tag:theconversation.com,2011:/us/topics/precision-medicine-14622/articlesPrecision medicine – The Conversation2024-03-21T18:58:32Ztag:theconversation.com,2011:article/2195942024-03-21T18:58:32Z2024-03-21T18:58:32ZTreatments tailored to you: how AI will change NZ healthcare, and what we have to get right first<p>Imagine this: a novel virus is rapidly breaking out nationwide, resulting in an epidemic. The government introduces vaccination mandates and a choice of different vaccines is available. </p>
<p>But not everyone is getting the same vaccine. When you sign up for vaccination, you are sent a vial with instructions to send a sample of your saliva to the nearest laboratory. Just a few hours later you receive a message telling you which vaccine you should get. Your neighbour also signed up for vaccination. But their vaccine is different from yours. </p>
<p>Both of you are now vaccinated and protected, although each of you received your vaccines depending on “who you are”. Your genetics, age, gender, and myriad of other factors are captured in a “model” that predicts and determines the best option to protect you from the virus.</p>
<p>It all sounds a bit like science fiction. But since the <a href="https://www.genome.gov/human-genome-project">decoding of the human genome in 2003</a>, we have entered the age of precision prevention. </p>
<p>New Zealand has a long-standing newborn screening programme. This includes <a href="https://www.auckland.ac.nz/en/news/2023/11/30/newborn-genomic-sequencing-sick-babies.html">genome sequencing machines available nationwide</a> and a <a href="https://www.tewhatuora.govt.nz/our-health-system/genetic-health-service-nz/about/">genetic health service</a>. Programmes such as these open up the possibilities of public health genomics and precision public health for everyone.</p>
<p>The further expansion of these programmes, as well as the expansion of the use of artificial intelligence and machine learning to enable a shift to more personalised preventive care, will change how public health care is delivered.</p>
<p>At the same time, these developments raise wider concerns over individual choice versus the greater good, personal privacy, and who is responsible for the protection of New Zealanders and their health information.</p>
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<h2>What is precision prevention?</h2>
<p>Think of precision prevention (also known as personalised prevention) as public health action tailored to the individual rather than broader groups of society. </p>
<p>This targeted healthcare is achieved by balancing a range of variables (including your genes, life history and environment) with your risks (including everything that changes within you as you grow older). </p>
<p>While advances in genomics are making precision prevention possible, machine learning algorithms fuelled by our personal data have made it closer to a reality. </p>
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<a href="https://theconversation.com/its-2030-and-precision-medicine-has-changed-health-care-this-is-what-it-looks-like-90539">It's 2030, and precision medicine has changed health care – this is what it looks like</a>
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<p>We generate data about ourselves every day – via social media, smartwatches and other wearable devices – helping to train algorithms to match medical prevention measures with individuals. </p>
<p>Combine all of these with AI-driven predictive modelling, and you have a system that can predict the current and future state of your health with an eerie level of accuracy, and <a href="https://www.forbes.com/sites/forbestechcouncil/2022/01/25/how-ai-could-predict-medical-conditions-and-revive-the-healthcare-system/?sh=362288726c47">help you take steps to prevent disease</a>. </p>
<h2>Safety and delay</h2>
<p>The Prime Minister’s Chief Science Advisor recently <a href="https://www.pmcsa.ac.nz/artificial-intelligence-2/ai-in-healthcare/">published a report</a> mapping out the landscape of artificial intelligence and machine learning in New Zealand over the next five years. </p>
<p>While the report authors didn’t specifically reference “precision prevention”, they did include examples of this approach, such as <a href="https://edition.cnn.com/2023/08/01/health/ai-breast-cancer-detection/index.html">computer vision augmented mammography</a>. </p>
<p>But as the report suggests, adoption tends to fall behind the pace of innovation in AI. Te Whatu Ora–Health New Zealand has also <a href="https://www.tewhatuora.govt.nz/our-health-system/digital-health/national-ai-and-algorithm-expert-advisory-group-naiaeag-te-whatu-ora-advice-on-the-use-of-large-language-models-and-generative-ai-in-healthcare/">not approved</a> emerging large language models and generative artificial intelligence tools as safe and effective for use in healthcare. </p>
<p>This means generative AI-driven precision prevention practices, such as conversational AI for public health messaging, may have to wait before they can be deemed safe to use. </p>
<h2>Move forward with caution</h2>
<p>There is much to be excited about the prospects of the use of artificial intelligence and machine learning in ushering in a new age of precision prevention and preventive health. But at the same time, we must temper this with caution. </p>
<p>Artificial intelligence and machine learning may increase access and utilisation of healthcare by lowering barriers to medical knowledge and reducing human bias. But government and medical agencies need to reduce barriers related to digital literacy and access to online platforms.</p>
<p>For those with limited access to online resources or who have limited digital literacy, the already existent inequity of access to care and health could worsen. </p>
<p>Artificial intelligence also has a <a href="https://arstechnica.com/gadgets/2023/04/generative-ai-is-cool-but-lets-not-forget-its-human-and-environmental-costs/">significant environmental impact</a>. <a href="https://arxiv.org/pdf/1906.02243.pdf">One study</a> found several common large AI models can emit over 270,000 tonnes of carbon dioxide during their life cycle.</p>
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Read more:
<a href="https://theconversation.com/these-scientists-are-using-dna-to-target-new-drugs-for-your-genes-medicine-made-for-you-part-1-131986">These scientists are using DNA to target new drugs for your genes – Medicine made for you part 1</a>
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<p>Finally, technology is a shifting landscape. Proponents of precision healthcare must be careful with children and marginalised communities and their access to resources. Maintaining privacy and choice is essential – everyone should be in a position to control what they share with the AI agents. </p>
<p>In the end, each of us is different, and we all have our different needs for our health and for our lives. Moving more people to preventive care through precision healthcare will reduce the financial burden on the health system. </p>
<p>But as the report from the prime minister’s chief science officer emphasises, machine learning algorithms are a nascent field. We need more public education and awareness before the technology becomes part of our everyday lives.</p><img src="https://counter.theconversation.com/content/219594/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Arindam Basu 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>As New Zealand readies itself for AI-assisted medical treatment targeted to individuals, officials need to ensure the benefits outweigh the risks.Arindam Basu, Associate Professor, Epidemiology and Environmental Health, University of CanterburyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2093122023-09-15T12:31:41Z2023-09-15T12:31:41ZCan at-home DNA tests predict how you’ll respond to your medications? Pharmacists explain the risks and benefits of pharmacogenetic testing<figure><img src="https://images.theconversation.com/files/545852/original/file-20230831-15-xftd5k.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2070%2C1449&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Pharmacogenetic testing is a form of precision medicine, using your genes to personalize your care.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/medicine-concept-royalty-free-image/815702424">D3Damon/E+ via Getty Images</a></span></figcaption></figure><p>Have you ever wondered why certain medications <a href="https://theconversation.com/why-prescription-drugs-can-work-differently-for-different-people-168645">don’t seem to work as well</a> for you as they do for others? This variability in drug response is what pharmacogenomic testing hopes to explain by looking at the genes within your DNA. </p>
