-26-u00thy.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=430&fit=crop&dpr=1 600w, https://images.theconversation.com/files/518545/original/file-20230330-26-u00thy.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=430&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/518545/original/file-20230330-26-u00thy.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=430&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/518545/original/file-20230330-26-u00thy.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=541&fit=crop&dpr=1 754w, https://images.theconversation.com/files/518545/original/file-20230330-26-u00thy.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=541&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/518545/original/file-20230330-26-u00thy.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=541&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Research shows that despite policies to promote diversity, equity and inclusion, men still fare better in medical careers.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/businessman-at-conference-table-portrait-royalty-free-image/BA60388?phrase=board%20room&adppopup=true">Darren Robb/The Image Bank via Getty Images</a></span>
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<p>For example, frequently search committees are encouraged to broaden and <a href="https://haas.berkeley.edu/wp-content/uploads/EGAL_DEIChecklist.pdf">diversify the pool of candidates</a> for a position. In my study, I found that hiring committees often associate attempts to hire or promote a woman or member of an underrepresented group as “meeting a quota” or “affirmative action,” which the hiring committee sees as an imposition on their ability to choose the best candidates.</p>
<p>A male faculty member I interviewed claimed that a new colleague was hired “because she’s a woman,” even though she was as qualified for the position as other male candidates. Such reactions are part of why this approach, though commonly employed, has not fixed the problem of <a href="https://doi.org/10.1056/nejmsa1916935">women getting fewer promotions than men</a>.</p>
<p>It is also clear that <a href="https://pubmed.ncbi.nlm.nih.gov/31513467/">blatant sexism is still present</a>. For a study I published in 2021, I was told stories of a male department chair putting a dog leash on the desk of a female co-worker, and a female candidate for a leadership position being criticized by the chair of the search committee for <a href="https://doi.org/10.1001/jamanetworkopen.2021.25843">not being “warm and fuzzy”</a>. </p>
<h2>Trainings fail to address implicit bias</h2>
<p>Implicit bias is any unconscious negative attitude a person holds <a href="https://www.apa.org/topics/implicit-bias">against a specific social group</a>. These unconscious biases can affect judgment, decision making and behavior. Implicit bias is often one of the <a href="https://www.statnews.com/2023/01/23/conversations-unconscious-bias-stop-discrimination-in-hiring/">underlying issues</a> that leads to discriminatory practices or harassment that DEI policies are meant to address.</p>
<p>Employee trainings are a staple of organizations’ efforts to meet diversity, equity and inclusion goals. Trainings can take various forms and cover a variety of topics, including implicit bias. These trainings, frequently done online, often “talk at” employees by simply offering information and directives rather than actively engaging them in discussion and analysis. </p>
<p>Trainings that fail to engage participants aren’t very effective in <a href="https://doi.org/10.1177%2F15291006211070781">lessening imlicit bias</a>. In fact, research has shown that some trainings suggest unconscious bias is an unchangeable fact of life and imply it <a href="https://hbr.org/2021/09/unconscious-bias-training-that-works">can therefore be ignored</a>.</p>
<h2>Effective ways to mitigate unconscious bias</h2>
<p>Describing how bias works and how it influences individuals is an important step in addressing discrimination. </p>
<p>Researchers have been studying <a href="https://theconversation.com/measuring-the-implicit-biases-we-may-not-even-be-aware-we-have-74912">how unconscious bias works and how to mitigate it</a> since the 1980s. These studies show that unconscious bias is a <a href="https://doi.org/10.1016/j.jesp.2017.04.009">habit that can be broken over time</a> with a clear, consistent and respectful series of evaluations, feedback and follow-ups. During this process, employees become more aware of bias in others, more likely to judge such bias as problematic and more able to mitigate bias in their own behavior. This type of intervention has been shown to produce measurable increases in the <a href="https://doi.org/10.1016/j.jesp.2017.07.002">number of female faculty in science and medicine</a>.</p>
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<a href="https://images.theconversation.com/files/518546/original/file-20230330-1797-8tm80s.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A group of people sitting in a semi-circle watching a woman give a presentation." src="https://images.theconversation.com/files/518546/original/file-20230330-1797-8tm80s.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/518546/original/file-20230330-1797-8tm80s.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/518546/original/file-20230330-1797-8tm80s.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/518546/original/file-20230330-1797-8tm80s.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/518546/original/file-20230330-1797-8tm80s.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/518546/original/file-20230330-1797-8tm80s.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/518546/original/file-20230330-1797-8tm80s.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">Many diversity, equity and inclusion policies rely on trainings that don’t do a good job of engaging employees.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/businesswoman-explaining-strategy-over-a-flip-chart-royalty-free-image/1166085818?phrase=professional%20training&adppopup=true">Luis Alvarez/Digital Vision via Getty Images</a></span>
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<p>The question is whether the mandatory trainings and public messaging that are the staples of many DEI policies today can produce similar results to these intensive interventions. </p>
<p>Creating situations or a culture where people can and do share their experiences with harassment and discrimination – without risk of retaliation – can lead to increased awareness of bias in others and clear communication of the negative aspects of this bias.</p>
<p>One interviewee in my study talked about an exercise in which the women wrote down their experiences of discrimination and harassment and then the men read the women’s stories out loud. This woman felt that the men, by reciting the experiences of their female colleagues, finally began to understand how practices that seemed to be inclusive and fair were actively harming others.</p>
<h2>A changing social environment</h2>
<p>Sharing personal experiences of harassment or discrimination with people who have biases is an understandably scary or intimidating thing to do – especially given the <a href="https://doi.org/10.1007/s00268-021-06432-6">history of retaliation or shaming</a>. But my recent experiences seem to suggest that the culture in medicine is shifting from one of avoidance to one of engagement.</p>
<p>I recently gave a talk on gender discrimination at <a href="https://www.cancer.org/research/we-fund-cancer-research/eds-research-programs/jiler-professors-and-fellows-conference/2022-jiler-conference-the-feedback.html">a major cancer conference</a> that brought together researchers from all across the U.S. I shared the results of my study as well as my personal experiences with the audience. At the end of my presentation, the crowd of men and women stood and applauded – a response I have rarely, if ever, seen in my 30 years of attending medical conferences. </p>
<p>This enthusiastic response may suggest that people are broadly becoming more open to and supportive of women and other underrepresented people sharing their own stories of facing discrimination. With a large body of research showing that sharing personal experiences with people who are actively listening and engaging is one of the most effective ways to combat unconscious bias, this standing ovation seemed to me a hopeful sign of things to come.</p><img src="https://counter.theconversation.com/content/200496/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jennifer R. Grandis 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>After decades of effort to reduce discrimination in the workplace, a cultural change may be happening that will enable people to move past their unconscious biases.Jennifer R. Grandis, Distinguished Professor of Otolaryngology-Head and Neck Surgery, University of California, San FranciscoLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1994872023-02-09T16:31:46Z2023-02-09T16:31:46ZLack of diversity in clinical trials is leaving women and patients of color behind and harming the future of medicine – Podcast<figure><img src="https://images.theconversation.com/files/509021/original/file-20230208-15-u9tmxa.jpg?ixlib=rb-1.1.0&rect=73%2C196%2C2652%2C1495&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Most clinical trials overrepresent young white males. </span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/illustration-of-a-group-of-people-wearing-royalty-free-illustration/1267173084?phrase=medicine%20diverse&adppopup=true">Andresr/Digital Vision via Getty Images</a></span></figcaption></figure><p>Its a great day when you find a piece of clothing that fits perfectly. A good shirt, the right pair of shoes or a well-cut dress is comfortable, looks nice and feels like it was made just for you. Now imagine a world where every shirt was the same size, every shoe was the same design and there weren’t even differences between the cut of men’s and women’s clothing. Getting dressed in the morning would be clunky, and clothes would be uncomfortable. In other words, one size does not fit all.</p>
<p>Yet, this lack of bespoke options is more or less the reality of medicine today. Despite the many biological differences between people of different genders, races, ages and life histories, chances are that if two people walk into a doctor’s office with the same symptoms, they are going to get roughly the same treatment. As you can imagine, a whole range of treatments – from drugs to testing – could be much more effective if they were designed to work with many different kinds of bodies, not just some abstract, generic human. </p>
<p>In this episode of <a href="https://theconversation.com/uk/topics/the-conversation-weekly-98901">The Conversation Weekly</a> podcast, we speak to three researchers who are looking at ways to make medicine better suited to you. It starts with simply making sure that clinical trial participants look like the actual population of patients a drug is meant to treat. And as we explore in this episode, in the future, precision medicine could help each person get <a href="https://theconversation.com/how-to-use-precision-medicine-to-personalize-covid-19-treatment-according-to-the-patients-genes-142142">medical care that is tailored to their own biology</a>, just like a custom shirt.</p>
<iframe src="https://embed.acast.com/60087127b9687759d637bade/63e4b69f21381a001164d059" frameborder="0" width="100%" height="190px"></iframe>
<p><iframe id="tc-infographic-561" class="tc-infographic" height="100" src="https://cdn.theconversation.com/infographics/561/4fbbd099d631750693d02bac632430b71b37cd5f/site/index.html" width="100%" style="border: none" frameborder="0"></iframe></p>
<p>In 1977, the U.S. Food and Drug Administration released a set of policy guidelines that explicitly banned “women of childbearing age” from <a href="https://www.womenshealth.gov/30-achievements/04">participating in clinical trials</a> of new drugs. Though done out of a fear of causing birth defects, the result was that for more than a decade, new drugs were going to market with little information about how they might affect women. Due to systemic biases, research has found that people of color are routinely underrepresented in clinical trials today, too. For the most part, medical research has been done on <a href="https://www.verywellmind.com/racial-disparities-clinical-trials-5114529">healthy, young and middle-aged men of European descent</a>.</p>
<p>This is a problem in the U.S, according to <a href="https://scholar.google.com/citations?user=wd-fP1EAAAAJ&hl=en&oi=sra">Jennifer Miller, a bioethicist at Yale University</a>. “If you’re not included in the trial, this raises questions about whether the drug’s safety and efficacy information applies to patients like you,” she says.</p>
<p>In recent years, a number of researchers across the U.S. – like <a href="https://www.msm.edu/about_us/FacultyDirectory/Medicine/JuliaLiu/index.php">Julia Liu</a>, a professor of medicine at Morehouse School of Medicine – have been trying to figure out ways to improve the diversity of clinical trial participants. Part of the problem, Liu explains, stems from a myth within medicine that Black people don’t like to participate in medical research due to the history of abuses the U.S. medical system has inflicted on African Americans, like the infamous Tuskegee Experiment. But when Liu began running her own trials on a new prostate cancer test at a hospital that serves a majority-African American population, she <a href="https://theconversation.com/yes-black-patients-do-want-to-help-with-medical-research-here-are-ways-to-overcome-the-barriers-that-keep-clinical-trials-from-recruiting-diverse-populations-185337">found quite the opposite</a>. </p>
<p>“It turned out that just about everyone I asked said, ‘I would love to do that,’” explains Liu. “Half of the eligible patients agreed.” Black patients were just as eager to participate in research as white patients, and according to Liu, a big reason for lack of diversity in clinical trials is that they are mostly run out research hospitals in wealthier, whiter cities, not out of hospitals with diverse patients.</p>
<p>According to Miller’s research, only <a href="https://doi.org/10.1001/jamanetworkopen.2021.7063">4% of trials in recent years used a representative population</a>, but she is optimistic. Women are now much better represented in trials, and with regard to equal racial representation, “that 4% does tell us is that it’s possible to get this right.” </p>
<p>Efforts like those of Liu and Miller are similar to how companies make shirts in different sizes to better fit different bodies. Once researchers do this work, health care providers can choose which drugs are likely to work better and have fewer risks for different patients based on their individual demographics. </p>
<p>Better representation is a start, but anyone who has been lucky enough to get custom-made clothing knows just how well a shirt can really fit. This is the idea behind precision medicine. According to <a href="https://profiles.ucsf.edu/Keith.Yamamoto">Keith Yamamoto</a>, who directs the precision medicine center at the University of California, San Francisco, in the U.S., in the near future it may be possible to “achieve an understanding of health and disease to the extent that we could give advice to Dan Merino, not just people like Dan.” </p>
<p>This approach to medicine would incorporate basic biology, a person’s individual genetics and life history and the wealth of all existing medical research – precision medicine is an information and computation problem. To work, it needs good data – the representative data missing from clinical trials. As Yamamoto said, “Precision medicine will fail if we don’t address those issues in a head-on way.”</p>
<p>Listen to the full episode of <a href="https://theconversation.com/uk/topics/the-conversation-weekly-98901">The Conversation Weekly</a> to find out more. </p>
<hr>
<p>This episode of The Conversation Weekly was produced by Katie Flood. It was written by Katie Flood and Daniel Merino. Sound design is by Eloise Stevens, and the theme music is by Neeta Sarl.</p>
<p>You can find us on Twitter <a href="https://twitter.com/TC_Audio">@TC_Audio</a>, on Instagram at <a href="https://www.instagram.com/theconversationdotcom/">@theconversationdotcom</a> or <a href="mailto:podcast@theconversation.com">via email</a>. You can also sign up for The Conversation’s <a href="https://theconversation.com/newsletter">free emails here</a>. A transcript of this episode will be available soon. </p>
<p>Listen to The Conversation Weekly via any of the apps listed above, download it directly via our <a href="https://feeds.acast.com/public/shows/60087127b9687759d637bade">RSS feed</a> or find out <a href="https://theconversation.com/how-to-listen-to-the-conversations-podcasts-154131">how else to listen here</a>.</p><img src="https://counter.theconversation.com/content/199487/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jennifer Miller has served on the advisory board for Alexion Pharmaceuticals and directs the Good Pharma Scorecard. She receives funding from from the FDA, NIH and Arnold Ventures and sits on the board of the nonprofit Bioethics International.
