tag:theconversation.com,2011:/global/topics/cystic-fibrosis-7438/articlesCystic fibrosis – The Conversation2023-04-24T21:42:07Ztag:theconversation.com,2011:article/2043402023-04-24T21:42:07Z2023-04-24T21:42:07ZCanadian science pioneers’ role in the Human Genome Project shows why it’s crucial to fund research<figure><img src="https://images.theconversation.com/files/522693/original/file-20230424-1269-xtr2u1.jpg?ixlib=rb-1.1.0&rect=149%2C17%2C1623%2C991&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The research and vision of Canadian scientists were key foundations of the Human Genome Project. Today, lack of funding threatens discovery research in Canada.</span> <span class="attribution"><span class="source">(Pixabay)</span></span></figcaption></figure><p>On April 25, the world will celebrate <a href="https://www.genome.gov/dna-day">DNA Day</a>, marking two events: the 70th anniversary of the <a href="https://www.cam.ac.uk/stories/DNA-structure-discovery-cambridge-70th-anniversary">discovery of the double helix</a> and the 20th anniversary of the <a href="https://www.genome.gov/human-genome-project">Human Genome Project</a>, which sequenced humans’ genetic blueprint for the first time.</p>
<p>For the Human Genome Project, Canadians were at the forefront. </p>
<p>The distinguished Canadian medical geneticist Charles Scriver of McGill University, <a href="https://healthenews.mcgill.ca/in-memoriam-charles-r-scriver/">who recently passed away</a>, convinced the Howard Hughes Medical Institute in the United States in 1986 to bring together the parties who could fund and execute the Human Genome project. This objective has been acknowledged as prescient. </p>
<p>The meeting was attended by Nobel Prize winners <a href="https://www.nobelprize.org/prizes/chemistry/1980/gilbert/biographical/">Walter Gilbert</a> and <a href="https://www.nobelprize.org/prizes/medicine/1962/watson/biographical/">James Watson</a>, and is described as a major catalyst for the Human Genome Project in <em><a href="https://books.google.ca/books/about/The_Book_of_Man.html?id=ys5qAAAAMAAJ&redir_esc=y">The Book of Man: The Human Genome Project and the Quest to Discover Our Genetic Heritage</a></em>.</p>
<h2>From inspiration to sequencing the genome</h2>
<p>Scriver was well aware of the <a href="https://www.ncbi.nlm.nih.gov/books/NBK234203/">significance sequencing the human genome</a> would have on clinical genetics and the impact it would have on the health of patients, including identifying genetic causes of diseases.</p>
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<figcaption><span class="caption">The Human Genome Project.</span></figcaption>
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<p>To move forward from Scriver’s inspiration, a proof of principle project was needed. This was provided by the discovery of the gene for cystic fibrosis (CF) by Lap-Chee Tsui and Jack Riordan, who were then at the University of Toronto, and Francis Collins, then at the University of Michigan. In 1990 they indicated: </p>
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<p>“<a href="https://doi.org/10.1080/21548331.1990.11704019">More broadly, the cloning of the CF gene provides a fast start in the international effort to clone and map the entire human genome</a>”</p>
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<p>These pioneers performed the very challenging task of <a href="https://doi.org/10.1126/science.2475911">identifying the gene mutation in unaffected people (those with a single mutated gene)</a>. CF is a recessive genetic condition, meaning a person must inherit two mutated genes — one from each parent — to develop the disease. Today as a result of Canadian discovery science, <a href="https://www.cysticfibrosis.ca/registry/2021AnnualDataReport.pdf">patients with cystic fibrosis have a median age of survival of 57 years</a>, compared to 35.9 years in 2001.</p>
<p>One of these pioneers went on to lead the even more challenging Human Genome Project. Collins received Canada’s Gairdner International Award in 2002 for “<a href="https://www.gairdner.org/winner/francis-s-collins">his outstanding leadership in the Human Genome Project and particularly for the international effort to map and sequence human and other genomes</a>.”</p>
<p>This was a rare occurrence of a scientist winning a second Gairdner International Award, with Collins receiving his first Gairdner for the CF gene discovery, along with Tsui and Riordan, in 1990.</p>
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Read more:
<a href="https://theconversation.com/solving-the-puzzle-of-cystic-fibrosis-and-its-treatments-is-a-nobel-prize-worthy-breakthrough-175335">Solving the puzzle of cystic fibrosis and its treatments is a Nobel Prize-worthy breakthrough</a>
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<p>Another Gairdner International award winner recognized for leadership in the Human Genome Project is <a href="https://www.gairdner.org/winner/james-d-watson">Watson</a>. This year’s DNA Day will celebrate the 70th anniversary of the double helix, for which Watson was later recognized with a <a href="https://www.nobelprize.org/prizes/medicine/1962/summary/">Nobel prize in 1962</a>.</p>
<p>It was belatedly recognized that the experimental data for the double helix was actually an <a href="https://www.nobelprize.org/prizes/medicine/1962/speedread/">X-ray of a crystal of DNA by the late Rosalind Franklin</a>.</p>
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Read more:
<a href="https://theconversation.com/closing-the-gender-gap-in-the-life-sciences-is-an-uphill-struggle-112920">Closing the gender gap in the life sciences is an uphill struggle</a>
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<p>The consequences of the discovery of DNA and the sequencing of the Human Genome have been monumental for health research globally. As <a href="https://doi.org/10.1056/NEJMp2030694">summarized in 2021 by Collins</a>, the genes for over 5,000 rare diseases were discovered as well as insight into Alzheimer’s disease, schizophrenia, heart disease and cancer.</p>
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<figcaption><span class="caption">Charles Scriver, Canadian Medical Hall of Fame laureate 2001.</span></figcaption>
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<p>Astonishingly, it is through DNA that all of us can follow the trajectory of our families through genetic genealogy. Remarkably, the Nobel Prize in 2022 was awarded to Svante Pääbo of the Max Planck Institute in Leipzig, Germany for the <a href="https://www.nobelprize.org/prizes/medicine/2022/press-release/">new field of paleogenomics</a>. His discoveries involving the intricate sequencing of genomic DNA from our extinct human ancestors led to the discovery of a new branch of human ancestors now known as the Denisovans.</p>
<p>Today, the genetic genealogy of modern and ancient humans has been extended through the analysis of the DNA of over 7,000 different genomes. This new study has defined the <a href="https://doi.org/10.1126%2Fscience.abi8264">geographic location of the trajectory of our ancestors</a> extending to over 800,000 years ago! DNA Day is a worthy celebration.</p>
<h2>Can DNA Day be of significance in Canada?</h2>
<p>The dedication of our accomplished discovery researchers Tsui, Riordan and Scriver inspired and led to the Human Genome Project. However, the project did not involve Canada. The major reason for this was funding. </p>
<p>The Human Genome Project was largely funded by the U.S. National Institutes of Health to the labs of <a href="https://doi.org/10.1073/pnas.042692499">Robert Waterston at Washington University and Eric Lander at MIT</a>. In addition, John Sulston was funded in the United Kingdom as part of the trio who actually sequenced the human genome.</p>
<p>Journalist and political commentator Paul Wells recently lamented the <a href="https://paulwells.substack.com/p/building-pyramids-from-the-top-down">decades of deteriorating funding for Canadian discovery research</a>. In 2019, Canada was ranked 18th globally in researchers per 1,000 population down from its 8th rank in 2011. </p>
<p>Without funding improvements, Canada will continue to lose the talent it was once proud to have. This loss is unsustainable for meeting the challenges of future pandemics, climate change and the continuing ravages of disease.</p>
<p>Scriver, Tsui and Riordan should inspire pride for the value of discovery research in Canada that globally saves human lives. Canada should remember their legacy on DNA day.</p>
<p><em>John Bergeron gratefully acknowledges Kathleen Dickson as co-author.</em></p><img src="https://counter.theconversation.com/content/204340/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>John Bergeron 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>On DNA Day, Canada should be inspired by the lifesaving discoveries of its researchers. However, lack of funding threatens Canadian researchers’ ability to meet the challenges of the future.John Bergeron, Emeritus Robert Reford Professor and Professor of Medicine, McGill UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1856542022-07-07T09:45:03Z2022-07-07T09:45:03ZThe human body has 37 trillion cells. If we can work out what they all do, the results could revolutionise healthcare<figure><img src="https://images.theconversation.com/files/472254/original/file-20220704-22-1y09ee.jpg?ixlib=rb-1.1.0&rect=95%2C15%2C1922%2C1201&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Priscilla Chan and Mark Zuckerberg with Moshe Biton (right) and Aviv Regev (left). The Chan Zuckerberg Initiative is one of the major funders of the Human Cell Atlas.</span> <span class="attribution"><span class="source">Chan Zuckerberg Initiative</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span></figcaption></figure><p>The average body contains about 37 trillion cells – and we are in the midst of a revolutionary quest to understand what they all do. Unravelling this requires the expertise of scientists from all different backgrounds – computer scientists, biologists, clinicians and mathematicians – as well as new technology and some pretty sophisticated algorithms. </p>
<p>Where once a primitive microscope, essentially little more than a magnifying glass, would reveal a new cell directly and viscerally – in the same way that <a href="https://377.medium.com/first-person-in-the-world-who-discovered-the-sperm-cells-6c91b17a8df5#:%7E:text=Sperm%20were%20unknown%20to%20science,filled%20with%20tiny%2C%20wiggling%20cells.">Antonie van Leeuwenhoek discovered sperm</a> in 1677 – today it is analysis on a computer screen which brings us such revelations. But it’s just as wonderful.</p>
<p>This type of research is hard in all sorts of ways – from the science itself to the sociology of large teams working on it – but the pay-off can be huge. It certainly was for a consortium of 29 scientists who set out to determine which types of cells make up the lining of the trachea, or windpipe – and stumbled upon a new type of cell that could transform our understanding and treatment of cystic fibrosis.</p>
<p>The first time the team – co-led by <a href="https://biology.mit.edu/profile/aviv-regev/">Aviv Regev</a> at the <a href="https://www.broadinstitute.org/about-us">Broad Institute</a> of MIT and Harvard – came across these cells, they were looking at an analysis of 300 cells in the trachea of mice. Three cells didn’t seem to correspond to anything that had been seen before. Had it been just two, they might have dismissed it as an outcome of noise in the data – but three strange cells warranted a closer look.</p>
<p>In lab banter, they became known as the “hot cells”. The scientists repeated the experiment several times, and it soon became clear they really had stumbled upon a new type of cell in the trachea.</p>
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<p><strong><em>This story is part of Conversation Insights</em></strong>
<br><em>The Insights team generates <a href="https://theconversation.com/uk/topics/insights-series-71218">long-form journalism</a> and is working with academics from different backgrounds who have been engaged in projects to tackle societal and scientific challenges.</em></p>
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<p>As it turned out, another team from the US and Switzerland had independently found the same thing. The two teams learnt of each other’s work by chance at a seminar in 2017. “It was one of those beautiful moments in science,” recalled <a href="http://www.weizmann.ac.il/dept/irb/Biton/">Moshe Biton</a> from the Broad Institute team, “when two groups found the same results separately.”</p>
<p>Both groups confirmed that these new cells exist in the human airways as well as in mice and, after meeting up, agreed to publish their <a href="https://www.nature.com/articles/s41586-018-0394-6">two papers</a> <a href="https://www.nature.com/articles/s41586-018-0393-7">side-by-side</a>. These new cells had not been noticed before, simply because they are so rare – they make up around 1% of cells in the airway. But that doesn’t mean they’re unimportant. When the two teams looked in detail at what made these cells stand out, they came across something astonishing.</p>
<p>One of the genes active in these new-found trachea cells turned out to be CFTR – the “cystic fibrosis transmembrane conductance regulator” gene. This gave their work a whole other level of meaning because <a href="https://www.cff.org/research-clinical-trials/basics-cftr-protein">mutations in this gene cause cystic fibrosis</a>.</p>
<p>Exactly how this disease is caused by the inheritance of a dysfunctional version of the CFTR gene has been a mystery ever since the link was <a href="https://www.science.org/doi/10.1126/science.2772644">discovered in 1989</a>. Cystic fibrosis is a complex disease, usually beginning in childhood, with symptoms often including lung infections and difficulty breathing. There are treatments but no cure.</p>
<p>Now it seems possible that the key to understanding the cause could lie in working out what these newly discovered cells do, and what happens to these cells if the CFTR gene is defective. The research continues.</p>
<p>But already from this discovery, and other research using similar methods, there is the sense that our understanding of the body’s cells is being transformed by a piercing new combination of biology and computer science. And this is where even more game-changing discoveries are about to be made.</p>
<h2>The diversity of human cells</h2>
<p>Every one of the 37 trillion-or-so cells in your body is unique to some extent. Types of cell are determined by the particular proteins they contain – so only a red blood cell has haemoglobin, for example, and a <a href="https://www.ninds.nih.gov/health-information/patient-caregiver-education/brain-basics-life-and-death-neuron#:%7E:text=Neurons%20are%20information%20messengers.,rest%20of%20the%20nervous%20system.">neuron</a> contains different proteins from an <a href="https://www.cancer.gov/publications/dictionaries/cancer-terms/def/immune-cell">immune cell</a>. No two cells in the body contain exactly the same amounts of each protein.</p>
<p><a href="https://www.penguin.co.uk/books/431895/the-beautiful-cure-by-daniel-m-davis/9781784702212">The immune system is especially complex</a>. It comprises many types of cells categorised by their core function – T cells, B cells and so on. But there are also countless subtle variations of these T cells and B cells. We don’t even really know how many variants there are – but if we could understand what they all do, we would better understand the immune system. This in turn would enable us to design new medicines to help the immune system to, for example, better fight cancer. </p>
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<img alt="Image of a human cell using super-resolution microscope" src="https://images.theconversation.com/files/472258/original/file-20220704-19-xwkp0u.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/472258/original/file-20220704-19-xwkp0u.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=521&fit=crop&dpr=1 600w, https://images.theconversation.com/files/472258/original/file-20220704-19-xwkp0u.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=521&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/472258/original/file-20220704-19-xwkp0u.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=521&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/472258/original/file-20220704-19-xwkp0u.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=655&fit=crop&dpr=1 754w, https://images.theconversation.com/files/472258/original/file-20220704-19-xwkp0u.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=655&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/472258/original/file-20220704-19-xwkp0u.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=655&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 human natural killer cell pictured using Stimulated Emission Depletion (STED) microscopy.</span>
<span class="attribution"><span class="source">Ashley Ambrose and Daniel M Davis</span>, <span class="license">Author provided</span></span>
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<p>One kind of immune cell that my research team at Manchester University studies is called the <a href="https://www.immunology.org/public-information/bitesized-immunology/cells/natural-killer-cells">natural killer cell</a>. There are about a thousand of these immune cells in each drop of your blood, and they are especially good at detecting and killing other cells that have turned cancerous or have become infected with a virus. Again, not all natural killer cells are alike. <a href="https://pubmed.ncbi.nlm.nih.gov/24154599/">One analysis</a> has estimated that there are many thousands of variants of this immune cell in any one person.</p>
<p>In 2020, my research lab carried out <a href="https://ashpublications.org/bloodadvances/article/4/7/1388/454300/Diversity-of-peripheral-blood-human-NK-cells">an analysis</a> which suggested that variants of natural killer cells in blood could be organised into eight categories. While their different roles in the body aren’t yet fully understood, it’s likely that some are especially adept at attacking particular kinds of virus, others are better at detecting cancer, and so on.</p>
<p>Other types of immune cell can be even more varied. Evidently, our component cells are as diverse as the human beings they make up, and understanding how such complex populations of cells work together (in this case, to defend against disease) is a vital frontier.</p>
<h2>Using the language of algorithms</h2>
<p>To penetrate this complexity, the diversity of human cells must be translated into the language of algorithms.</p>
<p>Imagine a cell contains just two kinds of protein, X and Y. Every individual cell will have a specific amount of each of these two proteins. This can be represented as a point on a graph where the level of protein X becomes a position along the x-axis, and the level of protein Y its location along the y-axis.</p>
<p>One cell may contain a high amount of protein X and a little of protein Y (which can be revealed by a <a href="https://www.beckman.com/resources/videos/scientific/introduction-to-flow-cytometry">flow cytometer</a> showing that the cell stains with a high amount of one antibody and a low amount of another antibody). This cell can then be represented as a point placed far along the x-axis and a little way up the y-axis.</p>
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<img alt="" src="https://images.theconversation.com/files/472263/original/file-20220704-21-dtlrr8.png?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/472263/original/file-20220704-21-dtlrr8.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=570&fit=crop&dpr=1 600w, https://images.theconversation.com/files/472263/original/file-20220704-21-dtlrr8.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=570&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/472263/original/file-20220704-21-dtlrr8.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=570&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/472263/original/file-20220704-21-dtlrr8.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=716&fit=crop&dpr=1 754w, https://images.theconversation.com/files/472263/original/file-20220704-21-dtlrr8.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=716&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/472263/original/file-20220704-21-dtlrr8.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=716&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">Illustration of cell identification process.</span>
<span class="attribution"><span class="source">Manon Chauvin via Wikimedia, modified</span>, <span class="license">Author provided</span></span>
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<p>As each cell takes up a position on the graph, those with similar levels of the X and also the Y protein – likely to be the same type of cell – appear as a cluster of points. If thousands or millions of cells are plotted in this way, the number of discrete clusters that emerge tells us how many types of cells there are. Also, the number of points within a cluster tells us how many cells there are of that type.</p>
<p>The wonderful thing is that this form of analysis can reveal how many kinds of cells are present in, say, a sample of blood or a tumour biopsy, without being guided in any way about which cells we are expecting to find. This means that unexpected results can turn up. A cluster of data points might appear with unexpected properties – implicating the discovery a new kind of cell.</p>
<p>Of course, cells need more than two coordinates to describe them. In fact, over the last decade, a type of analysis – known as <a href="https://genomemedicine.biomedcentral.com/articles/10.1186/s13073-017-0467-4">single-cell sequencing</a>– has been developed to measure the extent to which individual cells use each of the 20,000 human genes it contains.</p>
<p>Which ones out of all the 20,000 human genes a particular cell is using – called the cell’s <a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/transcriptome">transcriptome</a> – can then be analysed to create a “map” of different cells. We can’t imagine cells represented on a graph with 20,000 axes, but a computer algorithm can handle this analysis in just the same way it would one with only two variables. Similar cells are positioned close together, while cells using very different sets of genes are far apart.</p>
<p><a href="https://www.nature.com/articles/s41598-020-74567-y">Algorithms</a> to do this are borrowed from other fields of science, such as those used in analysing social networks. Then we get to spend days, if not years, mining the output, deciphering what the map means: how many types of cells there are, what defines their differences, and what they do in the body? </p>
<p>Right now, this endeavour is happening on an unprecedented scale thanks to the <a href="https://www.humancellatlas.org/learn-more/">Human Cell Atlas consortium</a> – leading to all kinds of <a href="https://www.penguin.co.uk/books/439335/the-secret-body-by-davis-daniel-m/9781529110975">discoveries about the human body</a>.</p>
<h2>The Human Cell Atlas</h2>
<p>In October 2016, Regev and <a href="https://www.sanger.ac.uk/person/teichmann-sarah/">Sarah Teichmann</a> from the <a href="https://www.sanger.ac.uk/about/">Wellcome Sanger Institute</a> organised an event in London for around 100 world-leading scientists to discuss how to chart every cell in the human body. The elevator pitch was to assemble something like Google Maps for the body: “We know the countries and main cities, now we need to map the streets and buildings.”</p>
<p>A year later, they had drafted a specific plan – to first try to profile 100 million cells from different systems and organs, using different people around the globe. Thousands of scientists in over 70 countries from every inhabited content have joined the consortiu since – it is an especially diverse community, as it should be for such a huge global scientific endeavour.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/472261/original/file-20220704-19-wlwce0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Large gathering of scientists" src="https://images.theconversation.com/files/472261/original/file-20220704-19-wlwce0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/472261/original/file-20220704-19-wlwce0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=388&fit=crop&dpr=1 600w, https://images.theconversation.com/files/472261/original/file-20220704-19-wlwce0.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=388&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/472261/original/file-20220704-19-wlwce0.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=388&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/472261/original/file-20220704-19-wlwce0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=488&fit=crop&dpr=1 754w, https://images.theconversation.com/files/472261/original/file-20220704-19-wlwce0.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=488&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/472261/original/file-20220704-19-wlwce0.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=488&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">First meeting of the Human Cell Atlas team in London, 2016.</span>
<span class="attribution"><span class="source">Thomas Farnetti/Wellcome</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<p>In many ways, this bold new ambition is a direct descendant of the <a href="https://www.genome.gov/human-genome-project/What">Human Genome Project</a>. By sequencing all the human genes contained in each human cell, officially completed in April 2003, all sorts of genetic variations have been linked to increased susceptibility to a specific illness.</p>
<p>However, genetic diseases manifest in the specific cells where that gene is normally used. So, crucially, an analysis of genes alone isn’t enough – we also need to know where in the human body these disease-causing genes are being switched on.</p>
<p>The Human Cell Atlas is bridging this gap between abstract genetic codes and the physicality of the human body. We’ve already seen one example of how important this is – the discovery of the cystic fibrosis gene being used by a new, rare cell. Another example comes from what happens during pregnancy.</p>
<h2>Unlocking the secrets of pregnancy</h2>
<p>For many years, we have known that <a href="https://www.penguin.co.uk/books/182952/the-compatibility-gene-by-davis-daniel-m/9780141972527">the immune system is intimately linked with pregnancy</a>. For example, some combinations of immune system genes are slightly more frequent than would be expected by chance in couples who have had three or more miscarriages. While we don’t yet understand why this is, working it out might be medically important in resolving problems in pregnancy.</p>
<p>To tackle the issue, a consortium of scientists (co-led by Teichmann as part of the Human Cell Atlas project) analysed around 70,000 cells from the placenta and lining of the womb from women who had terminated their pregnancy at between six and 14 weeks.</p>
<p>The placenta is the organ where nutrients and gases pass back and forth between the mother and developing baby. It was once thought the mother’s immune system must be switched off in the lining of the womb where the placenta embeds, so that the placenta and foetus aren’t attacked for being “alien” (like an unmatched transplant) on account of half the foetus’s genes coming from the father. But this view turned out to be wrong – or too simple at the very least.</p>
<p>We now know, from a variety of experiments including this analysis, that in the womb, the activity of the mother’s immune cells is somewhat lessened, presumably to prevent an adverse reaction against cells from the foetus, but the immune system is not switched off. Instead, the immune cells we met earlier, natural killer cells, well known for killing infected cells or cancer cells, take on a completely different, more constructive job in the womb; helping build the placenta.</p>