<p><a href="https://www.cdc.gov/genomics/disease/pharma.htm">Pharmacogenomics, or PGx</a>, is the study of how genes affect your response to medications. <a href="https://www.genome.gov/genetics-glossary/Gene">Genes are segments of DNA</a> that serve as an instruction manual for cells to make proteins. Some of these proteins break down or transport certain medications through the body. Others are proteins that medications target to generate a desired effect.</p>
<p><a href="https://www.pharmacy.pitt.edu/people/kayla-rowe">As pharmacists</a> <a href="https://scholar.google.com/citations?user=9Np7_DYAAAAJ&hl=en">who see</a> <a href="https://scholar.google.com/citations?user=LKG31OkAAAAJ&hl=en">patients who</a> have stopped multiple medications because of side effects or ineffectiveness, we believe pharmacogenomic testing has the potential to help guide health care professionals to more precise dosing and prescribing.</p>
<h2>How do PGx tests work?</h2>
<p><a href="https://medlineplus.gov/lab-tests/pharmacogenetic-tests/">PGx tests</a> look for variations within the genes of your DNA to predict drug response. For instance, the presence of one genetic variant might predict that the specific protein it codes for is unable to break down a particular medication. This could potentially lead to increased drug levels in your body and an increased risk of side effects. The presence of another genetic variant might predict the opposite: It might predict that the protein it codes for is breaking down a medication more rapidly than expected, which may decrease the drug’s effectiveness.</p>
<p>For example, <a href="https://doi.org/10.1002/cpt.2903">citalopram is an antidepressant</a> broken down by a protein called CYP2C19. Patients with genetic variants that code for a version of this protein with a reduced ability to break down the drug may have an increased risk of side effects.</p>
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<figcaption><span class="caption">PGx is a form of personalized or precision medicine.</span></figcaption>
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<p>Currently, there are over 80 medications with <a href="https://cpicpgx.org/">prescribing recommendations</a> based on PGx results, including treatments for depression, cancer and heart disease. There are commercially available PGx tests that patients can have sent directly to their doorstep with or without the involvement of a health care professional. These direct-to-consumer PGx tests collect DNA from either a saliva sample or cheek swab that is then sent to the laboratory. Results can take anywhere from a few days to a few weeks depending on the company. </p>
<p>Some companies <a href="https://doi.org/10.1038%2Fnature15817">require a consultation</a> with a health care provider, often a pharmacist or genetic counselor, who can facilitate a test order and discuss any medication changes once the results come back. </p>
<h2>Limitations of PGx testing</h2>
<p>PGx testing will not be able to predict how you will respond to all medications for several reasons.</p>
<p>First, most PGx tests <a href="https://doi.org/10.3390/genes11121456">do not look for every possible variant</a> of every gene in the human genome. Instead, they look only at a limited number of genes and variants strongly linked to specific drugs. PGx tests can predict how you will respond only to medications associated with the genes it tests for. </p>
<p>Some drugs are broken down in very complicated pathways entailing multiple proteins and byproducts, and the usefulness of PGx testing for them remains unclear. For example, the <a href="https://www.pharmgkb.org/pathway/PA166170276">antidepressant bupropion</a> has three major pathways involved in its breakdown and forms three active byproducts that can interact with other drugs or body processes. This makes predicting how you will respond to the drug much more challenging because there is more than one variable involved. In many cases, there also isn’t conclusive data to confidently predict the general function of a protein and how it would affect your response to a drug.</p>
<p>The applicability of PGx test results is additionally limited by a <a href="https://theconversation.com/uncovering-the-genetic-basis-of-mental-illness-requires-data-and-tools-that-arent-just-based-on-white-people-this-international-team-is-collecting-dna-samples-around-the-globe-185997">lack of diversity of study participants</a>. Typically, populations of European ancestry are overrepresented in clinical trials. An ongoing research initiative by the National Institutes of Health called the <a href="https://allofus.nih.gov/">All of Us Research Program</a> aims to address this issue by collecting genetic samples from people of diverse backgrounds. </p>
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<figcaption><span class="caption">The All of Us research program seeks to conduct research that is more representative of a diverse population.</span></figcaption>
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<p>Another limitation of direct-to-consumer PGx tests is that they can predict drug response based only on your genetics. <a href="https://my.clevelandclinic.org/health/diagnostics/21093-pharmacogenomics">Lifestyle and environmental factors</a> such as your age, liver or kidney function, tobacco use, drug interactions and other diseases can heavily influence how you may respond to medication. For example, leafy greens with high amounts of vitamin K can <a href="https://www.pennmedicine.org/updates/blogs/heart-and-vascular-blog/2015/june/consistency-not-avoidance-the-truth-about-blood-thinners-leafy-greens-and-vitamin-k">lower the effectiveness</a> of the blood thinner warfarin. But PGx tests don’t take these factors into account.</p>
<p>Finally, your PGx results may predict that you may respond to medications differently, but this does not guarantee that the medication won’t have its intended effect. In other words, PGx testing is predictive rather than deterministic.</p>
<h2>Risks of PGx testing</h2>
<p>PGx testing carries the risk of not telling the whole story of drug response. If variations within the gene are not found, the testing company often assumes the proteins those genes code for function normally. Because of this assumption, someone carrying a rare or unknown variant may receive inaccurate results.</p>
<p>It may be tempting for some people to see their results and want to change their dose or discontinue their medications. However, this can be dangerous. Abruptly stopping some medications may cause withdrawal effects. Never change the way you take your medications without consulting your pharmacist and physician first.</p>
<p>Sharing your PGx test results with all the clinicians involved in your care can help prevent medication failure and improve safety. Pharmacists are increasingly trained in pharmacogenomics and can serve as a resource to address medication-related questions or concerns.</p>
<p>PGx tests that are not authorized by the Food and Drug Administration cannot be clinically interpreted and therefore cannot be used to inform prescribing. Results from these tests should not be added to your medical record.</p>
<h2>Benefits of PGx testing</h2>
<p>Direct-to-consumer PGx testing can empower patients to advocate for themselves and be an active participant in their health care by increasing access to and knowledge of their genetic information.</p>
<p>Patients’ knowledge of their PGx genetic profile has the potential to improve treatment safety. For example, a 2023 study of over 6,000 patients in Europe found that those who used their PGx results to guide medication therapy were <a href="https://doi.org/10.1016/s0140-6736(22)01841-4">30% less likely</a> to experience adverse drug reactions.</p>
<p>Most PGx test results stay valid throughout a patient’s life, and <a href="https://mhealthfairview.org/services/pharmacogenomics">retesting is not needed</a> unless additional genes or variants need to be evaluated. As more research on gene variants is conducted, prescribing recommendations may be updated. </p>