Keith Yamamoto sits on the scientific advisory board of Mate Bioservices. He is the President of the American Association for the Advancement of Science (AAAS), chair of the Coalition for the Life Sciences, co-chair of the NASEM Roundtable on Aligning Incentives for Open Science and of the Science and Technology Action Committee, vice chair of the California Initiative to Advance Precision Medicine Advisory Council. He is a member of the Boards of Directors of the Public Library of Science, Research! America and Rapid Science, the Governing Board of the California Institute for Regenerative Medicine, the Board of Counselors for the Radiation Effects Research Foundation, the Advisory Board for Lawrence Berkeley National Laboratory and the Council of EBRC. </span></em></p><p class="fine-print"><em><span>Julia Liu does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and have disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Medicine works better when the treatments are tailored to fit each individual person’s biology and history. A first step is increasing diversity in clinical trials, but the end goal is precision medicine.Daniel Merino, Associate Science Editor & Co-Host of The Conversation Weekly Podcast, The ConversationNehal El-Hadi, Science + Technology Editor & Co-Host of The Conversation Weekly Podcast, The ConversationLicensed 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/1905302022-09-14T00:50:43Z2022-09-14T00:50:43ZScientists have mimicked an embryo’s heart to unlock the secrets of how blood cells are born<figure><img src="https://images.theconversation.com/files/484449/original/file-20220913-4701-66g2bb.jpg?ixlib=rb-1.1.0&rect=0%2C1846%2C4019%2C2842&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><span class="source">UNSW/Jingjing Li</span>, <span class="license">Author provided</span></span></figcaption></figure><p>Stem cells are the starting point for all other cells in our bodies. The <a href="https://www.eurostemcell.org/blood-stem-cells-pioneers-stem-cell-research">first such cells to be found</a> were blood stem cells – as the name suggests, they give rise to different types of blood cells. </p>
<p>But there’s much we don’t know about how these cells develop in the first place. In a study published today in <a href="https://doi.org/10.1016/j.celrep.2022.111339">Cell Reports</a>, we have shown how a lab simulation of an embryo’s beating heart and circulation lead to the development of human blood stem cell precursors.</p>
<p>The tiny device mimics embryonic blood flow, allowing us to directly observe human embryonic blood formation under the microscope. These results may help us understand how we can produce life-saving therapies for patients who need new blood stem cells.</p>
<h2>Growing life-saving therapies in the lab</h2>
<p>To treat aggressive blood cancers such as leukaemia, patients often need extremely high doses of chemotherapy; a <a href="https://www.cancer.nsw.gov.au/myeloma/diagnosis-and-treatment/treatment/types-of-treatment/stem-cell-transplant#:%7E:text=A%20stem%20cell%20transplant%20involves%20killing%20blood%20cells,they%20are%20collected%20beforehand%20and%20kept%20in%20storage.">blood stem cell transplant</a> then regenerates blood after the treatment. These are life-saving therapies but are restricted to patients who have a suitable tissue-matched donor of blood stem cells.</p>
<p>A way around this problem would be to grow more blood stem cells in the lab. Unfortunately, past experiments have shown that harvested adult blood stem cells lose their transplantation potential if grown in the lab. </p>
<p>The discovery of <a href="https://en.wikipedia.org/wiki/Induced_pluripotent_stem_cell">induced pluripotent stem cells</a> – stem cells made out of adult cells – in 2006 led to a promising new approach. Induced pluripotent stem cells are made from the patient’s own cells, so there is no problem with tissue rejection, or the ethical issues surrounding the use of IVF embryos.</p>
<p>These cell lines are similar to embryonic stem cells, so they have the potential to form any tissue or cell type – hence, they are “pluripotent”. In theory, pluripotent stem cell lines could provide an unlimited supply of cells for blood regeneration because <a href="https://en.wikipedia.org/wiki/Immortalised_cell_line">they are immortalised</a> – they can grow in the lab indefinitely.</p>
<p>But the development of processes to allow us to grow particular types of tissues, organs and cell types – such as blood – has been slow and will take decades to advance. One must mimic the complex process of embryogenesis in the dish!</p>
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Read more:
<a href="https://theconversation.com/worlds-first-synthetic-embryo-why-this-research-is-more-important-than-you-think-188217">World's first 'synthetic embryo': why this research is more important than you think</a>
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<h2>Engineering an embryonic heart</h2>
<p>Current understanding of how embryonic blood stem cells develop is based on animal models. Experiments with anaesthetised zebrafish embryos have shown that blood stem cells arise in the wall of <a href="https://pubmed.ncbi.nlm.nih.gov/20154733/">the main blood vessel, the aorta</a>, shortly after the first heartbeat. For ethical reasons, it’s obvious this type of study is not possible in human embryos.</p>
<p>This is why we wanted to engineer an embryonic heart model in the lab. To achieve this, we used <a href="https://www.elveflow.com/microfluidic-reviews/general-microfluidics/a-general-overview-of-microfluidics/">microfluidics</a> – an approach that involves manipulating extremely small volumes of liquids.</p>
<figure class="align-center ">
<img alt="A clear chip with colourful tubes coming out on both ends" src="https://images.theconversation.com/files/484242/original/file-20220913-18-2q7zzk.jpg?ixlib=rb-1.1.0&rect=7%2C12%2C698%2C516&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/484242/original/file-20220913-18-2q7zzk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=449&fit=crop&dpr=1 600w, https://images.theconversation.com/files/484242/original/file-20220913-18-2q7zzk.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=449&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/484242/original/file-20220913-18-2q7zzk.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=449&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/484242/original/file-20220913-18-2q7zzk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=565&fit=crop&dpr=1 754w, https://images.theconversation.com/files/484242/original/file-20220913-18-2q7zzk.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=565&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/484242/original/file-20220913-18-2q7zzk.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=565&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">The microfluidic device, with cell-seeding channels filled with red food dye; the heart ventricular contraction control channels and circulation valve control channels are filled with blue and green food dye respectively.</span>
<span class="attribution"><span class="source">UNSW/Jingjing Li</span>, <span class="license">Author provided</span></span>
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<p>The first step in generating blood stem cells from pluripotent stem cells is to coax the latter to form the site where blood stem cells start growing. This is known as the AGM region (aorta-gonad-mesonephros) of the embryo.</p>
<p>Our miniature heart pump and circulation (3 by 3 centimetres) mimics the mechanical environment in which blood stem cells form in the human embryo. The device pumps culture media – liquids used to grow cells – around a microfluidic circuit to copy what the embryo heart does.</p>
<h2>A step closer to treatment</h2>
<p>Once we got the cells to form the AGM region by stimulating cells on day two of starting our cell culture, we applied what’s known as pulsatile circulatory flow from day 10 to day 26. Blood precursors entered the artificial circulation from blood vessels lining the microfluidic channels. </p>
<p>Then, we harvested the circulating cells and grew them in culture, showing that they developed into various blood components – white blood cells, red blood cells, platelets, and others. In-depth analysis of gene expression in single cells showed that circulatory flow generated aortic and blood stem precursor cells found in the AGM of human embryos.</p>
<p>This means our study has shown how pulsatile circulatory flow enhances the formation of blood stem cell precursors from pluripotent stem cells. It’s knowledge we can use in the future.</p>
<p>The next step in our research is to scale up the production of blood stem cell precursors, and to test their transplant potential in immune-deficient mice that can accept human transplants. We can do this by using large numbers of pluripotent stem cells grown in bioreactors that also mechanically stimulate blood stem cell formation.</p>
<p>If we can easily produce blood stem cells from pluripotent stem cell lines, it would provide a plentiful supply of these cells to help treatments of cancer or genetic blood diseases.</p>
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Read more:
<a href="https://theconversation.com/gut-bacteria-nurture-the-immune-system-for-cancer-patients-a-diverse-microbiome-can-protect-against-dangerous-treatment-complications-184427">Gut bacteria nurture the immune system – for cancer patients, a diverse microbiome can protect against dangerous treatment complications</a>
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<img src="https://counter.theconversation.com/content/190530/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>This research was funded by Stem Cells Australia (ARC Special Research Initiative in Stem Cell Science) and an internal grant from the Faculty of Engineering, University of New South Wales.</span></em></p><p class="fine-print"><em><span> Jingjing Li received Australia Postgraduate Award (APA) scholarship, Women in Engineering Research Top-Up Award and Engineering Supplementary Award (ESA) from University of New South Wales. </span></em></p>Growing cells we can use to produce blood is key to life-saving therapies after cancer treatment – this device has taken us a step closer.Robert E Nordon, Associate Professor, Biomedical Engineering, UNSW SydneyJingjing Li, Postdoctoral Fellow, Biomedical Engineering, UNSW SydneyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1875032022-08-18T12:39:23Z2022-08-18T12:39:23ZFake research can be harmful to your health – a new study offers a tool for rooting it out<figure><img src="https://images.theconversation.com/files/479736/original/file-20220817-7931-21c2t3.jpg?ixlib=rb-1.1.0&rect=374%2C64%2C8240%2C5489&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Although most medical research is reliable, studies that are flawed or fake can lead to patients undergoing treatments that might cause harm.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/two-biotechnologists-examining-data-for-medical-royalty-free-image/881494610?adppopup=true">skynesher/E+ via Getty Images</a></span></figcaption></figure><p>If you are suffering with chronic pain, diabetes, heart problems or any other condition, you want to be confident that your doctor will offer you an effective treatment. You certainly don’t want to waste time or money on something that won’t work, or take something that could do you harm. </p>
<p>The best source of information to guide treatment is medical research. But how do you know when that information is reliable and evidence-based? And how can you tell the difference between shoddy research findings and those that have merit?</p>
<p>There’s a long journey to the publication of research findings. Scientists design experiments and studies to investigate questions about treatment or prevention, and follow certain scientific principles and standards. Then the finding is submitted for publication in a research journal. Editors and other people in the researchers’ field, called peer-reviewers, make suggestions to improve the research. When the study is deemed acceptable, it is published as a research journal article. </p>
<p>But a lot can go wrong on this long journey that could make a research journal article unreliable. And peer review is not designed to catch fake or misleading data. Unreliable scientific studies can be hard to spot – whether by reviewers or the general public – but by asking the right questions, it can be done. </p>
<p>While most research has been conducted according to rigorous standards, studies with fake or fatally flawed findings are sometimes published in the scientific literature. It is hard to get an exact estimate of the number of fraudulent studies because the scientific publication process catches some of them before they are published. One study of 526 patient trials in anesthesiology <a href="https://doi.org/10.1111/anae.15263">found that 8% had fake data and 26% were critically flawed</a>. </p>
<p>As a professor in medicine and public health, I have been studying bias in the <a href="https://www.cuanschutz.edu/centers/bioethicshumanities/facultystaff/lisa-bero-phd">design, conduct and publication of scientific research for 30 years</a>. I’ve been developing ways to prevent and detect research integrity problems so the best possible evidence can be synthesized and used for decisions about health. Sleuthing out data that cannot be trusted, whether this is due to intentional fraud or just bad research practices, is key to using the most reliable evidence for decisions. </p>
<h2>Systematic reviews help suss out weak studies</h2>
<p>The most reliable evidence of all comes when researchers pull the results of several studies together in what is <a href="https://doi.org/10.1136/bmj.309.6954.597">known as a systematic review</a>. Researchers who conduct systematic reviews identify, evaluate and summarize all studies on a particular topic. They not only sift through and combine results on perhaps tens of thousands of patients, but can use an extra filter to catch potentially fraudulent studies and ensure they do not feed into recommendations. This means that the more rigorous studies have the most weight in a systematic review and bad studies are excluded based on strict inclusion and exclusion criteria that are applied by the reviewers.</p>
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<p>To better understand how systematic reviewers and other researchers can identify unreliable studies, my research team interviewed a group of 30 international experts from 12 countries. They explained to us that a shoddy study can be hard to detect because, as one expert explained, it is “designed to pass muster on first glance.” </p>
<p>As our <a href="https://doi.org/10.1016/j.jclinepi.2022.07.006">recently published study reports</a>, some studies look like their data has been massaged, some studies are not as well designed as they claim to be, and some may even be completely fabricated. </p>
<p>Our study provides some important ideas about how to spot medical research that is deeply flawed or fake and should not be trusted. </p>
<p>The experts we interviewed suggested some key questions that reviewers should ask about a study: For instance, did it have ethics approval? Was the <a href="https://www.biomedcentral.com/getpublished/writing-resources/trial-registration#">clinical trial registered</a>? Do the results seem plausible? Was the study funded by an independent source and not the company whose product is being tested?</p>
<p>If the answers to any of these questions is no, then further investigation of the study is needed. </p>
<p>In particular, my colleagues and I found that it’s possible for researchers who review and synthesize evidence to create a checklist of warning signs. These signs don’t categorically prove that research is fraudulent, but they do show researchers as well as the general public which studies need to be looked at more carefully. We used these warning signs to create a screening tool – a set of questions to ask about how a study is done and reported – that provide clues about whether a study is real or not.</p>
<p>Signs include important information that’s missing, like details of ethical approval or where the study was carried out, and data that seems too good to be true. One example might be if the number of patients in a study exceeds the number of people with the disease in the whole country. </p>
<h2>Spotting flimsy research</h2>
<p>It’s important to note that our new study does not mean all research can’t be trusted. </p>
<p>The COVID-19 pandemic offers examples of how systematic review ultimately filtered out fake research that had been published in the medical literature and disseminated by the media. Early in the pandemic, when the pace of medical research was accelerating, robust and well-run patient trials – and the systematic reviews that followed – helped the public learn which interventions work well and which were not supported by science.</p>
<p>For example, <a href="https://theconversation.com/ivermectin-is-a-nobel-prize-winning-wonder-drug-but-not-for-covid-19-168449">ivermectin, an antiparasitic drug</a> that is typically used in veterinary medicine and that was promoted by some without evidence as a treatment for COVID-19, <a href="https://doi.org/10.1038/d41586-020-02958-2">was widely embraced</a> in some parts of the world. However, after ruling out fake or flawed studies, a systematic review of research on ivermectin found that <a href="https://doi.org/10.1002/14651858.CD015017.pub3">it had “no beneficial effects</a> for people with COVID-19.”</p>
<p>On the other hand, a systematic review of corticosteroid drugs like dexamethasone found that <a href="https://doi.org/10.1002/14651858.CD014963">the drugs help prevent death</a> when used as a treatment for COVID-19.</p>
<p>There are efforts underway across the globe to ensure that the highest standards of medical research are upheld. Research funders are asking scientists to publish all of their data so it can be fully scrutinized, and medical journals that publish new studies are beginning to screen for suspect data. But everyone involved in research funding, production and publication <a href="https://doi.org/10.1038/d41586-022-00025-6">should be aware</a> that fake data and studies are out there. </p>