<p>The scientists’ analysis of 70,000 cells <a href="https://www.nature.com/articles/s41586-018-0698-6">has also highlighted</a> that all sorts of other immune cells are also important in the construction of a placenta. What they all do, though, isn’t yet clear – this is at the edge of our knowledge.</p>
<figure class="align-center ">
<img alt="Scientist talking at meeting" src="https://images.theconversation.com/files/472281/original/file-20220704-21-v511u5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/472281/original/file-20220704-21-v511u5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=417&fit=crop&dpr=1 600w, https://images.theconversation.com/files/472281/original/file-20220704-21-v511u5.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=417&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/472281/original/file-20220704-21-v511u5.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=417&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/472281/original/file-20220704-21-v511u5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=523&fit=crop&dpr=1 754w, https://images.theconversation.com/files/472281/original/file-20220704-21-v511u5.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=523&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/472281/original/file-20220704-21-v511u5.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=523&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Muzlifah Haniffa at the Human Cell Atlas launch meeting in 2016.</span>
<span class="attribution"><span class="source">Thomas Farnetti/Wellcome</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<p><a href="https://www.ncl.ac.uk/medical-sciences/people/profile/mahaniffa.html">Muzlifah “Muzz” Haniffa</a> is one of the three women who led this analysis. As a physician and scientist, she sees the body from two perspectives on an almost daily basis: as a computational analysis of cells on a screen, and as patients who walk through the door. Both as stones and the arch they make.</p>
<p>Right now, these two views don’t easily mesh. But in time, they will. In the future, Haniffa thinks the tools doctors use on a daily basis – such as a stethoscope to listen to a person’s lungs, or a simple blood count – will be replaced by instruments that profile our body’s cells. Algorithms will analyse the results, clarify the underlying problem, and predict the best treatment. Many other physicians agree with her – this is the coming future of healthcare.</p>
<h2>What this could mean for you</h2>
<p>Babies are now routinely born by IVF, organ transplants have become common, and overall cancer survival rates in the UK have roughly doubled in recent years – but all these achievements are nothing to what’s coming.</p>
<p>As I’ve written about in <a href="https://www.amazon.co.uk/Secret-Body-Science-Human-Changing/dp/1529110971/">The Secret Body</a>, progress in human biology is accelerating at an unprecedented rate – not only through the Human Cell Atlas but in many other areas too. Analysis of our genes presents a <a href="https://www.theguardian.com/books/2013/aug/08/compatibility-gene-daniel-davis-review">new understanding of how we differ</a>; the actions of brain cells give clues to how our minds work; new structures found inside our cells lead to new ideas for medicine; proteins and other molecules found to be circulating in our blood change our view of mental health.</p>
<p>Of course, all science has an ever-increasing impact on our lives, but nothing affects us as deeply or directly as new revelations about the human body. On the horizon now, from all this research, are entirely new ways of defining, screening and manipulating health.</p>
<p>We are already accustomed to the idea that our personal genetic information can be used to guide our health. But a quieter – almost secret – revolution is also under way and it may have an even bigger impact on the future of healthcare: deep analytics of the human body’s cells.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/472745/original/file-20220706-23-vv620k.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/472745/original/file-20220706-23-vv620k.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=329&fit=crop&dpr=1 600w, https://images.theconversation.com/files/472745/original/file-20220706-23-vv620k.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=329&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/472745/original/file-20220706-23-vv620k.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=329&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/472745/original/file-20220706-23-vv620k.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=414&fit=crop&dpr=1 754w, https://images.theconversation.com/files/472745/original/file-20220706-23-vv620k.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=414&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/472745/original/file-20220706-23-vv620k.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=414&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">In the future a whole cloud of health information will be available to you, if you want to delve into it.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/genetic-research-biotech-science-concept-human-1084540790">Shutterstock</a></span>
</figcaption>
</figure>
<p>One day, a watch that can measure a few simple things about your body will be seen as a laughably primitive tool. In the future, maybe within ten years or so, a whole cloud of information will be available – including an analysis of your body’s cells – and you will have to decide how much you want to delve into it. This revolution in human biology will equip us individually with new powers – and we will each need to decide for ourselves if and when to deploy them.</p>
<p>You may, for example, one day visit your doctor with something abnormal on your skin – a rash, itch, or something else. The doctor may then take a small sample of your skin, or perhaps a blood sample, and from a complete cell-by-cell analysis of what’s there, be able to precisely diagnose the problem and know the best treatment. Indeed, some of this might even be automated. Further into the future, if the equipment needed to do this gets small and cheap enough, perhaps the analysis could be done by yourself at home.</p>
<p>Diseases will also be more frequently predicted before any symptoms are present at all. Of course, this is one of the most vital missions of science: to stop human disease before it even begins. For some illnesses, this has been achieved already – with vaccines, clean water and improved sanitation. Now, with the human body opening up to us through computational analysis of cells, genes and more, new ways of pre-empting disease are emerging. We are compelled to seize this new opportunity – yet in practice, there are challenges and unintended consequences to contend with.</p>
<p>Take a familiar example: the idea of the body-mass index, a value derived from a person’s weight and height. This is used to label us as underweight, normal weight, overweight or obese. It’s useful as it indicates an increased risk of health problems arising, such as type 2 diabetes, and steps can be taken to reduce the likelihood of this occurring. But the label itself can also trigger other sorts of problems relating to a person’s self-worth, and how society views obesity and human diversity.</p>
<h2>Difficult decisions about how you live</h2>
<p>Every one of us is susceptible to some disease or other, to some extent. So as science progresses and we learn more and more about ourselves, we will surely all find ourselves drowning in data about ourselves, awash with estimates and probabilities that play games with our mind and our identity, and require us to make difficult decisions about our health and how we live.</p>
<p>It seems feasible, for example, that the state of a person’s immune system, analysed in depth, could help predict the symptoms they are likely to have if infected with the Sars-CoV-2 virus, for example. Markers of immune activity might even correlate with a person’s mental health. One analysis concluded that particular pro-inflammatory secretions from immune cells (called cytokines) are found at higher levels in <a href="https://www.sciencedirect.com/science/article/pii/S088915911830789X?via%3Dihub">people who are depressed</a>.</p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/coronavirus-we-must-step-up-research-to-harness-immense-power-of-the-immune-system-138071">Coronavirus: we must step up research to harness immense power of the immune system</a>
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</em>
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<p>As we learn about the composition and status of the human body, this will inevitably establish new ways of assessing health. And it may very well help resolve problems in pregnancy too, as we’ve seen. But there are problems here too – if an analysis suggests a chance of a problem, say 50%, how would you act on this information if the medical intervention that could help has its own risks too?</p>
<p>There is seemingly no end to how the metric analysis of the human body will lead to important but complex new health decisions. <a href="https://www.nytimes.com/2013/05/14/opinion/my-medical-choice.html">Angelina Jolie</a> famously acted on genetic information when she had both of her breasts surgically removed in 2013, and later her ovaries and fallopian tubes, following a genetic test which established that she had inherited a particular variation in a gene known as BRCA1. Crucially, she had been given a very high – 87% – chance of developing breast cancer. In general, risks and probabilities about our health are much less clear than this.</p>
<p>So the question arises, how are we to act on all this new information? What if something has been identified that means your risk of developing an autoimmune disease or cancer is one in six in the next ten years? Would it be different if it was one in four? At what point would you decide to take medicine as a precaution, or undergo surgery, knowing that they also carry their own risks? And would this knowledge in itself make you feel ill? Would your identity be affected?</p>
<p>I don’t have the answers – but that’s the point. As this new science progresses, each of us will have to decide how much we really want to know about ourselves.</p>
<hr>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/313478/original/file-20200204-41481-1n8vco4.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/313478/original/file-20200204-41481-1n8vco4.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=112&fit=crop&dpr=1 600w, https://images.theconversation.com/files/313478/original/file-20200204-41481-1n8vco4.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=112&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/313478/original/file-20200204-41481-1n8vco4.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=112&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/313478/original/file-20200204-41481-1n8vco4.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=140&fit=crop&dpr=1 754w, https://images.theconversation.com/files/313478/original/file-20200204-41481-1n8vco4.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=140&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/313478/original/file-20200204-41481-1n8vco4.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=140&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<p><em>For you: more from our <a href="https://theconversation.com/uk/topics/insights-series-71218?utm_source=TCUK&utm_medium=linkback&utm_campaign=TCUKengagement&utm_content=InsightsUK">Insights series</a>:</em></p>
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<li><p><em><a href="https://theconversation.com/the-inside-story-of-recovery-how-the-worlds-largest-covid-19-trial-transformed-treatment-and-what-it-could-do-for-other-diseases-184772?utm_source=TCUK&utm_medium=linkback&utm_campaign=TCUKengagement&utm_content=InsightsUK">The inside story of Recovery: how the world’s largest COVID-19 trial transformed treatment – and what it could do for other diseases
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<li><p><em><a href="https://theconversation.com/the-discovery-of-insulin-a-story-of-monstrous-egos-and-toxic-rivalries-172820?utm_source=TCUK&utm_medium=linkback&utm_campaign=TCUKengagement&utm_content=InsightsUK">The discovery of insulin: a story of monstrous egos and toxic rivalries
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<p class="fine-print"><em><span>This article is an edited extract from Daniel M. Davis' new book The Secret Body (Vintage paperback, 2022). Davis is also the author of two previous books The Beautiful Cure and The Compatibility Gene. He receives research funding from The Medical Research Council, Cancer Research UK, Wellcome, GSK and Bristol Myers Squibb. He tweets at @dandavis101
</span></em></p>Pioneered by the Human Cell Atlas consortium, our understanding of the human body is about to be transformed – and with it, the way we treat and prevent diseaseDaniel M Davis, Professor of Immunology, University of ManchesterLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1753352022-01-20T21:27:18Z2022-01-20T21:27:18ZSolving the puzzle of cystic fibrosis and its treatments is a Nobel Prize-worthy breakthrough<figure><img src="https://images.theconversation.com/files/441672/original/file-20220120-21-rmnr2k.jpeg?ixlib=rb-1.1.0&rect=492%2C140%2C5844%2C4275&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The discovery of the cystic fibrosis gene led to treatments and long-term survival for patients.</span> <span class="attribution"><span class="source">(Shutterstock)</span></span></figcaption></figure><p>The nomination deadline to recognize transformative discoveries for the Nobel prize in physiology or medicine is fast approaching. These <a href="https://www.nobelprize.org/nomination/medicine/">nominations are by invitation only and are due by the end of January</a>.</p>
<p>Besides those for the lifesaving COVID-19 vaccines, several others are prominent. This includes <a href="https://dx.doi.org/10.3390/genes11060589">the discovery of the cystic fibrosis gene and the drugs to treat the disease</a>. The disease was <a href="https://doi.org/10.1164/rccm.200505-840OE">first identified in 1938</a>, and is no longer a cause of near-certain deaths in infants. Today, Canada leads the world with a 52-year median age of survival for patients with cystic fibrosis.</p>
<p>Indeed, it was in Canada that the field of cystic fibrosis research had its <a href="http://www.science.ca/scientists/scientistprofile.php?pID=19">breakthrough in 1989 when the gene that causes cystic fibrosis was discovered</a> along with the prevalent mutation that caused the disease. It was in Toronto that geneticist Lap-Chee Tsui, working with biochemist Jack Riordan and physician and geneticist Francis Collins, who then at the University of Michigan, designed a strategy to discover not only the gene but also the mutation that causes cystic fibrosis.</p>
<h2>Single gene mutation</h2>
<p>Cystic fibrosis affects the fluidity of secretions from lungs, pancreas, liver, sweat glands and other organs, making them thicker and stickier. The recessive genetic defect is due to a mutation in a single gene. Tsui had <a href="https://doi.org/10.1126/science.2570460">discovered that a segment of chromosome 7 harboured the mutant gene in patients</a>.</p>
<figure class="align-center ">
<img alt="A woman holding a child wearing a nebulizer face mask to inhale medicine" src="https://images.theconversation.com/files/441819/original/file-20220120-9603-8vm4zp.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/441819/original/file-20220120-9603-8vm4zp.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/441819/original/file-20220120-9603-8vm4zp.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/441819/original/file-20220120-9603-8vm4zp.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/441819/original/file-20220120-9603-8vm4zp.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/441819/original/file-20220120-9603-8vm4zp.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/441819/original/file-20220120-9603-8vm4zp.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">When the disease was first identified in 1938, cystic fibrosis killed most patients in infancy. Now many live into their 50s.</span>
<span class="attribution"><span class="source">(Shutterstock)</span></span>
</figcaption>
</figure>
<p><a href="https://doi.org/10.1126/science.2772657">Collins innovated methods</a> to zero in and whittle down the DNA into fragments, and used genetic mapping markers to narrow down DNA sequences housing the cystic fibrosis gene. Using these fragments, the team fished out corresponding DNA fragments extracted from sweat gland cells of patients.</p>
<p>Sweat glands in cystic fibrosis patients are unable to reabsorb salts during perspiration. Riordan used easily accessible tissue samples with sweat glands from cystic fibrosis patients and their parents to grow sweat gland cells. Extracted RNA was then used to make a DNA copy, exactly as we do today for <a href="https://theconversation.com/the-road-to-covid-19-testing-the-role-of-a-canadian-biotech-pioneer-143176">PCR tests to detect the presence of the coronavirus that causes COVID-19</a>. </p>
<p>The sequencing of this DNA then enabled them to deduce a single gene product from the patients’ sweat gland cells. They then used a computer to translate the sequence into the protein this gene product generates. In this way, <a href="https://doi.org/10.1126/science.2475911">Tsui, Riordan and Collins deduced a single protein made up of 1,479 amino acids</a>.</p>
<h2>Comparing sequenced proteins</h2>
<p>The genius of the experimental design was now to do the same for sweat gland cells isolated from the parents of cystic fibrosis patients. Proteins are made of long sequences of amino acids. When the normal protein amino acid sequence was compared with the cystic fibrosis sequence, a single amino acid known as phenylalanine was missing from the mutant protein. They had discovered the major mutation affecting about 70 per cent of cystic fibrosis patients.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/Fhro0JlR9Pc?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Lap-Chee Tsui, Canadian Medical Hall of Fame Laureate 2012.</span></figcaption>
</figure>
<p>The function of the protein they had uncovered was unknown at that time but there were clues that revealed its similarity to other proteins that transported substances including ions into and out of cells. Today we understand <a href="https://www.cff.org/research-clinical-trials/basics-cftr-protein">the mechanism of how the protein works as a channel that enables chloride ions to leave cells</a>. </p>
<p>It is these chloride ions that enable the surface of the lungs, pancreas, sweat glands and the liver, as well as the kidney and male reproductive tract, to remain bathed in fluid and unclogged.</p>
<h2>Treatment breakthroughs</h2>
<p>Patients and their families have been in the forefront of the discovery process. Besides being caregivers and advocates for their children, they also supplied tissues for the discovery research. As the diagnosis and care of patients have improved, a further breakthrough was the development of drugs to treat cystic fibrosis. These have had a dramatic effect, doubling the life expectancy of patients such that today patients may reach adulthood and beyond.</p>
<p>Two types of drugs are available; these are known as potentiators and correctors. The potentiators help the cystic fibrosis protein maintain a channel for the chloride ions that help keep the surface of the lungs and other organs bathed in fluid. </p>
<p>The correctors stabilize the fragile mutant protein. The enhanced stability enables enough of the protein to bypass the quality control machinery that otherwise would target the mutant protein for degradation in one of the trash systems of the cell (the proteasome). With the combination of the corrector drugs that enable the mutant protein to access the surface of lung, pancreas, liver and sweat gland cells, and potentiator drugs that keep the ion channel open, the protein can perform its duty. </p>
<p>In the lungs, this chloride channel enables the fluidity of mucus that would otherwise accumulate infectious bacteria and prevent normal lung functioning, especially breathing.</p>
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<figcaption><span class="caption">How fluid builds up in the lungs of people with cystic fibrosis.</span></figcaption>
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<p>Remarkably, the gene causing cystic fibrosis was discovered without knowledge of how the protein worked in cells. Furthermore, the discovery of the drugs used to treat it were discovered without knowledge of exactly how the drugs worked. </p>
<p>Thousands of labs globally uncovered how proteins such as the chloride channel work in cells, how they are made, how the quality control machinery could select such a subtle change as a single amino acid loss to target the mutant protein for degradation and exactly what is meant by increased protein fragility, how cells decode this and how the potentiator and corrector drugs work. This is basic science research at its best.</p>
<h2>Applying the discoveries</h2>
<p>The immediate consequences of the breakthrough of Tsui, Riordan and Collins in 1989 were not only for the cystic fibrosis community. In 1990, they proposed the Human Genome Project based on the <a href="https://doi.org/10.1080/21548331.1990.11704019">proof of principle discovery of the cystic fibrosis gene they had uncovered</a>.</p>
<p>Collins left the University of Michigan to direct the Human Genome Project as head of the U.S. National Human Genome Research Institute of the National Institutes of Health (NIH). This was followed in 2009 by his appointment as overall director of the NIH, a post he held until December 2021. For the drug discovery effort, it is the talented researchers in biotech and academia that <a href="https://www.hhmi.org/news/cystic-fibrosis-drugs-can-be-life-changing-patients-new-images-reveal-how-these-molecules-work">discovered how to make the drugs and how they worked, with the most recent discovery in January 2022</a>.</p>
<p>That the breakthroughs made by Tsui, Riordan and Collins are still yielding new insights speaks to its significance and ongoing relevance in science and medicine. The much longer lives of people with cystic fibrosis speak to its great importance to patients and their families. </p>
<p><em>John Bergeron gratefully acknowledges Kathleen Dickson as co-author.</em></p><img src="https://counter.theconversation.com/content/175335/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>John Bergeron 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>Unlocking the genetic cause of cystic fibrosis, and identifying treatments, has moved the prognosis from near certain death in infancy, to a median survival in Canada of 52 years.John Bergeron, Emeritus Robert Reford Professor and Professor of Medicine, McGill UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1359352020-04-08T05:40:48Z2020-04-08T05:40:48ZDoes JK Rowling’s breathing technique cure the coronavirus? No, it could help spread it<p>Harry Potter author JK Rowling says a breathing technique has helped her coronavirus-like respiratory symptoms, a claim that has been <a href="https://thenewdaily.com.au/entertainment/celebrity/2020/04/07/coronavirus-breathing-jk-rowling/">widely reported</a> and shared on social media.</p>
<p>Her tweet includes a video from a UK hospital doctor describing the technique, a type of controlled coughing. This involves taking six deep breaths and on the last one covering your mouth and coughing. </p>
<p><div data-react-class="Tweet" data-react-props="{"tweetId":"1247121896082157568"}"></div></p>
<p>The internet is full of home grown cures for the coronavirus. And when doctors propose them, they appear credible. </p>
<p>While special breathing techniques have their place in hospital, under the supervision of a respiratory physiotherapist or respiratory doctor, and for certain medical conditions, using them at home to manage coronavirus symptoms could be dangerous.</p>
<p>The technique in the video could help spread the coronavirus to people close by. </p>
<p>By coughing, you could directly infect people with droplets, or these droplets on someone’s hands can be transferred to a surface others can touch.</p>
<p>So JK Rowling’s well-meaning advice could inadvertently help spread the virus to your family, or to the person next to you on the bus.</p>
<h2>Controlled coughing helps with cystic fibrosis</h2>
<p>The cells in our lungs produce a sticky mucus as part of our body’s defence system. And when we have a viral lung infection, such as with the virus that causes COVID-19 or the influenza virus, we produce more of it. </p>
<p>The mucus traps the invading pathogen. Normally, this mucus is removed from the lungs by the movement of tiny hair-like projections in our airways. From there, we either swallow the mucus or cough it out as phlegm. </p>
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Read more:
<a href="https://theconversation.com/health-check-why-do-i-have-a-cough-and-what-can-i-do-about-it-119172">Health Check: why do I have a cough and what can I do about it?</a>
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<p>However, sometimes we produce so much mucus it is difficult to breathe. The mucus can block our tiny airways, preventing us from obtaining oxygen from our lungs.</p>
<p>In other diseases, such as <a href="https://www.cff.org/What-is-CF/About-Cystic-Fibrosis/">cystic fibrosis</a>, controlled coughing <a href="https://books.google.com.au/books?id=mOqODwAAQBAJ&pg=PA107&lpg=PA107&dq=hypoxemia++%22controlled+cough%22&source=bl&ots=k254DYbDkD&sig=ACfU3U2C5lJuGblV3mgKdKX2Ej5Dcp1XyA&hl=en&sa=X&ved=2ahUKEwjOqdm0xtfoAhUQzDgGHWAVDuQQ6AEwA3oECAgQNQ#v=onepage&q=controlled%20cough&f=false">can help</a> remove the mucus and make it easier for people to breathe. </p>
<p>This technique may be done as part of chest physiotherapy, along with other lung clearance techniques, in a hospital. The technique is not dangerous, but the contents of what is coughed out can be.</p>
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Read more:
<a href="https://theconversation.com/explainer-what-is-cystic-fibrosis-and-how-is-it-treated-59681">Explainer: what is cystic fibrosis and how is it treated?</a>
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<h2>So can it help with the coronavirus?</h2>
<p>So what’s the evidence controlled coughing could help people manage their coronavirus symptoms? Put simply, there are no clinical trials or good evidence. </p>
<p>One common COVID-19 symptom is a <a href="https://www.who.int/news-room/q-a-detail/q-a-coronaviruses#:%7E:text=symptoms">dry cough</a>. So it’s difficult to imagine why controlled coughing would help when you’re coughing so much anyway.</p>
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Read more:
<a href="https://theconversation.com/can-coronavirus-spread-through-food-can-anti-inflammatories-like-ibuprofen-make-it-worse-coronavirus-claims-checked-by-experts-133911">Can coronavirus spread through food? Can anti-inflammatories like ibuprofen make it worse? Coronavirus claims checked by experts</a>
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<h2>Is there any harm in trying?</h2>
<p>There is a very real risk that unintentionally this technique would actually spread the virus. </p>
<p>When we cough we produce a lot of droplets of mucus from the <a href="https://academic.oup.com/cid/article/46/1/93/338992">lungs</a> that are spread as a spray.