<p>Overall, genetic information from direct-to-consumer PGx tests can help you collaborate with health care professionals to select more effective medications with a lower risk of side effects.</p><img src="https://counter.theconversation.com/content/209312/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>Genetic testing can help take the guesswork out of finding the right treatment. For certain diseases. To an extent.Kayla B. Rowe, Fellow in Clinical Pharmacogenomics, University of PittsburghLucas A. Berenbrok, Associate Professor of Pharmacy and Therapeutics, University of PittsburghPhilip Empey, Associate Professor of Pharmacogenomics, University of PittsburghLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2051852023-07-25T12:23:27Z2023-07-25T12:23:27ZHorse health research will help humans stay healthy, too, with insights on reining in diabetes and obesity<figure><img src="https://images.theconversation.com/files/537361/original/file-20230713-29-i9gl5q.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2121%2C1406&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Learning how to treat endocrine disorders in horses may also lead to treatments in people, and vice versa.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/horse-royalty-free-image/1168570610">Catherine Falls Commercial/Moment via Getty Images</a></span></figcaption></figure><p>As a <a href="https://scholar.google.com/citations?user=61GznXIAAAAJ&hl=en">veterinary science researcher</a>, equine surgeon and sports medicine and rehabilitation specialist, I’ve seen firsthand the similarities between horses and humans. </p>
<p>Both horses and people with endocrine disorders like Type 2 diabetes can suffer multiple types of musculoskeletal disorders. For example, horses with <a href="https://cvm.msu.edu/vdl/client-education/guides-for-pet-owners/equine-endocrinology-pituitary-pars-intermedia-dysfunction-ppid">pituitary pars intermedia dysfunction</a> – similar to Cushing’s disease in people – suffer <a href="https://doi.org/10.1016/j.ando.2008.06.003">from tendon</a> and <a href="https://doi.org/10.1016/j.tvjl.2014.12.037">ligament degeneration</a>. Horses can also experience <a href="https://doi.org/10.1016/j.domaniend.2021.106620">muscle loss</a>, which can cause joint instability. That, and the chronic low-grade inflammation associated with endocrine disorders, can contribute to osteoarthritis.</p>
<p>There’s a principle in medicine called <a href="https://www.cdc.gov/onehealth/index.html">One Health</a>, which says that animals, humans and the environment are inextricably connected – for one to be healthy, all must be healthy. It also means that we can learn a lot about our own health by studying the health of animals, and vice versa, including the many parallels in endocrine disorders between humans and horses.</p>
<h2>Human and horse endocrine systems</h2>
<p>Your <a href="https://www.cancer.gov/publications/dictionaries/cancer-terms/def/endocrine-system#">endocrine system</a> produces hormones that support many of your body’s basic functions, including growth and development, metabolism, <a href="https://theconversation.com/your-body-has-an-internal-clock-that-dictates-when-you-eat-sleep-and-might-have-a-heart-attack-all-based-on-time-of-day-178601">sleep</a> and more. Your hormones also play a role in the health of your bones, tendons and ligaments. Some endocrine disorders change how your body produces and releases hormones and can lead to <a href="https://doi.org/10.1155/2015/206853">osteoporosis</a>, <a href="https://doi.org/10.7759/cureus.26726">arthritis</a>, <a href="https://doi.org/10.1111/sms.13984">ligament</a> <a href="https://doi.org/10.1016/j.ando.2008.06.003">injury</a> <a href="https://doi.org/10.1016/j.otsr.2018.01.009">and other</a> orthopedic diseases. </p>
<p>Humans aren’t the only species affected by this dynamic – <a href="https://doi.org/10.1016/j.tvjl.2018.03.002">horses</a> <a href="https://doi.org/10.1371/journal.pone.0190309">are</a>, <a href="https://doi.org/10.1016/j.tvjl.2014.12.037">too</a>. In fact, <a href="https://doi.org/10.1111/evj.13378">approximately 20% of horses</a> and <a href="http://dx.doi.org/10.5888/pcd14.160287">over 34% of people in the U.S.</a> are affected by endocrine disorders such as metabolic syndrome. These disorders are often accompanied by obesity.</p>
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<span class="caption">Like people, horses with endocrine disorders are also prone to orthopedic diseases.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/come-to-me-baby-royalty-free-image/127850478">Alberto BN Junior/Moment via Getty Images</a></span>
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<p>For both species, the degree to which endocrine disorders are connected to obesity and its associated negative health effects is complex. As mammals, horses and people share <a href="https://doi.org/10.1530/EC-14-0038">similar anatomy and endocrine physiology</a>, and researchers have noted their parallel <a href="https://doi.org/10.3390/genes11111378">genetic links between obesity and metabolic disease</a>.</p>
<p>Like people, obese horses with endocrine disorders often develop <a href="https://doi.org/10.1186/s13028-020-00515-5">low-grade inflammation</a>. Inflammation is a normal response to injuries and sickness. But chronic, low-grade inflammation can have long-term negative effects on the body. For example, low-grade inflammation is associated with <a href="https://doi.org/10.1038/nrrheum.2012.135">metabolic osteoarthritis in people</a>, and my laboratory is studying this possible link in horses.</p>
<p>In people, childhood obesity, which is related to <a href="https://doi.org/10.1136/bmj.j1">maternal obesity</a>, is associated with a type of <a href="https://doi.org/10.1097/BPO.0000000000001158">joint disease called osteochondrosis</a>. Foals born from obese mares are also predisposed to this <a href="https://doi.org/10.1371/journal.pone.0190309">same type of joint disease</a>.</p>
<h2>Research to note</h2>
<p>Because of the similarities between people and horses, research on diagnostics and treatments for metabolic conditions could provide health benefits to both species.</p>
<p>For example, a class of drug called <a href="https://doi.org/10.1016/j.molmet.2020.101102">glucagonlike peptide-1 agonists</a>, which includes such brands as Trulicity (dulaglutide) and Ozempic (semaglutide), is commonly used to treat metabolic syndrome and Type II diabetes in people. This class of medication is also effective in <a href="https://doi.org/10.1186/s12917-022-03394-2">treating these conditions in horses</a>, similarly slowing down how quickly food empties the stomach and blunting glucose release into the bloodstream.</p>
<p>Another class of drugs called <a href="https://doi.org/10.1136/bmj.m4573">sodium-glucose cotransporter protein-2 inhibitors</a>, which include such treatments as Jardiance (empagliflozin) and Farxiga (dapagliflozin), are used to treat Type 2 diabetes in people and <a href="http://dx.doi.org/10.5455/OVJ.2023.v13.i3.14">a similar condition in horses</a>. These drugs alter the kidneys’ ability to absorb sugar from urine such that the body eliminates some of the glucose it would normally absorb. This greatly reduces blood insulin spikes, which can help prevent obesity, metabolic syndrome and cardiovascular disease in both horses and people.</p>
<p>Some dietary supplements, <a href="https://theconversation.com/many-drugs-have-mirror-image-chemical-structures-while-one-may-be-helpful-the-other-may-be-harmful-186975">such as resveratrol</a>, especially when used <a href="https://doi.org/10.1016/j.jevs.2020.102930">in combination with an amino acid</a> called leucine, also help with weight loss, <a href="https://doi.org/10.2460/javma.249.6.650">mobility</a> and insulin sensitivity in people and horses. Lowering blood insulin concentrations can also prevent horses from <a href="https://ceh.vetmed.ucdavis.edu/health-topics/laminitis">developing laminitis</a>, a disease that inflames tissues in hooves that can necessitate euthanasia because of incurable pain. </p>