<p>The screening tool proposed in our new research is designed for systematic reviewers of scientific studies, so a certain level of expertise is needed to apply it. However, using some of the questions from the tool, both researchers and the general public can be better equipped to read about the latest research with an informed and critical eye.</p><img src="https://counter.theconversation.com/content/187503/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Lisa Bero is Senior Editor, Research Integrity for Cochrane, an international non-profit organization that publishes systematic reviews.</span></em></p>A new screening tool to help study reviewers identify what’s fake or shoddy in research may be on the horizon. And everyday people can apply some of the same critical analysis tools.Lisa Bero, Research Professor Public Health and Medicine, University of Colorado Anschutz Medical CampusLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1880032022-08-03T02:19:14Z2022-08-03T02:19:14ZMore money and smarter choices: how to fix Australia’s broken NHMRC medical research funding system<figure><img src="https://images.theconversation.com/files/477068/original/file-20220802-20-61z3pd.jpeg?ixlib=rb-1.1.0&rect=0%2C0%2C3000%2C1998&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/health-care-researchers-working-life-science-639884194">Shutterstock</a></span></figcaption></figure><p>Most health research in Australia is funded by the National Health and Medical Research Council (NHMRC), which distributes around <a href="https://www.nhmrc.gov.au/funding/new-grant-program/overview">$800 million each year</a> through competitive grant schemes. An additional $650 million a year is funded via the <a href="https://www.health.gov.au/resources/collections/medical-research-future-fund-mrff-2nd-10-year-investment-plan-2022-23-to-2031-32">Medical Research Future Fund</a>, but this focuses more on big-picture “missions” than researcher-initiated projects. </p>
<p>Ten years ago, around 20% of applications for NHMRC funding were successful. Now, only about 10–15% are approved. </p>
<p>Over the same ten-year period, NHMRC funding has stayed flat while prices and population have increased. In inflation-adjusted and per capita terms, the NHMRC funding available has fallen by 30%.</p>
<p>As growing numbers of researchers compete for dwindling real NHMRC funding, research risks becoming “<a href="https://www.smh.com.au/national/a-high-status-gig-economy-how-we-have-failed-our-researchers-20220720-p5b347.html">a high-status gig economy</a>”. To fix it, we need to spend more on research – and we need to spend it smarter.</p>
<h2>More funding</h2>
<p>To keep pace with other countries, and to keep health research a viable career, Australia first of all needs to increase the total amount of research funding.</p>
<p>Between 2008 and 2010, Australia matched the average among OECD countries of investing 2.2% of GDP in research and development. More recently, Australia’s spending has fallen to 1.8%, while the <a href="https://data.oecd.org/chart/6Mot">OECD average</a> has risen to 2.7%.</p>
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Read more:
<a href="https://theconversation.com/covid-has-left-australias-biomedical-research-sector-gasping-for-air-145022">COVID has left Australia's biomedical research sector gasping for air</a>
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<p>When as few as one in ten applications is funded, there is a big element of chance in who succeeds. </p>
<p>Think of it like this: applications are ranked in order from best to worst, and then funded in order from the top down. If a successful application’s ranking is within say five percentage points of the funding cut-off, it might well have missed out if the assessment process were run again – because the process is always somewhat subjective and will never produce exactly the same results twice.</p>
<p>So 5% of the applications are “lucky” to get funding. When only 10% of applications get funding, that means half of the successful ones were lucky. But if there is more money to go around and 20% of applicants are funded, the lucky 5% are only a quarter of the successful applicants.</p>
<p>This is a simplistic explanation, but you can see that the lower the percentage of grants funded, the more of a lottery it becomes.</p>
<p>This increasing element of “luck” is demoralising for the research workforce of Australia, leading to depletion of academics and brain drain.</p>
<h2>The ‘application-centric’ model</h2>
<p>As well as increasing total funding, we need to look at how the NHMRC allocates these precious funds. </p>
<p>In the past five years, the NHMRC has moved to a system called “application-centric” funding. Five (or so) reviewers are selected for each grant and asked to independently score applications. </p>
<p>There are usually no panels for discussion and scoring of applications – which is what used to happen. </p>
<p>The advantages of application-centric assessment include (hopefully) getting the best experts on a particular grant to assess it, and a less logistically challenging task for the NHMRC (convening panels is hard work and time-consuming).</p>
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<p>However, application-centric assessment has disadvantages. </p>
<p>First, assessor reviews are not subject to any scrutiny. In a panel system, differences of opinion and errors can be managed through discussion.</p>
<p>Second, many assessors will be working in a “grey zone”. If you are expert in the area of a proposal, and not already working with the applicants, you are likely to be competing with them for funding. This may result in unconscious bias or even deliberate manipulation of scores.</p>
<p>And third, there is simple “noise”. Imagine each score an assessor gives is made up of two components: the “true score” an application would receive on some unobservable gold standard assessment, plus or minus some “noise” or random error. That noise is probably half or more of the current variation between assessor scores.</p>
<h2>Smarter scoring</h2>
<p>So how do we reduce the influence of both assessor bias and simple “noise”?</p>
<p>First, assessor scores need to be “standardised” or “normalised”. This means rescaling all assessors’ scores to have the same mean (standardisation) or same mean and standard deviation (normalisation). </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>This is a no-brainer. You can use a pretty simple Excel model (I have done it) to show this would substantially reduce the noise.</p>
<p>Second, the NHMRC could use other statistical tools to reduce both bias and noise. </p>
<p>One method would be to take the average ranking of applications across five methods:</p>
<ul>
<li>with the raw scores (i.e. as done now)</li>
<li>with standardised scores</li>
<li>with normalised scores</li>
<li>dropping the lowest score for each application</li>
<li>dropping the highest score for each application.</li>
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<p>The last two “drop one score” methods aim to remove the influence of potentially biased assessors.</p>
<p>The applications that make the cutoff rank on all the methods are funded. Those that are always beneath the threshold are not funded.</p>
<p>Applications that make the cut on some tests but fail on others could be sent out for further scrutiny – or the NHMRC could judge them by their average rank across the five methods. </p>
<p>This proposal won’t fix the problem with the total amount of funding available, but it would make the system fairer and less open to game-playing.</p>
<h2>A less noisy and fairer system</h2>
<p>Researchers know any funding system contains an element of chance. One <a href="https://bmjopen.bmj.com/content/3/5/e002800">study of Australian researchers</a> found they would be happy with a funding system that, if run twice in parallel, would see at least 75% of the funded grants funded in both runs.</p>
<p>I strongly suspect (and have modelled) that the current NHMRC system is achieving well below this 75% repeatability target. </p>
<p>Further improvements to the NHMRC system are possible and needed. Assessors could provide comments, as well as scores, to applicants. Better training for assessors would also help. And the biggest interdisciplinary grants should really be assessed by panels.</p>
<p>No funding system will be perfect. And when funding rates are low, those imperfections stand out more. But, at the moment, we are neither making the system as robust as we can nor sufficiently guarding against wayward scoring that goes under the radar.</p>
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Read more:
<a href="https://theconversation.com/7-things-the-australian-research-council-review-should-tackle-from-a-researchers-point-of-view-186629">7 things the Australian Research Council review should tackle, from a researcher's point of view</a>
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<img src="https://counter.theconversation.com/content/188003/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Tony Blakely was a member of the Peer Review Advisory Committee of the NHMRC, convened in 2021–22 to advise the NHMRC on improving the peer review process. However, this analysis and recommendations are Tony Blakely's, not a reflection of the final report of the committee.</span></em></p>The first thing Australian medical research needs is more money. The second thing is making funding allocation less of a lottery.Tony Blakely, Professor of Epidemiology, Population Interventions Unit, Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of MelbourneLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1825752022-06-28T16:03:30Z2022-06-28T16:03:30ZCanada needs to invest more money into science innovation to help prevent the next global crisis<figure><img src="https://images.theconversation.com/files/470375/original/file-20220622-26-15d611.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C5074%2C2851&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">If Canada wants to establish itself as a leading country in innovation, it has to invest in scientist-entrepreneurs and their projects.</span> <span class="attribution"><span class="source">(Shutterstock)</span></span></figcaption></figure><p>Canada has <a href="https://www.conferenceboard.ca/focus-areas/innovation-technology/innovation-report-card">lagged behind its peer nations in innovation</a> for decades. Currently, Canada is ranked 11th out of the 16 similarly developed countries assessed. While our “C” grade is a moderate improvement over our previous “D” grade, innovation still remains a barrier to high-quality job creation and economic prosperity in Canada.</p>
<p>It’s not that Canadians aren’t creative and inventive — Canadian science was able to rapidly deliver the medical technology needed to provide the first FDA-approved COVID-19 treatment and enabled the most effective COVID-19 vaccines. The problem is that Canada <a href="https://www.youtube.com/watch?v=BLG4e57cIMw">doesn’t convert enough inventions into patents, products and science-based ventures</a>. </p>
<p>While Canada’s COVID-19 breakthroughs are a feat worthy of celebration, other innovative breakthroughs still remain underdeveloped, languishing away in research labs. In innovation circles, this purgatory of untapped science innovation is commonly <a href="https://doi.org/10.1016/j.drudis.2013.01.012">referred to as the “valley of death.”</a> </p>
<h2>University scientists are key innovators</h2>
<p>Innovation in lipid nanoparticle drug delivery — a key component of the mRNA COVID-19 vaccines — was led by <a href="https://www.cbc.ca/radio/quirks/jun-12-missions-to-venus-learning-instant-replay-wrens-spectacular-duet-and-more-1.6061094/meet-the-canadian-scientist-who-paved-the-way-for-groundbreaking-mrna-covid-vaccines-1.6061099">Canadian scientist and entrepreneur Pieter Cullis</a>, a professor who reduced his tenured appointment to half-time decades ago to take on a leadership role in his co-founded ventures and innovation initiatives. </p>
<p>Thanks to Cullis, <a href="https://doi.org/10.1038/s41578-021-00379-9">the potential of lipid nanoparticles was unlocked and commercialized over several years</a> with partners and founders from both Moderna and Pfizer-BioNTech. </p>
<p>One of his ventures, <a href="https://acuitastx.com/company/">Acuitas</a>, manufactures the lipid nanoparticle technology used in the Pfizer BioNTech vaccine. Without these earlier commercialization efforts, the novel COVID-19 vaccine would not have been developed. Similarly, the first FDA-produced treatment for COVID-19 <a href="https://www.theglobeandmail.com/business/rob-magazine/article-the-innovator-carl-hansen-abcellera-biologics/">was developed in the lab of then University of British Columbia professor</a> and <a href="https://www.abcellera.com/technology">AbCellera</a> CEO Carl Hansen. </p>
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<img alt="Close up shot of a woman in a hijab holding a vaccine vial" src="https://images.theconversation.com/files/470372/original/file-20220622-3417-d955d.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/470372/original/file-20220622-3417-d955d.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/470372/original/file-20220622-3417-d955d.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/470372/original/file-20220622-3417-d955d.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/470372/original/file-20220622-3417-d955d.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/470372/original/file-20220622-3417-d955d.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/470372/original/file-20220622-3417-d955d.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">A volunteer holds a vial of the Pfizer-BioNTech COVID-19 vaccine.</span>
<span class="attribution"><span class="source">(AP Photo/Maya Alleruzzo)</span></span>
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<p>Hansen is a key example of a <a href="https://doi.org/10.1038/s41565-022-01103-6">university scholar who demonstrated entrepreneurial capabilities</a> while still in the research lab, as well as later within the new science-based venture. Without Hansen and his lab researchers’ entrepreneurship, much social and economic benefit would have been lost.</p>
<p>Given that we heavily rely on entrepreneurial scientists to initiate breakthrough invention, and that <a href="https://www.sfu.ca/research/scholarly-impacts/support-scientist-entrepreneurs-crucial-rapid-crisis-response">science-based spinoffs have been a crucial component of global responses to crises</a>, it is surprising <a href="https://techtransfercentral.com/marketplace/innovosource/mind-the-gap-report/">how little is done to support the development</a> of entrepreneurial capabilities in scientists or their science-based ventures. </p>
<h2>The role of university spinoffs</h2>
<p>During the global COVID-19 pandemic, the <a href="https://doi.org/10.1038/s41565-022-01103-6">rapid development and commercialization of highly efficacious vaccines and treatments</a> was unprecedented, and university spinoff ventures played a critical role in their success. </p>
<p>Companies founded by professors or spun out of university research labs include <a href="https://www.gene.com/about-us">Genentech</a>, <a href="https://en.wikipedia.org/wiki/Genzyme">Genzyme</a>, <a href="https://www.biontech.com/int/en/home/about/who-we-are/history.html">BioNTech</a> and <a href="https://en.wikipedia.org/wiki/Google#Early_years">Google</a>. These companies impact their regions and countries by providing high-skilled and high-paying jobs. They export products and services globally. Even when small, such ventures also serve as a bridge between university research labs and established industry.</p>
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<img alt="A building that has a logo on the front that says 'MDA'" src="https://images.theconversation.com/files/470374/original/file-20220622-17-n6zzcc.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/470374/original/file-20220622-17-n6zzcc.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=423&fit=crop&dpr=1 600w, https://images.theconversation.com/files/470374/original/file-20220622-17-n6zzcc.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=423&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/470374/original/file-20220622-17-n6zzcc.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=423&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/470374/original/file-20220622-17-n6zzcc.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=531&fit=crop&dpr=1 754w, https://images.theconversation.com/files/470374/original/file-20220622-17-n6zzcc.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=531&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/470374/original/file-20220622-17-n6zzcc.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=531&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">MacDonald-Dettwiler is one of many university spinoff companies in Canada that provide high-quality and high-paying jobs and contribute to the regional and national economy.</span>
<span class="attribution"><span class="source">THE CANADIAN PRESS/Richard Lam</span></span>
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<p>In Canada, university spinoff companies include <a href="https://mda.space/en/fifty-years">MacDonald-Dettwiler</a>, <a href="https://www.stemcell.com/about-us">STEMCELL Technologies</a>, <a href="https://carbonengineering.com/our-story/">Carbon Engineering</a> and the previously mentioned AbCellera and Acuitas. These companies also provide high-quality and high-paying jobs, help solve pressing global scientific challenges — like the pandemic — and contribute to the regional and national economy.</p>
<p>The <a href="https://www.cdc.gov/coronavirus/2019-ncov/vaccines/different-vaccines/mrna.html">most novel, highly efficacious and rapidly developed vaccines</a> — both incorporating mRNA and delivered by lipid nanoparticles — were driven by BioNTech, Moderna and Acuitis, working in partnership with the large pharmaceutical firm <a href="https://www.pfizer.ca/">Pfizer</a>. </p>
<p>Critically, <a href="https://www.theglobeandmail.com/canada/article-mrna-technology-vaccines/">no mRNA product had ever been developed and approved</a> anywhere in the world <a href="https://publichealth.jhu.edu/2021/the-long-history-of-mrna-vaccines">before the COVID-19 vaccine was developed</a>. This kind of breakthrough invention <a href="https://doi.org/10.1038/nmat4625">rarely originates in large incumbent firms, but rather in science-based university spinoff ventures</a>. </p>
<h2>Innovation gaps</h2>