My research <a href="https://iopscience.iop.org/article/10.1088/1752-7155/10/4/046002">has also shown</a> breathing out forcefully is enough to propel viruses from the lungs this way.</p>
<p>Either way large sprays of viruses could infect other people. </p>
<p>In hospital, this risk is minimised by having specialised negative pressure rooms that remove the contaminated air. Patients wear masks to capture the sprays and clinical staff wear personal protective equipment, including masks and face shields. There are also strict infection control measures, such as limits on visitors and hand washing. Yet the risks of transmission remain high.</p>
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<strong>
Read more:
<a href="https://theconversation.com/no-5g-radiation-doesnt-cause-or-spread-the-coronavirus-saying-it-does-is-destructive-135695">No, 5G radiation doesn't cause or spread the coronavirus. Saying it does is destructive</a>
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<p>But if you practise controlled coughing at home or on the bus, it’s easy to see how you could inadvertently spread the virus.</p>
<p>And of course, the technique doesn’t kill the virus or cure anyone.</p>
<h2>So what are we to make of all this?</h2>
<p>So why did JK Rowling endorse this technique? In essence, it’s because she believed it helped her, and thought it would help others.</p>
<p>However, her tweet says she <a href="https://twitter.com/jk_rowling/status/1247121896082157568">hadn’t been tested</a> for COVID-19, so it’s not certain she had the infection. And she may or may not have benefited from the technique. Perhaps her symptoms may have improved by themselves anyway. It’s hard to know.</p>
<p>My advice is to seek medical advice if you suspect you have the coronavirus rather than rely on testimonials, however well meaning. </p>
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<em>
<strong>
Read more:
<a href="https://theconversation.com/coronavirus-how-long-does-it-take-to-get-sick-how-infectious-is-it-will-you-always-have-a-fever-covid-19-basics-explained-132963">Coronavirus: how long does it take to get sick? How infectious is it? Will you always have a fever? COVID-19 basics explained</a>
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<img src="https://counter.theconversation.com/content/135935/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Brian Oliver receives funding from the NHMRC and the ARC.
Brian Oliver is the co-director of the Respiratory, Sleep, Environmental and Occupational Health Clinical Academic group of Maridulu Budyari Gumal, the Sydney Partnership for Health, Education, Research and Enterprise (SPHERE), A NHMRC AHRTC. He is also president of the NSW branch of the thoracic society of Australia and New Zealand. </span></em></p>Controlled coughing can help people with cystic fibrosis, under supervision and in hospital. But when done at home, it could help spread the coronavirus.Brian Oliver, Research Leader in Respiratory cellular and molecular biology at the Woolcock Institute of Medical Research and Professor, Faculty of Science, University of Technology SydneyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1119082019-03-06T11:40:41Z2019-03-06T11:40:41ZAre viruses the best weapon for fighting superbugs?<figure><img src="https://images.theconversation.com/files/261720/original/file-20190301-110134-1u7yr0g.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">These are viruses called bacteriophages that infect only bacterial cells. </span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/3d-render-bacteriophage-viruses-infecting-bacterial-479306521">Ewa Parylak/shutterstock.com</a></span></figcaption></figure><p>Antibiotics won the battle against resistant bacteria, but they may not win the war.</p>
<p>You probably know that antibiotic-resistant bacteria, also known as superbugs, have hampered physicians’ ability to treat infections. You may also be aware that there has been a steep <a href="https://www.cdc.gov/drugresistance/pdf/11-2013-508.pdf">decline in the number of new antibiotics</a> coming to market. Some headlines suggest humanity is doomed by antimicrobial resistance; <a href="https://www.cnn.com/2019/01/24/health/antibiotic-resistance-climate-change-gbr-scli-intl/index.html?no-st=1551070126">even politicians and governments have weighed in</a>, comparing rising antimicrobial resistance to other popular crises such as climate change. Although I believe these assertions are exaggerated, antimicrobial resistance is a serious problem. </p>
<p><a href="http://www.thepridelaboratory.org">I am a physician scientist</a> with a <a href="http://www.thepridelaboratory.org/publications.html">specialty in infectious diseases</a>. I have been fascinated by the role that bacteria play in human health, and the potential for using viruses to treat bacterial infections. </p>
<h2>What causes antimicrobial resistance?</h2>
<p>One significant factor contributing to antimicrobial resistance is the <a href="https://www.ncbi.nlm.nih.gov/pubmed/25859123">excessive use of antibiotics</a>. In the U.S., where antibiotics are widely available, some patients demand these drugs for many different illnesses. Many physicians appease their patients because they <a href="https://www.pewtrusts.org/en/research-and-analysis/articles/2017/06/30/why-doctors-prescribe-antibiotics-even-when-they-shouldnt">don’t understand when and when not</a> to use them and because there is <a href="https://www.cddep.org/wp-content/uploads/2017/06/antibiotic_legislation_timeline.pdf">no regulatory structure to limit their use</a>. Anyone with a prescription pad can prescribe any antibiotic to treat any condition and rarely, if ever, face any consequences. There are some <a href="https://www.cdc.gov/antibiotic-use/stewardship-report/outpatient.html">efforts to reduce antibiotic</a> use, but the scope of the problem in the U.S. remains large.</p>
<p>Some countries, <a href="https://www.who.int/bulletin/volumes/95/11/16-184374/en/">such as Sweden</a>, use incentives to encourage doctors to improve antibiotic uses. But there is no counterpart for this system in U.S. hospitals and clinics. </p>
<p>The problem goes beyond humans; 70 percent of all antibiotics <a href="http://www.cidrap.umn.edu/news-perspective/2016/12/fda-antibiotic-use-food-animals-continues-rise">are actually used on animals</a>. This means that humans can be exposed to antibiotics by <a href="http://doi.org/10.3390/antibiotics6040034">just handling animal products</a>. The drumstick you are preparing for dinner might also have <a href="https://doi.org/10.1093/jac/dkg483">antibiotic-resistant bacteria</a> <a href="http://doi.org/10.1177/003335491212700103">tagging along</a>. </p>
<p>Once antimicrobial resistance develops in a bacterium, it doesn’t always go away. For example, methicillin-resistant <em>Staphylococcus aureus</em> (MRSA) evolved resistance to multiple different antibiotics; yet, despite efforts to reduce its spread by <a href="https://doi.org/10.1086/500664">limiting the use of antibiotics</a> that led to its emergence, <a href="https://doi.org/10.1086/597296">MRSA still persists</a> in hospitals and the community.</p>
<h2>An alternative to antibiotics</h2>
<p>Another reason for finding alternatives to antibiotics is that <a href="http://doi.org/10.7554/eLife.00458">we share our microbes with the people and pets who live around us</a>; thus, others can acquire one of these superbugs without ever taking an antibiotic.</p>
<p>A not-so-obvious reason for developing new therapies is that our bodies are home to a large community of microorganisms, including bacteria, called our microbiome. These microorganisms are necessary to maintain our health. Those same antibiotics that kill harmful bacteria also kill the good ones. </p>
<p>There is an alternative to antibiotics, but it was dismissed by medicine years ago. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/261739/original/file-20190301-110143-1ch0sto.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/261739/original/file-20190301-110143-1ch0sto.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/261739/original/file-20190301-110143-1ch0sto.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=307&fit=crop&dpr=1 600w, https://images.theconversation.com/files/261739/original/file-20190301-110143-1ch0sto.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=307&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/261739/original/file-20190301-110143-1ch0sto.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=307&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/261739/original/file-20190301-110143-1ch0sto.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=386&fit=crop&dpr=1 754w, https://images.theconversation.com/files/261739/original/file-20190301-110143-1ch0sto.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=386&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/261739/original/file-20190301-110143-1ch0sto.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=386&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">Antibiotics or wrong diet damage the good and bad bacteria flora living in the gut.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/antibiotics-wrong-diet-damage-good-bad-1225328413">Soleil Nordic/Shutterstockcom</a></span>
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<h2>The original phage therapy story</h2>
<p>That alternative was something called phage therapy, which uses viruses that infect bacteria, called bacteriophages, to kill disease-causing bacteria. Bacteriophages, or phages, were used frequently in the <a href="http://doi.org/10.4161/viru.25991">early- and pre- antibiotic eras</a> between the 1920s and ‘40s to treat life-threatening infections. </p>
<p>But phage therapy had many disadvantages. The first was that phages were unpredictable. One type of phage might wipe out the bad bacteria in one individual but not another’s. So hospitals had to keep a broad collection of phages to kill disease-causing bacteria from all their patients. An antibiotic such as vancomycin, by comparison, predictably kills entire groups of bacteria. </p>
<p>Another downside is that phage collections require maintenance. So not only did hospitals have to keep a large variety of phages on hand, but they had to keep them in shape. So medicine chose antibiotics for convenience, and hadn’t looked back in any meaningful way, until recently.</p>
<h2>Making a comeback?</h2>
<p>So, why is phage therapy making a comeback? Antibiotic resistance is an obvious answer, but doesn’t explain the full story. </p>
<p>As a specialist in infectious diseases, I have been interested in phage therapy as long as I can remember, but only recently have I felt comfortable saying this out loud. Why? A physician might be considered a “quack” just for mentioning phage therapy because the early attempts were neither a rousing success or a colossal failure. Like any therapeutic, it had its strengths and weaknesses. </p>
<p>However, now scientific advances can guide us toward which phage is best for destroying a particular microbe. With the rising antimicrobial resistance crisis, physicians and scientists have a well-timed opportunity to work together to develop effective phage therapies. </p>
<p>The proof of this comes from recent landmark phage therapy cases. The successful treatment of a <a href="http://doi.org/10.1128/AAC.00954-17">physician with a life-threatening infection and a grave prognosis caused by a multi-drug resistant bacterium</a> at my institution serves as a great example. Another pivotal case <a href="https://www.buzzfeednews.com/article/azeenghorayshi/phage-therapy-follow-this">circulating in popular media</a> has kept this trend going. We physicians may be able to treat just about any disease-causing bacterium; it is just a matter of finding a suitable phage. </p>
<p>A big part of phage therapy research is devoted to “<a href="https://seaphages.org/">phage hunting</a>,” where we microbiologists scour the soil, the oceans and the human body to identify phages with the potential to kill the bacteria that ail us. While the pace of these studies has been slow, the new research is revealing the therapeutic potential of phages in medicine.</p>
<p>You might think that with all the phage hunting and landmark cases that we would start using phage therapy all the time, but we don’t. </p>
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<a href="https://images.theconversation.com/files/261740/original/file-20190301-110110-8ixh81.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/261740/original/file-20190301-110110-8ixh81.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/261740/original/file-20190301-110110-8ixh81.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=338&fit=crop&dpr=1 600w, https://images.theconversation.com/files/261740/original/file-20190301-110110-8ixh81.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=338&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/261740/original/file-20190301-110110-8ixh81.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=338&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/261740/original/file-20190301-110110-8ixh81.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=424&fit=crop&dpr=1 754w, https://images.theconversation.com/files/261740/original/file-20190301-110110-8ixh81.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=424&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/261740/original/file-20190301-110110-8ixh81.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">Bacteriophages target only specific stains of bacteria.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/3d-illustration-bacteriophage-infecting-bacterium-1126283543">Design_Cells/Shutterstock.com</a></span>
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<h2>The case for using phages</h2>
<p>One advantage of antibiotics is that since they have been used for decades, we know a lot about their safety. Physicians make simple calculations every day about the risk-benefit ratio of using antibiotics, but aren’t equipped to make the same calculations about phages. Does anyone really want a doctor injecting them with a virus to cure a bacterial infection? I doubt that would be anyone’s choice when the question is posed that way. </p>
<p>But, remember that phages are natural. They’re on every surface of your body. They are in the ocean and soil, and in your toilet and sink. They are literally everywhere. Thus, putting a phage into your body to kill a bacterium quite frankly is something that nature does to us every single day, and as far as we know, we are no worse for the wear. </p>
<p>Phages are estimated to <a href="https://daily.jstor.org/fighting-bacterial-infection-with-viruses/?utm_source=marketing&utm_medium=social&utm_campaign=twitter">kill half the world’s bacteria</a> every 48 hours and are probably the most potent antibacterial agents out there. Is there really a compelling reason to be concerned when a doctor gives us a phage instead of us acquiring that same phage from our sink at home? Only time will tell. Unfortunately, as antimicrobial resistance continues to rise, time may not be on our side.</p><img src="https://counter.theconversation.com/content/111908/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 organization that would benefit from this article, and have disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Bacteria are becoming resistant to even the most powerful antibiotics. These expensive, hard-to-treat infections are prompting physicians to reassess using viruses to destroy bacteria.David Pride, Associate Director of Microbiology, University of California, San DiegoLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1044492018-10-05T12:12:10Z2018-10-05T12:12:10ZHow astrophysics could transform the treatment of cystic fibrosis and other rare diseases<figure><img src="https://images.theconversation.com/files/239362/original/file-20181004-52669-14svhu1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><span class="source">NASA, ESA, H</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span></figcaption></figure><p>It’s a cruel disease which <a href="https://www.nhs.uk/conditions/cystic-fibrosis/">dramatically shortens life expectancy</a>. One in 25 Europeans carry the cystic fibrosis gene and, in the UK, about 10,400 people currently have the condition. But people are living longer and longer thanks to improvements in screening at birth, early treatment and medication. </p>
<p>One of the most important things is for patients to be put on the medication that will most effectively inhibit the progression of the disease – there are a <a href="https://www.nhs.uk/conditions/cystic-fibrosis/treatment/">number of different options</a> available. Understanding the progression of the disease over time – and how this is influenced by medication and environmental factors – is vital to improving patient prognosis. But different people respond differently to drugs, inhabit different environments and the timescale of progression is long. </p>
<p>So the question is, how can doctors predict which patient will respond best to which treatment? Unfortunately this remains quite challenging. Curiously though, we have developed a new technique based on astrophysical research, <a href="https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0199815">published in PLOS One</a>, that may be a game changer.</p>
<p>The key to any research on the treatment of diseases is big data. In common diseases, such as cancer, high-quality datasets for many patients over time can be constructed within one administrative system – such as a regional or national health authority. These can be efficiently anonymised so that researchers can study the progression of individuals or groups of patients over time using anonymous identifiers. </p>
<p>The challenge with cystic fibrosis, as a rare disease, is how to assemble large samples of patients. Countries hold their own datasets of patients, but the sample sizes are small. The <a href="https://www.ecfs.eu/ecfspr">European Cystic Fibrosis Society Patient Registry</a>, which today includes data from more than 42,000 people, was established to merge national data sets. But the data quality is not always uniform and – with the anonymisation required to share data – often the vital threads that linked the different data for a single patient over time were broken. Without anonymous identifiers it is impossible to carry out longitudinal studies following groups of patients over time.</p>
<h2>Telescopes versus clinics</h2>
<p>Working with my student – and then colleague – <a href="http://www.sussex.ac.uk/profiles/188689">Peter Hurley</a>, who has cystic fibrosis, we realised that at as astrophysicists familiar with analysing the data of hundreds of thousands of galaxies, we might have a potential solution. In astronomy, one of our challenges is to link a celestial object such as a distant galaxy in an image taken by one telescope with the same object in another image from a different telescope. </p>
<p>This is harder than you might think, as some telescopes are much lower resolution than others. A bright “blob” that you think is a galaxy in one image might overlap with many galaxies in a higher resolution image. Also, different galaxies have different colours, so may or may not be visible to different telescopes (they typically only detect specific wavelengths of light). We match galaxies using a <a href="https://www.analyticsvidhya.com/blog/2016/06/bayesian-statistics-beginners-simple-english/">computational framework</a> which calculates the probability that a pair of celestial objects in two images are actually the same and compare this with an alternative hypothesis that they might be two different objects that just happen to be close. </p>
<p>For example, given an observed separation and the known positional errors of the objects in our catalogues we can calculate the probability that the true separation is zero (they are the same). Likewise, knowing the density of galaxies, we can calculate how likely it is that one would happen, by chance, to lie within a circle with radius of that observed separation. </p>
<p>We therefore hoped that by using the same techniques we might be able to link different records that belong to the same patient. The obvious way to link objects in two astronomical catalogues is by position. One object would be linked to an object at the same position in the second catalogue. By analogy we could link two records in a patient registry if they had the same age, gender, genetic or other characteristics. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/239484/original/file-20181005-72124-1kdrncx.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/239484/original/file-20181005-72124-1kdrncx.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=449&fit=crop&dpr=1 600w, https://images.theconversation.com/files/239484/original/file-20181005-72124-1kdrncx.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=449&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/239484/original/file-20181005-72124-1kdrncx.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=449&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/239484/original/file-20181005-72124-1kdrncx.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=564&fit=crop&dpr=1 754w, https://images.theconversation.com/files/239484/original/file-20181005-72124-1kdrncx.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=564&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/239484/original/file-20181005-72124-1kdrncx.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=564&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Clubbing of the fingers is a common feature of Cystic Fibrosis.</span>
<span class="attribution"><span class="source">Jerry Nick, M.D./wikipedia</span>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
</figcaption>
</figure>
<p>But this is often not enough. Two different galaxies can have similar positions and two different patients can have the same age, gender and <a href="http://www.bbc.co.uk/bitesize/intermediate2/biology/environmental_and_genetics/phenotype_and_genotype/revision/1/">genotype</a>. To refine the matches, we need to consider more characteristics. But these may vary – for example, a galaxy’s brightness may be different depending on which telescope measures it. And a patient’s weight may change from one clinic visit to another. In astronomy we solve this by having a model of how galaxy light varies as seen through different telescopes.</p>
<p>A key factor of our method was that we included an analogous model for how patients’ body mass index was expected to vary over time. Body mass index appears in every patient record and we know how it varies with age and progression of cystic fibrosis. </p>
<h2>New answer book</h2>
<p>Working with <a href="https://www.dundee.ac.uk/medicine/staff/profile/anil-mehta.php">Anil Mehta at the University of Dundee</a>, who had been instrumental in establishing the European Cystic Fibrosis Society Patient registry, we tested the algorithm on a subset of the data that came from Denmark. This was believed to the best data set – the records belonging to any one patient could be reliably linked through an anonymous identifier that was provided. This meant we had an answer book. </p>
<p>We matched the records blindly without using this identifier and then checked our answers. We were reasonably happy with our results. However, on closer inspection, it transpired that many of the cases where we appeared to be wrong were actually clerical errors arising in the manual entry of the anonymous patient identifiers into the Danish database. So, our matches were correct but the answer book was wrong. That meant that in the European Cystic Fibrosis Society Patient Registry, thanks to the algorithm derived from astrophysics, there is a complete and accurate version of the Danish dataset showing the progress of patients year on year which can be matched against their medication or any other factor desired.</p>
<p>We published our method in a paper so that others working on patient registry databases, particularly those for rare diseases, could apply this technique to join records for patients where they don’t already exist or to check and clean their data sets. We hope to do further work with the European Cystic Fibrosis Society Patient Registry to provide links for all their records, and are awaiting for approval for this.</p>
<p>Hopefully this will offer some hope to people with cystic fibrosis and other rare diseases that researchers may soon have a better chance to find factors and medicines that can improve their quality of life.</p><img src="https://counter.theconversation.com/content/104449/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Seb Oliver receives or has received funding from the UK's Science Technology Facilities Council and from the European Research Executive agency for research in astronomy and interdisciplinary research
Seb Oliver is an advisor for DataJavelin - a machine-learning and statistical consultancy company co-founded by Peter Hurley who was a co-author on this work before he left astronomy.