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<a href="https://images.theconversation.com/files/537362/original/file-20230713-27-e17gns.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Veterinarian in scrubs examining a horse's mane in a stable" src="https://images.theconversation.com/files/537362/original/file-20230713-27-e17gns.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/537362/original/file-20230713-27-e17gns.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/537362/original/file-20230713-27-e17gns.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/537362/original/file-20230713-27-e17gns.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/537362/original/file-20230713-27-e17gns.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/537362/original/file-20230713-27-e17gns.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/537362/original/file-20230713-27-e17gns.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">Certain drugs can treat similar conditions in both horses and people.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/black-young-woman-as-veterinarian-royalty-free-image/1408512719">SeventyFour/iStock via Getty Images Plus</a></span>
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<h2>Expanding precision medicine</h2>
<p>I find one of the most exciting avenues of research in both animals and people to be the expansion of <a href="https://theconversation.com/lack-of-diversity-in-clinical-trials-is-leaving-women-and-patients-of-color-behind-and-harming-the-future-of-medicine-podcast-199487">precision medicine</a>. Instead of the standard one-size-fits-all protocol, precision medicine uses information from a person’s genes, environment and medical history to create a customized treatment plan. For example, precision medicine is <a href="https://theconversation.com/every-cancer-is-unique-why-different-cancers-require-different-treatments-and-how-evolution-drives-drug-resistance-199249">often applied in oncology</a> when doctors gather genetic information about the patient’s tumor to inform which treatments might work best for them.</p>
<p>In horses, precision medicine currently focuses on <a href="https://www.aqha.com/-/genetic-test-roundup">DNA-based diagnostic tests</a> to inform exercise regimens, treatment and breeding decisions. Recent work with horses also suggests that measuring the <a href="https://doi.org/10.1111/evj.13053">heritability of certain metabolic traits</a> could be used to screen for metabolic syndrome in the future.</p>
<p>Within precision medicine, doctors aim to get a full-picture view of an individual and their metabolic health by using <a href="https://pubmed.ncbi.nlm.nih.gov/36817343">multiomic analysis</a>. Multiomics entails looking at <a href="https://www.britannica.com/science/omics">multiple “omics</a>” – or information from a range of biological disciplines, such as epigenomics, lipidomics, genomics and transcriptomics – to better treat an individual patient.</p>
<p>The more researchers learn from individual patients, including horses, the better doctors will be able to treat every patient. My lab and others <a href="https://doi.org/10.2460/ajvr.22.11.0194">use multiomic analysis</a> to generate data that may one day help us identify more effective and safer therapies for horses and – likely – people with metabolic conditions.</p><img src="https://counter.theconversation.com/content/205185/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jane Manfredi receives funding from the Michigan Alliance for Animal Agriculture, USDA NIFA, AAVMC CIVME. </span></em></p>Horses and humans share biological similarities that lead them to suffer from similar endocrine and orthopedic diseases. A number of treatments that work for one species often work for the other.Jane Manfredi, Associate Professor of Pathobiology and Diagnostic Investigation, Michigan State UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1994872023-02-09T16:31:46Z2023-02-09T16:31:46ZLack of diversity in clinical trials is leaving women and patients of color behind and harming the future of medicine – Podcast<figure><img src="https://images.theconversation.com/files/509021/original/file-20230208-15-u9tmxa.jpg?ixlib=rb-1.1.0&rect=73%2C196%2C2652%2C1495&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Most clinical trials overrepresent young white males. </span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/illustration-of-a-group-of-people-wearing-royalty-free-illustration/1267173084?phrase=medicine%20diverse&adppopup=true">Andresr/Digital Vision via Getty Images</a></span></figcaption></figure><p>Its a great day when you find a piece of clothing that fits perfectly. A good shirt, the right pair of shoes or a well-cut dress is comfortable, looks nice and feels like it was made just for you. Now imagine a world where every shirt was the same size, every shoe was the same design and there weren’t even differences between the cut of men’s and women’s clothing. Getting dressed in the morning would be clunky, and clothes would be uncomfortable. In other words, one size does not fit all.</p>
<p>Yet, this lack of bespoke options is more or less the reality of medicine today. Despite the many biological differences between people of different genders, races, ages and life histories, chances are that if two people walk into a doctor’s office with the same symptoms, they are going to get roughly the same treatment. As you can imagine, a whole range of treatments – from drugs to testing – could be much more effective if they were designed to work with many different kinds of bodies, not just some abstract, generic human. </p>
<p>In this episode of <a href="https://theconversation.com/uk/topics/the-conversation-weekly-98901">The Conversation Weekly</a> podcast, we speak to three researchers who are looking at ways to make medicine better suited to you. It starts with simply making sure that clinical trial participants look like the actual population of patients a drug is meant to treat. And as we explore in this episode, in the future, precision medicine could help each person get <a href="https://theconversation.com/how-to-use-precision-medicine-to-personalize-covid-19-treatment-according-to-the-patients-genes-142142">medical care that is tailored to their own biology</a>, just like a custom shirt.</p>
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<p>In 1977, the U.S. Food and Drug Administration released a set of policy guidelines that explicitly banned “women of childbearing age” from <a href="https://www.womenshealth.gov/30-achievements/04">participating in clinical trials</a> of new drugs. Though done out of a fear of causing birth defects, the result was that for more than a decade, new drugs were going to market with little information about how they might affect women. Due to systemic biases, research has found that people of color are routinely underrepresented in clinical trials today, too. For the most part, medical research has been done on <a href="https://www.verywellmind.com/racial-disparities-clinical-trials-5114529">healthy, young and middle-aged men of European descent</a>.</p>
<p>This is a problem in the U.S, according to <a href="https://scholar.google.com/citations?user=wd-fP1EAAAAJ&hl=en&oi=sra">Jennifer Miller, a bioethicist at Yale University</a>. “If you’re not included in the trial, this raises questions about whether the drug’s safety and efficacy information applies to patients like you,” she says.</p>
<p>In recent years, a number of researchers across the U.S. – like <a href="https://www.msm.edu/about_us/FacultyDirectory/Medicine/JuliaLiu/index.php">Julia Liu</a>, a professor of medicine at Morehouse School of Medicine – have been trying to figure out ways to improve the diversity of clinical trial participants. Part of the problem, Liu explains, stems from a myth within medicine that Black people don’t like to participate in medical research due to the history of abuses the U.S. medical system has inflicted on African Americans, like the infamous Tuskegee Experiment. But when Liu began running her own trials on a new prostate cancer test at a hospital that serves a majority-African American population, she <a href="https://theconversation.com/yes-black-patients-do-want-to-help-with-medical-research-here-are-ways-to-overcome-the-barriers-that-keep-clinical-trials-from-recruiting-diverse-populations-185337">found quite the opposite</a>. </p>