<p>The current Canadian innovation ecosystem does a good job supporting innovations that can reach market success in three to five years, like software. But it is not conducive for slower-developing innovations like vaccine development or biomedical treatments. Canada needs to support the slower, more complex ones because having a development pipeline enables us to <a href="https://www.mckinsey.com/business-functions/strategy-and-corporate-finance/our-insights/innovation-in-a-crisis-why-it-is-more-critical-than-ever">rapidly respond to global crises and emerging needs</a>. </p>
<p>Currently, the biggest gap in science innovation support <a href="https://techtransfercentral.com/marketplace/innovosource/mind-the-gap-report/">occurs when the researcher is still in the lab</a> developing their invention. Scientist researchers are being asked to swim upstream for too long, instead of being given the support they need. Thus too many potentially impactful ventures are never founded, and too many breakthrough inventions remain within university walls rather than out in the world. </p>
<p>Founding and growing an impactful science-based company takes persistence, determination, skill — and some luck — and more scientists will embark on the innovation journey if they have a better chance of a positive outcome. </p>
<h2>A new innovation strategy</h2>
<p>The key to better supporting science innovation is funding and <a href="https://www.sciencedirect.com/science/article/pii/S0166497218307302">shaping it at its earliest stages</a>, while innovative ventures are still housed within universities — and even before the ventures are founded. </p>
<p>Known as a <a href="https://researchmoneyinc.com/articles/canadas-university-science-innovation-ecosystem-needs-a-build-for-scale-strategy/">build-for-scale strategy</a>, this approach would involve more flexible funding, <a href="https://www.mitacs.ca/en/invention-to-innovation">skills training</a>, stipends for post-doctoral fellows, intellectual property protection, incubation and acceleration services, enhanced access to prototyping, scale-up, and living lab facilities and government investment.</p>
<figure class="align-center ">
<img alt="A man in a suit standing behind a podium" src="https://images.theconversation.com/files/470373/original/file-20220622-17-6u37es.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/470373/original/file-20220622-17-6u37es.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/470373/original/file-20220622-17-6u37es.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/470373/original/file-20220622-17-6u37es.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/470373/original/file-20220622-17-6u37es.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/470373/original/file-20220622-17-6u37es.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/470373/original/file-20220622-17-6u37es.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">Minister of Innovation, Science and Industry, Francois-Philippe Champagne, participates in a press conference. The Canadian government announced in April that it will create a funding agency focused on innovation in science and technology.</span>
<span class="attribution"><span class="source">THE CANADIAN PRESS/Justin Tang</span></span>
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<p>If we <a href="https://beedie.sfu.ca/ideas/2022/05/from-spinal-cord-research-to-circular-plastics-mitacs-i2i-skills-training-finale-celebrates-scientist-innovators/">train scientists to have an entrepreneurial mindset while still in the research lab</a>, their innovation decisions will give subsequent spinoff ventures a far better chance of success. These nascent science-based ventures can then be scaled by existing university accelerators, by a <a href="https://www.iincanada.ca/">continuum of science entrepreneurship programming</a> and by <a href="https://creativedestructionlab.com/">investor-focused mentoring and venture building programs</a>.</p>
<p>If Canada <a href="https://ised-isde.canada.ca/site/innovation-better-canada/en">truly wants establish itself as a leading country in innovation</a>, it will have to purposefully support scientist-entrepreneurs as they seek to translate their research into impactful innovation.</p>
<p>Canada’s <a href="https://doi.org/10.1038/d41586-022-01190-4">newly announced innovation agency</a> could play an important role in enabling universities and scientist-entrepreneurs to be more successful in bridging the “valley of death” with breakthrough science innovation. </p>
<p>Investing in <a href="https://researchmoneyinc.com/articles/canadas-university-science-innovation-ecosystem-needs-a-build-for-scale-strategy/">build-for-scale</a> supports will strengthen the Canadian economy by creating good jobs and knowledge-intensive export companies, and benefit our health, the environment and society as a whole. Such “<a href="https://link.springer.com/article/10.1007/s10961-018-09714-9">high quality</a>” university spinoff ventures will also be key to responding to — or helping prevent — future global crises.</p><img src="https://counter.theconversation.com/content/182575/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Elicia Maine 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>The key to supporting science innovation is funding and shaping it at its earliest stages, while innovative ventures are still housed within universities — and even before the ventures are founded.Elicia Maine, Van Dusen Professor of Innovation and Entrepreneurship , Simon Fraser UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1826242022-05-10T18:25:19Z2022-05-10T18:25:19ZPig-human transplants may be a misguided attempt to address the organ shortage<figure><img src="https://images.theconversation.com/files/461887/original/file-20220509-20-agjzud.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C6000%2C4500&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Cross-species transplants require us to examine the relationships between humans and animals.</span> <span class="attribution"><span class="source">(Shutterstock)</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/pig-human-transplants-may-be-a-misguided-attempt-to-address-the-organ-shortage" width="100%" height="400"></iframe>
<p>At the end of 2021, 57-year old David Bennett Sr. was bedridden and on life-support with irreversible heart failure. He was not eligible for a human heart transplant or an implanted mechanical heart pump because of his underlying health condition and, allegedly, “<a href="https://www.technologyreview.com/2022/05/04/1051725/xenotransplant-patient-died-received-heart-infected-with-pig-virus/">a history of disregarding medical advice</a>.”</p>
<p>Certain death was on the horizon and this fatal prognosis made Bennett a candidate for a highly experimental and never-before-attempted surgical procedure involving the transplantation of a heart from a genetically modified pig.</p>
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Read more:
<a href="https://theconversation.com/pig-heart-transplant-was-david-bennett-the-right-person-to-receive-groundbreaking-surgery-174991">Pig heart transplant: was David Bennett the right person to receive groundbreaking surgery?</a>
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<p>The pig-to-human cardiac transplant — or xenotransplant — was <a href="https://www.technologyreview.com/2022/01/11/1043374/gene-edited-pigs-heart-transplant/">authorized by the U.S. Food and Drug Administration on compassionate grounds on New Year’s Eve 2021</a> and the surgery was performed on Jan. 7, 2022.</p>
<p>Initial reports following the experimental surgery suggested that <a href="https://doi.org/10.1038/d41586-022-00111-9">the genetically modified, human-compatible pig heart was functioning well and infection was not a problem</a>. </p>
<p>Bennett died on March 8 — at the time, “no obvious cause” of death was identified. Now, it has been reported that the pig heart was <a href="https://www.newscientist.com/article/2319108-man-who-received-pig-heart-transplant-has-died-after-pig-virus-found/">infected with a virus called porcine cytomegalovirus and that this virus may have contributed to Bennett’s death</a>. </p>
<p>Though the cause of death remains unclear, infection has been implicated in previous xenotransplantation failures involving baboons as the recipients.</p>
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<iframe width="440" height="260" src="https://www.youtube.com/embed/42bwa85g1DM?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">The BBC reports on the initial pig-to-human heart transplant surgery.</span></figcaption>
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<h2>More demand than supply</h2>
<p>There is an ongoing chronic <a href="https://hillnotes.ca/2021/04/16/organ-donation-in-canada-2/">shortage of suitable human organs for life-saving transplantation</a>. Indeed, many <a href="https://www.cihi.ca/en/organ-transplants-in-canada-2020-donations-and-need-infographic">Canadian transplant candidates die waiting for an organ donation</a>.</p>
<p>Attempts to increase the limited supply of human organs have included changes to consent rules: <a href="https://doi.org/10.1016/S2468-1253(17)30037-7">moving to an opt-out system</a>, <a href="https://doi.org/10.1016/S0140-6736(18)31870-1">introducing directed living donation and deceased donor-initiated chains</a> and, in some countries, <a href="https://doi.org/10.1097/MOT.0000000000000617">offering financial compensation</a>. </p>
<p>Still, patients die on transplant waiting lists. For this reason, there is ever increasing interest in xenotransplantation — an ethically controversial practice. </p>
<h2>Nonhuman primates and pigs</h2>
<p>In 1984, <a href="https://time.com/4086900/baby-fae-history/">the heart of a young baboon was transplanted into Baby Fae</a>, an infant born with a fatal heart defect called <a href="https://www.mayoclinic.org/diseases-conditions/hypoplastic-left-heart-syndrome/symptoms-causes/syc-20350599">hypoplastic left heart syndrome</a>. Baby Fae lived for three weeks, but eventually died of heart failure caused by rejection of the transplanted baboon heart.</p>
<p>Prior to this, there had been three other experimental nonhuman heart transplants, <a href="https://dx.doi.org/10.1080/08998280.2012.11928783">the earliest in 1964 using a chimpanzee heart</a>.</p>
<p>More recent efforts at xenotransplantation have involved the <a href="https://www.uab.edu/news/campus/item/12566-uab-announces-first-clinical-grade-transplant-of-gene-edited-pig-kidneys-into-brain-dead-human">transplantation of pig kidneys into brain-dead humans</a>. The most dramatic recent example, however, remains Bennett’s first-in-human cardiac xenotransplant using a genetically modified pig heart.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/462150/original/file-20220510-17-ol00fx.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="a baboon behind a cage" src="https://images.theconversation.com/files/462150/original/file-20220510-17-ol00fx.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/462150/original/file-20220510-17-ol00fx.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/462150/original/file-20220510-17-ol00fx.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/462150/original/file-20220510-17-ol00fx.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/462150/original/file-20220510-17-ol00fx.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/462150/original/file-20220510-17-ol00fx.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/462150/original/file-20220510-17-ol00fx.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">One of the earliest xenotransplants involved a baboon heart transplanted into an infant.</span>
<span class="attribution"><span class="source">(Shutterstock)</span></span>
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<p>For some, the use of pig hearts for xenotransplantation may be ethically preferable to the use of nonhuman primate hearts because pigs are already used for medicine: for example, <a href="https://www.npr.org/2021/10/20/1047560631/in-a-major-scientific-advance-a-pig-kidney-is-successfully-transplanted-into-a-h">pig heart valves, corneas and skin are used in various treatments</a>.</p>
<p>Or it could be that pigs are preferable “organ donors” because they are already used for food. When it comes to food animals — those who are consumed by humans — people can be biased against accurately seeing the subjectivity of the animal. This is referred to as the “<a href="https://dx.doi.org/10.3390/ani9121125">meat paradox</a>,” where people perceive food animals as “<a href="https://www.bbc.com/future/article/20190206-what-the-meat-paradox-reveals-about-moral-decision-making">objects and thereby avoid the discomfort caused by knowing about the suffering behind consumer goods</a>.”</p>
<p>A third reason to prefer killing pigs for human benefit instead of killing nonhuman primates is that pigs are biologically less similar to humans.</p>
<h2>Prioritizing humans</h2>
<p>Moral worth — <a href="https://impactethics.ca/2014/09/05/which-lives-are-you-pro/">the value assigned to others in ways that affect how we treat them</a> — is not species specific. Rather, it is associated with specific capacities such as the ability to think, make choices, experience pain, communicate and have social relationships.</p>
<p>Because a human zygote lacks such capacities, not many believe that they have the same moral worth as a human two-year old, and there is nothing obviously irrational about this belief. Though a zygote may have the potential to reach a comparable level of development as a two-year old, they are not yet comparable. Their shared human identity is beside the point. </p>
<p>On occasion, humans may choose to prioritize the interests of their companion animals without doing something obviously wrong. For example, it is not irrational to spend money on the care of pets, even if that money could have gone towards helping fellow humans. This choice may reflect a shared social relationship and the emotional bonds that come with it. It may also reflect a sense of duty toward nonhuman animals that are dependent on the care provided by humans. </p>
<p>Having said this, clearly, there are times when it is appropriate to prioritize the interests of humans over other animals; it is just that <a href="https://aeon.co/essays/human-exceptionalism-is-a-danger-to-all-human-and-nonhuman">this perspective shouldn’t be the default position</a>. In any case, it is not clear, nor is it easy to determine, that Bennett’s extraordinary xenotransplant falls into this category.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/462152/original/file-20220510-16-xxiv1e.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="pigs standing at a trough in a shed" src="https://images.theconversation.com/files/462152/original/file-20220510-16-xxiv1e.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/462152/original/file-20220510-16-xxiv1e.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/462152/original/file-20220510-16-xxiv1e.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/462152/original/file-20220510-16-xxiv1e.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/462152/original/file-20220510-16-xxiv1e.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/462152/original/file-20220510-16-xxiv1e.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/462152/original/file-20220510-16-xxiv1e.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">The killing and consumption of pigs is normalized as they are produced for food.</span>
<span class="attribution"><span class="source">(Shutterstock)</span></span>
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<h2>Animal welfare</h2>
<p>In Canada, support for animal-based research is anchored in a commitment to <a href="https://www.ccac.ca/Documents/2013_National_Survey.pdf">prevent — or at the very least reduce — unnecessary suffering</a>. The problem with this stance is that current animal welfare considerations do not typically support strong constraints on the scientific use of animals. </p>
<p>Notably, there are pressures to limit, but <a href="https://ccac.ca/en/facts-and-legislation/animal-data/annual-animal-data-reports.html">not to eliminate</a>, the use of animals in research likely to have severe welfare impacts. Also, common animal welfare considerations do not prohibit killing the animals, they just constrain how they are killed. </p>
<p>Part of the problem here is that there are <a href="https://doi.org/10.1017/S0963180119000732">no substantive ethical principles governing animal use in science</a>. The three Rs, which are pervasive in regulated animal use in science, emphasize <em>replacing</em> sentient animals (animals capable of experiencing pain and pleasure) where possible, <em>reducing</em> the number of sentient animals used in studies to a “bare minimum” and <em>refining</em> their experiences of use to minimize suffering. </p>
<p>As such, the three Rs seem to assume something like a principled commitment to non-maleficence — <a href="https://doi.org/10.1093/ilar/ilaa014">avoiding unnecessary harm</a>. However, the continued dependency on harmful animal-based research that almost always ends with the killing of the animals belies this claim, given the known <a href="https://www.cbc.ca/radio/quirks/may-7-endangered-tiny-porpoise-mars-quakes-thermal-batteries-and-more-1.6443011/meet-the-canadian-researcher-determined-to-take-the-animals-out-of-lab-testing-1.6443917">significant problems of extrapolation of research findings</a>.</p>
<p>Given the ethical challenges with animal-based research in general and more specifically the ethical challenges with animal-to-human xenotransplantation, there is good reason to look for <a href="https://www.thehastingscenter.org/xenotransplantation-three-areas-of-concern/">other strategies to increase the supply of organs</a> for transplantation.</p><img src="https://counter.theconversation.com/content/182624/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Andrew Fenton is a member of the (Canadian) Society for Humane Science and is currently serving on a subcommittee for the Canadian Council on Animal Care (revising their core ethics document) and a panel on nonhuman primate research for the National Anti-Vivisection Society. </span></em></p><p class="fine-print"><em><span>Françoise Baylis 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>The heart used in the first pig-human transplant was infected with a pig virus. This reveals that using other species as organ donors may not provide a solution for organ shortages.Françoise Baylis, University Research Professor, Philosophy, Dalhousie UniversityAndrew Fenton, Associate Professor, Philosophy, Dalhousie UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1721452021-12-29T21:26:56Z2021-12-29T21:26:56Z5 things research from twins taught us about health, behaviour and what makes us unique<figure><img src="https://images.theconversation.com/files/436555/original/file-20211209-140109-1g6swwj.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://unsplash.com/photos/M-adWhDQd7Y">Keisha Montfleury/Unsplash</a></span></figcaption></figure><p>Researchers often compare the differences between identical and fraternal twins to better understand health and behaviour. </p>