</span></em></p>Galaxy images and patient records can be equally confusing. Now a team of astrophysicists have realised their methods could help medical professionals.Seb Oliver, Professor of Astrophysics, University of SussexLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1004992018-09-07T10:44:46Z2018-09-07T10:44:46ZDiscovering the ancient origin of cystic fibrosis, the most common genetic disease in Caucasians<figure><img src="https://images.theconversation.com/files/234132/original/file-20180829-195310-iy112y.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The airways inside the human lung.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/human-respiratory-system-lungs-inside-anatomy-1039667662?src=KjqZGrlNVZp4XYjszzMEuA-1-13">Magic mine/Shutterstock.com</a></span></figcaption></figure><p>Imagine the thrill of discovery when more than 10 years of research on the origin of a common genetic disease, cystic fibrosis (CF), results in tracing it to a group of distinct but mysterious Europeans who lived about 5,000 years ago. </p>
<p>CF is the most common, potentially lethal, inherited disease among Caucasians – about one in 40 carry the so-called F508del mutation. Typically only beneficial mutations, which provide a survival advantage, spread widely through a population. </p>
<p>CF hinders the release of digestive enzymes from the pancreas, which triggers malnutrition, causes lung disease that is eventually fatal and produces high levels of salt in sweat that can be life-threatening.</p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/234126/original/file-20180829-195331-1kvwznv.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/234126/original/file-20180829-195331-1kvwznv.png?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/234126/original/file-20180829-195331-1kvwznv.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=702&fit=crop&dpr=1 600w, https://images.theconversation.com/files/234126/original/file-20180829-195331-1kvwznv.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=702&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/234126/original/file-20180829-195331-1kvwznv.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=702&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/234126/original/file-20180829-195331-1kvwznv.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=882&fit=crop&dpr=1 754w, https://images.theconversation.com/files/234126/original/file-20180829-195331-1kvwznv.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=882&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/234126/original/file-20180829-195331-1kvwznv.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=882&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Depending on the mutation a patient carries, they may experience some or all symptoms of cystic fibrosis.</span>
<span class="attribution"><a class="source" href="https://upload.wikimedia.org/wikipedia/commons/9/9e/Blausen_0286_CysticFibrosis.png">Blausen.com staff (2014)</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
</figcaption>
</figure>
<p>In recent years, scientists have revealed many aspects of this deadly lung disease which have led to routine early diagnosis in screened babies, better treatments and longer lives. On the other hand, the scientific community hasn’t been able to figure out when, where and why the mutation became so common. Collaborating with an extraordinary team of European scientists such as <a href="http://www.ucd.ie/research/people/medicine/professordavidbarton/">David Barton</a> in Ireland and <a href="https://rd-connect.eu/person/milan-macek/">Milan Macek</a> in the Czech Republic, in particular a group of brilliant geneticists in Brest, France led by <a href="https://www.univ-brest.fr/umr1078/">Emmanuelle Génin and Claude Férec</a>, we believe that we now know where and when the original mutation arose and in which ancient tribe of people. </p>
<p>We share these findings in <a href="http://doi.org/10.1038/s41431-018-0234-z">an article</a> in the European Journal of Human Genetics which represents the culmination of 20 years’ work involving nine countries. </p>
<h2>What is cystic fibrosis?</h2>
<p>My quest to determine how CF arose and why it’s so common began soon after scientists discovered the <a href="http://doi.org/10.1126/science.2570460">CFTR gene causing the disease in 1989</a>. The most common mutation of that gene that causes the disease was called F508del. Two copies of the mutation – one inherited from the mother and the other from the father – caused the lethal disease. But, inheriting just a single copy caused no symptoms, and made the person a “carrier.” </p>
<p>I had been employed at the University of Wisconsin since 1977 as a physician-scientist focusing on the early diagnosis of CF through newborn screening. Before the gene discovery, we identified babies at high risk for CF using a blood test that measured levels of protein called immunoreactive trypsinogen (IRT). High levels of IRT suggested the baby had CF. When I learned of the gene discovery, I was convinced that it would be a game-changer for both screening test development and epidemiological research. </p>
<p>That’s because with the gene we could offer parents a more informative test. We could tell them not just whether their child had CF, but also whether they carried two copies of a CFTR mutation, which caused disease, or just one copy which made them a carrier. </p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/234899/original/file-20180904-45163-r7ri2q.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/234899/original/file-20180904-45163-r7ri2q.png?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/234899/original/file-20180904-45163-r7ri2q.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=717&fit=crop&dpr=1 600w, https://images.theconversation.com/files/234899/original/file-20180904-45163-r7ri2q.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=717&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/234899/original/file-20180904-45163-r7ri2q.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=717&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/234899/original/file-20180904-45163-r7ri2q.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=901&fit=crop&dpr=1 754w, https://images.theconversation.com/files/234899/original/file-20180904-45163-r7ri2q.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=901&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/234899/original/file-20180904-45163-r7ri2q.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=901&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Parents carrying one good copy of the CF gene (R) and one bad copy of the mutated CF gene (r) are called carriers. When both parents transmit a bad copy of the CF gene to their offspring, the child will suffer from cystic fibrosis. Children who inherit just one bad copy will be carriers like their parents and can transmit the gene to their children.</span>
<span class="attribution"><a class="source" href="https://upload.wikimedia.org/wikipedia/commons/3/3e/Autorecessive.svg">Cburnett</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
</figcaption>
</figure>
<p>One might ask what is the connection between studying CF newborn screening and learning about the disease origin. The answer lies in how our research team in Wisconsin transformed a biochemical screening test using the IRT marker to a two-tiered method called <a href="https://www.ncbi.nlm.nih.gov/pubmed/7680526">IRT/DNA</a>. </p>
<p>Because about 90 percent of CF patients in the U.S. and Europe have at least one F508del mutation, we began analyzing newborn blood for its presence whenever the IRT level was high. But when this two-step IRT/DNA screening is done, not only are patients with the disease diagnosed but also tenfold more infants who are genetic carriers of the disease are identified. </p>
<p>As preconception-, prenatal- and neonatal screening for CF have proliferated during the past two decades, the many thousands of individuals who discovered they were F508del carriers and their concerned parents often raised questions about the origin and significance of carrying this mutation themselves or in their children. Would they suffer with one copy? Was there a health benefit? It has been frustrating for a pediatrician specializing in CF to have no answer for them. </p>
<h2>The challenge of finding origin of the CF mutation</h2>
<p>I wanted to zero in on when this genetic mutation first starting appearing. Pinpointing this period would allow us to understand how it could have evolved to provide a benefit – at least initially – to those people in Europe who had it. To expand my research, I decided to take a sabbatical and train in epidemiology while taking courses in 1993 at the London School of Hygiene and Tropical Medicine. </p>
<p>The timing was perfect because the field of ancient DNA research was starting to blossom. New breakthrough techniques like the <a href="https://www.genome.gov/10000207/polymerase-chain-reaction-pcr-fact-sheet/">Polymerase Chain Reaction</a> made it possible to study the DNA of mummies and other human archaeological specimens from prehistoric burials. For example, early studies were performed on the DNA from the 5,000-year-old Tyrolean Iceman, which later became known as Ötzi. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/234886/original/file-20180904-45178-1or9mgf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/234886/original/file-20180904-45178-1or9mgf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/234886/original/file-20180904-45178-1or9mgf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/234886/original/file-20180904-45178-1or9mgf.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/234886/original/file-20180904-45178-1or9mgf.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/234886/original/file-20180904-45178-1or9mgf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/234886/original/file-20180904-45178-1or9mgf.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/234886/original/file-20180904-45178-1or9mgf.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 typical prehistoric burial in a crouched fetal position.</span>
<span class="attribution"><span class="source">Philip Farrell</span>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
</figcaption>
</figure>
<p>I decided that we might be able to discover the origin of CF by analyzing the DNA in the teeth of Iron Age people buried between 700-100 B.C. in cemeteries throughout Europe. </p>
<p>Using this strategy, I teamed up with archaeologists and anthropologists such as <a href="http://www.nhm-wien.ac.at/en/maria_teschler-nicola">Maria Teschler-Nicola</a> at the Natural History Museum in Vienna, who provided access to 32 skeletons buried around 350 B.C. near Vienna. Geneticists in France collected DNA from the ancient molars and analyzed the DNA. To our surprise, we discovered the presence of the F508del mutation in DNA from <a href="http://hdl.nature.com/10101/npre.2007.1276.1">three of 32 skeletons</a>. </p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/234887/original/file-20180904-45163-1ot0fo8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/234887/original/file-20180904-45163-1ot0fo8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/234887/original/file-20180904-45163-1ot0fo8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/234887/original/file-20180904-45163-1ot0fo8.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/234887/original/file-20180904-45163-1ot0fo8.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/234887/original/file-20180904-45163-1ot0fo8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/234887/original/file-20180904-45163-1ot0fo8.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/234887/original/file-20180904-45163-1ot0fo8.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">The Natural History Museum in Vienna, Austria, houses a large collection of Iron Age and Bronze Age skeletons which are curated by Dr. Maria Teschler-Nicola. These collections were the source of teeth and bones for investigation of ancient DNA and studies on ‘The Ancient Origin of Cystic Fibrosis.’</span>
<span class="attribution"><span class="source">Philip Farrell</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<p>This discovery of F508del in Central European Iron Age burials radiocarbon-dated to 350 B.C. suggested to us that the original CF mutation may have arisen earlier. But obtaining Bronze Age and Neolithic specimens for such direct studies proved difficult because fewer burials are available, skeletons are not as well-preserved and each cemetery merely represents a tribe or village. So rather than depend on ancient DNA, we shifted our strategy to examine the genes of modern humans to figure out when this mutation first arose. </p>
<h2>Why would a harmful mutation spread?</h2>
<p>To find the origin of CF in modern patients, we knew we needed to learn more about the signature mutation – F508del – in people who are carriers or have the disease.</p>
<p>This tiny mutation causes loss of one amino acid out of the 1,480 amino acid chain and changes the shape of a protein on the surface of the cell that moves chloride in and out of the cell. When this protein is mutated, people carrying two copies of it – one from the mother and one from the father – are plagued with thick sticky mucus in their lungs, pancreas and other organs. The mucus in their lungs allows bacteria to thrive, destroying the tissue and eventually causing the lungs to fail. In the pancreas, the thick secretions prevent the gland from delivering the enzymes the body needs to digest food.</p>
<p>So why would such a harmful mutation continue to be transmitted from generation to generation? </p>
<p>A mutation as harmful as F508del would never have survived among people with two copies of the mutated CFTR gene because they likely died soon after birth. On the other hand, those with one mutation may have a survival advantage, as predicted in Darwin’s “survival of the fittest” theory. </p>
<figure class="align-left zoomable">
<a href="https://images.theconversation.com/files/234127/original/file-20180829-195316-1w7clvs.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/234127/original/file-20180829-195316-1w7clvs.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/234127/original/file-20180829-195316-1w7clvs.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=504&fit=crop&dpr=1 600w, https://images.theconversation.com/files/234127/original/file-20180829-195316-1w7clvs.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=504&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/234127/original/file-20180829-195316-1w7clvs.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=504&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/234127/original/file-20180829-195316-1w7clvs.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=633&fit=crop&dpr=1 754w, https://images.theconversation.com/files/234127/original/file-20180829-195316-1w7clvs.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=633&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/234127/original/file-20180829-195316-1w7clvs.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=633&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Individuals who carry two copies of the sickle cell gene suffer from sickle cell anemia, in which the blood cells become rigid sickle shapes and get stuck in the blood vessels, causing pain. Normal red blood cells are flexible discs that slide easily through vessels.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/anemia-sickle-cell-normal-red-blood-241008361">Designua/Shutterstock.com</a></span>
</figcaption>
</figure>
<figure class="align-left zoomable">
<a href="https://images.theconversation.com/files/234129/original/file-20180829-195304-1aihbbe.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/234129/original/file-20180829-195304-1aihbbe.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/234129/original/file-20180829-195304-1aihbbe.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=507&fit=crop&dpr=1 600w, https://images.theconversation.com/files/234129/original/file-20180829-195304-1aihbbe.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=507&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/234129/original/file-20180829-195304-1aihbbe.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=507&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/234129/original/file-20180829-195304-1aihbbe.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=637&fit=crop&dpr=1 754w, https://images.theconversation.com/files/234129/original/file-20180829-195304-1aihbbe.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=637&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/234129/original/file-20180829-195304-1aihbbe.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=637&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 copies of the sickle cell gene cause the disease. But carrying one copy reduces the risk of malaria. The gene is widespread among people who live in regions of the world (red) where malaria is endemic.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-vector/sickle-cell-anemia-geographic-distribution-252812350">ellepigrafica</a></span>
</figcaption>
</figure>
<p>Perhaps the best example of a mutation favoring survival under stressful environmental conditions can be found in Africa, where fatal malaria has been endemic for centuries. The parasite that causes malaria infects the red blood cells in which the major constituent is the oxygen-carrying protein hemoglobin. Individuals who carry the normal hemoglobin gene are vulnerable to this mosquito-borne disease. But those who are carriers of the mutated “hemoglobin S” gene, with only one copy, are protected from severe malaria. However two copies of the hemoglobin S gene causes sickle cell disease, which can be fatal. </p>
<p>Here there is a <a href="http://doi.org/10.1016/j.amepre.2011.09.013">clear advantage to carrying one mutant gene</a> – in fact, about one in 10 Africans carries a single copy. Thus, for many centuries an environmental factor has favored the survival of individuals carrying a single copy of the sickle hemoglobin mutation. </p>
<p>Similarly we wondered whether there was a health benefit to carrying a single copy of this specific CF mutation during exposures to environmentally stressful conditions. Perhaps, we reasoned, that’s why the F508del mutation was common among Caucasian Europeans and Europe-derived populations. </p>
<h2>Clues from modern DNA</h2>
<p>To figure out the advantage of transmitting a single mutated F508del gene from generation to generation, we first had to determine when and where the mutation arose so that we could uncover the benefit this mutation conferred.</p>
<p>We obtained DNA samples from 190 CF patients bearing F508del and their parents residing in geographically distinct European populations from Ireland to Greece plus a Germany-derived population in the U.S. We then identified a collection of genetic markers – essentially sequences of DNA – within the CF gene and flanking locations on the chromosome. By identifying when these mutations emerged in the populations we studied, we were able to estimate the age of the most recent common ancestor.</p>
<p>Next, by rigorous computer analyses, we estimated the age of the CF mutation in each population residing in the various countries. </p>
<p>We then determined that the age of the oldest common ancestor is between 4,600 and 4,725 years and arose in southwestern Europe, probably in settlements along the Atlantic Ocean and perhaps in the region of France or Portugal. We believe that the mutation spread quickly from there to Britain and Ireland, and then later to central and southeastern European populations such as Greece, where F508del was introduced only about 1,000 years ago. </p>
<h2>Who spread the CF mutation throughout Europe?</h2>
<p>Thus, our <a href="http://doi.org/10.1038/s41431-018-0234-z">newly published data</a> suggest that the F508del mutation arose in the early Bronze Age and spread from west to southeast Europe during ancient migrations. </p>
<p>Moreover, taking the archaeological record into account, our results allow us to introduce a novel concept by suggesting that a population known as the Bell Beaker folk were the probable migrating population responsible for the early dissemination of F508del in prehistoric Europe. They appeared at the transition from the Late Neolithic period, around 4000 B.C., to the Early Bronze Age during the third millennium B.C. somewhere in Western Europe. They were distinguished by their ceramic beakers, pioneering copper and bronze metallurgy north of the Alps and great mobility. All studies, in fact, show that they were into heavy migration, traveling all over Western Europe.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/234121/original/file-20180829-195331-ziy46k.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/234121/original/file-20180829-195331-ziy46k.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=551&fit=crop&dpr=1 600w, https://images.theconversation.com/files/234121/original/file-20180829-195331-ziy46k.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=551&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/234121/original/file-20180829-195331-ziy46k.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=551&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/234121/original/file-20180829-195331-ziy46k.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=693&fit=crop&dpr=1 754w, https://images.theconversation.com/files/234121/original/file-20180829-195331-ziy46k.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=693&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/234121/original/file-20180829-195331-ziy46k.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=693&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Distribution of Bell Beaker sites throughout Europe.</span>
<span class="attribution"><a class="source" href="https://upload.wikimedia.org/wikipedia/commons/6/63/Bellbeaker_map_europe.jpg">DieKraft via Wikimedia Commons</a></span>
</figcaption>
</figure>
<p>Over approximately 1,000 years, a network of small families and/or elite tribes spread their culture from west to east into regions that correspond closely to the present-day European Union, <a href="http://doi.org/10.1016/j.jcf.2008.03.007">where the highest incidence of CF is found</a>. Their migrations are linked to the advent of Western and Central European metallurgy, as they manufactured and traded metal goods, especially weapons, while traveling over long distances. It is also speculated that their travels were motivated by establishing marriage networks. Most relevant to our study is evidence that they migrated in a direction and over a time period that fit well with our results. Recent genomic data suggest that both migration and cultural transmission played a major role in diffusion of the “Beaker Complex” and led to a “<a href="http://doi.org/10.1038/nature25738">profound demographic transformation</a>” of Britain and elsewhere after 2400 B.C. </p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/234124/original/file-20180829-195304-17hmnee.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/234124/original/file-20180829-195304-17hmnee.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/234124/original/file-20180829-195304-17hmnee.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=776&fit=crop&dpr=1 600w, https://images.theconversation.com/files/234124/original/file-20180829-195304-17hmnee.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=776&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/234124/original/file-20180829-195304-17hmnee.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=776&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/234124/original/file-20180829-195304-17hmnee.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=975&fit=crop&dpr=1 754w, https://images.theconversation.com/files/234124/original/file-20180829-195304-17hmnee.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=975&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/234124/original/file-20180829-195304-17hmnee.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=975&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Examples of tools and ceramics created by the Bell Beaker people.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:Beakerculture.jpg">Benutzer:Thomas Ihle via German Wikipedia</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
</figcaption>
</figure>
<p>Determining when F508del was first introduced in Europe and discovering where it arose should provide new insights about the high prevalence of carriers – and whether the mutation confers an evolutionary advantage. For instance, Bronze Age Europeans, while migrating extensively, were apparently spared from exposure to endemic infectious diseases or epidemics; thus, protection from an infectious disease, as in the sickle cell mutation, through this genetic mutation seems unlikely. </p>
<p>As more information on Bronze Age people and their practices during migrations become available through archaeological and genomics research, more clues about environmental factors that favored people who had this gene variant should emerge. Then, we may be able to answer questions from patients and parents about why they have a CFTR mutation in their family and what advantage this endows.</p><img src="https://counter.theconversation.com/content/100499/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Philip Farrell receives funding from the NIH and CF Foundation. </span></em></p>Cystic fibrosis is the most common genetic disease among Caucasians. Now scientists believe they have discovered the origin of this often lethal genetic mutation and how it spread throughout Europe.Philip Farrell, Professor of Pediatrics and Population Health Sciences, University of Wisconsin-MadisonLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/980632018-07-11T11:15:22Z2018-07-11T11:15:22ZTriclosan, often maligned, may have a good side — treating cystic fibrosis infections<figure><img src="https://images.theconversation.com/files/226366/original/file-20180705-122274-zwsz42.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Antibiotic-resistant bacteria inside a biofilm.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/antibiotic-resistant-bacteria-inside-biofilm-3d-733165693?src=S-PIB9t8jY1oDGnWwDSB3w-1-0">Kateryna Kon/Shutterstock.com</a></span></figcaption></figure><p>Maybe you’ve had the experience of wading in a stream and struggling to keep your balance on the slick rocks, or forgetting to brush your teeth in the morning and feeling a slimy coating in your mouth. These are examples of <a href="http://www.biofilm.montana.edu/biofilm-basics/index.html">bacterial biofilms</a> that are found anywhere a surface is exposed to bacteria in a moist environment.</p>
<p>Besides leading to falls in streams or creating unhealthy teeth, <a href="https://theconversation.com/unlocking-the-secrets-of-bacterial-biofilms-to-use-against-them-59148">biofilms</a> can cause large problems when they infect people. Biofilms, multicellular communities of bacteria that can grow on a surface encased in their own self-produced matrix of slime, <a href="https://www.sciencedirect.com/science/article/pii/B9780128002629000019?via%3Dihub">can block immune cells</a> from engulfing and killing the bacteria or prevent antibodies from binding to their surface. </p>
<p>On top of this, bacteria in a biofilm <a href="http://www.jbc.org/content/291/24/12565.long">resist being killed</a> by antibiotics due to the sticky nature of the matrix and activation of inherent resistant mechanisms, such as slow-growing cells or the ability to pump antibiotics out of the cell. </p>
<p>Biofilms are one of the primary growth modes of bacteria, but all antibiotics currently used clinically were developed against <a href="http://www.mdpi.com/1420-3049/20/4/5286/htm">free-swimming planktonic bacteria</a>. This is why they do not work well against biofilms. </p>
<p><a href="https://msu.edu/%7Ewatersc3/">My laboratory</a> studies how and why bacteria make biofilms, and we develop new therapeutics to target them. Because <a href="https://www.nature.com/articles/s41579-018-0019-y">antibiotic resistance</a> is the most problematic aspect of biofilms during infections, we set out to identify novel molecules that could enhance antibiotic activity against these communities. </p>
<p>We discovered that an antimicrobial that has recently obtained a bad reputation for overuse in many household products could be the secret sauce to kill biofilms.</p>
<h2>The hunt for antibiotic superchargers</h2>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/226772/original/file-20180709-122277-1xmz7kg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/226772/original/file-20180709-122277-1xmz7kg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=472&fit=crop&dpr=1 600w, https://images.theconversation.com/files/226772/original/file-20180709-122277-1xmz7kg.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=472&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/226772/original/file-20180709-122277-1xmz7kg.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=472&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/226772/original/file-20180709-122277-1xmz7kg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=593&fit=crop&dpr=1 754w, https://images.theconversation.com/files/226772/original/file-20180709-122277-1xmz7kg.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=593&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/226772/original/file-20180709-122277-1xmz7kg.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=593&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Dr. Alessandra Agostinho Hunt measures biofilm formation of <em>Psuedomonas aerugionsa</em> by pipetting in the purple dye crystal violet to stain the microbial structure.</span>
<span class="attribution"><span class="source">Derrick Turner/Michigan State University</span>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
</figcaption>
</figure>