<p>“It turned out that just about everyone I asked said, ‘I would love to do that,’” explains Liu. “Half of the eligible patients agreed.” Black patients were just as eager to participate in research as white patients, and according to Liu, a big reason for lack of diversity in clinical trials is that they are mostly run out research hospitals in wealthier, whiter cities, not out of hospitals with diverse patients.</p>
<p>According to Miller’s research, only <a href="https://doi.org/10.1001/jamanetworkopen.2021.7063">4% of trials in recent years used a representative population</a>, but she is optimistic. Women are now much better represented in trials, and with regard to equal racial representation, “that 4% does tell us is that it’s possible to get this right.” </p>
<p>Efforts like those of Liu and Miller are similar to how companies make shirts in different sizes to better fit different bodies. Once researchers do this work, health care providers can choose which drugs are likely to work better and have fewer risks for different patients based on their individual demographics. </p>
<p>Better representation is a start, but anyone who has been lucky enough to get custom-made clothing knows just how well a shirt can really fit. This is the idea behind precision medicine. According to <a href="https://profiles.ucsf.edu/Keith.Yamamoto">Keith Yamamoto</a>, who directs the precision medicine center at the University of California, San Francisco, in the U.S., in the near future it may be possible to “achieve an understanding of health and disease to the extent that we could give advice to Dan Merino, not just people like Dan.” </p>
<p>This approach to medicine would incorporate basic biology, a person’s individual genetics and life history and the wealth of all existing medical research – precision medicine is an information and computation problem. To work, it needs good data – the representative data missing from clinical trials. As Yamamoto said, “Precision medicine will fail if we don’t address those issues in a head-on way.”</p>
<p>Listen to the full episode of <a href="https://theconversation.com/uk/topics/the-conversation-weekly-98901">The Conversation Weekly</a> to find out more. </p>
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<p>This episode of The Conversation Weekly was produced by Katie Flood. It was written by Katie Flood and Daniel Merino. Sound design is by Eloise Stevens, and the theme music is by Neeta Sarl.</p>
<p>You can find us on Twitter <a href="https://twitter.com/TC_Audio">@TC_Audio</a>, on Instagram at <a href="https://www.instagram.com/theconversationdotcom/">@theconversationdotcom</a> or <a href="mailto:podcast@theconversation.com">via email</a>. You can also sign up for The Conversation’s <a href="https://theconversation.com/newsletter">free emails here</a>. A transcript of this episode will be available soon. </p>
<p>Listen to The Conversation Weekly via any of the apps listed above, download it directly via our <a href="https://feeds.acast.com/public/shows/60087127b9687759d637bade">RSS feed</a> or find out <a href="https://theconversation.com/how-to-listen-to-the-conversations-podcasts-154131">how else to listen here</a>.</p><img src="https://counter.theconversation.com/content/199487/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jennifer Miller has served on the advisory board for Alexion Pharmaceuticals and directs the Good Pharma Scorecard. She receives funding from from the FDA, NIH and Arnold Ventures and sits on the board of the nonprofit Bioethics International.
Keith Yamamoto sits on the scientific advisory board of Mate Bioservices. He is the President of the American Association for the Advancement of Science (AAAS), chair of the Coalition for the Life Sciences, co-chair of the NASEM Roundtable on Aligning Incentives for Open Science and of the Science and Technology Action Committee, vice chair of the California Initiative to Advance Precision Medicine Advisory Council. He is a member of the Boards of Directors of the Public Library of Science, Research! America and Rapid Science, the Governing Board of the California Institute for Regenerative Medicine, the Board of Counselors for the Radiation Effects Research Foundation, the Advisory Board for Lawrence Berkeley National Laboratory and the Council of EBRC. </span></em></p><p class="fine-print"><em><span>Julia Liu does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and have disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Medicine works better when the treatments are tailored to fit each individual person’s biology and history. A first step is increasing diversity in clinical trials, but the end goal is precision medicine.Daniel Merino, Associate Science Editor & Co-Host of The Conversation Weekly Podcast, The ConversationNehal El-Hadi, Science + Technology Editor & Co-Host of The Conversation Weekly Podcast, The ConversationLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1942652022-12-01T15:21:49Z2022-12-01T15:21:49ZMini bio-devices could help TB patients stick to their treatments<figure><img src="https://images.theconversation.com/files/496953/original/file-20221123-12-8elsb5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Handheld devices like this one, used for testing blood sugar levels, could help TB patients monitor their own drug levels.</span> <span class="attribution"><span class="source">Andrey_Popov/Shutterstock</span></span></figcaption></figure><p>Imagine the scenario: you’ve been told you have a disease that will kill you. But, the doctor adds, your life can be saved if you diligently take your medication. Don’t skip a day, don’t skip a dosage. Soon, however, you discover that the medication has a slew of side effects, including a loss of appetite, fatigue, and nausea. So you do stop.</p>
<p>This process plays itself out every day among people who have been diagnosed with tuberculosis (TB). Treatment <a href="https://www.cdc.gov/tb/topic/treatment/tbdisease.htm#">lasts for months</a>. The adherence rate is low. Numbers are hard to come by. But one <a href="https://link.springer.com/article/10.1186/1471-2458-11-393">national survey</a> in China – which is among the <a href="https://www.who.int/china/health-topics/tuberculosis">30 high-burden</a> TB countries that account for 87% of the world’s estimated cases – showed that as many as 73% of TB patients had, at the time of the survey, interrupted or suspended treatment. </p>
<p>South Africa is another of those 30 high-burden countries. The <a href="https://www.nicd.ac.za/wp-content/uploads/2021/02/TB-Prevalence-survey-report_A4_SA_TPS-Short_Feb-2021.pdf">First National TB Prevalence Survey</a> of 2018 found a prevalence rate of around 737 per 100,000 people, among the highest in the world. Again, numbers are hard to determine, but <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4410008/">one study</a> looking at co-infection between extensively drug-resistant tuberculosis (XDR-TB) and HIV found that only around 70% of patients stuck to the optimal six-month treatment.</p>
<p>This poses risks for the individual and for entire communities. It is associated with higher transmission rates, fatalities, soaring costs for TB treatment programmes as well as the development of <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4561400/">multi-drug resistant strains</a>.</p>
<p>Multiple approaches are being taken to improve adherence to medication. These include the use of <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7462706/">higher doses</a> of certain medications in the hope of reducing treatment duration, although <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7462706/">side-effects</a> like hearing loss have been reported, as has the building up of resistance to drugs.</p>
<p>Building on the sequencing of the human genome and improved technologies to determine individual genetic variations, there has been a growing movement towards personalised or precision medicine and <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6297695/#">personalised treatment regimens</a>. This works on the premise that medical treatments, including those for TB, can be customised to an individual patient. Hurdles include the costs involved in making those technologies accessible, and understanding how to tailor treatments to each person. </p>
<p>In the case of TB, there are also <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8982531/">other factors</a> to consider, like variation in the disease-causing strain and individual drug-metabolising capacity.</p>