<p>The first major insight is that genes and environments almost always combine to influence our life trajectory. Sometimes the largest factor is genetics (think genetic disorders). Sometimes it’s environment (think infections). Mostly, it’s somewhere in between. </p>
<p>Such studies have accelerated the search for genes and environmental agents that cause or trigger diseases. This has helped us understand, treat and even prevent diseases. As twin research has <a href="https://www.twins.org.au/research/tools-and-resources/125-conversation-in-twin-research/377-twin-research-designs-and-analytic-approaches">matured</a>, it has progressed to addressing important questions about when and how diseases originate. </p>
<p>So what has research from twins taught us about specific diseases and the human body?</p>
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Read more:
<a href="https://theconversation.com/seeing-double-why-twins-are-so-important-for-health-and-medical-research-5273">Seeing double: why twins are so important for health and medical research</a>
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<h2>1. Smoking increases the risk of bone fracture</h2>
<p>Most studies linking environment and disease are complicated by genetic factors. To get around this, we can work with twins who differ in environmental factors. </p>
<p>One such <a href="https://www.nejm.org/doi/full/10.1056/nejm199402103300603">Australian study from 1994</a> compared 20 pairs of female twins in which only one of each pair was a long-term, heavy smoker. </p>
<p>The researchers found smoking one pack of cigarettes a day for 20 years resulted in sufficient loss in bone density to cause osteoporosis. This doubled the risk of having a bone fracture. </p>
<p>This provided compelling evidence that smoking causes osteoporosis and an increased risk of bone fractures.</p>
<h2>2. Events around the time of birth are not a major cause of epilepsy</h2>
<p>Epilepsy is a group of disorders where brain activity is abnormal and seizures are the presenting feature. Traditionally, diagnosis was not possible until after a person’s first seizure, which can occur at any stage of life, from babies to the elderly.</p>
<p><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4166361/">Twin studies</a> since the 1960s have shown a mix of genes and environment cause epilepsy. However, until the early 1990s, it was assumed that problems during the birthing process were a major cause of epilepsy.</p>
<figure class="align-center ">
<img alt="Older men stand beside each other, smiling." src="https://images.theconversation.com/files/436563/original/file-20211209-68670-15wadz1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/436563/original/file-20211209-68670-15wadz1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/436563/original/file-20211209-68670-15wadz1.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/436563/original/file-20211209-68670-15wadz1.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/436563/original/file-20211209-68670-15wadz1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/436563/original/file-20211209-68670-15wadz1.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/436563/original/file-20211209-68670-15wadz1.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">Identical twins share almost all their DNA.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/senior-twin-men-smiling-on-camera-1919843804">Shutterstock</a></span>
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<p>Obstetricians and midwives were often blamed for causing epilepsy. However, a <a href="https://pubmed.ncbi.nlm.nih.gov/8255449/">twin study</a> in 1993 did not support a link between minor problems during birth and the later development of epilepsy. </p>
<p>This information has helped doctors and their patients better understand the causes of epilepsy and not necessarily attribute blame to the birthing process.</p>
<h2>3. Identical twins are different under the skin from before birth</h2>
<p>Genetically identical twins nearly always look identical. Yet, at birth, they have already accumulated differences in the structure and function of their genes. </p>
<p>These <a href="https://press.princeton.edu/books/hardcover/9780691173887/innate">differences</a> are caused by a mix of chance events and individual experiences in the womb.</p>
<p>The location a fertilised egg implants in the womb is random, but some locations are more favourable to growth. For the subset of identical twins who split before they reach the womb, different locations could create different environments in which a baby develops. </p>
<figure class="align-center ">
<img alt="Twin newborn babies sleep, their arms raised." src="https://images.theconversation.com/files/436558/original/file-20211209-142574-qu4qd5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/436558/original/file-20211209-142574-qu4qd5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=305&fit=crop&dpr=1 600w, https://images.theconversation.com/files/436558/original/file-20211209-142574-qu4qd5.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=305&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/436558/original/file-20211209-142574-qu4qd5.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=305&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/436558/original/file-20211209-142574-qu4qd5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=384&fit=crop&dpr=1 754w, https://images.theconversation.com/files/436558/original/file-20211209-142574-qu4qd5.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=384&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/436558/original/file-20211209-142574-qu4qd5.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=384&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Identical, but still different.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/sleeping-newborn-identical-boy-twins-267663011">Shutterstock</a></span>
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<p>As a result of this or other chance events, around one in six twins differ more than 20% in weight at birth, which may be associated with an increased <a href="https://obgyn.onlinelibrary.wiley.com/doi/10.1111/aogs.13613">risk</a> of illness at birth, especially for the smaller twin. </p>
<p>Such individual experiences could also help explain Brazilian twin pairs in which only one child was born with <a href="https://www.mdpi.com/2414-6366/5/4/188">Zika virus</a> infection.</p>
<h2>4. Leukaemia originates before birth</h2>
<p>Changes in the genetic sequence of blood cells can predispose people to develop leukaemia (cancer of the blood). </p>
<p>Such changes are unique to each person but <em>when</em> these changes happened to people used to be a mystery. That was until identical twin children were <a href="https://www.sciencedirect.com/science/article/pii/S0006497120768072?via%3Dihub">discovered with leukaemias</a> originating from the same cell. </p>
<p>Lymphocytes (white blood cells) of the immune system shuffle their immune genes at random, making each person genetically unique, even identical twins. </p>
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<strong>
Read more:
<a href="https://theconversation.com/same-same-but-different-when-identical-twins-are-non-identical-112684">Same same but different: when identical twins are non-identical</a>
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<p>The researchers <a href="https://www.sciencedirect.com/science/article/pii/S0006497120768072?via%3Dihub">concluded</a> the leukaemia started in one twin in the womb and spread to the other twin through blood vessels in a shared placenta. </p>
<p>But while the first step towards leukaemia happened before birth, the cancer progression differed among the twins, resulting in leukaemia being diagnosed at different ages.</p>
<p>This provided the first evidence that some leukaemias can lay dormant for years and enabled future research that would pinpoint the events along this process. </p>
<h2>5. Many twins don’t know if they’re identical or fraternal</h2>
<p>Identical twins start as one fertilised egg that splits after a few days. They share almost 100% of their DNA and are almost always the same sex. </p>
<p>Fraternal twins result from two eggs fertilised around the same time. They’re as genetically different as any pair of siblings and can have the same, or different sex. </p>
<figure class="align-center ">
<img alt="Twin women hug outside in the sunshine." src="https://images.theconversation.com/files/437106/original/file-20211213-25-1fbing6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/437106/original/file-20211213-25-1fbing6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/437106/original/file-20211213-25-1fbing6.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/437106/original/file-20211213-25-1fbing6.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/437106/original/file-20211213-25-1fbing6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/437106/original/file-20211213-25-1fbing6.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/437106/original/file-20211213-25-1fbing6.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">Fraternal twins are as genetically different as a pair of siblings.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/portrait-identical-ginger-twin-sisters-smiling-723502963">Shutterstock</a></span>
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<p>In 2012, my colleagues and I at <a href="https://www.twins.org.au/">Twins Research Australia</a> conducted a study at a national twins festival on pairs who had any uncertainty about their genetic identity. We used “genetic fingerprinting” on DNA from cheek swabs provided by same-sex twins of all ages. This test is the definitive way of discovering whether twins are identical or fraternal. </p>
<p>We compared this with perceptions of the twins themselves before they took the test. </p>
<p>We <a href="https://www.twins.org.au/research/tools-and-resources/125-conversation-in-twin-research/374-the-importance-of-zygosity-knowledge-for-twins-and-science">found</a> almost one-third of the twins we tested had been either incorrect or unsure about their genetic identity. Some had even been misinformed by medical professionals. </p>
<p>The universal sentiment was twins and their families felt better knowing the truth. Our data enabled us to develop better educational <a href="https://www.twins.org.au/twins-and-families/expecting-twins">resources</a> for twins and their advocates to know more about themselves. </p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/not-all-twins-are-identical-and-thats-been-an-evolutionary-puzzle-until-now-138209">Not all twins are identical and that's been an evolutionary puzzle, until now</a>
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<img src="https://counter.theconversation.com/content/172145/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jeffrey Craig is Deputy Director of Twins Research Australia and President of the International Society for Twin Studies. He receives funding from the IMPACT Institute, Deakin University, the National Health and Medical Research Council, Australia, and the Waterloo Foundation, UK. He is affiliated with the Gene(e)quality Network. </span></em></p>Genes and environments almost always combine to influence our risk of diseases. Research in twins has helped us understand how.Jeffrey Craig, Professor in Medical Sciences, Deakin 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>
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<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>
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<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>
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<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>
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<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/1712172021-11-17T05:15:01Z2021-11-17T05:15:01ZCOVID vaccines don’t violate the Nuremberg Code. Here’s how to convince the doubters<p>People opposing vaccine mandates, or COVID vaccines more broadly, <a href="https://www.facebook.com/groups/138599678102481/permalink/184874376808344">have claimed</a> the vaccines violate the Nuremberg Code.</p>
<p>They say COVID vaccines are <a href="https://twitter.com/VigilantFox/status/1458925515205660678">experimental and people have been coerced</a> into vaccination. They say this breaches the ethical code drawn up after the second world war to guide medical research and human clinical trials.</p>
<p>But this argument is flawed. Here’s why the Nuremberg Code doesn’t apply, and how to correct this misunderstanding. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/no-thats-not-the-law-the-danger-of-using-pseudolegal-arguments-against-covid-19-rules-170630">No, that's not the law: the danger of using pseudolegal arguments against COVID-19 rules</a>
</strong>
</em>
</p>
<hr>
<h2>What is the Nuremberg Code?</h2>
<p>The Nuremberg Code was a direct response to atrocities Nazi doctors performed in concentration camps during WWII. They perpetrated this so-called medical experimentation on people with no capacity to consent, and this frequently led to lifelong disability, or death. </p>
<p>The doctors who performed these experiments <a href="https://www.nejm.org/doi/full/10.1056/nejm199711133372006">were tried</a> in Nuremberg in 1947.</p>
<p>The doctors’ defence argued their experiments were not significantly different to other research practices. So two American doctors working for the prosecution produced a document that aimed to draw together what made for ethical research.</p>
<p><div data-react-class="Tweet" data-react-props="{"tweetId":"1435603579646132226"}"></div></p>
<p>This document identified <a href="https://www.nejm.org/doi/full/10.1056/nejm199711133372006">three ethical, legal, and scientific requirements</a> for conducting human experiments, which were later expanded to ten. This ten-point document became known <a href="https://jamanetwork.com/journals/jama/fullarticle/2649074">as the Nuremburg Code</a>.</p>
<p>It details the process of seeking legally valid voluntary consent, covers the need to establish the humanitarian nature and purpose of the experiment, as well as ensuring the scientific integrity and obligations of the investigator to the subjects’ welfare. </p>
<p>However, the Nuremberg Code is no longer used to guide research ethics. The World Medical Association’s <a href="https://www.wma.net/what-we-do/medical-ethics/declaration-of-helsinki/">Declaration of Helsinki</a> replaced it in 1964. And there’s been more ethical guidance since.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/two-steps-forward-one-step-back-how-world-war-ii-changed-how-we-do-human-research-39929">Two steps forward, one step back: how World War II changed how we do human research</a>
</strong>
</em>
</p>
<hr>
<h2>No, COVID vaccines are not experimental</h2>
<p>Online commentary <a href="https://twitter.com/AbolishtheFeds/status/1428751073448181770">says</a> COVID vaccines are “experimental”.</p>
<p>But COVID vaccines have been thoroughly tested, and they have been <a href="https://theconversation.com/how-well-do-covid-vaccines-work-in-the-real-world-162926">shown to work</a>. Their side-effects have been extensively examined. They have been approved for use around the world and have been credited for <a href="https://theconversation.com/how-many-lives-have-coronavirus-vaccines-saved-we-used-state-data-on-deaths-and-vaccination-rates-to-find-out-169513">saving many lives</a>.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/how-well-do-covid-vaccines-work-in-the-real-world-162926">How well do COVID vaccines work in the real world?</a>
</strong>
</em>
</p>
<hr>
<p>So COVID vaccines are not “experimental”. Now COVID vaccines are part of standard public health response, it is not appropriate to refer to codes or documents developed to guide clinical trials and other research studies. </p>
<h2>How do you convince someone?</h2>
<p>If you come across someone claiming COVID vaccines are experimental, you can try the “<a href="https://www.independent.co.uk/news/health/coronavirus-vaccines-misinformation-scientists-truth-sandwich-b1783401.html">truth sandwich</a>” to try to <a href="https://medium.com/wehearthealthliteracy/the-truth-sandwich-a-better-way-to-mythbust-8021d2cf8730">myth bust</a>.</p>
<p><div data-react-class="Tweet" data-react-props="{"tweetId":"1330728487938904064"}"></div></p>
<p>If you imagine two pieces of bread, then the filling in the middle, you are on your way to using the truth sandwich.</p>
<p>First, we take a piece of bread, where we state the truth:</p>
<blockquote>
<p>COVID vaccines have been tested in pre-clinical and clinical trials, and their efficacy and effectiveness has been proven, and their side effects profiles have been extensively examined. </p>
</blockquote>
<p>Then we come to the filling in the middle, where we talk about a false claim and how it relates to the truth:</p>
<blockquote>
<p>You may have heard someone suggest the COVID-19 vaccine program infringes people’s rights under the Nuremberg Code. But the claim that COVID-19 vaccines are experimental is simply not true. Regulatory authorities have approved these vaccines nationally and internationally. Safety monitoring is ongoing, but these processes are routine and commonly used for other vaccines or drugs. Check out <a href="https://ausvaxsafety.org.au/safety-data/covid-19-vaccines">AusVaxSafety</a>.</p>
</blockquote>
<p>Our final piece of bread comes next, repeating the truth:</p>
<blockquote>
<p>The Nuremberg Code focuses on clinical research on humans. Therefore, it is no longer relevant once a vaccine moves beyond the clinical trial phase and has been authorised or approved for use globally. </p>
</blockquote>
<h2>The issue of informed consent</h2>