<p>To find such compounds, we developed an <a href="https://www.medicinenet.com/script/main/art.asp?articlekey=8412">assay</a> to grow plates of 384 tiny <a href="http://aac.asm.org/content/62/6/e00146-18.long">biofilms</a> of the bacterium <a href="https://www.tandfonline.com/doi/abs/10.1517/14728220903454988?journalCode=iett20"><em>Pseudomonas aeruginosa</em></a>. We did this to screen for molecules that enhance killing by the antibiotic <a href="https://www.rxlist.com/consumer_tobramycin_nebcin/drugs-condition.htm">tobramycin</a>. We chose this bacterium and this antibiotic as our test subjects because they are commonly associated with <a href="https://www.cff.org/Life-With-CF/Daily-Life/Germs-and-Staying-Healthy/What-Are-Germs/Pseudomonas/">cystic fibrosis lung infections</a> and treatment.</p>
<p>People with cystic fibrosis (CF) are at particular risk from <a href="https://www.ncbi.nlm.nih.gov/pubmed/19374653">biofilm-based infections</a>. These infections often become chronic in the lungs of cystic fibrosis patients and are often never cleared, even with aggressive antibiotic therapy.</p>
<p>After we screened 6,080 small molecules in the presence of tobramycin, we found multiple compounds that showed the antibiotic enhancement activity we were searching for. Of particular interest was the antimicrobial <a href="https://www.fda.gov/ForConsumers/ConsumerUpdates/ucm205999.htm">triclosan</a> because it has been widely used in household products like toothpaste, soaps and hand sanitizers for decades, indicating that it had potential to be safely used in CF patients. <a href="https://onlinelibrary.wiley.com/doi/abs/10.1002/jat.1660">Triclosan</a> has also garnered a <a href="https://theconversation.com/why-you-should-dispense-with-antibacterial-soaps-65297">bad reputation</a> due to its overuse, and states like Minnesota have banned it from these products. The <a href="https://theconversation.com/why-you-should-dispense-with-antibacterial-soaps-65297">Food and Drug Administration banned</a> its use from hand soaps in September 2016. This ruling was not based on safety concerns, but rather because the companies that made these products did not demonstrate higher microbial killing when triclosan was added, compared to the base products alone.</p>
<p>Another fact that piqued our interest is that <em>P. aeruginosa</em> is resistant to triclosan. Indeed, treatment with either tobramycin or triclosan alone had very little activity against <em>P. aeruginosa</em> biofilms, but we found that the combination was 100 times more active, killing over 99 percent of the bacteria.</p>
<p>We further studied this combination and found that it worked against <em>P. aeruginosa</em> and other bacterial species that had been isolated from the lungs of CF patients. The combination also significantly enhanced the speed of killing so that at two hours of treatment, virtually all of the biofilm is eradicated. </p>
<p>Our efforts are now focused on pre-clinical development of the <a href="https://www.tobipodhaler.com/index.jsp?usertrack.filter_applied=true&NovaId=2935377102246013691">tobramycin-triclosan combination</a>. For CF, we envision patients will inhale these antimicrobials as a combination therapy, but it could also be used for other applications such as diabetic non-healing wounds. </p>
<p>Although questions about the safety of triclosan have emerged in the mainstream media, there are actually dozens of studies, including in humans, <a href="https://ec.europa.eu/health/ph_risk/committees/04_sccp/docs/sccp_o_166.pdf">concluding that it is well tolerated</a>, summarized in this extensive EU report from 2009. My laboratory completely agrees that triclosan has been significantly overused, and it should be reserved to combat life-threatening infections.</p>
<p>The next steps for development are to initiate safety, efficacy and pharmacological studies. And thus far, our own studies indicate that <a href="http://aac.asm.org/content/early/2018/04/10/AAC.00146-18.full.pdf+html">triclosan is well tolerated</a> when directly administered to the lungs. We hope that in the near future we will have enough data to initiate clinical trials with the FDA to test the activity of this combination in people afflicted with biofilm-based infections.</p>
<p>We think our approach of enhancing biofilm activity with the addition of novel compounds will increase the usefulness of currently used antibiotics. Learning about how these compounds work will also shed light on how bacterial biofilms resist antibiotic therapy.</p><img src="https://counter.theconversation.com/content/98063/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Chris Waters receives funding from the NIH, NSF, Michigan State University, and Hunt for a Cure Foundation to support this research.</span></em></p>Triclosan, an ingredient in soap and many household cleansers, has gained a bad reputation. A recent study looking for a way to boost an antibiotic, however, found that tricloscan did a great job.Chris Waters, Associate Professor of Microbiology, Michigan State UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/879102017-12-21T22:26:52Z2017-12-21T22:26:52ZWhy can’t Canada win another Nobel Prize in medicine?<figure><img src="https://images.theconversation.com/files/200284/original/file-20171220-4965-k2ddi9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Only one Canadian researcher has ever received the Nobel Prize for medicine, for the discovery of insulin in 1923. And yet Canadians have been essential to developments in stem cell research, gene sequencing and treatments for cancer and brain trauma.</span> <span class="attribution"><span class="source">(Shutterstock)</span></span></figcaption></figure><p>In 1923, the first and only Nobel Prize in medicine for a Canadian discovery was awarded to <a href="https://www.youtube.com/watch?v=WnME08SiJ0k">Frederick Banting</a> for <a href="http://www.thecanadianencyclopedia.ca/en/article/the-discovery-of-insulin/">the discovery of insulin</a>.</p>
<p>The isolation and purification of insulin, and its first injection into humans, has likely saved tens of millions of lives. Nearly 100 years later, insulin injections remain the standard treatment for Type 1 diabetes since no proven alternative exists. </p>
<p>Yet Canada has received no further recognition in the form of <a href="https://www.nobelprize.org/nobel_prizes/lists/all/">the Nobel Prize in medicine</a>, lagging far behind our G7 partners in this respect. </p>
<p>Why has this recognition eluded us? Perhaps it’s because of <a href="http://www.sciencereview.ca/eic/site/059.nsf/eng/home">a lack of public awareness and support in Canada for fundamental research in the life sciences</a>. </p>
<p>One thing is certain: The absence of Nobel attention is not for lack of Canadian advances in the life sciences. </p>
<p>I am a cell biologist, fortunate to have worked alongside Nobel Laureates in the United States and the United Kingdom. As 2017 draws to a close, I would like to take you through some of the astonishing Canadian breakthroughs since 1923 that have transformed our world for the better.</p>
<h2>How to mutate genes</h2>
<p>The foundation for discovering how to mutate genes is based on the work of a self-taught microbiologist, <a href="https://www.youtube.com/watch?v=ksrNX7r0t1U">Félix d’Hérelle</a>, who claimed birth in Montreal and won the prestigious Leeuwenhoek Medal in 1926 (Louis Pasteur was a prior winner). </p>
<p>He discovered, in 1917, that certain viruses he called “<a href="https://www.britannica.com/science/bacteriophage">bacteriophages</a>” lived by infecting bacteria.</p>
<p>Since then, the bacteriophage has become a workhorse of biomedical research with the creation of a new field known as <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4418462/">molecular biology</a>. Resulting discoveries such as the elucidation of the DNA code in the human genome and how to manipulate DNA are all a consequence of bacteriophage-based molecular biology.</p>
<p>A scientist at the University of British Columbia, <a href="https://www.youtube.com/watch?v=iylHtEuUrR8">Michael Smith</a>, used bacteriophages to discover how to mutate genes. This technology led to many applications — from cancer research to commonly used detergents that contain enzymes to remove laundry stains. A Nobel Prize in chemistry was awarded to Smith in 1993.</p>
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<p>Today, the <a href="https://www.phage.ulaval.ca/en/home/">largest collection of bacteriophages</a>, named after its discoverer, d’Hérelle, is housed at Laval University outside Quebec City. </p>
<p>The curator of this collection co-discovered how bacteria become immune to infections by bacteriophages. <a href="https://www.youtube.com/watch?v=Bz0aN5qEkyw">Sylvain Moineau</a> and his team at Laval University then discovered that bacterial resistance to infection was through the severing of the DNA of invading bacteriophages by a bacterial enzyme known as CAS9.</p>
<p>This is well known today as the <a href="https://www.wired.com/story/what-is-crispr-gene-editing/">CRISPR/CAS9 machinery used to mutate and manipulate genes</a>.</p>
<h2>Stem cells</h2>
<p>In 1953, <a href="http://www.ascb.org/ascb-post/the-stem-cell-renewal-theory-the-other-big-paper-of-1953/">Charles Leblond</a>, a McGill-based scientist, proposed the stem cell renewal theory, having discovered the asymmetry of cell division that occurs when stem cells differentiate into adult cells. </p>
<p>The key observation that stem cells divide to generate a new stem cell, and one that then undergoes further division to generate adult cells, explained how adult organs could undergo their maintenance and renewal.</p>
<p>In 1963, Toronto scientists <a href="https://www.youtube.com/watch?v=P7N-fUKjT-s">James Till</a> and <a href="https://www.youtube.com/watch?v=P7N-fUKjT-s">Ernest McCulloch</a> independently discovered the basis of bone marrow transplantation with their demonstration that all cells in the bone marrow (red blood cells, platelets and white blood cells) came from a common stem cell.</p>
<h2>The cystic fibrosis gene</h2>
<p>Two Toronto-based scientists, <a href="https://www.youtube.com/watch?v=Fhro0JlR9Pc">Lap Chee Tsui</a> and <a href="http://expired.gairdner.org/content/john-r-riordan">Jack Riordan</a>, used molecular biology to discover the cystic fibrosis gene and the mutation in the gene that caused disease. </p>
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<p>The discovery changed biomedical research, since virtually any disease caused by mutations in any gene could now be discovered. </p>
<p>This made an overwhelming case to elucidate the exact string of constituents in DNA strands that make up the DNA code in our chromosomes, and thereby define the 20,000 genes in the human genome. This was initiated through <a href="https://www.genome.gov/10001772/all-about-the--human-genome-project-hgp/">The Human Genome Project</a>, led by two labs in the U.S. and one in the U.K. Canada did not participate in the project.</p>
<h2>Cancer</h2>
<p>In 1958 at the University of Western Ontario, a scientist named <a href="http://www.cdnmedhall.org/inductees/dr-robert-noble">Robert Noble</a> extracted, from the <a href="http://www.arkive.org/madagascar-periwinkle/catharanthus-roseus/">Madagascar periwinkle plant</a>, the first compound to prevent chromosomes from separating during cell division and thereby prevent cancer cells from proliferating. </p>
<p>A pharmaceutical company in the United States commercialized this drug, known as vinblastine, prolonging the lives of thousands of cancer patients. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/200245/original/file-20171220-4951-cn3liu.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/200245/original/file-20171220-4951-cn3liu.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=402&fit=crop&dpr=1 600w, https://images.theconversation.com/files/200245/original/file-20171220-4951-cn3liu.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=402&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/200245/original/file-20171220-4951-cn3liu.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=402&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/200245/original/file-20171220-4951-cn3liu.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=505&fit=crop&dpr=1 754w, https://images.theconversation.com/files/200245/original/file-20171220-4951-cn3liu.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=505&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/200245/original/file-20171220-4951-cn3liu.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=505&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">The Madagascar Periwinkle plant.</span>
<span class="attribution"><span class="source">(Shutterstock)</span></span>
</figcaption>
</figure>
<p>Patients who take such plant-derived drugs, however, eventually become resistant. </p>
<p>It was in Toronto that scientist <a href="http://expired.gairdner.org/content/victor-ling">Victor Ling</a> discovered a protein made by a gene in humans that renders patients resistant to such chemotherapy. This discovery established a new field of drug resistance that again has led to enormous health benefits worldwide. </p>
<p>How cells communicate in cancer is also a Toronto discovery. Using viruses known to cause cancer in chickens, Toronto-based scientist <a href="https://www.youtube.com/watch?v=lVxBbwCR52o">Tony Pawson</a> discovered in 1986 a hidden code within proteins that cancer cells use to increase their runaway proliferation. </p>
<p>This discovery has led to new cancer drugs that have already benefited <a href="http://www.macleans.ca/politics/ottawa/how-do-you-fund-great-science-ask-a-great-scientist/.">thousands of patients.</a></p>
<p>Early detection of cancer in blood samples enables early, and often successful, treatment of cancer. The first such marker for cancer approved by the U.S. Food and Drug Administration was for a protein discovered by McGill scientist <a href="https://www.youtube.com/watch?v=UVB895MBh_w">Phil Gold</a> in 1965. Today, this is the single most used test globally to detect cancer.</p>
<p>With the United States hoping to launch a “<a href="https://www.cancer.gov/research/key-initiatives/moonshot-cancer-initiative">moonshot</a>” to cure cancer in our lifetime, one idea gaining popularity is to use our own immune systems to fight off cancer based on the discovery by Toronto scientist <a href="https://www.youtube.com/watch?v=k8YJx8XINyA">Tak Mak</a>. Through molecular biology, a receptor on immune cells of our body was discovered that is at the centre of therapies that utilize our own immune system to fight cancer.</p>
<p>While studying fundamental mechanisms that initiate when and where proteins are made in different cells in our body, McGill scientist <a href="http://expired.gairdner.org/content/nahum-sonenberg">Nahum Sonenberg</a> discovered how this process can result in the uncontrolled growth of cancer cells. Today, <a href="https://www.nature.com/articles/nrd4505">cancer drugs are targeted at this newly discovered mechanism</a> to alleviate cancer in patients.</p>
<h2>Autism Spectrum Disorder, memory & brain trauma</h2>
<p>Sonenberg also discovered an “initiation factor” for making proteins in cancer cells and was astonished to find that <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3906422/">mutations in this same factor</a> could lead to autism spectrum disorder in children.</p>
<p>Next, intrigued by this link to the brain, Sonenberg discovered, totally unexpectedly, that other “initiation factors” could control memory by the same process that initiates when, how much and <a href="http://www.sciencedirect.com/science/article/pii/S0896627308010891">which protein is made in the brain.</a> In collaboration with a scientist in California, they <a href="https://www.statnews.com/2016/09/28/memory-isrib-peter-walter/">discovered a drug that readily crosses the blood-brain barrier and improves memory in animal models</a> and even after brain trauma in animals.</p>
<p>With respect to neurological discoveries, two scientists, <a href="https://www.youtube.com/watch?v=QkzUocE3d3o">Wilder Penfield</a> and <a href="https://www.youtube.com/watch?v=JZSF2pkBcSw">Brenda Milner</a>, pioneered the study of the human brain in living patients at the famed Montreal Neurological institute. </p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/JZSF2pkBcSw?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
</figure>
<p>Milner, the founder of neuropsychology, discovered the networks in the brain responsible for memory and cognition. Another Montreal scientist, <a href="https://www.youtube.com/watch?v=vhylTWiG6Ow">Albert Aguayo</a> was the first to discover that nerve fibres in the spinal cord could regenerate even after trauma and injury.</p>
<h2>A Nobel before 2023?</h2>
<p>With such outstanding candidates for recognition, why has a Nobel in medicine eluded Canada since the one and only award to Frederick Banting in 1923? Nominations have been prolific for all of the above discoveries. </p>
<p>Raising public awareness may be an avenue that scientists, their host universities, research institutes and even funding agencies should consider.</p>
<p>Since it is one of the few avenues available to us, perhaps an effort to stoke genuine public interest may help us nab a Nobel Prize in medicine before the 100-year mark of 2023.</p>
<p><em>John Bergeron gratefully acknowledges Kathleen Dickson as co-author.</em></p><img src="https://counter.theconversation.com/content/87910/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>John Bergeron 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>Only one Canadian has ever received the Nobel Prize for medicine, in 1923. But Canadian discoveries have been essential to stem cell research, gene sequencing and treatments for cancer.John Bergeron, Emeritus Robert Reford Professor and Professor of Medicine, McGill UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/870832017-11-16T19:10:53Z2017-11-16T19:10:53ZWhat prospective parents need to know about gene tests such as ‘prepair’<figure><img src="https://images.theconversation.com/files/194903/original/file-20171115-19789-17t9dhk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Couples who are carriers of genes for recessive diseases don't show any symptoms.</span> <span class="attribution"><a class="source" href="https://unsplash.com/photos/7tGqLzHcjZ8">Photo by Drew Hays on Unsplash</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span></figcaption></figure><p>Researchers <a href="http://www.theage.com.au/victoria/most-wouldbe-parents-carrying-severe-genetic-disorders-are-unaware-20171102-gzd9vi.html">recently renewed calls</a> for all prospective parents to be offered testing for gene mutations that could be transferred to their child. This came after a study published in the journal <a href="https://www.nature.com/articles/gim2017134.epdf?referrer_access_token=vUswM29CZMNFQjzlclpL0NRgN0jAjWel9jnR3ZoTv0N5FKXZRBZzyrsg1x6BF7gWGcq5yVwW6B0Wzooc5EJ8jwvZGqeMfDai5LT6rCSx7IvdvZnxf-N9ynrk32fv6HJKo3FAyW2FI-QIvTbeQ4LGYR4_DuoStR47YWScTuzSRV0hsyl2RVimGDZfIS59fKHA7ZCVGkvi8y69kpbBRc13KXarZyJdI8loMbJS0V2j-MbP8JB2cuFZCfUU2hf6BXso9sBbqLbM2T6NhghxXvXV1Q%3D%3D&tracking_referrer=www.abc.net.au">Genetics in Medicine</a> found 88% of couples weren’t aware they were carrying mutations for three serious diseases: cystic fibrosis, spinal muscular atrophy and fragile X syndrome. </p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/194914/original/file-20171115-19823-xhiz6k.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/194914/original/file-20171115-19823-xhiz6k.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/194914/original/file-20171115-19823-xhiz6k.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=900&fit=crop&dpr=1 600w, https://images.theconversation.com/files/194914/original/file-20171115-19823-xhiz6k.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=900&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/194914/original/file-20171115-19823-xhiz6k.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=900&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/194914/original/file-20171115-19823-xhiz6k.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1130&fit=crop&dpr=1 754w, https://images.theconversation.com/files/194914/original/file-20171115-19823-xhiz6k.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1130&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/194914/original/file-20171115-19823-xhiz6k.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1130&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Diseases like cystic fibrosis have significant health consequences.</span>
<span class="attribution"><span class="source">from shutterstock.com</span></span>
</figcaption>
</figure>
<p>These three diseases have significant health consequences and are among the most common recessive diseases. This is where only one parent carries a copy of the gene mutation (both parents need a copy for the child to become sick) and shows no symptoms. A healthy individual who carries a single recessive mutation is called a carrier. </p>
<p>Recessive diseases cause many severe disorders in children, but most of us who are healthy carriers <a href="https://www.ncbi.nlm.nih.gov/pubmed/21228398?dopt=Citation">don’t know</a> how many or what mutations we carry. Pre-pregnancy or <a href="https://theconversation.com/explainer-what-is-pre-pregnancy-carrier-screening-and-should-potential-parents-consider-it-79184">preconception carrier screening</a> allows healthy couples to identify mutations they carry before they become pregnant. </p>
<p>So, what is the test used in the recent study, and should it be available to all prospective parents?</p>
<h2>What genetic tests are available?</h2>
<p>The recent study used the “<a href="https://www.vcgs.org.au/tests/prepair">prepair™ test</a>” to screen couples. It was conducted by the Victorian Clinical Genetics Service (VCGS), which provides the test to the public. The number of pregnancies affected with one of these three diseases (cystic fibrosis, spinal muscular atrophy and fragile X syndrome) during the course of the study was one in every 1,006 women. This figure is comparable to that of live births affected by <a href="http://www.who.int/genomics/public/geneticdiseases/en/index1.html">Down syndrome</a>. </p>
<p>Currently, <a href="https://www.alrc.gov.au/publications/10-genetic-testing/access-genetic-testing">government subsidies</a> for genetic testing and counselling are only available for couples once they have had a child with a suspected inherited disease or if there is a history for a particular disease in the extended family.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/why-should-we-offer-screening-for-down-syndrome-anyway-30351">Why should we offer screening for Down syndrome anyway?</a>
</strong>
</em>
</p>
<hr>
<p>Aside from the VCGS, there are at least five other providers in most Australian eastern states offering tests for different sets of recessive disorders. All five are consumer-pays tests. They range from A$350 to A$750, depending on the number of genes tested. </p>
<p>The largest gene panel tests for <a href="https://www.ivf.com.au/about-fertility/how-to-get-pregnant/preconception-screen">590 diseases</a> and costs the most, while <a href="https://www.sonicgenetics.com.au/tests/preconception-carrier-screening-panel-cf-sma-fragile-x/">others</a> only test for the same three recessive diseases VCGS offers. Another test screening for 175 recessive conditions is provided by <a href="https://www.counsyl.com/services/foresight/">Counsyl</a> through Australian clinicians.</p>
<h2>What can I expect from the prepair™ test?</h2>
<p>The VCGS prepair™ screens for specific mutations in the three genes causing the three diseases. Couples or individuals are considered at “increased risk” if they both carry a mutation for the same one of the three screened diseases. </p>
<p>The VCGS prepair™ genetic test is usually first offered to women before, or early, in their pregnancy (less than 12 weeks) by health professionals. These are usually GPs and obstetricians, as they are generally the first point of medical contact for soon-to-be-parents. Partners of carrier women are then offered testing.</p>
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<figcaption>
<span class="caption">If each member of the couple carry the gene mutation for the same disease, their child has a 25% chance of the disorder.</span>
<span class="attribution"><span class="source">from shutterstock.com</span></span>
</figcaption>
</figure>
<p>All carriers are offered a genetic counselling appointment and an appointment with a paediatric sub-specialist who has expertise in the specific disease. Results are also discussed with the referring health professional. For individuals or couples not identified as carriers, the report is sent to the referring health professional and no further testing or follow-up is required. </p>
<p>If couples are carriers for mutations in the same gene, any of their children have a 25% chance of being affected by the disease. If couples do not carry any of the mutations the VCGS test screens for, they are considered at “low risk” of having an affected child. </p>
<p>But while the risk of having a child affected by a genetic mutation is greatly reduced, it is not eliminated. The main benefit of tests screening for hundreds of genes is that a couple can know their carrier status for many more recessive diseases. </p>
<h2>How can couples use the test to make decisions?</h2>
<p>Understanding what it means to be a carrier and a high-risk couple allows prospective parents to decide how they want to approach conception and pregnancy. At-risk couples and those with a previous history of recessive disease frequently want to <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3149658/">avoid having an affected child</a>. Couples may then opt for in-vitro fertilisation (IVF) to select only healthy embryos (without two mutations) for implantation. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/rest-assured-ivf-babies-grow-into-healthy-adults-23432">Rest assured, IVF babies grow into healthy adults</a>
</strong>
</em>
</p>
<hr>
<p>Couples may also decide to fall pregnant naturally and then test the fetus, through a test called <a href="http://www.pregnancybirthbaby.org.au/chorionic-villus-sampling-cvs">chorionic villus sampling</a>, towards the end of the first trimester to determine whether the baby carries two mutations. Or they may decide to adopt or forego having children. </p>
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<figcaption><span class="caption">TedXTalks.</span></figcaption>
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<p>If a couple decide to continue a pregnancy, knowing ahead of time their baby will be affected allows them time to process and make lifestyle plans to accommodate for their changing circumstances and engage with support groups. Rare disease groups such as <a href="https://smaaustralia.org.au/support-services/">Spinal Muscular Atrophy Australia</a> provide support in care options, resources and choices for families living with spinal muscular atrophy. If therapies are available, it also allows for <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3392137/">treatment of the disease from birth</a>. </p>
<p>As no screening test guarantees a healthy baby, genetic counselling is crucial to explain the limitations and risks to couples. <a href="https://www.youtube.com/watch?v=7yIW0L9dLCQ">Counselling</a> involves communicating complex genetic information clearly to couples, clarifying any doubts and misconceptions and more importantly to interpret and explain test results. </p>
<h2>Should all couples have this test?</h2>
<p>Our experience shows access to this kind of genetic testing can be challenging. Generally this is because health care professionals can be unaware such tests are available locally; or be unfamiliar with how blood should be collected, or where to send specimens for testing. </p>
<p>Preconception carrier screening tests have also been confused with other prenatal tests, particularly the non-invasive prenatal test (<a href="https://theconversation.com/australians-can-be-denied-life-insurance-based-on-genetic-test-results-and-there-is-little-protection-81335">NIPT</a>), by both parents and health care professionals. In this situation, parents may feel reassured their child does not have a genetic disease, but NIPT only tests for chromosomal problems (like Down Syndrome or trisomy 21) not single gene disorders. </p>
<p>This clearly shows awareness and education is critical among health care workers for preconception carrier screening programs to be successful.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/explainer-what-is-pre-pregnancy-carrier-screening-and-should-potential-parents-consider-it-79184">Explainer: what is pre-pregnancy carrier screening and should potential parents consider it?</a>
</strong>
</em>
</p>
<hr>
<p>Given the risk for an affected child for the three common recessive diseases is similar to Down syndrome, it may be considered carrier screening should be made available to everyone in Australia. But there are a number of issues that need to be addressed for this to happen.</p>
<p>These include consideration of the number of severe childhood disorders to be included for screening and who the target population would be. Studies are also required to inform the government of the most cost-effective method of offering such a test. </p>
<p>If a carrier screening program is to be implemented by the government, the infrastructure and clinical resources required to appropriately administer and sustain such testing must be explored to ensure all couples are informed and counselled as required. And <a href="http://www.health.gov.au/internet/msac/publishing.nsf/Content/17BAA5247F22729DCA25801000123C2C/$File/1165.1-FinalPSD-accessible.pdf">subsidy</a> of pre-implantation genetic diagnosis should also be considered for all carrier couples. </p>
<p>Pilot studies in different states may help explore how best a carrier screening program can fit into the different health systems in Australia.</p><img src="https://counter.theconversation.com/content/87083/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Gina Ravenscroft receives funding from the National Health and Medical Research Council and the French Muscular Dystrophy Association (AFM). </span></em></p><p class="fine-print"><em><span>Michelle Farrar receives funding from Motor Neuron Diseases Research Institute of Australia </span></em></p><p class="fine-print"><em><span>Nigel Laing receives funding from The Australian National Health and Medical Research Council (NHMRC), the Association Francaise contre les Myopathies (AFM), the US Muscular Dystrophy Association (MDA), a Foundation Building Strength for Nemaline Myopathy (AFBS).