<p>That’s where <a href="https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/abs/10.1002/elan.202060384?af=R">my work</a> comes in. I am working to develop technologies that can accurately and reliably calculate an individual’s drug-metabolising capacity by measuring the “leftover” drugs in the TB patient’s blood or urine samples. The method involves the use of enzyme-based biosensors – a device used to detect chemical or biological substances. A popular application for such devices is the rapid detection of glucose levels in diabetics.</p>
<p>The results from my tests are promising. They reflect what other scholars doing similar experiments around the world show: these enzymatic biosensors could soon (scientists don’t like timelines) become a crucial weapon in efforts to make it easier for TB patients to adhere to their treatments.</p>
<h2>Finding the right enzyme</h2>
<p>One element of my work is to determine the right enzyme, already present in the human body, to include in the biosensor and serve as an amplifier or enhancer.</p>
<p>Biosensors should not be confused with the devices in which they sit – like the portable finger-prick testing kits used by diabetics, for example. They are simply a part of those devices. </p>
<p>Biosensors are typically made up of an electronic part, namely the transducer, that converts energy from one form to another; and a biological element such as an enzyme or even an antibody that acts as the sensor. </p>
<p>The electrochemical sensor itself does most of the hard measuring work. Essentially, the biological recognition element (the enzyme or antibody) interacts with the chemical component that you are seeking to identify and track, while the biological response is converted into an electric signal by the transducer, giving essential measurements. The biological element – in our case, the enzyme – simply boosts the signal.</p>
<p>My go-to enzyme is called CYP3A4. It forms part of a group of enzymes named cytochrome 450 or CYP450, which are known to play a key part in the <a href="https://pubmed.ncbi.nlm.nih.gov/23333322/">absorption of drugs</a> – and not just TB drugs. Because these enzymes react with 50% of all prescribed medication, they serve as a useful detector of the drug’s presence in a sample. </p>
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<strong>
Read more:
<a href="https://theconversation.com/tb-prevention-has-relied-on-the-same-vaccine-for-100-years-its-time-for-innovation-164735">TB prevention has relied on the same vaccine for 100 years. It's time for innovation</a>
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<p>What makes CYP3A4 so useful is that it reacts with all four of the first-line drugs used to treat TB: namely isoniazid, ethambutol, pyrazinamide and rifampicin. </p>
<p>For purposes of <a href="https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/abs/10.1002/elan.202060384?af=R">my study</a>, I developed a sensor by modifying the surface of a working electrode with nanoparticles of a range of materials. The enzyme was then electrostatically applied to this electrode. The completed biosensor was then tested on my samples: synthetic urine and plasma spiked with the four drugs.</p>
<p>My results showed that the biosensor could detected the drug “remnants” in my samples with high levels (90% and above) of accuracy. </p>
<h2>Real-world value</h2>
<p>So, what would the value of such a biosensor be in the real world? For one thing, it could allow clinicians to gauge whether a patient is a fast or poor metaboliser of the medication. </p>
<p>Typically, fast metabolisers quickly absorb the drugs, and only small vestiges remain in a blood or urine sample. They are likely to have few side effects since their bodies would not allow a build-up of the drug in their systems. However, they may need to take medication more regularly to make up for this quick absorption. </p>
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<em>
<strong>
Read more:
<a href="https://theconversation.com/the-key-to-treating-tb-may-be-in-a-common-carbohydrate-what-we-know-so-far-188412">The key to treating TB may be in a common carbohydrate. What we know so far</a>
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<p>Poor absorbers, on the other hand, do not process the drugs well enough to do much good. The drug then builds up in the body and can lead to adverse side effects. These patients may require lower or less regular dosages.</p>
<p>There is even the potential that such enzyme-based biosensors could be put in devices that patients can use on their own, much like diabetics use monitors to measure their glucose levels. People with TB can then then do the same, modifying their regimens based on the readings and their doctors’ guidance. </p>
<p>Such improved management can, ultimately, keep adherence rates from slipping – which is good news for TB patients, their communities and public health systems across the world.</p><img src="https://counter.theconversation.com/content/194265/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Candice Franke receives funding from the National Research Foundation of South Africa. </span></em></p>There are several reasons that TB patients don’t or can’t adhere to their treatment.Candice Franke, Lecturer, University of the Western CapeLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1849222022-07-11T12:29:55Z2022-07-11T12:29:55ZMany medications affect more than one target in the body – some drug designers are embracing the ‘side effects’ that had been seen as a drawback<figure><img src="https://images.theconversation.com/files/473235/original/file-20220708-14-kbl694.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2035%2C1471&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Depending on how you look at it, drugs that can act on multiple targets could be a boon instead of a challenge.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/multi-exposure-photogram-of-molecular-structure-of-royalty-free-image/886907874">Andrew Brookes/Image Source via Getty Images</a></span></figcaption></figure><p>Drugs don’t always behave exactly as expected. While researchers may develop a drug to perform one specific function that’s perhaps tailored to work for a specific genetic profile, sometimes the drug might perform several other functions outside of its intended purpose. </p>
<p>This concept of drugs having multiple functions, called <a href="https://doi.org/10.1021/acs.jmedchem.8b00760">polypharmacology</a>, may lead to unintended consequences. This is a common occurrence for <a href="https://doi.org/10.1126/scitranslmed.aaw8412">cancer drugs in clinical trials</a> that can have <a href="https://doi.org/10.1586/ecp.12.74">harmful side effects and treatment toxity</a>. </p>
<p>But polypharmacology may in fact be the norm for most drugs, not the exception. So rather than seeing a drug’s ability to perform many functions as a flaw, <a href="https://scholar.google.com/citations?user=iDKZaA4AAAAJ&hl=en">biomedical data scientists like me</a> and my <a href="https://www.waysciencelab.com/">lab colleagues</a> believe that it can be used to our advantage in designing drugs that address the full complexity of biology.</p>
<h2>Drugs often multitask in cells</h2>
<p>When scientists talk about drugs, they like to refer to its <a href="https://www.verywellmind.com/meaning-of-mechanism-of-action-in-health-care-425245">mechanism of action, or MOA</a> – essentially, exactly what a drug does when it enters the body. A drug’s official MOA, however, may not actually include all the ways it can affect cells.</p>
<p>For example, the mechanism of action of a drug labeled as a <a href="https://www.drugs.com/drug-class/vegf-vegfr-inhibitors.html">VEGF inhibitor</a> is to block the activity of a protein called VEGF, or vascular endothelial growth factor, in a cell. While VEGF plays an important role making new blood vessels, a process that’s integral to healthy tissue development, it can also be a <a href="https://doi.org/10.1016/j.cell.2011.02.013">hallmark of cancer</a>. <a href="https://www.webmd.com/cancer/cancer-angiogenesis-inhibitors">Blocking VEGF</a> can stop the formation of new blood vessels that supply nutrients to tumors and prevent the growth and spread of many types of cancers.</p>