<p>Online commentary usually cites the <a href="https://www.ushmm.org/information/exhibitions/online-exhibitions/special-focus/doctors-trial/nuremberg-code">first clause</a> of the Nuremberg Code about the need for informed consent in human experiments:</p>
<blockquote>
<p>The voluntary consent of the human subject is absolutely essential.</p>
</blockquote>
<p>This argument is used as evidence there’s something unethical about using COVID vaccines or introducing mandates.</p>
<p>Indeed, voluntary informed consent is an ethical bedrock for clinical research. Any form of compulsion is unacceptable because clinical research has inherent risks and can’t be quantified precisely. Research also may not have any direct benefit for participants, which again requires consent. </p>
<p>To be ethical, therefore, researchers must ensure participants in clinical trials understand potential risks and benefits, and give voluntarily consent to participate.</p>
<h2>How do you convince someone?</h2>
<p>Again, we can use the “truth sandwich” to myth bust. </p>
<p>Take your first piece of bread, stating the truth (the facts): </p>
<blockquote>
<p>The Nuremberg Code relates to research, where the emphasis of informed consent is on “<a href="https://www.usatoday.com/story/news/factcheck/2021/08/10/fact-check-covid-19-vaccine-mandates-nuremberg-code-not-related/5530548001/">preventing research participants from being used as a means to an end</a>”. The need for informed consent is still required for receiving a COVID-19 vaccine (or any vaccine) but the need does not stem from the Nuremberg Code. </p>
</blockquote>
<p>Here’s the filling (the false claim and how it relates to the truth):</p>
<blockquote>
<p>The introduction of a vaccine mandate is not medical research but rather a public health intervention. In every setting where COVID vaccines are mandated, no-one is being forced to be vaccinated against their will or consent. Informed consent is still sought before vaccination, and people retain the right to choose whether to be vaccinated. </p>
<p>However, in these settings, the public health goal of COVID-19 vaccination is seen as outweighing the rights of the individual to remain un-vaccinated. Other people in these settings have a right to health and security. Therefore there are outcomes for those who don’t comply. Exemptions are provided for those who cannot receive the vaccine for medical reasons. </p>
</blockquote>
<p>If you want to expand further:</p>
<blockquote>
<p>Mandates of this nature have previously been used in occupational settings to reduce the risk from vaccine preventable diseases for the employee and for the people they come into contact with, whether they be hospital patients or aged care residents. Beyond these settings, we have accepted vaccines as requirements of travel (such as yellow fever) both to protect ourselves and to reduce any risk of bringing this infection back to Australia. </p>
</blockquote>
<p>Final piece of bread (repeating the truth):</p>
<blockquote>
<p>There has been misinformation about linking COVID-19 vaccination, and/or the requirements within some occupations to the Nuremberg Code. The code relates to research and claims that mandates violate it are not accurate. </p>
</blockquote>
<h2>Why is this important?</h2>
<p>This type of misinformation often thrives in situations <a href="https://fullfact.org/health/how-to-fact-check-coronavirus/">where feelings are manipulated</a>. And emotional posts on social media referring to Nazi doctors and Nuremberg are more likely to be shared.</p>
<p>We can keep fact checking. But it’s also time for every one of us to get out there with our truth sandwiches.</p><img src="https://counter.theconversation.com/content/171217/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Holly Seale is an investigator on research studies funded by NHMRC and has previously received funding for investigator driven research from NSW Ministry of Health, as well as from Sanofi Pasteur and Seqirus. She is the Deputy Chair of the Collaboration on Social Science and Immunisation.</span></em></p><p class="fine-print"><em><span>Ben Harris-Roxas is an investigator on projects funded by the Cancer Institute NSW, the National Health and Medical Research Council (NHMRC), the Sydney Partnership for Health Education Research & Enterprise (SPHERE), and NSW Health. In the past he has received funding from the Australian Research Council, the World Health Organization, the Australian Government Department of Health, the Public Health Agency of Canada, the Heart Foundation, NPS MedicineWise, the Sax Institute, and the City of Gold Coast.</span></em></p><p class="fine-print"><em><span>Bridget Haire has received funding from National Health and Medical Research Council (NHMRC)</span></em></p>Emotive claims, like COVID vaccination being unethical or coercive, are more likely to be shared on social media. But we can fight back.Holly Seale, Associate professor, UNSW SydneyBen Harris-Roxas, Senior Lecturer, UNSW SydneyBridget Haire, Postdoctoral Research Fellow, Kirby Institute, UNSW SydneyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1675452021-10-04T06:19:32Z2021-10-04T06:19:32ZWhy are males still the default subjects in medical research?<figure><img src="https://images.theconversation.com/files/424370/original/file-20211004-25-1asa1sy.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/group-serious-diverse-people-casual-clothes-1879478557">Shutterstock</a></span></figcaption></figure><p>Women and girls account for 50% of the population, yet <a href="https://www.nature.com/articles/550S18a">most health and physiology research</a> is conducted in males. </p>
<p>This is especially true for fundamental research (which builds knowledge but doesn’t have an application yet) and pre-clinical (animal) research. These types of research often only focus on male humans, animals and even cells.</p>
<p>In our discipline of exercise physiology, <a href="https://journals.humankinetics.com/view/journals/wspaj/29/2/article-p146.xml">6% of research studies</a> include female-only participant groups. </p>
<p>So why do so many scientists seem oblivious to the existence of half of the world’s population?</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/equal-but-not-the-same-a-male-bias-reigns-in-medical-research-28408">Equal but not the same: a male bias reigns in medical research</a>
</strong>
</em>
</p>
<hr>
<h2>Females, women, trans men and non-binary folks</h2>
<p>Firstly, it’s important to understand key terminology in society and research. As referred to throughout this article, “male” and “female” are categories of <a href="https://pubmed.ncbi.nlm.nih.gov/29451543/">sex</a>, defined by a set of biological attributes associated with physical and physiological characteristics. </p>
<p>In comparison, “men”, “women” and “non-binary people” are categories of <a href="https://pubmed.ncbi.nlm.nih.gov/29451543/">gender</a>: a societal construct that encompasses behaviours, power relationships, roles and identities. </p>
<p>Here we discuss research on specific sexes, but further consideration of gender-diverse groups, such as transgender people, also remains a gap in science.</p>
<h2>Why aren’t females studied?</h2>
<p>The main reasoning is that females are a more “complicated” model organism than males. </p>
<p>The physiological changes associated with the menstrual cycle add a whole lot of complexities when it comes to understanding how the body may respond to an external stimulus, such as taking a drug or performing a specific type of exercise. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/from-energy-levels-to-metabolism-understanding-your-menstrual-cycle-can-be-key-to-achieving-exercise-goals-131561">From energy levels to metabolism: understanding your menstrual cycle can be key to achieving exercise goals</a>
</strong>
</em>
</p>
<hr>
<p>Some females use contraception, and those who do use different types. This adds to the variability between them. </p>
<p>Females also undergo menopause around the age of 50, another physiological change that fundamentally impacts the way the body functions and adapts. </p>
<p>Even when research with females is performed properly, the findings may not apply to all females. This includes whether a female individual is cisgender or gender nonconforming. </p>
<p>Altogether, this makes female research more time-consuming and expensive — and research is nearly always limited by time and money. </p>
<h2>Does it really matter?</h2>
<p>Yes, because males and females are physiologically different. </p>
<p>This does not only involve visually obvious differences (the so-called primary sex characteristics, such as body shape or genitals), but also a whole range of hidden differences in hormones and <a href="https://pubmed.ncbi.nlm.nih.gov/32913072/">genetics</a>.</p>
<p>There’s also emerging evidence from our research team that sex differences impact <a href="https://www.biorxiv.org/content/10.1101/2021.03.16.435733v1">epigenetics</a>: how your behaviours and environment affect the expression of your genes. </p>
<figure class="align-center ">
<img alt="A mother walking on a paved street, helps her child who is riding a bike." src="https://images.theconversation.com/files/424372/original/file-20211004-23-w23ogh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/424372/original/file-20211004-23-w23ogh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=401&fit=crop&dpr=1 600w, https://images.theconversation.com/files/424372/original/file-20211004-23-w23ogh.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=401&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/424372/original/file-20211004-23-w23ogh.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=401&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/424372/original/file-20211004-23-w23ogh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/424372/original/file-20211004-23-w23ogh.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/424372/original/file-20211004-23-w23ogh.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 are a range of hormonal and genetic differences between males and females.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/belgrade-serbia-march-28-2020-mother-1685718061">Shutterstock</a></span>
</figcaption>
</figure>
<p>Conducting health and physiology research in males exclusively disregards these differences. So our knowledge of the human body, which is mostly inferred from what is observed in males, may not always hold true for females. </p>
<p>Some diseases, such as <a href="https://pubmed.ncbi.nlm.nih.gov/32640661/">cardiovascular</a> (heart) disease, present differently in males and females. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/women-who-have-heart-attacks-receive-poorer-care-than-men-100161">Women who have heart attacks receive poorer care than men</a>
</strong>
</em>
</p>
<hr>
<p>Males and females may also <a href="https://www.aafp.org/afp/2009/1201/p1254.html">metabolise drugs</a> in a different way, meaning they may need different quantities or formulations. These drugs can have sex-specific <a href="https://bsd.biomedcentral.com/articles/10.1186/s13293-020-00308-5">side effects</a>. </p>
<p>This may have major consequences in the way we treat diseases or the preferred drugs we use in the clinic. </p>
<p>Take COVID-19, for example. The <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7498997/">severity and death</a> rates of COVID-19 are higher in males than females. Sex differences in immunity and hormonal pathways <a href="https://journals.physiology.org/doi/full/10.1152/ajpheart.00755.2020">may explain this</a>, therefore researchers are advocating for sex-specific research to aid viral treatment.</p>
<h2>We’re finally starting to see some change</h2>
<p>No matter the cost or added complexity, research should be for everyone and apply to everyone. International medical research bodies are now starting to acknowledge this.</p>
<p>A March 2021 <a href="https://academic.oup.com/edrv/article/42/3/219/6159361">statement</a> from the Endocrine Society, the international body for doctors and researchers who study hormones and treat associated problems, recognises:</p>
<blockquote>
<p>Before mechanisms behind sex differences in physiology and disease can be elucidated, a fundamental understanding of sex differences that exist at baseline, is needed.</p>
</blockquote>
<p>The <a href="https://www.nih.gov/">National Institutes of Health</a> (NIH), the largest medical research board in the United States, <a href="https://orwh.od.nih.gov/sex-gender/nih-policy-sex-biological-variable">recently called</a> for researchers to account for “sex as a biological variable”. </p>
<p>Unless a strong case can be made to study only one sex, studying both sexes is now a <a href="https://orwh.od.nih.gov/sex-gender/nih-policy-sex-biological-variable">requirement</a> to receive NIH research funding.</p>
<p>The Australian equivalent, the <a href="https://www.nhmrc.gov.au/">National Health and Medical Research Council</a> (NHMRC), indirectly recommends the collection and analysis of sex-specific data in <a href="https://www.nhmrc.gov.au/guidelines-publications/ea20">animals</a> and <a href="https://www.nhmrc.gov.au/guidelines-publications/e72">humans</a>. </p>
<p>However the <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7027556/">inclusion</a> of both sexes is <a href="https://www.mja.com.au/journal/2019/sex-and-gender-health-research-australia-lags-behind">not yet a requirement to receive funding</a> in Australia. </p>
<h2>But researchers can start now</h2>
<p>Because sex matters, we created a <a href="https://doi.org/10.6084/m9.figshare.15506295.v1">freely available infographic</a> based on <a href="https://pubmed.ncbi.nlm.nih.gov/31190324/">our research</a> that aims at making female health and physiology research easier to design. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/424374/original/file-20211004-15-ekeglw.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/424374/original/file-20211004-15-ekeglw.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/424374/original/file-20211004-15-ekeglw.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=755&fit=crop&dpr=1 600w, https://images.theconversation.com/files/424374/original/file-20211004-15-ekeglw.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=755&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/424374/original/file-20211004-15-ekeglw.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=755&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/424374/original/file-20211004-15-ekeglw.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=948&fit=crop&dpr=1 754w, https://images.theconversation.com/files/424374/original/file-20211004-15-ekeglw.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=948&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/424374/original/file-20211004-15-ekeglw.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=948&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 Future is Female: A framework to design female physiology research.</span>
<span class="attribution"><a class="source" href="https://figshare.com/articles/poster/The_Future_is_Female_A_framework_to_design_female_physiology_research/15506295/1">Olivia Knowles & Severine Lamon</a></span>
</figcaption>
</figure>
<p>It presents as a simple flow through diagram that researchers can use before starting their project and prompts them to consider questions such as: </p>
<ul>
<li><p>is the phenomenon I am investigating influenced by female hormones? </p></li>
<li><p>should all females in my cohort use the same contraception? </p></li>
<li><p>on which day of the menstrual cycle should I test my participants for the most reliable result? </p></li>
</ul>
<p>Depending on the answers, our infographic proposes strategies (that can be practical — such as who to recruit and when — or statistical) to design research that takes into account the complexity of the female body. </p>
<p>It’s easy to follow and accessible to all. And, while initially designed for exercise physiology research, it can be applied to any type of female health and physiology research.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/medicines-gender-revolution-how-women-stopped-being-treated-as-small-men-77171">Medicine's gender revolution: how women stopped being treated as 'small men'</a>
</strong>
</em>
</p>
<hr>
<p>Based on our infographics, we designed a female-only, four-year research project to map the process of muscle ageing in females. Females <a href="https://www.abs.gov.au/ausstats/abs@.nsf/0/1cd2b1952afc5e7aca257298000f2e76">live longer than males</a> but, paradoxically, are <a href="https://bsd.biomedcentral.com/articles/10.1186/s13293-019-0257-3">more susceptible</a> to some of the consequences of ageing. Despite lots of ageing research in males, we still know very little about the female-specific characteristics at play.</p>
<p>So yes, the future is female — so is our research. And we hope to inspire health and physiology researchers all over the world to do the same.</p><img src="https://counter.theconversation.com/content/167545/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Severine Lamon receives funding from the Australian Research Council. </span></em></p><p class="fine-print"><em><span>Olivia Knowles 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>Our knowledge of the human body, which is mostly inferred from what is observed in males, may not always hold true for females.Severine Lamon, Associate professor, Nutrition and Exercise Physiology, Deakin UniversityOlivia Knowles, PhD candidate, Deakin UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1659072021-08-15T09:02:43Z2021-08-15T09:02:43ZNigerian health research needs more regular funding<figure><img src="https://images.theconversation.com/files/415687/original/file-20210811-15-sy8umz.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption"> Nigeria must increase funding for health research </span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/technician-handles-samples-from-truck-drivers-testing-for-news-photo/1212974088?adppopup=true">Brian/AFP via Getty Images</a></span></figcaption></figure><p><em>Nigeria’s <a href="https://tetfundserver.com/">Tertiary Education Trust Fund</a> has <a href="https://punchng.com/fg-approves-n8-5bn-for-medical-research-others/">approved</a> N8.5bn (US$16.83m) for medical research this year an increase of 13.33%. Of this amount, N1bn (US$1.98m) is specifically for research on COVID-19. The fund was set up in 1993 to improve federal and state tertiary education in Nigeria, partly by supporting research and publications. Its main source of income is the 2% education tax paid by registered companies. It’s managed by an 11-member board of trustees. The Conversation Africa’s Wale Fatade asked Friday Okonofua, professor of medicine and <a href="https://www.ondoevents.com/unimed-ondo-gets-new-vice-chancellor/">pioneer vice-chancellor</a> of Nigeria’s <a href="https://www.unimed.edu.ng/news.php">first</a> university of medical sciences, to comment on the latest announcement.</em></p>