</span></em></p><p class="fine-print"><em><span>Royston Ong receives scholarship funding from the Australian Postgraduate Award and the Australian Genomic Health Alliance. </span></em></p>Cystic fibrosis, spinal muscular atrophy and fragile X syndrome are serious diseases, and most couples carrying the genetic mutations for these don’t know it. Should they all be tested?Gina Ravenscroft, Research Fellow in neuromuscular disease and genetics, The University of Western AustraliaMichelle Farrar, Senior lecturer in Paediatric Neurology, UNSW SydneyNigel Laing, Professor, The University of Western AustraliaRoyston Ong, Phd Student in Population Genetics, The University of Western AustraliaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/842052017-10-30T19:02:57Z2017-10-30T19:02:57ZPalliative care for children often involves treating the whole family<figure><img src="https://images.theconversation.com/files/189352/original/file-20171009-6971-1dsuze5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Palliative care specialists also need to pay attention to a sick child's siblings.</span> <span class="attribution"><a class="source" href="https://unsplash.com/photos/VNjNtdu0yCw">Joshua Clay/Unsplash</a></span></figcaption></figure><p><em>This article is part of our series on <a href="https://theconversation.com/au/topics/demystifying-palliative-care-45213">demystifying palliative care</a>, where experts explain the process of end-of-life care in Australia.</em></p>
<hr>
<p>While we prefer not to think about it, death affects us all at some point. But that conversation is forced much earlier than anticipated for families whose child is diagnosed with a life-limiting illness. Also referred to as life-shortening, these illnesses put someone at increased risk of dying. Often, palliative care is needed.</p>
<p>According to <a href="http://paedspal.org.za/about-us/what-is-paediatric-palliative-care/#">Mattie Stepanek</a>, a child who died from a life-limiting neuromuscular illness, paediatric palliative care</p>
<blockquote>
<p>[…] no longer means helping children die well, it means helping children and their families to live well and then, when the time is certain, to help them die gently.</p>
</blockquote>
<p>Palliative care focuses on a child’s <a href="http://www.who.int/cancer/palliative/definition/en/">quality of life</a> and support for the whole family, including siblings and grandparents. Such care not only addresses the child’s illness but also their overall well-being – physical, emotional, cultural and spiritual.</p>
<p>While there are similarities in the general principles of palliative care provided to children and adults, there are also key differences. These include the types of conditions more common in children, and the need to pay special attention to the whole family, particularly the sick child’s siblings.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/what-is-palliative-care-a-patients-journey-through-the-system-82246">What is palliative care? A patient's journey through the system</a>
</strong>
</em>
</p>
<hr>
<h2>Why a child may need palliative care</h2>
<p>A life-limiting condition means a child could die before the age of 18. In the UK, around 32 children (aged up to 19) per 10,000 are living with a <a href="https://www.ncbi.nlm.nih.gov/pubmed/22412035">life-limiting condition</a>. In Australia, we estimate around 14,000 children under 15 have a life-limiting condition. </p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/191771/original/file-20171025-5838-1hw333r.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/191771/original/file-20171025-5838-1hw333r.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/191771/original/file-20171025-5838-1hw333r.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=507&fit=crop&dpr=1 600w, https://images.theconversation.com/files/191771/original/file-20171025-5838-1hw333r.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=507&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/191771/original/file-20171025-5838-1hw333r.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=507&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/191771/original/file-20171025-5838-1hw333r.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=637&fit=crop&dpr=1 754w, https://images.theconversation.com/files/191771/original/file-20171025-5838-1hw333r.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=637&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/191771/original/file-20171025-5838-1hw333r.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=637&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Infants are most at risk of dying from a life-limiting condition.</span>
<span class="attribution"><span class="source">from shutterstock.com</span></span>
</figcaption>
</figure>
<p>Of these, 1,400 would be <a href="https://www.ncbi.nlm.nih.gov/m/pubmed/27682139/">particularly fragile</a> and at increased at risk of dying in the next 12 months. Infants (aged less than 12 months) are most at risk due to the prevalence of severe congenital and genetic conditions around the time of birth.</p>
<p>Children are often referred to palliative care when their condition deteriorates or progresses. For children with cancer, this may be when it spreads despite chemotherapy, or returns after treatment. </p>
<p>But <a href="https://www.ncbi.nlm.nih.gov/pubmed/24528125">more than half</a> the diagnoses in children with life-limiting illnesses are non-cancerous conditions. There are <a href="http://www.icpcn.org/directory-of-life-limiting-conditions-in-children/">more than 400</a> of <a href="http://www.togetherforshortlives.org.uk/assets/0000/7089/Directory_of_LLC_v1.3.pdf">these</a>, affecting newborns through to young adults. </p>
<p>These include neurodegenerative conditions (mainly affecting neurons in the brain and spinal cord), neuromuscular conditions, various conditions affecting their metabolism (the ability to convert food into energy) usually caused by enzyme deficiency from a defective gene, and severe cerebral palsy. Any system in the body can be affected, but children are most likely to <a href="https://www.ncbi.nlm.nih.gov/pubmed/?term=siden+collins+hospice">get serious illnesses</a> in the nervous and metabolic systems.</p>
<p>Many will require palliative care soon after diagnosis. For some conditions, such as the neurodegenerative disease leukodystrophy, the child will experience a gradual deterioration in function over a number of years, becoming dependent on their parents and carers. Earlier referral to palliative care allows the paediatric palliative care team time to meet and get to know the child, family and their needs. Usually the child’s original paediatrician will stay involved and the palliative care service will act as an extra layer of support.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/we-need-better-treatments-for-childhood-cancer-with-fewer-side-effects-67310">We need better treatments for childhood cancer, with fewer side effects</a>
</strong>
</em>
</p>
<hr>
<p>A child may be referred to palliative care for reasons such as pain management, or other physical symptoms such as vomiting, difficulty managing seizures or constipation. Caring for the child’s emotions is also important. Sometimes palliative care may assist in caring for a child at home, or provide support so the child can continue to attend school. </p>
<p>Palliative care also provides parents with practical supports, such as equipment and “<a href="https://www.ncbi.nlm.nih.gov/pubmed/26951065">short breaks</a>”. These can occur in the home (where a carer gives the parents a break) or in a children’s hospice. Such care can have a <a href="https://www.ncbi.nlm.nih.gov/pubmed/26951065">huge impact on the well-being</a> of the child and their family.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/190296/original/file-20171016-27705-197y7mm.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/190296/original/file-20171016-27705-197y7mm.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/190296/original/file-20171016-27705-197y7mm.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=401&fit=crop&dpr=1 600w, https://images.theconversation.com/files/190296/original/file-20171016-27705-197y7mm.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=401&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/190296/original/file-20171016-27705-197y7mm.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=401&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/190296/original/file-20171016-27705-197y7mm.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=504&fit=crop&dpr=1 754w, https://images.theconversation.com/files/190296/original/file-20171016-27705-197y7mm.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=504&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/190296/original/file-20171016-27705-197y7mm.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">Children with some neurodegenerative conditions often have a gradual deterioration in function and become increasingly dependent on their parents and carers.</span>
<span class="attribution"><span class="source">from shutterstock.com</span></span>
</figcaption>
</figure>
<h2>Caring for whole family</h2>
<p>Palliative care for children is especially concerned with not only treating the child, but the whole family. All family members may be vulnerable as they face the changes the child’s diagnosis imposes on their lives.</p>
<p>It is particularly important to support the siblings of the sick child. Some siblings may not share their thoughts and feelings of distress with their parents because they do not want to add to their parent’s difficulties. Siblings often have unique bonds with each other, and the illness or death of a brother or sister may represent the loss of a friend they have shared many life experiences with. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/adults-can-help-children-cope-with-death-by-understanding-how-they-process-it-58057">Adults can help children cope with death by understanding how they process it</a>
</strong>
</em>
</p>
<hr>
<p>Support for siblings is particularly important given a sibling’s death will affect their future. It may cause behavioural problems, school failure, developmental regression or physical symptoms. A <a href="https://www.ncbi.nlm.nih.gov/pubmed/28949788">Swedish study found</a> the perception a sibling did not have a peaceful death and poor communication with family, friends and health professionals increased the risk for unresolved grief in surviving siblings.</p>
<p>Another Swedish study showed it is possible for siblings to <a href="https://www.ncbi.nlm.nih.gov/pubmed/28641585">have positive memories</a> about their brother’s or sister’s death. With the right support, some have expressed the feeling they grew as individuals in the process. Others experienced stagnation because of the physical and mental distress they bore throughout their sibling’s illness and death, often feeling forgotten.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/190298/original/file-20171016-27757-13hapmy.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/190298/original/file-20171016-27757-13hapmy.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/190298/original/file-20171016-27757-13hapmy.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/190298/original/file-20171016-27757-13hapmy.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/190298/original/file-20171016-27757-13hapmy.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/190298/original/file-20171016-27757-13hapmy.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/190298/original/file-20171016-27757-13hapmy.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/190298/original/file-20171016-27757-13hapmy.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">Siblings often have unique bonds with each other.</span>
<span class="attribution"><a class="source" href="https://unsplash.com/photos/UYDoE_AyJQs">Jenn Evelyn-Ann/Unsplash</a></span>
</figcaption>
</figure>
<h2>Different approach for children</h2>
<p>Children have evolving physical, emotional and cognitive development. So palliative care professionals and other carers <a href="http://www.togetherforshortlives.org.uk/assets/0001/1649/ACT_Guide_to_Developing_Services.pdf">must be aware</a> of and responsive to each child’s changing levels of communication and ability to understand their illness and treatments. Decision-making on medical care is also different than with adults, as parents (or a guardian) will make decisions for their child.</p>
<p>Planning (or thinking) ahead is important in the context of a life-limiting condition. This is why there is increasing emphasis on <a href="http://pediatrics.aappublications.org/content/131/3/e873">developing advance care plans</a> for children. </p>
<p>Such plans give children and parents the option of writing down what treatments they may or may not wish to have if their condition progresses or if there comes a time when they are unable to participate in such decisions.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/children-can-decide-their-medical-treatments-under-victorias-unique-advance-directive-laws-83356">Children can decide their medical treatments under Victoria’s unique advance directive laws</a>
</strong>
</em>
</p>
<hr>
<p>Most Australian children’s hospitals have a paediatric palliative care service that can work with other health professionals and families to support children requiring palliative care.</p>
<p>There are also three <a href="https://www.caresearch.com.au/caresearch/tabid/4173/Default.aspx">children’s hospices</a> located in Victoria, New South Wales and Queensland. In recent times, small teams of health professionals have been able to visit patients and health professionals living outside capital cities in “pop-up” visits. The <a href="http://www.health.gov.au/internet/main/publishing.nsf/Content/palliativecare-program.htm#6">federal Health Department</a> has funded these. </p>
<p>This is just a start, as we need further development of the workforce that supports families receiving palliative care, more funding support for families caring for their children, as well as more bereavement support services that can care for parents and siblings after a child dies.</p>
<ul>
<li><em>Palliative Care Australia is updating and developing a <a href="http://palliativecare.org.au/">suite of resources</a> for families.</em><br></li>
<li><em>Queensland Health has recently developed a charter for children and young people affected by a life-limiting condition, which provides other <a href="https://www.health.qld.gov.au/__data/assets/pdf_file/0030/636087/qcs-children-charter.pdf">helpful information for children</a> and their families.</em></li>
</ul>
<hr>
<p><em>Read more in the series:</em></p>
<ul>
<li><p><em><a href="https://theconversation.com/its-not-all-about-death-conversations-with-patients-in-palliative-care-82247">It’s not all about death: conversations with patients in palliative care</a></em></p></li>
<li><p><em><a href="https://theconversation.com/what-is-palliative-care-a-patients-journey-through-the-system-82246">What is palliative care? A patient’s journey through the system</a></em></p></li>
<li><p><em><a href="https://theconversation.com/looking-after-a-dying-loved-one-at-home-heres-what-you-need-to-know-83499">Looking after a dying loved one at home? Here’s what you need to know</a></em></p></li>
<li><p><em><a href="https://theconversation.com/five-common-myths-about-palliative-care-and-what-the-science-really-says-82248">Five common myths about palliative care and what the science really says</a></em></p></li>
</ul><img src="https://counter.theconversation.com/content/84205/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Anthony Herbert receives funding from Department of Health Commonwealth for the QuoCCA project (<a href="http://www.quocca.com.au">www.quocca.com.au</a>). </span></em></p>While there are similarities in the general principles of palliative care provided to children and adults, there are also key differences.Anthony Herbert, Senior Lecturer, The University of QueenslandLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/770902017-05-04T01:46:00Z2017-05-04T01:46:00ZNew drugs on the PBS: what they do and why we need them<figure><img src="https://images.theconversation.com/files/167678/original/file-20170503-21637-4oi5od.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Some of the notable additions to the PBS include drugs to treat eye and HIV infections, cystic fibrosis, multiple sclerosis, and cancer.</span> <span class="attribution"><span class="source">from shutterstock.com</span></span></figcaption></figure><p>This week, the government <a href="http://www.pbs.gov.au/browse/changes">announced the latest additions, amendments, and deletions</a> from the Pharmaceutical Benefits Scheme (PBS): the program through which essential medicines are subsidised for Australian patients. The new medicines on the scheme are reportedly worth <a href="http://www.greghunt.com.au/Media/MediaReleases/tabid/86/ID/4230/Making-310-million-of-new-vital-drugs-available-for-Australian-patients.aspx">A$310 million</a>.</p>
<p>Listing on the PBS is different to a drug being approved for sale by Australia’s drug regulator, the <a href="http://www.tga.gov.au">Therapeutic Goods Administration (TGA)</a>. Once approved by the TGA, it is available to patients and hospitals at the full price. It only becomes subsidised if later listed on the PBS. </p>
<p>Some of the notable additions to the list include drugs to treat eye infections, human immunodeficiency virus (HIV), cystic fibrosis, multiple sclerosis, cancer, and <a href="http://lungfoundation.com.au/wp-content/uploads/2012/06/Idiopathic-Pulmonary-Fibrosis.pdf">idiopathic pulmonary fibrosis</a> – a type of scarring in the lungs. Below is a list of seven most notable new additions to the scheme.</p>
<h2>1. Chloramphenicol eye drops (Chlorsig)</h2>
<ul>
<li><p><strong>Maximum cost to Aboriginal and Torres Strait Islanders: A$0-6.10</strong></p></li>
<li><p><strong>Maximum cost to other patients: A$20.11</strong></p></li>
</ul>
<p>Chloramphenicol is the generic name of an antibiotic drug used to treat eye infections. It has been <a href="http://www.pbs.gov.au/medicine/item/11112W">added to the PBS</a> with the restriction that it is only available to patients who identify as Aboriginal or Torres Strait Islander (ATSI). </p>
<p>The rate of eye infections, like <a href="https://theconversation.com/why-is-trachoma-blinding-aboriginal-children-when-mainstream-australia-eliminated-it-100-years-ago-63526">trachoma</a> (which leads to blindness), is three times higher for ATSI patients than for other Australians. The lower price for ATSI patients is because of extra funding under the government’s <a href="http://www.pbs.gov.au/info/publication/factsheets/closing-the-gap-pbs-co-payment-measure">Closing the Gap PBS co-payment</a> program.</p>
<h2>2. Ivacaftor (Kalydeco)</h2>
<ul>
<li><p><strong>Maximum price from the manufacturer: A$22,547.02</strong></p></li>
<li><p><strong>Maximum cost to the patient: A$38.80</strong></p></li>
</ul>
<p>Ivacaftor – <a href="https://www.ebs.tga.gov.au/servlet/xmlmillr6?dbid=ebs/PublicHTML/pdfStore.nsf&docid=E059E457A00C1B93CA2580D0003CA6C0&agid=(PrintDetailsPublic)&actionid=1">first approved by the TGA in September 2016</a> – is used to treat <a href="http://www.cysticfibrosis.org.au/all/learn/">cystic fibrosis</a>, a genetic disorder that affects the digestive system and lungs of patients. It causes a buildup of thick and sticky mucus in the airways. </p>
<p>There is no cure for cystis fibrosis, but <a href="http://www.kalydeco.com/">ivacaftor</a> acts by better regulating the flow of salts and water in and out of cells, which leads to less mucus buildup. </p>
<p>While <a href="https://www.cysticfibrosis.org.au/media/wysiwyg/CF-Australia/medical-documents/CFA_DataRegistryReport_2014_Final.pdf">around 3,300 people in Australia live with cystic fibrosis</a>, only around 10% of patients will benefit from the drug. This is because patients need to have a specific mutation in their DNA called <em>R117H</em> for the drug to be effective. </p>
<hr>
<p><em><strong>More information - <a href="https://theconversation.com/weekly-dose-kalydeco-the-drug-that-treats-the-cause-of-cystic-fibrosis-not-just-symptoms-76934">Weekly Dose: Kalydeco, the drug that treats the cause of cystic fibrosis, not just symptoms</a></strong></em></p>
<hr>
<h2>3. Blinatumomab (Blincyto)</h2>
<ul>
<li><p><strong>Maximum price from the manufacturer: A$61,975.54</strong></p></li>
<li><p><strong>Maximum cost to the patient: A$38.80</strong></p></li>
</ul>
<p><a href="http://www.pbs.gov.au/medicine/item/11115B-11116C-11117D-11118E-11119F-11120G">Blinatumomab</a> is a new type of immunotherapy – a treatment that <a href="https://theconversation.com/au/search?utf8=%E2%9C%93&q=immunotherapy+">empowers the body’s immune system</a> to fight diseases such as cancer.</p>
<p>The drug is approved for use to treat a specific subset of <a href="http://www.leukaemia.org.au/blood-cancers/leukaemias/acute-lymphoblastic-leukaemia-all">acute lymphoblastic leukaemias</a> (ALL). Around 350 Australians each year are diagnosed with some form of ALL, and it is the most common type of cancer in children.</p>
<p>Blinatumomab was first approved by the TGA in November 2015 but an application to list the medicine on the PBS that same year <a href="http://www.pbs.gov.au/industry/listing/elements/pbac-meetings/psd/2015-11/files/blinatumomab-psd-november-2015.pdf">was rejected</a>. It <a href="https://www.greghunt.com.au/Home/LatestNews/tabid/133/ID/4230/Making-310-million-of-new-vital-drugs-available-for-Australian-patients.aspx">has been reported</a> that the cost for patients before the PBS subsidy was A$127,700 per course of treatment. </p>
<h2>4. Fosaprepitant (Emend IV)</h2>
<ul>
<li><p><strong>Maximum price from the manufacturer: A$115.03</strong></p></li>
<li><p><strong>Maximum cost to the patient: A$38.80</strong></p></li>
</ul>
<p>This drug is used to help patients overcome the nausea and vomiting side-effects
associated with chemotherapy treatment. <a href="http://www.pbs.gov.au/medicine/item/11103J-11107N">Fosaprepitant</a> has been available for doctors to prescribe since 2011, when it was <a href="https://www.pbs.gov.au/pbs/industry/listing/elements/pbac-meetings/pbac-outcomes/2011-03/positive-recommendations">first recommended</a> to be put on the PBS.</p>
<h2>5. Emtricitabine</h2>
<ul>
<li><p><strong>Maximum price from the manufacturer: A$1,500 - $2,600 depending on the formulation</strong></p></li>
<li><p><strong>Maximum cost to the patient: A$38.80</strong></p></li>
</ul>
<p>Four <a href="http://www.pbs.gov.au/pbs/search?term=EMTRICITABINE&analyse=false&search-type=medicines">formulations of this drug</a> have been added to the PBS as part of a cocktail of medicines used to treat HIV infection. </p>
<p>Emtricitabine acts by stopping the HIV virus from copying itself into human cells. It was first <a href="https://www.ebs.tga.gov.au/servlet/xmlmillr6?dbid=ebs/PublicHTML/pdfStore.nsf&docid=5C59BB9C228068B0CA257FE8004216C7&agid=(PrintDetailsPublic)&actionid=1">approved by the TGA in 2005</a> and other formulations of the drug – such as it being <a href="http://www.pbs.gov.au/medicine/item/10347N">coupled with antiviral Tenofovir</a> under the brand name Truvada – have been listed on the PBS previously. In Australia, there are around <a href="http://www.hivmediaguide.org.au/hiv-in-australia/hiv-statistics-australia/">25,000 people living with HIV</a>.</p>
<hr>
<p><em><strong>More information: <a href="https://theconversation.com/weekly-dose-truvada-the-drug-that-can-prevent-hiv-infection-61525">Weekly Dose: Truvada, the drug that can prevent HIV infection</a></strong></em></p>
<hr>
<h2>6. Daclizumab (Zinbryta)</h2>
<ul>
<li><p><strong>Maximum price from the manufacturer: A$2,231</strong></p></li>
<li><p><strong>Maximum cost to the patient: A$38.80</strong></p></li>
</ul>
<p><a href="http://www.pbs.gov.au/medicine/item/11101G">Daclizumab</a> is used to treat <a href="https://www.msaustralia.org.au/what-ms">multiple sclerosis (MS)</a>, a condition that affects the nervous system and interferes with nerve impulses in the brain, spinal chord, and optic nerves (those responsible for vision). It was first <a href="https://www.ebs.tga.gov.au/servlet/xmlmillr6?dbid=ebs/PublicHTML/pdfStore.nsf&docid=CC481F65EA7BE336CA258060003CA91D&agid=(PrintDetailsPublic)&actionid=1">approved by the TGA in September 2016</a>. </p>
<p>While there is no cure for MS, this drug helps to stop infection-fighting blood cells called <a href="http://www.medicinenet.com/script/main/art.asp?articlekey=11300">T-cells</a> from getting into the brain. This protects the brain from swelling. There are currently around 24,000 Australians who live with MS.</p>