<p>There are currently <a href="https://www.cancer.gov/about-cancer/treatment/types/immunotherapy/angiogenesis-inhibitors-fact-sheet">14 drugs inhibiting new blood vessel formation</a> approved in the U.S. to treat cancer, and most target VEGF. You may be wondering why there are so many different drugs available if they’re all inhibiting the same protein. The answer comes down to polypharmacology: While they all most likely work by blocking VEGF in some way, each likely has some other function that may be unique to that drug. That alternative function might cause side effects, or only work in certain conditions. </p>
<p>VEGF belongs to a larger group of proteins called <a href="https://doi.org/10.3390/cancers12030731">receptor tyrosine kinases, or RTKs</a>, that are challenging to target individually. Many drugs that target one type of RTK, like VEGF, also end up indiscriminately <a href="https://pubmed.ncbi.nlm.nih.gov/29888050/">targeting other RTKs</a> because they share a <a href="https://doi.org/10.1016/j.chembiol.2018.11.005">similar chemical structure</a>, potentially causing unwanted side effects.</p>
<p>For example, in 1999, scientists discovered that the infamous morning sickness drug thalidomide also worked as a VEGF inhibitor to <a href="https://doi.org/10.1056/nejm199911183412102">treat multiple myeloma</a>, a type of blood cancer. This was a triumph for a drug that, just 70 years prior, was banned worldwide after causing severe birth detects in an estimated <a href="https://doi.org/10.1016/s0140-6736(04)16308-3">10,000 infants</a>, not including miscarriages and stillbirths.</p>
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<figcaption><span class="caption">As in the case of thalidomide, a slight difference in chemical structure can make a huge difference in how a drug affects the body.</span></figcaption>
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<p>Like thalidomide, many chemicals affect the body in many different ways, and their full mechanism of action still isn’t fully understood. Even some approved drugs like lithium, acetaminophen and many antidepressants still have an <a href="https://doi.org/10.1016/j.isci.2020.101487">unclear MOA</a>.</p>
<p>Perhaps the most famous example of the serendipity of polypharmacology is <a href="https://www.history.com/this-day-in-history/fda-approves-viagra">Viagra</a>, a drug that was originally developed for cardiovascular problems but was later approved for erectile dysfunction. Interestingly, there is emerging evidence that Viagra also works as a <a href="https://doi.org/10.1111%2Fj.1582-4934.2008.00319.x">VEGF activator</a>, which may help treat stroke or heart attack. </p>
<h2>Taking advantage of polypharmacology</h2>
<p>The problem is that when you take a drug with multiple functions, you can’t isolate one desired effect from all the others – you get all of them all at once. Researchers can react to polypharmacology in two ways. Scientists can try to design better drugs that home in on just one specific target. Alternatively, scientists can instead embrace the complexity of biology and try to leverage the multifaceted effects drugs can offer.</p>
<p>Many existing drugs have unknown mechanisms that can be harnessed as a strength, rather than a weakness. Researchers can use polypharmacology to <a href="https://theconversation.com/repurposing-generic-drugs-can-reduce-time-and-cost-to-develop-new-treatments-but-low-profitability-remains-a-barrier-174874">repurpose existing drugs</a> to use for other conditions, reducing the time and cost of developing new treatments. There is an entire industry of doctors and scientists currently trying to do exactly that. Chemists and drug designers are also purposefully <a href="https://doi.org/10.1021/acs.jmedchem.8b00760">designing drugs with multiple functions</a> to combat complex diseases like cancer and type 2 diabetes, which may have multiple targets that can escape single-function treatments.</p>
<p>But in order to take advantage of the polypharmacology of existing drugs, researchers require a way to measure it. Typically, chemists study drug mechanisms through laborious experiments that test drugs one at a time and don’t always lead to conclusive answers. However, new experimental approaches, like <a href="https://doi.org/10.1038/s41573-022-00472-w">phenotypic drug screening</a>, that measure the overall effect of the drug instead of trying to narrow down its mechanism of action, allow researchers to measure thousands of different drugs in a single experiment.</p>
<p>My colleagues and I <a href="https://doi.org/10.1371/journal.pcbi.1009888">used this approach</a> to predict all the effects of specific drugs, using nothing but images of cells. We collected 159 million snapshots of cells reacting to over 1,300 different drugs, then applied a machine learning algorithm to identify important patterns in the images. Instead of teaching the algorithm to look for specific details, we allowed it to search for pieces of data in the pictures that allowed it to better predict how a cell would react to different types of drugs. </p>
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<figcaption><span class="caption">Machine learning can help predict how the chemical structure of any particular drug might affect the body.</span></figcaption>
</figure>
<p>Our model repurposed an approach called <a href="http://dx.doi.org/10.48550/arXiv.1511.06434">latent space arithmetic</a>, originally developed using pictures of human faces, to predict drugs with polypharmacology. Just as the original algorithm could simulate a picture of a man wearing glasses, we could simulate what a cell looks like when treated with a drug that has multiple mechanisms of action.</p>
<p>Our model was far from perfect, though. Many drug mechanisms of action could not be simulated well, and we were limited by existing, likely incomplete, knowledge about how different drugs worked. Additional work to demystify how different drug mechanisms affect cells in a wider context could help improve predicting all of a drug’s potential functions, leading to more treatment possibilities for each compound. </p>
<p>I believe that embracing polypharmacology as an unavoidable consequence of using drugs to treat diseases can help researchers reimagine the drug discovery process. Could we design a drug that targets all the receptors going haywire in a specific patient’s tumor? Could we use artificial intelligence to simulate how such a potential drug compound might look and behave in the body? Could polypharmacology actually be the answer to precision medicine instead of one of its biggest challenges? A shift in mindset might be the first step to answering these questions.</p><img src="https://counter.theconversation.com/content/184922/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Gregory Way does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Many approved drugs work on the body in ways that researchers still aren’t entirely clear about. Seeing this as an opportunity instead of a flaw may lead to better treatments for complex conditions.Gregory Way, Assistant Professor of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical CampusLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1811382022-04-15T18:01:27Z2022-04-15T18:01:27ZWhat is that rash? Genetic fingerprints can help doctors diagnose and treat skin conditions more effectively<figure><img src="https://images.theconversation.com/files/458016/original/file-20220413-23-kvcimv.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2121%2C1412&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Skin conditions like psoriasis and eczema can have rashes that are difficult to distinguish by eye.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/dermatitis-eczema-texture-of-ill-human-skin-royalty-free-image/1270950737">tylim/iStock via Getty Images Plus</a></span></figcaption></figure><p>Rashes can be thought of as a dysfunctional community of skin cells. Your skin harbors <a href="https://dermnetnz.org/topics/the-structure-of-normal-skin">dozens of distinct cell types</a>, including those that form blood vessels, nerves and the local immune system of the skin. For decades, clinicians have largely been <a href="https://doi.org/10.1097/01.pcr.0000117274.16187.de">diagnosing rashes by eye</a>. While examining the physical appearance of a skin sample under a microscope may work for more obvious skin conditions, many rashes can be difficult to distinguish from one another.</p>