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<h2>Is this a step in the right direction in funding medical research?</h2>
<p>I believe so. Nigeria is currently one of the countries with the lowest health research funding in the world. It contributes <a href="http://www.jogh.org/documents/issue202001/jogh-10-010321.htm#R2">0.22% of its GDP</a> to research. Despite the plethora of health issues in the country, and the <a href="https://data.humdata.org/dataset/who-data-for-nigeria">poor health indicators</a>, very little appropriation exists in the <a href="https://www.budgetoffice.gov.ng/index.php/resources/internal-resources/budget-documents/2021-budget">national budget</a> for addressing health research. The budget for research was N5bn ($9.9mn) in <a href="https://nairametrics.com/2021/07/29/buhari-promises-50-increase-in-education-budget-approves-n8-5-billion-for-medical-research/">2019</a> under the National Research Fund. It was raised to N7.5bn ($14.85mn) in 2020 and is still the same this year. It is to this fund that N1bn ($1.98mn) has just been added. This extra is specifically for research around COVID-19. The National Research Fund is managed by the Tertiary Education Trust Fund. I believe this intervention is not enough to address the inadequate provision for health research in the country. It is also important because global research and development pipelines for diseases that affect African countries are <a href="https://gh.bmj.com/content/4/2/e001047#T2">inadequate</a>.</p>
<h2>How is medical research funded generally in Nigeria?</h2>
<p>Medical research is not well funded in Nigeria. I have never seen any provision made for health research funding by any teaching hospital in Nigeria. Most universities provide little or no funding for health research. Existing funds for research come from donor organisations. These include the Gates Foundation, the <a href="https://www.idrc.ca/en">International Development Research Centre, Canada</a> and the World Health Organisation. The federal government got a <a href="https://www.worldbank.org/en/news/press-release/2014/04/15/world-bank-centers-excellence-science-technology-education-africa">loan</a> in 2014 from the World Bank which enabled the establishment of some centres of excellence in Nigerian universities. A few of these centres focus on health issues. Very little funding for health research comes from within the country. </p>
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Read more:
<a href="https://theconversation.com/science-and-technology-hold-the-key-to-nigeria-reaching-its-full-potential-45055">Science and technology hold the key to Nigeria reaching its full potential</a>
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<h2>What percentage of medical research funding comes from the federal government in Nigeria?</h2>
<p>It is tough to say specifically apart from figures we have on research generally. While the education trust fund has done well in funding specific health-related research in some Nigerian universities, it is not enough. Some medical researchers across the country have accessed these funds for their research. Apart from this, I am not aware of any other intervention of the federal government to address health research in Nigeria. </p>
<h2>How can we improve funding for medical research?</h2>
<p>The answer is simple. The federal government and all state governments should allocate funds for health research in their annual budgets. This should be for health research specifically and not research generally. The education trust fund should continue its present great work. But its contribution is not sufficient to handle the quantum of health challenges that need to be resolved in Nigeria, along with innovations that need to be identified to promote the health and social well-being of all Nigerians. </p>
<p>Health is a critical component of the <a href="https://www.undp.org/sustainable-development-goals?utm_source=EN&utm_medium=GSR&utm_content=US_UNDP_PaidSearch_Brand_English&utm_campaign=CENTRAL&c_src=CENTRAL&c_src2=GSR&gclid=CjwKCAjwx8iIBhBwEiwA2quaq3EcK5XfnWcUA7C6cTwmVnYs7R_gdWC6Nl4MFW00pdQGUOO9mIBKERoCBhMQAvD_BwE">Sustainable Development Goals</a>. And as COVID-19 has demonstrated, it is essential for any country’s prospective development. Research is needed to galvanise Nigeria’s health system, which ranks <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6811780/">187th out of 195</a> countries (according to the World Health Organisation).</p>
<h2>What lessons can we learn from other countries’ approach to funding medical research?</h2>
<p>Regarding the contribution of governments to research, it is evident that African countries have performed relatively poorly as compared to other countries. In total, available evidence indicates that sub-Saharan African countries contribute <a href="http://www.jogh.org/documents/issue202001/jogh-10-010321.htm#R2">0.4%</a> of their gross domestic product (GDP) to research, compared to Europe, Asia, and North America that contribute 27%, 31%, and 37%. Nigeria contributes <a href="http://www.jogh.org/documents/issue202001/jogh-10-010321.htm#R2">0.22%</a>, one of the lowest in the world. </p>
<p>Furthermore, the Nigerian government is often unable to synthesise research evidence for decision-making. This limits its ability to understand and prioritise the importance of indigenous research in health within the context of health improvement and social development. A proper integration of research frameworks within policy making in Nigeria is critically important to improve the integrated performance of the country’s healthcare system. This should include capacity building for managers and policymakers to enable them to make adequate provisions in the annual budget and development planning for research, their involvement in setting research agendas, planning for the delivery of health research, and the effective use of research results.</p>
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Read more:
<a href="https://theconversation.com/what-it-will-take-to-produce-vaccines-in-nigeria-moneys-just-the-first-step-153497">What it will take to produce vaccines in Nigeria: money's just the first step</a>
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<img src="https://counter.theconversation.com/content/165907/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Friday Okonofua 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>More funding is needed to galvanise
Nigeria’s health system as medical research is not well funded.Friday Okonofua, Professor of Obstetrics and Gynaecology, University of BeninLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1650412021-08-12T14:50:21Z2021-08-12T14:50:21ZFungus in Nigeria’s industrial waste produces a promising antibiotic compound<figure><img src="https://images.theconversation.com/files/415499/original/file-20210810-23-kumlnb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Waste products from factories like this could hold the key to more novel antibiotic discoveries.
</span> <span class="attribution"><span class="source">Stefan Heunis/AFP via Getty Images</span></span></figcaption></figure><p><a href="https://doi.org/10.1111/j.1469-185X.1948.tb00567.x">Antibiotics</a> are life-saving drugs produced primarily by microorganisms which have been found in a variety of environments.</p>
<p>From <a href="https://dx.doi.org/10.11622%2Fsmedj.2015105">penicillin</a> discovered on mouldy old laboratory plates to <a href="https://doi.org/10.1111/j.1749-6632.2011.06354.x">tetracycline</a> from soil, these compounds revolutionised medicine. The antibiotic industry is now worth over <a href="https://www.grandviewresearch.com/industry-analysis/antibiotic-market">US$40 billion</a>.</p>
<p>Yet despite the importance of antibiotics, the size of drug companies and continuous research in developed countries, the <a href="https://doi.org/10.1128/AAC.01277-13">antibiotic pipeline</a> is almost empty. Few compounds that can be turned into drugs are being discovered, and pharmaceutical companies are more interested in improving known drugs. This means there aren’t new classes of antibiotics coming onto the market. And we need new ones because disease-causing bacteria continue to overcome most of the antibiotics in use globally. </p>
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Read more:
<a href="https://theconversation.com/the-world-needs-antibiotic-guardians-to-safeguard-their-future-use-127465">The world needs 'antibiotic guardians' to safeguard their future use</a>
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<p>Whether in hospitals or veterinary services, there are also <a href="https://www.downtoearth.org.in/news/health/antibiotic-resistance-nigeria-stares-at-a-major-catastrophe-68915">increasing cases</a> of drug resistance in Nigeria. </p>
<p>However, Nigeria’s contribution to antibiotic discovery from microscopic organisms is almost non-existent. One reason is that research of this nature takes a lot of time and money. A compound can be under consideration for a decade and end up failing the global standard. </p>
<p>Plant-based products (herbal mixtures and concoctions) can be formulated quickly and some get approval from the National Agency for Food and Drugs Administration and Control as marketable products. But drug products of microbial origin are uncommon.</p>
<p>The last time Nigeria reported a novel antimicrobial compound of microbial origin was in <a href="https://patents.google.com/patent/US5206263A/en?oq=US+Patent+5%2c206%2c263">1986</a>, under a project commissioned by Pfizer. The compound was used to treat coccidiosis in poultry and to promote growth in swine. It was the second such compound from Nigeria, but research stalled in the decades that followed.</p>
<p>While work continued on the potential of microorganisms as antibiotic producers, no novel compound was reported. The question became where to look next. Previous environmental clean-up <a href="https://iwaponline.com/aqua/article-abstract/63/1/66/28955/Biosorption-studies-for-the-removal-of-ferrous-ion?redirectedFrom=fulltext">research</a> suggested a way of filling the gap: using fungi found in waste produced by chemical industries.</p>
<h2>Industries as habitats for novel drug producers</h2>
<p>Sango-Ota, Ogun State’s industrial city, southwest Nigeria, is home to many industries, including producers of chemicals. In <a href="https://www.researchgate.net/publication/337909079_Potential_antibiotic-producing_fungal_strains_isolated_from_pharmaceutical_waste_sludge">our research</a>, we explored the waste (sludge) from these companies, looking for fungi with potential to produce antibiotics. We found six species that showed some promise. </p>
<p>The reason we targeted industrial sludge was that indiscriminate disposal of chemicals can alter the genes of organisms found in that habitat. It happens through long-term exposure, giving the organisms specialised properties. They might, for example, be able to produce new compounds.</p>
<p>Chemical wastes of selected companies stored in wells, tanks and other collection areas awaiting disposal into <a href="https://doi.org/10.1186/s43088-019-0026-8">the environment were sampled</a>. The sludge was collected from areas that have been undisturbed for a long time (bottom of wells, tanks and collection area). This approach was adopted to increase the chance of isolating fungi that possibly use the chemicals as food, and also produce substances that would help them survive at the expense of other intruding microorganisms. </p>
<p>We found that out of six fungi isolates, the organism <em>Geotrichum candidum</em> OMON-1 produced a novel compound that stops growth of and ultimately kills <em>Staphylococcus aureus</em>. This is a bacterium found on human skin which causes infections that are difficult to treat when they enter tissues. The compound also shows activity against other similar disease-causing pathogens found in food and water. </p>
<p>Working with India’s Institute of Microbial Technology, we purified the compound and identified it as carboxymethylcystyl-asparagyl-aspartate. It’s a peptide antibiotic with three amino acids in its sequence and has a low molecular weight compared to known antibiotics. It stopped growth of disease-causing pathogens after two hours.</p>
<h2>Need to explore similar environments</h2>
<p>Discovery of a new antibiotic compound from a Nigerian environment is good news for researchers in this field. The focus in recent years has been to look for <a href="https://doi.org/10.1016/j.jtusci.2017.01.006">novel microbial compounds</a> in the polluted Lagos lagoon. Now we see that strains of fungi, and indeed other organisms with modified properties, might also be found in other industrial wastes. It could lead to treatments for infections and other disease-related conditions or to other products of medical or industrial importance. </p>
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Read more:
<a href="https://theconversation.com/how-we-learnt-more-about-dangerous-pollutants-in-lagos-lagoon-139987">How we learnt more about dangerous pollutants in Lagos lagoon</a>
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<p>There are many industries in Nigeria that produce large volumes of waste which is poorly processed and disposed of. In Lagos State, chemical and pharmaceutical plants are the most polluting from over <a href="https://www.intechopen.com/chapters/16289">7,000 industries</a>, with less than 10% capacity to properly treat their waste. Plastic and textile manufacturing plants closely follow. </p>
<p>The next step could be to try to improve the compound we found. But instead we recommend exploring other modified or specialised environments for isolates with possible antibiotic action against some of the deadliest disease-causing bacteria. These include <em>Pseudomonas aeruginosa</em>, <em>Klebsiella pneumoniae</em>, <em>Acinetobacter baumannii</em>, <em>Neisseria meningitidis</em> and <em>Neisseria gonorrhoeae</em>.</p>
<p>It is a more important task because these bacteria are <a href="https://doi.org/10.3389/fmicb.2019.00539">tagged ESKAPE pathogens</a> and are priority organisms according to the World Health Organisation. They have reduced the effect of known antibiotics, or made them ineffective, through antimicrobial resistance. </p>
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Read more:
<a href="https://theconversation.com/drug-resistant-gonorrhoea-is-a-growing-threat-a-south-african-case-study-148012">Drug-resistant gonorrhoea is a growing threat: a South African case study</a>
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<p>Last hope antibiotics are <a href="https://doi.org/10.1016/j.cmi.2015.12.002">beginning to fail</a> in their treatment, keeping many people in hospital and leading to death of others. While the Lagos lagoon and other natural water bodies are vast and a tenacious search could uncover useful compounds there, modified industrial environments could be a faster road to the prize.</p><img src="https://counter.theconversation.com/content/165041/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Sunday Omeike. PhD 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>Discovery of a new antibiotic compound from a Nigerian environment is good news for researchers in this field.Sunday Omeike. PhD, Lecturer in Industrial Microbiology (Antimicrobial compounds discovery and resistance research), McPherson UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1644452021-07-20T10:24:42Z2021-07-20T10:24:42ZLong COVID: with one in three patients back in hospital after three months, where are the treatments?<p>The pace of acute therapy and vaccine development for COVID have been dizzying. But even as we hope a route to bringing the pandemic under control is within sight, we’re now facing the possibility of another urgent public health emergency thanks to what’s known as long COVID, a group of symptoms that last long after the initial infection. With such a potential crisis looming, it is reasonable to ask what we are doing about it, and why treatments don’t appear to be forthcoming.</p>
<p>There are a few reasons why the long COVID story may pan out differently. Let’s take the first problem: long COVID is not a diagnosis itself. It encompasses <a href="https://theconversation.com/no-we-cant-treat-covid-19-like-the-flu-we-have-to-consider-the-lasting-health-problems-it-causes-164072">many different problems</a>, from blood clots and lung scarring to commonly recognised symptoms, with <a href="https://www.medrxiv.org/content/10.1101/2021.03.22.21254057v1.full.pdf">up to 82%</a> still reporting symptoms like breathlessness, fatigue and brain fog 3-6 months after discharge from hospital.</p>
<p>Though this aspect of recovery has received much attention, most people are less aware that one in three COVID patients who leave hospital <a href="https://www.bmj.com/content/372/bmj.n693">are back</a> within three months of their apparent recovery – and one in ten are dead. Stark numbers and not many people are talking about them.</p>
<p>This complexity is a major challenge for those wanting to develop and trial treatments. One of the most important questions is the measure of health you wish to improve, or the primary endpoint. Each of the above diagnoses may need a different endpoint. If you have a clot you might die. If you have lung scarring you might be breathless and it might have changed your lung function. If your primary problem is fatigue, the most important thing may be improving the symptoms, getting you back to work or reducing the support you need. </p>
<p>Patient-led research has associated as many as <a href="https://patientresearchcovid19.com">200 symptoms with long COVID</a>. It is probable that some of these are not truly COVID-related, but how do you choose what to measure in a trial? Each time you add a new measurement in a trial you increase the size the trial needs to be to avoid false positive results. Compromises need to be made about what can be done versus what the patient might value as an outcome.</p>
<figure class="align-center ">