<h2>7. Nintedanib (Ofev)</h2>
<ul>
<li><p><strong>Maximum price from the manufacturer: A$3,385.48</strong></p></li>
<li><p><strong>Maximum cost to the patient: A$38.80</strong></p></li>
</ul>
<p><a href="http://www.pbs.gov.au/medicine/item/11100F-11106M">Nintedanib</a> was <a href="https://www.ebs.tga.gov.au/servlet/xmlmillr6?dbid=ebs/PublicHTML/pdfStore.nsf&docid=0AEB4B2429304039CA2580B2003CA221&agid=(PrintDetailsPublic)&actionid=1">approved by the TGA in September 2015</a>. It is used to treat <a href="http://lungfoundation.com.au/wp-content/uploads/2012/06/Idiopathic-Pulmonary-Fibrosis.pdf">idiopathic pulmonary fibrosis</a>, a condition that causes scarring in the lungs. The amount of scar disease builds up over time. While nintedanib does not cure patients, it provides relief by stopping the enzymes that help create the scarring, thus slowing the disease.</p>
<p>The condition is most prevalent in people over 60 years of age, and <a href="http://lungfoundation.com.au/wp-content/uploads/2012/06/Idiopathic-Pulmonary-Fibrosis.pdf">affects around 2,600 Australians</a>.</p><img src="https://counter.theconversation.com/content/77090/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Dr Wheate in the past has received funding from the ACT Cancer Council, Tenovus Scotland, Medical Research Scotland, Scottish Crucible, and the Scottish Universities Life Sciences Alliance. He is affiliated with the Royal Australian Chemical Institute.</span></em></p>An independent expert provides his pick of the most notable drugs added to the PBS on May 1, 2017.Nial Wheate, Senior Lecturer in Pharmaceutics, University of SydneyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/769342017-05-03T04:22:05Z2017-05-03T04:22:05ZWeekly Dose: Kalydeco, the drug that treats the cause of cystic fibrosis, not just symptoms<figure><img src="https://images.theconversation.com/files/167444/original/file-20170502-17322-1f2k6hm.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">People with cystic fibrosis, Australia's most common inherited condition, have thick mucus, including on the lungs.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/download/confirm/396255907?src=OOFB-3qYwLVlctPd4ckqTw-1-16&size=medium_jpg">from www.shutterstock.com</a></span></figcaption></figure><p>Kalydeco (ivacaftor) is a drug used to treat <a href="http://www.cysticfibrosis.org.au/all/learn/">cystic fibrosis</a>, a disorder that affects many organs, particularly the lungs. Cystic fibrosis is Australia’s most commonly inherited disorder.</p>
<p>The drug has been <a href="http://www.smh.com.au/federal-politics/political-news/cystic-fibrosis-miracle-drug-among-turnbull-governments-310m-pbs-listing-20170430-gvvl0l.html">in the</a> <a href="http://www.theaustralian.com.au/news/latest-news/lifesaving-drugs-lose-hefty-pricetags/news-story/344e8dcc4fbb9f99b0a929a7f2a4cdd1">news</a> recently because, as of <a href="http://www.health.gov.au/internet/ministers/publishing.nsf/Content/health-mediarel-yr2017-hunt040.htm">May 1</a>, 2017 a wider range of people are now eligible to receive it under the <a href="http://www.pbs.gov.au/pbs/home">Pharmaceutical Benefits Scheme</a> (PBS).</p>
<p>Before May 1, <a href="https://www.cysticfibrosis.org.au/media/wysiwyg/CF-Australia/medical-documents/CFA_DataRegistryReport_2014_Final.pdf">more than 200</a> Australians over the age of six years were eligible for Kalydeco. <a href="https://www.vrtx.com/story/children-ages-2-5-gating-mutations-australia-be-provided-immediate-access-kalydeco-ivacaftor">Widening its subsidy</a> to certain younger patients aged two to five means <a href="https://www.cysticfibrosis.org.au/media/wysiwyg/CF-Australia/medical-documents/CFA_DataRegistryReport_2014_Final.pdf">another 30</a> children can benefit. This accounts for <a href="https://www.cysticfibrosis.org.au/media/wysiwyg/CF-Australia/medical-documents/CFA_DataRegistryReport_2014_Final.pdf">10 to 12%</a> of patients with cystic fibrosis.</p>
<p>Before PBS listing in 2014, patients and families needed to find A$300,000 per year to fund the drug. Now, for eligible patients, it is available for A$6.30 a script for concession-card holders and A$38.80 for general patients. But patients will still need to satisfy specific criteria (have specific gene mutations) to qualify.</p>
<h2>What is cystic fibrosis?</h2>
<p>Cystic fibrosis affects <a href="https://www.cysticfibrosis.org.au/media/wysiwyg/CF-Australia/medical-documents/CFA_DataRegistryReport_2014_Final.pdf">one in 3,600</a> live births in Australia. It is caused by defects in a single gene, known as the cystic fibrosis transmembrane regulator (CFTR).</p>
<p>The gene has a critical role in controlling how chloride ions (salt) move in and out of cells via proteins called chloride channels. Too much salt and not enough water can lead to mucus becoming very thick and sticky, which can build up in the lungs (and other organs).</p>
<p>This sticky mucus clogs the tiny air passages in the lungs and traps bacteria. Repeated infections and blockages can cause irreversible lung damage, which is the most common cause of death in people with this condition.</p>
<p>Mucus can also cause problems in the pancreas, preventing the release of enzymes needed to digest food and so leading to nutrition problems.</p>
<p>Patients can also have liver disease, chronic sinus infections, diabetes and fertility problems due to this faulty gene.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/167649/original/file-20170503-4128-9jawn0.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/167649/original/file-20170503-4128-9jawn0.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/167649/original/file-20170503-4128-9jawn0.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=870&fit=crop&dpr=1 600w, https://images.theconversation.com/files/167649/original/file-20170503-4128-9jawn0.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=870&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/167649/original/file-20170503-4128-9jawn0.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=870&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/167649/original/file-20170503-4128-9jawn0.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1093&fit=crop&dpr=1 754w, https://images.theconversation.com/files/167649/original/file-20170503-4128-9jawn0.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1093&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/167649/original/file-20170503-4128-9jawn0.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1093&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Kalydeco.</span>
</figcaption>
</figure>
<h2>How does Kalydeco work?</h2>
<p>The drug was discovered as part of a collaboration with Vertex Pharmaceuticals Inc in the USA and Cystic Fibrosis Foundation, US. It took more than 14 years to develop. </p>
<p>Until it became available, drug therapies for cystic fibrosis were less targeted and only aimed at reducing symptoms in an attempt to slow the disease. </p>
<p>Researchers have found more than 2,000 genetic mutations in the CFTR gene and each leads to a different defect in the chloride channels. Kalydeco is the first medicine to treat the underlying cause of cystic fibrosis in people with specific mutations in this CFTR gene. </p>
<p>It works by targeting certain abnormal chloride channels and opening them to allow chloride ions to move in and out of the cell. This leads to an increase in water levels in the airways helping to thin the mucus.</p>
<p>By keeping the airways well hydrated, mucus can be cleared from the airways, <a href="http://www.kalydeco.com/how-kalydeco-works">reducing the risk of lung infections and progressive lung damage</a>. The reduction in mucus also affects the pancreatic ducts, which in turn results in improvement in glucose levels reducing patients’ risk of cystic fibrosis-related diabetes. </p>
<p><a href="https://dx.doi.org/10.1056/NEJMoa0909825">Studies</a> <a href="https://dx.doi.org/10.1164/rccm.201301-0153OC">of drugs</a> <a href="https://dx.doi.org/10.1056/NEJMoa1105185">like Kalydeco</a>, which work to counter the effects of the faulty CFTR gene, suggest they increase the lifespan of people with cystic fibrosis and decrease the severity of illness. Treating the condition at an earlier stage in the progression of disease may also limit organ damage, reduce illness due to chest infections and improve respiratory-related quality of life. </p>
<h2>How do patients take it?</h2>
<p>In Australia, the medication is available on the <a href="https://www.pbs.gov.au/info/browse/section-100/s100-highly-specialised-drugs">Highly Specialised Drugs Program</a>, which means only doctors with experience in treating cystic fibrosis can prescribe it. The drug comes as a tablet or oral solution that patients take twice a day.</p>
<p>To increase the absorption of Kalydeco, patients take the medication with fatty foods such as butter, eggs, cheese, nuts, avocados, or whole milk.</p>
<h2>How about side-effects and interactions?</h2>
<p>Some patients have high levels of certain liver enzymes while on the drug (which might be a sign of a stressed liver) so doctors need to keep an eye on these. And some adolescents and children develop cataracts (clouding of the eye lens) while on the drug so need to have their eyes monitored.</p>
<p>Most common side effects include: headache, upper respiratory tract infection, stomach pain, diarrhoea, rash, nausea and dizziness. People should also not drive or operate machinery until they know how Kalydeco affects them.</p>
<p>Taking the drug with some antibiotics (like rifampicin and rifabutin); seizure medications (phenytoin, carbamazepine or phenobarbital); and the herbal supplement St John’s Wort can substantially decrease the effectiveness of Kalydeco.</p>
<p>Patients are also recommended to avoid taking it with grapefruit juice, grapefruits or Seville oranges because this makes them increasingly sensitive to it. Anti-fungal medications (ketoconazole, itraconazole, posaconazole, voriconazole or fluconazole), other antibiotics (such as clarithromycin or erythromycin) can also increase Kalydeco exposure, so if taking these medicines at the same time, patients need lower doses of the cystic fibrosis drug.</p>
<p>With the <a href="https://www.pbs.gov.au/medicine/item/10170G-10175M-11097C-11098D-11105L-11109Q">new PBS listing for Kalydeco</a>, younger patients have been provided access to the life-saving treatment aimed at addressing the underlying cause of cystic fibrosis, instead of only treating its symptoms.</p><img src="https://counter.theconversation.com/content/76934/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Odette Erskine is a sub-investigator for clinical trials conducted by Vertex Pharmaceuticals Inc, Australia. She does not receive any direct funding from the company.</span></em></p>Wider availability of the cystic fibrosis drug Kalydeco since May 1, 2017 means younger patients can now access it.Odette Erskine, Respiratory and Sleep Medicine Physician; Clinical Lecturer, University of SydneyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/596812016-09-27T02:18:15Z2016-09-27T02:18:15ZExplainer: what is cystic fibrosis and how is it treated?<figure><img src="https://images.theconversation.com/files/133065/original/image-20160804-478-ravl6f.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">CF can’t currently be cured but some emerging treatments show promise. </span> <span class="attribution"><a class="source" href="http://www.shutterstock.com/pic-435851746/stock-photo-portrait-of-young-man-inhaling-through-inhaler-mask.html?src=IFWfunqCGy60N0f8Lk64Aw-1-3">Vadim Zakharishchev/Shutterstock</a></span></figcaption></figure><p>Cystic fibrosis (CF) affects around <a href="https://www.cysticfibrosis.org.au/media/wysiwyg/CF-Australia/PDF_files/40023-ACFDR_Annual_Report_2013vweb.pdf">3,000 people in Australia</a> and <a href="http://www.cysticfibrosisdata.org/LiteratureRetrieve.aspx?ID=149756">70,000 worldwide</a>. It’s an inherited disease caused by a mutation in a single gene called <a href="https://en.wikipedia.org/wiki/Cystic_fibrosis_transmembrane_conductance_regulator">CFTR</a>. </p>
<p>This gene defect means the protein it produces, also called CFTR, is absent or does not function correctly. This disturbs the salt balance in most tubes within the body, including in the airways, gut and the reproductive system.</p>
<h2>What does the gene mutation do?</h2>
<p>Scientists have identified more than <a href="http://www.genet.sickkids.on.ca/StatisticsPage.html">2,000 different mutations</a> in the CFTR gene. These mutations can be separated into <a href="http://www.cftr.info/about-cf/cftr-mutations/the-six-classes-of-cftr-defects/">six different classes</a> that affect how the CFTR protein is produced or functions, and how it affects health.</p>
<p>The CFTR protein is an ion channel that controls salt and water balance. Although many organs in the body are impacted, people with CF are mostly affected by lung disease. The absent or poorly functioning CFTR protein causes the airway to become dehydrated. This results in production of thick sticky mucus that is hard to clear.</p>
<p>The mucus is a perfect breeding ground for bacteria, fungi and viruses. The resulting cycle of infection and inflammation slowly destroys the lung tissue. </p>
<p>Lung function in people with CF gradually and continually worsens, reducing their quality of life and causing early death for many. </p>
<p>Seventy years ago, the average life expectancy of a person born with cystic fibrosis was less than one year. Improvements in care have greatly improved survival to <a href="https://www.cff.org/What-is-CF/About-Cystic-Fibrosis/">around 40 years</a>. These include early detection, better nutrition and enzymes to aid digestion, as well as intensive daily physiotherapy, antibiotics and other drugs to treat lung disease. There is still no cure.</p>
<p>CF has almost become a hidden disease. You may not realise an acquaintance or co-worker has CF until the disease becomes well established and their quality of life deteriorates.</p>
<h2>How is CF lung disease treated?</h2>
<p>CF lung disease cannot currently be cured. Instead, most treatment approaches try to minimise symptoms and slow the progression of lung disease. </p>
<p>One example is <a href="http://www.ncbi.nlm.nih.gov/pubmed/16421364">twice-daily treatment</a> with inhaled hypertonic saline (salty water). This has been used for more than a decade to treat CF lung disease by drawing water onto the airway surface, rehydrating the mucus, and allowing it to clear. Others include daily physiotherapy, which helps to clear mucus, and <a href="https://www.cff.org/Living-with-CF/Treatments-and-Therapies/Inhaled-Medications/Antibiotics/">antibiotics</a>, which treat bacterial infections. </p>
<p>Although CF treatments have improved dramatically over the last decades, most are designed to address the symptoms rather than the cause – the defective CFTR gene present in the cells.</p>
<p>When a person with CF nears the point of lung failure, a lung transplant becomes the only life-saving option. However, suitable donor lungs for transplant are rare and recipients must take daily medications to suppress their immune system so their bodies do not reject the implanted organ. This often produces substantial side-effects, and complications are inevitable. </p>
<p>Currently, <a href="http://www.ncbi.nlm.nih.gov/pubmed/26087666">the five-year survival rate</a> of CF patients following double lung transplant is around 66%. </p>
<p>The disease creates a heavy physical and emotional cost to patients and their families, as well as <a href="http://www.ncbi.nlm.nih.gov/pubmed/23538187">substantial financial cost to the health system</a> and more recently the Pharmaceutical Benefits Scheme (PBS). </p>
<h2>What are genetically focused medicines?</h2>
<p>Genetically focused medicines are a component of <a href="https://www.nhmrc.gov.au/_files_nhmrc/publications/attachments/ps0001_clinical_utility_personalised_medicine_feb_2011.pdf">personalised medicine</a>, in which a diagnostic test to determine a patient’s genetic makeup is used to select an appropriate therapy. Such medicines are beginning to show their real potential for treating CF.</p>
<p>Two new mutation-focused pharmaceuticals are now available. Kalydeco, a drug that improves the defective CFTR protein function, is available on the PBS for the 4% of CF patients with the G551D CFTR mutation. But it’s expensive, currently costing the Australian government <a href="https://www.health.gov.au/internet/ministers/publishing.nsf/Content/health-mediarel-yr2014-dutton092.htm">A$174.5 million over four years</a> (about $300,000 per patient each year). </p>
<p>The other mutation-focused pharmaceutical is Orkambi, a treatment for about 70% of CF patients (those with the F508del CFTR mutation). In April 2016, the Pharmaceutical Benefits Advisory Commission <a href="https://www.pbs.gov.au/industry/listing/elements/pbac-meetings/pbac-outcomes/2016-03/first-time-decisions-not-to-recommend-2016-03.docx">rejected Orkambi</a> on the basis that the A$100 million annual cost was not accompanied by a demonstrated substantial benefit. </p>
<p>Similar rejections of Orkambi have occurred in Ireland and the United Kingdom; Canada has delayed its decision.</p>
<p>Other mutation-specific drugs that restore CFTR function are <a href="https://www.cff.org/Trials/pipeline">in development</a> and in clinical trials. But it’s unclear whether they will be made available to patients through the PBS. </p>
<h2>What is airway gene therapy?</h2>
<p>Another particularly attractive genetically-focused option is gene therapy. This is designed to treat the cause, not the symptoms, of the disease. Airway gene therapy works by delivering a correct copy of the CFTR gene into airway cells to rectify the salt imbalance and improve lung health. </p>
<p>CF is potentially a good target for gene therapies because we probably only need to correct the CFTR gene, unlike cancer in which many genes are implicated and not all are known. The lung is also a relatively accessible organ for delivery.</p>
<p>A <a href="http://www.ncbi.nlm.nih.gov/pubmed/26149841">recent clinical trial in the UK</a> showed that gene therapy was effective for CF lung disease. Monthly deliveries of the CFTR gene inhaled into the airways in small “fatty” globules called liposomes briefly stabilised the decline in lung health in some patients.</p>
<p>A far more efficient method of gene therapy delivery is under development which uses a highly modified and harmless virus as the vehicle that carries in the CFTR gene. </p>
<p>Some viral vectors (carriers) are capable of targeting airway stem cells, the specialised cells of the airway that constantly repair and replenish the cells of the lung. If stem cells are treated, patients might expect lasting benefit as their bodies automatically pass on the correctly functioning CFTR gene to their “daughter” cells. </p>
<p>Such treatment offers hope for lifetime or very long-lived benefits after a single set of treatments. </p>
<p>Importantly, an airway gene therapy of this nature would provide benefits regardless of a person’s CF mutation. </p>
<p>Pre-clinical studies <a href="http://www.ncbi.nlm.nih.gov/pubmed/19634193">look promising</a>, but clinical trials of this method have not yet begun. The <a href="http://www.cfgenetherapy.org.uk/">UK CF Gene Therapy Consortium</a> is preparing for a trial in patients, but the effectiveness and cost are not currently known.</p>
<p>Genetic medicines will undoubtedly be the medicines of our future. But the emergence of effective, potentially curative, but often extraordinarily expensive genetically focused treatments is driving new debate about the cost versus benefit for CF and other diseases, and how these should be funded.</p>
<hr>
<p><em>Update: Since this article was first published, the government has expanded the number of patients eligible to access <a href="https://theconversation.com/weekly-dose-kalydeco-the-drug-that-treats-the-cause-of-cystic-fibrosis-not-just-symptoms-76934">Kalydeco</a> on the Pharmaceutical Benefits Scheme (PBS). The <a href="http://www.health.gov.au/internet/ministers/publishing.nsf/Content/health-mediarel-yr2018-hunt180903.htm?OpenDocument&yr=2018&mth=09">government has also announced</a> Orkambi will be added to the PBS from October 2018.</em></p><img src="https://counter.theconversation.com/content/59681/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Martin Donnelley receives funding from the NHMRC, Women's and Children's Hospital Foundation, Cure4CF Foundation and Australian Synchrotron.</span></em></p><p class="fine-print"><em><span>David Parsons receives research funding from the NHMRC, Cure4CF Foundation SA, the USA CF Foundation, and the Australian Synchrotron.</span></em></p>Cystic fibrosis (CF) affects around 3,000 people in Australia and 70,000 worldwide. It’s an inherited disease caused by a mutation in a single gene called CFTR.Martin Donnelley, Senior research fellow, University of AdelaideDavid Parsons, Chief Medical Scientist and Team Leader, CF Airway Research Group, University of AdelaideLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/649052016-09-15T10:10:00Z2016-09-15T10:10:00ZHow studying a disease that affects hundreds of people could save millions of lives<figure><img src="https://images.theconversation.com/files/137602/original/image-20160913-4968-enb67j.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="http://www.shutterstock.com/pic-82806622/stock-photo-hand-with-a-magnifying-glass-on-the-banded-dna-sequences.html?src=-lJO3gkI_g67yDtJ6OGB9g-1-12">science photo/Shutterstock.com</a></span></figcaption></figure><p>A rare disease is one that affects fewer than <a href="http://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:32000R0141&qid=1421232987002&from=EN">five in 10,000</a> people. You might wonder why anyone would dedicate their life to studying a disease when only a handful of people would benefit from a cure. Why not study one of the big killers, such as cancer, tuberculosis or malaria?</p>
<p>The significance of rare diseases is often not appreciated by people outside of the field. Rare diseases can provide valuable insights into the causes and progression of far more common diseases. The study of these diseases can also lead to the development of life-saving drugs. In fact, that’s how statins were developed. The <a href="http://www.nhs.uk/conditions/Cholesterol-lowering-medicines-statins/Pages/Introduction.aspx">cholesterol-lowering drug</a> is one of the most frequently prescribed medicines in the developed world and it has saved countless lives.</p>
<figure class="align-right ">
<img alt="" src="https://images.theconversation.com/files/137654/original/image-20160913-4983-1xy0nzf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/137654/original/image-20160913-4983-1xy0nzf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=754&fit=crop&dpr=1 600w, https://images.theconversation.com/files/137654/original/image-20160913-4983-1xy0nzf.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=754&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/137654/original/image-20160913-4983-1xy0nzf.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=754&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/137654/original/image-20160913-4983-1xy0nzf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=947&fit=crop&dpr=1 754w, https://images.theconversation.com/files/137654/original/image-20160913-4983-1xy0nzf.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=947&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/137654/original/image-20160913-4983-1xy0nzf.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=947&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Life-savers.</span>
<span class="attribution"><a class="source" href="http://www.epa.eu/economy-business-and-finance-photos/company-information-photos/court-rules-pfizer-product-lipitor-protected-from-generic-competition-until-2011-photos-00599957">TANNEN MAURY/EPA</a></span>
</figcaption>
</figure>
<p>The journey to develop drugs that reduce cholesterol began in the late 1960s when a young Japanese biochemist named <a href="http://www.americanscientist.org/issues/pub/statins-from-fungus-to-pharma">Akira Endo</a> scoured thousands of strains of fungi looking for something that inhibited cholesterol production. He assumed that there are enzymes involved in producing cholesterol and something must inhibit one or more of these enzymes. </p>
<p>On discovering a product in fungi that did exactly this, tests moved to experiments in petri dishes. This was followed by clinical trials with participants who had dangerously high levels of cholesterol and were susceptible to heart attacks in their early years. The trial participants suffered from <a href="https://www.bhf.org.uk/heart-matters-magazine/medical/familial-hypercholesterolaemia">familial hypercholesterolemia</a>, a rare but life threatening condition, the most severe form of which affects <a href="http://www.sciencedirect.com/science/article/pii/S1933287416301891">one in 300,000</a> people. </p>