<img alt="A COVID patient being treated" src="https://images.theconversation.com/files/411901/original/file-20210719-15-151vwoa.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/411901/original/file-20210719-15-151vwoa.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=401&fit=crop&dpr=1 600w, https://images.theconversation.com/files/411901/original/file-20210719-15-151vwoa.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=401&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/411901/original/file-20210719-15-151vwoa.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=401&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/411901/original/file-20210719-15-151vwoa.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/411901/original/file-20210719-15-151vwoa.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/411901/original/file-20210719-15-151vwoa.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">Around 200 symptoms are associated with long Covid.</span>
<span class="attribution"><span class="source">Pordee Aomboon/Shutterstock</span></span>
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<h2>Recovery data</h2>
<p>Next up is the underlying biology, of which we have a limited understanding. We know, for example, that clots form, but still not clearly why. We know that patients’ blood vessels are not normal, but not for how long this persists. And we know that some patients have prolonged inflammation, but we cannot predict who. </p>
<p>This makes it hard to choose therapies to trial and patients to include in those trials. It means we need to make some educated guesses who and when to treat, and with what. </p>
<p>Many patients recover, so should we enrol all patients when most of them will get better, pick out patients at higher risk of problems or wait until symptoms are established? No treatment comes without side-effects. We need to minimise the chances of harming someone who was going to get better anyway. </p>
<p>Added to this, the group we are studying may change with the advent of acute treatments and vaccines. Early reports suggest a younger population in the current wave. </p>
<p>This can have big effects on clinical trials. If you set a trial up to pick up a signal with an assumption of a third of people having long-term problems, if this reduces, then your trial might not be able to answer the question.</p>
<p>So what can we do about all this? The first thing is to run trials that are big enough for definitive answers and flexible enough to react to evolving knowledge, by including extra treatment arms if evidence changes. </p>
<p>The second is to have a mix of trials looking at different populations. Post-hospital patients are almost definitely at higher risk of problems like <a href="https://www.medrxiv.org/content/10.1101/2021.02.02.21251043v1">clots</a> or scarring than those that were never admitted. Prevention is always better than treatment, so therapies aimed early in the disease course are important. The community patients who are living with persistent problems may need different trials. </p>
<h2>Complex funding</h2>
<p>The good news is that a lot of <a href="https://www.nihr.ac.uk/news/196-million-awarded-to-new-research-studies-to-help-diagnose-and-treat-long-covid/28205">funding</a> is being released to point at the problem, even if we don’t yet know the best areas to focus on. Another positive is that big trials like the vaccine studies and the <a href="https://www.recoverytrial.net">Recovery</a> trial (the world’s biggest clinical trial to identify treatments for people hospitalised with COVID), have shown we can do big trials at pace and scale.</p>
<p>Unfortunately, the current funding system is competitive, lacks co-ordination and doesn’t really reward collaboration. These big trials were the exceptions, not the rule. So we need pressure on funders and researchers to do things differently. </p>
<p>In the UK, we have set up an early example of the sort of trials we think we need, called <a href="https://heal-covid.net">Heal-COVID</a>. It already has around 100 centres in the UK involved and puts into practice some of the ideas above. If you had told me before the pandemic that this type of trial could be set up in weeks, I would not have taken you seriously. </p>
<p>Despite this, the long-term nature of the problems mean it will be months before trials start to report and we need to explain to the public why. There are a lot of people out there desperate for something/anything and this will be fertile ground for charlatans and opportunists. So in the meantime, if patients are going to experiment they must always ask who benefits, make sure the treatments are at least safe, and take heart that a lot of patients are still on a journey of improvement. There remains hope.</p><img src="https://counter.theconversation.com/content/164445/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Mark Toshner receives funding from the NIHR to investigate treatments in COVID and is an investigator on NIHR funded vaccine and Covid observational studies. He has previously received research funding from companies unrelated to COVID including Actelion, Roche, and Bayer. He has received advisory fees from GSK for work also not related to COVID.</span></em></p>How investigation into long COVID will help us create treatments.Mark Toshner, Lecturer in Translational Respiratory Medicine, University of CambridgeLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1609992021-05-18T20:11:35Z2021-05-18T20:11:35Z‘Devastated and sad’ after 36 years of research — early detection of ovarian cancer doesn’t save lives<figure><img src="https://images.theconversation.com/files/401148/original/file-20210518-23-1uo0j2f.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/women-touching-lower-abdomen-629505710">Shutterstock</a></span></figcaption></figure><p>My colleagues’ and my efforts to develop a screening test for the early detection of ovarian cancer capable of saving lives arrived at a sad moment last week. The <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00731-5/fulltext">final trial results</a> of the research I’ve focused on for 36 years, published in The Lancet, found early ovarian cancer detection doesn’t save lives. </p>
<p>The advances we have seen in science and technology over the past three decades have been nothing short of phenomenal. Each smartphone has more computational power than NASA had at its disposal during the moon landings. In medicine, researchers have sequenced the human genome, created life-saving treatment for HIV and rapidly developed vaccines for COVID-19.</p>
<p>There have been significant improvements in ovarian cancer treatment involving surgery and chemotherapy, but the sad and frustrating truth is of the <a href="https://www.ovariancancer.net.au/page/152/the-statistics#:%7E:text=Each%2520day%2520in%2520Australia%252C%2520four,with%2520breast%2520cancer%2520is%252091%2525">four women diagnosed with ovarian cancer</a> in Australia each day, three will eventually die from the disease. </p>
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Read more:
<a href="https://theconversation.com/interactive-we-mapped-cancer-rates-across-australia-search-for-your-postcode-here-102256">INTERACTIVE: We mapped cancer rates across Australia – search for your postcode here</a>
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<p>The diagnosis of ovarian cancer is dependent on women reporting symptoms to their doctor. However, few develop symptoms until they have advanced stage cancer, by which time the outlook is poor. Of all women’s cancers, ovarian cancer has the lowest survival rate, with just <a href="https://www.ovariancancer.net.au/page/152/the-statistics#:%7E:text=Each%2520day%2520in%2520Australia%252C%2520four,with%2520breast%2520cancer%2520is%252091%2525">46% of patients in Australia</a> surviving five years. For breast cancer, it’s <a href="https://www.cancer.org.au/cancer-information/types-of-cancer/breast-cancer">now 91%</a>.</p>
<h2>Back in the 80s</h2>
<p>I was motivated to improve the outcome for women with ovarian cancer by my experience as a junior doctor in London in 1985. I was training with a brilliant surgeon who undertook operations for many women with ovarian cancer. In spite of the exhaustive surgery and the chemotherapy that followed, we saw far too many women suffer and die from ovarian cancer. </p>
<p>That experience inspired me to initiate a program of research designed to find a screening test to detect this cancer early. Women with the earliest stage of ovarian cancer had survival rates of 70%, but less than 20% of women with ovarian cancer were diagnosed that early. </p>
<p>My hypothesis was that if we could detect more cancers at an early stage it would save lives. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/401154/original/file-20210518-19-1iawr2h.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/401154/original/file-20210518-19-1iawr2h.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/401154/original/file-20210518-19-1iawr2h.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/401154/original/file-20210518-19-1iawr2h.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/401154/original/file-20210518-19-1iawr2h.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/401154/original/file-20210518-19-1iawr2h.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/401154/original/file-20210518-19-1iawr2h.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">
<figcaption>
<span class="caption">We saw too many women suffer and die from ovarian cancer.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/hospital-interior-corridor-bue-greece-1256860270">Shutterstock</a></span>
</figcaption>
</figure>
<p>Based on evidence from other cancers, there was reason to be hopeful and two potential tests were available – a <a href="https://pubmed.ncbi.nlm.nih.gov/6310399">blood test</a> called CA 125 and <a href="https://doi.org/10.1016/S0140-6736(82)91622-1">the use of ultrasound scanning</a> which was then widely used in obstetrics.</p>
<p>Over the next 15 years, working with colleagues in the United Kingdom and United States, I developed and refined the screening tests and had great hope for what we called “multimodal screening”. This involved a “risk of ovarian cancer algorithm” for interpreting the change in blood levels of CA 125 over time to identify women who had a rising pattern, indicating an elevated risk of ovarian cancer. Women with an elevated risk could then have a secondary test involving ultrasound scanning. </p>
<p>During those 15 years, we published <a href="https://doi.org/10.1016/S0140-6736(88)90351-0">convincing evidence</a> <a href="https://doi.org/10.1016/S0140-6736(98)10261-1">in studies</a> involving over 50,000 women that this approach to screening was safe, acceptable to women, could detect over 85% of the cancers early and would probably be cost effective <em>if</em> sufficient lives were saved.</p>
<h2>Promising early results</h2>
<p>Before advocating screening of the general population, a massive trial would be needed to determine whether the screening would actually save lives. </p>
<p>The trial needed to involve screening and follow up of approximately 200,000 women for around 20 years. This would eventually include 2,000 women with ovarian cancer – enough to determine whether or not screening saved lives.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/401161/original/file-20210518-19-1lq971.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/401161/original/file-20210518-19-1lq971.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/401161/original/file-20210518-19-1lq971.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/401161/original/file-20210518-19-1lq971.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/401161/original/file-20210518-19-1lq971.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/401161/original/file-20210518-19-1lq971.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/401161/original/file-20210518-19-1lq971.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">The trial involved great numbers of participants.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/people-walking-work-street-new-york-420091906">Shutterstock</a></span>
</figcaption>
</figure>
<p>Work got underway in the United Kingdom in 2000 and optimism grew as <a href="https://doi.org/10.1016/S1470-2045(09)70026-9">initial results confirmed</a> the ability of multimodal screening to detect cancer early in over 85% of cases. </p>
<p>By 2015, the <a href="https://doi.org/10.1016/S0140-6736(15)01224-6">preliminary mortality data</a> were available and were tantalising. The curves hinted at a 20% or more reduction in deaths from ovarian cancer, but the findings did not quite reach statistical significance. So another five years of painstaking follow up was needed.</p>
<h2>Disappointing final results</h2>
<p>The <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00731-5/fulltext">final results of the UK Collaborative Trial of Ovarian Cancer Screening</a> showed the multimodal screening approach could detect cancers early and increase the number of early-stage ovarian cancers by almost 50%. </p>
<p>But to our surprise and despair, that did not reduce the number of deaths from ovarian cancer. All it seemed to do was to bring forward the time of diagnosis of the cancers in these women, without improving their survival.</p>
<figure class="align-center ">
<img alt="Woman has blood taken for a blood test." src="https://images.theconversation.com/files/401254/original/file-20210518-15-1djldr.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/401254/original/file-20210518-15-1djldr.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/401254/original/file-20210518-15-1djldr.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/401254/original/file-20210518-15-1djldr.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/401254/original/file-20210518-15-1djldr.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/401254/original/file-20210518-15-1djldr.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/401254/original/file-20210518-15-1djldr.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">Under the multimodal screening program, women were first given a blood test for levels of CA 125.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/swab-pressed-onto-injection-site-during-521751805">Shutterstock</a></span>
</figcaption>
</figure>
<p>This is deeply disappointing. Disappointing of course for those who like myself have dedicated much of their professional lives to this effort, but much more importantly for the women across the world who we had hoped would have access to an effective screening test able to save lives. </p>
<p>The hope had been to deploy ovarian cancer screening for women in the general population alongside breast and cervical cancer screening, but that will not happen – for a while at least.</p>
<h2>Why didn’t early detection save lives?</h2>
<p>To answer that, we need to further analyse samples and data from the trial. Our suspicion is that the women whose cancers were detected early by screening had more aggressive cancers than those (the 10%) whose cancers were detected early without screening, on the basis of symptoms. </p>
<p>So even with early detection, their cancers progressed relentlessly despite them receiving the best available surgery and chemotherapy. </p>
<p>If that is the case, we are likely to require screening tests which can detect ovarian cancer even earlier than our algorithm, which we estimate picks up ovarian cancer 18 to 24 months early. Saving lives may require a test capable of picking up the cancers five or more years early. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/why-we-need-to-pay-more-attention-to-negative-clinical-trials-59904">Why we need to pay more attention to negative clinical trials</a>
</strong>
</em>
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<p>Fortunately, there are exciting avenues of research involving advances in protein and DNA technologies which researchers in Australia and around the world are exploring. So there is hope. </p>
<p>But realistically, given the five-plus years needed to develop better screening tests and the ten to 15-plus years needed to have enough cases to conduct another large randomised trial, the solution is likely to be more than 20 years away.</p>
<h2>Still, we’ve learnt a lot</h2>
<p>This massive commitment of expertise, time, energy and funding has most definitely not been wasted. Much has been achieved along the way in this 36-year journey in developing ways to assess risk, diagnose cancer and prevent ovarian cancer which are now used in clinical practice. </p>
<p>New generations of researchers have been trained. The data and the blood bank collected is available to all researchers seeking new and better screening tests and is a unique resource. And the ability to detect ovarian cancer early may be invaluable in assessing new treatments. </p>
<p>I feel privileged to have led this effort and will always be grateful to the collaborators, researchers, health professionals, funding agencies and above all the 200,000 women who took part in the trial. </p>
<p>I feel a deep sadness that lives will not yet be saved by ovarian cancer screening, but I’m confident the next generation of researchers will build on our work and find approaches to screening and treatment of ovarian cancer which dramatically reduce the loss and suffering caused by this insidious disease.</p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/covid-has-left-australias-biomedical-research-sector-gasping-for-air-145022">COVID has left Australia's biomedical research sector gasping for air</a>
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<img src="https://counter.theconversation.com/content/160999/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Ian Jacobs is a President and Vice-Chancellor of UNSW Sydney and a Board member of Ovarian Cancer Australia. He is a director and shareholder of Abcodia Ltd which holds a licence from Massuchusetts General Hospital for the Risk of Ovarian Cancer Algorithm and as a Co-Inventor of the Algorithm he has a potential royalty stream. He received funding awards for UKCTOCS from the Medical Research Council, Cancer Research UK, the National Institute of Health Research and the Eve Appeal.</span></em></p>I was motivated to improve the outcome for women with ovarian cancer by my experience as a junior doctor in London in 1985. But 36 years on, the results aren’t what we’d hoped.Ian Jacobs, President and Vice-Chancellor, UNSW SydneyLicensed as Creative Commons – attribution, no derivatives.