<p>Although Endo’s drug, Mevastatin, didn’t make it to the market, his study prompted further research into similar drugs, eventually culminating in the statins that are available on the market today and are used to treat more than <a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3108295/">30m people</a> globally.</p>
<h2>Insights into osteoporosis</h2>
<p>Similarly, a trio of rare diseases – two of which have fewer than 50 sufferers each worldwide – have advanced our understanding of “bone turnover and remodelling” in the human body. Bone turnover and remodelling ensure we have just the right amount of bone for the things we do in life, whether working in an office, competing as a professional athlete or going into space. Whatever we do on a daily basis, the cells that make and break down bone need to ensure that the right amount is there – enough to keep us strong enough to function but not so much that it becomes too heavy and slows us down.</p>
<p>Understanding these rare diseases has also aided the development of therapies to help treat bone diseases including <a href="http://www.nhs.uk/Conditions/Osteoporosis/Pages/Introduction.aspx">osteoporosis</a>. The first of the three diseases – <a href="http://www.omim.org/entry/146300">hypophosphotasia</a> – is an inherited disorder where sufferers struggle to make hard bones. It affects one in 100,000 people. <a href="http://www.omim.org/entry/239100">Van Buchem disease</a> and <a href="http://www.omim.org/entry/269500?search=269500&highlight=269500">sclerosteosis</a> have about 30 and 40 reported cases <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1735035/pdf/v039p00091.pdf">respectively</a> and sufferers of these two conditions make so much bone that it traps nerves needed to control breathing, hearing and other essential functions.</p>
<p>Osteoporosis is often treated using a group of drugs called <a href="https://en.wikipedia.org/wiki/Bisphosphonate">bisphosphonates</a>. These drugs mimic a molecule in the body which inhibits cells taking away bone; discovered from studies into understanding hypophosphotastia. The two rarer conditions have opened up our understanding of pathways that are involved in helping cells make new bone and this has potential for development of further treatment for osteoporosis and other conditions. </p>
<h2>Black bone disease</h2>
<p>More recently, another rare disease, alkaptonuria (“black bone disease”), has yielded clues about a very common condition: osteoarthritis. </p>
<p>People with alkaptonuria do not have enough of a particular enzyme, leading to a build up of a chemical in the body called homogentisic acid. The build up of this acid results in black and brittle bones. About one in every 250,000 people has this genetic disorder.</p>
<p>In my <a href="http://www.ecmjournal.org/journal/papers/vol023/pdf/v023a23.pdf">own research</a>, my colleagues and I examined bone samples from people with black bone disease and people with osteoarthritis. We discovered new bone formations that were common to both conditions. This finding helps us to understand a bit more about osteoarthritis and potentially offers new options to treat it. The new bone formations appear microscopically inside bones. Although we don’t know exactly how they are formed, when we find out, we may be able to use this understanding to treat osteoporosis or help repair broken bones more quickly. </p>
<p>A <a href="http://onlinelibrary.wiley.com/doi/10.1111/joa.12226/abstract">new mineralised structure</a> in cartilage that forms and contributes to joint damage has also been found in people with alkaptonuria. It is unusual to see hard mineralised structures in cartilage, which is very soft. The presence of these new mineralised structures in cartilage may help us to understand how cartilage is mechanically damage in osteoarthritis. If we can understand how they are formed, we may be able to stop them damaging cartilage. </p>
<p>These recent discoveries offer new opportunities for understanding common diseases and highlight the significance of rare diseases to everyone. </p>
<p>Two British physicians understood the value of studying rare and unusual disorders many years ago. <a href="https://en.wikipedia.org/wiki/William_Harvey">William Harvey</a>, discoverer of the circulatory system in the 17th century, said: </p>
<blockquote>
<p><a href="http://www.ncbi.nlm.nih.gov/books/NBK56194/">Nature</a> is nowhere accustomed more openly to display her secret mysteries than in cases where she shows tracings of her workings apart from the beaten paths; nor is there any better way to advance the proper practice of medicine than to give our minds to the discovery of the usual law of nature, by careful investigation of cases of rarer forms of disease.</p>
</blockquote>
<p><a href="https://en.wikipedia.org/wiki/William_Bateson">William Bateson</a>, an English biologist and coiner of the term “genetics”, put it more succinctly: “Treasure your exceptions!”</p><img src="https://counter.theconversation.com/content/64905/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Adam Taylor is affiliated with The Anatomical Society, his research has been supported by the AKU Society and Rosetrees Trust </span></em></p>Rare diseases are yielding secrets about very common conditions.Adam Taylor, Director of the Clinical Anatomy Learning Centre & Senior Lecturer in Anatomy, Lancaster UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/572282016-04-26T09:27:04Z2016-04-26T09:27:04ZYour lungs are full of microorganisms … and that’s a good thing<figure><img src="https://images.theconversation.com/files/120063/original/image-20160425-22352-155prtx.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The types of bugs that may be calling your lungs home</span> <span class="attribution"><a class="source" href="http://www.shutterstock.com/pic-214336648/stock-photo-growth-of-pathogenic-bacteria-populations-populations-from-commercial-toilet-in-petri-dish.html?src=m1iaLRV6vRDo-nk7WcUnlw-1-34">www.shutterstock.com</a></span></figcaption></figure><p>When we’re born, our lungs are thought to be sterile. But from the moment we take our first breath, our pristine lungs are exposed to all the bugs that are in the air. It has become clear in the last 10 years that the lungs rapidly acquire a population of many different microorganisms (mostly bacteria and viruses) that colonise the lungs and remain with us for the rest of our lives. This population of bugs is called the lung microbiome.</p>
<p>We now know more about the lung microbiome thanks to genetics. In the past, identifying the types of bugs present in the lungs depended on being able to grow them in a laboratory, and for many types of bug this was difficult. The big change that happened recently is our ability to recognise both the different bug species, and their relative abundance, by using <a href="https://www.genome.gov/10001177/dna-sequencing-fact-sheet/">DNA sequencing</a>. This can be done either from a sample taken from the lungs or from sputum (the mucus we cough up when we have an infection).</p>
<h2>Is the lung microbiome a good or a bad thing?</h2>
<p>We all know that bacteria in the lungs can be harmful. When harmful bacteria multiply, they cause <a href="http://www.nhs.uk/conditions/pneumonia/Pages/Introduction.aspx">pneumonia</a> which, despite the existence of antibiotics, can still be deadly. However, it seems that the lung microbiome usually exists in a balanced state, such that harmful types of bugs do not increase in number sufficiently to cause pneumonia. In fact, it’s possible that the very presence of such a diverse range of bugs in the lungs is one of the reasons it’s quite difficult for harmful bugs to multiply and cause disease.</p>
<p>There are a number of reasons why the lung microbiome is important. It can alter when we have underlying chest diseases, especially those in which there are marked structural changes in the lungs. A good example is <a href="http://www.nhs.uk/conditions/Cystic-fibrosis/pages/introduction.aspx">cystic fibrosis</a>. In this disorder, a fault in a gene changes a protein that regulates the movement of salt in and out of cells. It results in sticky sputum and infections, which in turn can cause structural damage to the airways – a condition called <a href="http://www.nhs.uk/Conditions/Bronchiectasis/Pages/Introduction.aspx">bronchiectasis</a>. </p>
<p>This makes it easier for some kinds of bacteria – especially <em><a href="https://www.blf.org.uk/support-for-you/pseudomonas">Pseudomonas</a></em> – to grow in the lungs, and it becomes very difficult to get rid of these bacteria. The continuing inflammation in the lungs leads to more damage and the chest disease worsens. Treatment is therefore aimed at trying to eradicate these damaging bacteria, but it’s very difficult to eradicate infection once it has become established.</p>
<p>The difficulties of treating infection in patients with cystic fibrosis have been known for a long time. Recently, attention has been focused on trying to identify if changes in the lung microbiome are present in other more common chest diseases, <a href="http://www.ncbi.nlm.nih.gov/pubmed/27078029">such as asthma</a> or <a href="http://www.ncbi.nlm.nih.gov/pubmed/?term=PMID%3A+26917613">chronic obstructive pulmonary disease</a> (COPD). Recent work has suggested that the bugs grown from airways in patients with these conditions can be different from bugs grown in healthy people. This raises the intriguing possibility that the different bugs present may, in part, be responsible for either the development of these diseases, or for altering the severity of disease once it develops. </p>
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<img alt="" src="https://images.theconversation.com/files/119641/original/image-20160421-26976-1xeigbi.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/119641/original/image-20160421-26976-1xeigbi.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/119641/original/image-20160421-26976-1xeigbi.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/119641/original/image-20160421-26976-1xeigbi.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/119641/original/image-20160421-26976-1xeigbi.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/119641/original/image-20160421-26976-1xeigbi.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/119641/original/image-20160421-26976-1xeigbi.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">COPD symptoms include an ongoing cough that produces a lot of mucus.</span>
<span class="attribution"><a class="source" href="http://www.shutterstock.com/pic-174190997/stock-photo-auscultation-elderly-person.html?src=gEZjH2gL5CnAiGy7z55jIQ-1-2">Image Point Fr</a></span>
</figcaption>
</figure>
<p>If it does prove to be the case that the different types of bugs in our lungs are in part responsible for development of chest disease, it follows that altering the lung microbiome might be a useful treatment. Directly altering the lung microbiome by administering “friendly” bacteria into the gut or lungs has mostly been <a href="http://www.ncbi.nlm.nih.gov/pubmed/?term=PMID%3A+26548605">tested in animals</a> to date. There are, however, examples of this approach working in other kinds of disease, particularly for conditions affecting the gut, for example for the <a href="http://www.ncbi.nlm.nih.gov/pubmed/?term=PMID%3A+25780308">treatment of irritable bowel syndrome</a>.</p>
<h2>Altering the lung microbiome</h2>
<p>I think the most important question about the lung microbiome is whether or not altering it could be helpful in treating or preventing chest disease. A good example is asthma. It’s well recognised that asthma seems to be more common in countries where early childhood exposure to infection is low. It has also been suggested that this increase in risk is due to lack of exposure to bugs in early life (an idea called the <a href="https://theconversation.com/infants-with-siblings-and-pets-less-likely-to-develop-allergies-9523">hygiene hypothesis</a>. </p>
<p>Some work has suggested that asthma risk could be reduced by encouraging early exposure to bugs, for example by spending more time in dirtier environments such as farms. Whether or not this approach works in the long term remains unclear, but if it does, it seems likely that changes in the lung microbiome may in part be responsible for the beneficial effects.</p><img src="https://counter.theconversation.com/content/57228/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span> I have research grants on asthma and COPD although none are related to work on the lung microbiome.</span></em></p>Understanding the bugs in our lungs could help treat certain diseases, including asthma.Ian Hall, Dean of the Faculty of Medicine and Health Sciences, University of NottinghamLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/402462015-06-30T20:10:43Z2015-06-30T20:10:43ZBrace yourself, genetic testing might give you more than you bargained for<p>Drink red wine to prevent cancer. But don’t drink too much! Get some exercise. But don’t overdo it. Give up, it’s all genetic anyway – think of Angelina Jolie! </p>
<p>We are constantly bombarded with conflicting information about our risk of developing cancer. It is difficult to know who to believe, let alone how to respond. </p>
<p>What if you could take a simple test that would reveal your individual risk of developing not only a range of cancers, but hundreds of other diseases? Imagine if it could also tell you which drugs would be most effective for you, if you did develop cancer or other diseases. </p>
<p>The rapidly reducing cost of DNA sequencing has made this one-time fantastical idea an emerging reality. Only 10 years ago it <a href="https://www.nhmrc.gov.au/health-topics/genetics-and-human-health/genetics-101-overview/sequencing-your-genome">cost about US$10 million</a> to sequence a human genome, so there was little prospect that individuals would, or could, seek out their own unique genetic maps to find out more about their ancestry or their inherited health risks. </p>
<p>Recent advances in genetics mean genetic sequencing is <a href="https://www.scienceexchange.com/services/whole-genome-seq">more affordable</a> (US$1,000 to US$3,000) and already guiding treatment across a range of illnesses from cancer to degenerative brain diseases. </p>
<p>New unregulated direct-to-consumer businesses are emerging, making it possible for anyone to order their individual genetic profile by posting off a saliva sample taken at home. But do you really know what you are signing up for?</p>
<h2>The age of personalised medicine</h2>
<p>Personalised medicine means using a patient’s genome to both predict their likelihood of developing certain diseases, and to guide which treatments are most likely to be effective in a particular individual. It’s also called customised medicine, precision medicine, individualised medicine, bespoke medicine and targeted medicine. </p>
<p>Our genes hold our hereditary information. Every cell in the human body is made up of about 20,000 genes that are passed down from parents to child. Genes contain information that instructs the growth, development and function of the human body. Some genes control simple characteristics such as hair colour and height, others influence complex characteristics such as intelligence. Some genes control how other genes work, telling them when to switch on and off. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/84995/original/image-20150615-6496-1eh4xg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/84995/original/image-20150615-6496-1eh4xg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=397&fit=crop&dpr=1 600w, https://images.theconversation.com/files/84995/original/image-20150615-6496-1eh4xg.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=397&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/84995/original/image-20150615-6496-1eh4xg.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=397&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/84995/original/image-20150615-6496-1eh4xg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=499&fit=crop&dpr=1 754w, https://images.theconversation.com/files/84995/original/image-20150615-6496-1eh4xg.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=499&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/84995/original/image-20150615-6496-1eh4xg.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">
<figcaption>
<span class="caption">Some genes control simple characteristics such as hair colour and height, others influence more complex characteristics like intelligence.</span>
<span class="attribution"><span class="source">from www.shutterstock.com</span></span>
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</figure>
<p>We all have alterations, or mutations, in our DNA. Mutations can be passed down from parents to children, or can occur spontaneously, especially as we age. Some are harmless and may determine, for example, <a href="http://udel.edu/%7Emcdonald/mythearwax.html">whether our ear wax</a> is wet or dry.</p>
<p>However, a mutation in an important gene that prevents it from working properly, or a gene that is missing altogether, can have serious consequences. Early genetic testing focused on debilitating inherited diseases, such as cystic fibrosis and Huntington’s disease, that are caused by mutations in single genes. Tests looked only for a known mutation in a specific gene to confirm or rule out the associated condition. </p>
<p>As testing has become more sophisticated, we have been able to extend this approach to more complex conditions such as cancer. Mutations in two genes called BRCA1 and BRCA2 are associated with an increased risk of developing breast and ovarian cancer, and can be inherited within families. </p>
<p>BRCA1 and BRCA2 normally help clean up mistakes in our DNA that our cells can make when they divide, a process called DNA repair. When either of these genes is altered or mutated, this protective function is disabled, leading to uncontrolled replication of cells with mistakes. This can lead to cancer. </p>
<p>The good news is that we can test for these mutations, and patients can then use the results of this test to assess their risk of developing cancer, and make informed choices. This is the same hereditary genetic mutation that prompted Angelina Jolie to have a preventative <a href="http://www.nytimes.com/2013/05/14/opinion/my-medical-choice.html?_r=0">double mastectomy</a> two years ago, and preventative <a href="http://www.nytimes.com/2015/03/24/opinion/angelina-jolie-pitt-diary-of-a-surgery.html?referrer=&_r=3">surgery to remove her ovaries</a> this year.</p>
<p>The other good news is that in recent years scientists have discovered that patients with mutations in BRCA1 and BRCA2 are exquisitely sensitive to some forms of chemotherapy and a second type of drug called a PARP inhibitor. The same mutation that generates the mistakes in these cells can actually <a href="http://www.onclive.com/conference-coverage/mbcc-2015/Excitement-Building-for-PARP-Inhibitors-in-BRCA-Mutated-Breast-Cancer">make them more responsive</a> to this drug. Decisions about treatment can then be “personalised” to the individual.</p>
<h2>What does the future hold?</h2>
<p>Currently, health systems in Australia and overseas do not offer patients the option of sequencing their entire genome as a means of identifying and managing future health risks. Today genetic testing is only available in Australia for specific genes, is tightly regulated and is used only when symptoms are apparent, or a genetic risk is likely, such as a close relative developing a particular cancer or condition.</p>
<p>In five to 10 years’ time, however, we may be facing very different choices, including the option to look for future diseases before they actually occur. </p>
<p>As many cancers do not appear until middle age or later, a young healthy person might discover they have various elevated risks among the many anomalies a DNA test could throw up. Such results might not be provided by a medical professional, but by a commercial operator, and without genetic counselling to explain what they mean to the individual and their family.</p>
<figure class="align-left ">
<img alt="" src="https://images.theconversation.com/files/84996/original/image-20150615-6479-enisbm.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/84996/original/image-20150615-6479-enisbm.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=705&fit=crop&dpr=1 600w, https://images.theconversation.com/files/84996/original/image-20150615-6479-enisbm.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=705&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/84996/original/image-20150615-6479-enisbm.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=705&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/84996/original/image-20150615-6479-enisbm.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=886&fit=crop&dpr=1 754w, https://images.theconversation.com/files/84996/original/image-20150615-6479-enisbm.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=886&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/84996/original/image-20150615-6479-enisbm.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=886&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Insurance companies could use genetic profiles to deny higher-risk individuals various types of insurance, or increase their premiums.</span>
<span class="attribution"><span class="source">from www.shutterstock.com</span></span>
</figcaption>
</figure>
<p>What might the implication be of a high-risk result? Should an individual’s relatives be informed, as their risk may also be high, or do they have a right not to know? And what about minors: will parents have the right, or even an obligation, to test babies and children for potential genetic risks, even if medical science offers no prevention or treatment options? </p>
<p>Are we psychologically equipped for these kinds of dilemmas and scientifically literate enough to interpret our own results? </p>
<p>There are currently many reasons to be cautious. First, there are potentially millions of genetic alterations. Most are still not understood. Personalised medicine cannot currently give anyone a comprehensive picture of individual risk simply because far too much remains unknown.</p>
<p>Second, personalised medicine can only indicate elevated risks, it cannot determine whether or not a patient will actually go on to develop a certain type of cancer. Environment and lifestyle also play a big role in our health. </p>
<p>Insurance companies, however, deal entirely in risk. That means genetic profiles could be used to deny higher-risk individuals various types of insurance, or increase their insurance premiums.</p>
<p>Third, health outcomes for some individuals may be based on the financial viability of developing drugs. Many drugs and therapies are currently used for large numbers of patients, making them financially viable for pharmaceutical companies to develop. Genetically targeted cancer drugs, suitable for much smaller groups of patients, may be extremely expensive or might not be brought onto the market at all if society is not willing or cannot afford to pay for them. </p>
<p>Fourth, we may be at risk of eroding our quality of life by creating a new state of “worried wellness”, waiting for disease to strike.</p>
<p>Finally, we may not be sufficiently savvy consumers. New commercial operators are coming onto the global market offering a range of largely unregulated services. Currently, you don’t get much more than details of your ancestry for a US$99 DNA test. But more specialised businesses are emerging that <a href="https://lifeletters.com/">offer</a>, for example, to “identify potential health risks that are present now or may develop in the future”. </p>
<p>Is this just hype, and offering unsubstantiated hope to consumers, or does this represent the first stage of patient empowerment over their own health and lifestyle choices? It will be fascinating to watch this new age of personalised medicine develop in the coming years.</p><img src="https://counter.theconversation.com/content/40246/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>What if you could take a simple test to reveal your individual risk of developing a range of cancers and hundreds of other diseases?Caroline Ford, Lab Head, Metastasis Research Group, Lowy Cancer Rearch Centre, UNSW SydneyOrin Chisholm, Program Authority and Senior Lecturer, Pharmaceutical Medicine, UNSW SydneyLicensed as Creative Commons – attribution, no derivatives.