<p>At the molecular level, however, the differences between rashes become more clear. </p>
<p>Scientists have long known that <a href="https://doi.org/10.1038/jid.2009.71">molecular abnormalities</a> in skin cells cause the redness and scaliness seen in conditions like psoriasis and eczema. While almost all the various cell types in your skin can release chemicals that worsen inflammation, which ones leads to rash formation remains a mystery and may <a href="https://doi.org/10.1016/j.immuni.2018.05.012">vary from patient to patient</a>.</p>
<p>But molecular testing of skin rashes isn’t a common practice because of technological limitations. Using a new approach, my colleagues and I were able to analyze the <a href="https://www.science.org/doi/10.1126/sciimmunol.abl9165">genetic profiles of skin rashes</a> and quantitatively diagnose their root causes.</p>
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<figcaption><span class="caption">Skin is a complex organ that performs a wide variety of functions.</span></figcaption>
</figure>
<h2>High-res skin profiles</h2>
<p>Traditional genetic analyses work by averaging out the activity of <a href="https://doi.org/10.1038/jid.2014.28">thousands of genes across millions of cells</a>.</p>
<p>Genetically testing tissue samples is standard practice for conditions like cancer. Clinicians collect and analyze tumor biopsies from patients to determine a particular cancer’s unique molecular characteristics. This genetic fingerprint helps oncologists <a href="https://doi.org/10.1016/j.semcancer.2017.08.010">predict whether a cancer will spread or which treatments might work best</a>. Cancer cells lend themselves to this form of testing because they often grow into recognizable masses that make them easy to <a href="https://www.cancer.gov/about-cancer/treatment/types/biomarker-testing-cancer-treatment">isolate and analyze</a>.</p>
<p>But skin is a complex mixture of cells. Collapsing these unique cell communities into a single group may obscure genetic signatures essential to diagnosis.</p>
<p>Recent technological advances called <a href="https://doi.org/10.1016/j.jdin.2020.08.001?">single-cell RNA sequencing</a>, however, have enabled scientists to preserve the identity of each type of cell that lives in the skin. Instead of averaging the genetic signatures across all cell types in bulk, single-cell RNA sequencing analyses allow each cell to preserve its unique characteristics.</p>
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<figcaption><span class="caption">Single-cell RNA sequencing is used to analyze samples where many different types of cells are present.</span></figcaption>
</figure>
<p>Using this approach, my colleagues and I isolated over 158,000 immune cells from the skin samples of 31 patients. We measured the activity of about 1,000 genes from each of those cells to create detailed molecular fingerprints for each patient. By analyzing these fingerprints, we were able to pinpoint the genetic abnormalities unique to the immune cells residing in each rash type. This allowed us to quantitatively diagnose otherwise visually ambiguous rashes. </p>
<p>We also observed that some patients had treatment responses consistent with what we expected with our predicted diagnoses. This suggests that our concept could viably be expanded for further testing.</p>
<p>To make our approach available to clinicians and scientists, we developed an open source web database called <a href="https://rashx.ucsf.edu/">RashX</a> that contains the genetic fingerprints of different rashes. This database will allow clinicians to compare the genetic profile of their patients’ rashes to similar profiles in our database. A closely matching genetic fingerprint might yield clues as to what caused their patient’s rash and lead to potential treatment avenues.</p>
<h2>Open source diagnostics</h2>
<p>The <a href="https://www.scientificamerican.com/article/biologics-the-pricey-drugs-transforming-medicine/">rapid development of drugs that target the immune system</a> in recent years has inundated doctors with difficult treatment decisions for individual patients. For example, while certain drugs that act on the immune system are known to work well for conditions like psoriasis or eczema, many patients have atypical rashes that can’t be precisely diagnosed. </p>
<p>An <a href="https://rashx.ucsf.edu/">open source database</a> like ours could help enable clinicians to profile and diagnose these rashes, providing a stepping stone to choose a suitable treatment. </p>
<p>Furthermore, <a href="https://doi.org/10.1126/science.abf3041">chronic inflammatory diseases</a> that affect organs other than the skin share similar genetic abnormalities. Lab tests that can illuminate the root causes of skin diseases can likely be expanded to many other conditions.</p>
<p>Our <a href="https://rashx.ucsf.edu/">RashX</a> project initially focused on just two very common types of rashes, psoriasis and eczema. It is unknown whether <a href="https://www.aad.org/public/diseases/a-z">other types of rashes</a> will have similar genetic profiles to psoriasis and eczema or instead have their own unique fingerprints. It is also unclear which parts of the fingerprint would best predict drug response.</p>
<p>But <a href="https://rashx.ucsf.edu/">RashX</a> is a living web resource that will grow more useful as more scientists collaborate and contribute new data. Our lab is also working to simplify the process of developing genetic profiles of rashes to make participating in this area of research more accessible for clinics around the world. With more data, we believe that projects like RashX will make precision testing for rashes an essential next step in diagnosis and treatment.</p>
<p>[<em>Understand new developments in science, health and technology, each week.</em> <a href="https://memberservices.theconversation.com/newsletters/?nl=science&source=inline-science-understand">Subscribe to The Conversation’s science newsletter</a>.]</p><img src="https://counter.theconversation.com/content/181138/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Raymond J. Cho, MD, PhD receives funding from the LEO Foundation, the National Psoriasis Foundation, the National Eczema Assocation, Sun Pharmaceutical Industries, Sanofi, and Pfizer. </span></em></p>Many doctors currently diagnose skin conditions by eye. Advances in molecular testing could lead to more precise and accurate diagnoses for ambiguous rashes and skin lesions.Raymond J. Cho, Associate Professor of Dermatology, University of California, San FranciscoLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1582802021-04-07T21:49:27Z2021-04-07T21:49:27ZMedical schools need to prepare doctors for revolutionary advances in genetics<figure><img src="https://images.theconversation.com/files/393358/original/file-20210405-15-105n7n5.jpg?ixlib=rb-1.1.0&rect=7%2C0%2C5117%2C3427&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Medical education needs to include understanding how genetic conditions can occur.</span> <span class="attribution"><span class="source">(Shutterstock)</span></span></figcaption></figure><p>Human diversity did not appear to matter to modern medicine. At the time, the state of medical practice <a href="https://dx.doi.org/10.1038/embor.2012.87">ignored the differences between individuals and between men and women</a>. </p>
<p>This practice was reflected in how doctors were trained. They took courses in basic biology, biochemistry, anatomy and physiology. But genetics, the science of variation, was not a required course until recently.</p>
<p>Advances in genetics research have <a href="https://dx.doi.org/10.3399/bjgp12X629955">slowly transformed the practice of medicine</a>. There has been a slow accumulation of <a href="https://dx.doi.org/10.1086/514346">a long list of diseases caused by variations in a single gene</a>. Since the disease-causing variants generally occurred — with some exception — in low frequency, these diseases did not occupy the mainstream concern of the medical profession.</p>
<p>All this changed with <a href="https://www.genome.gov/human-genome-project/What">the Human Genome Project (HGP)</a>. Completed in 2003, the <a href="https://www.genome.gov/25520492/online-education-kit-2003-human-genome-project-completed">sequencing of human genome</a> pushed us into a new era of how genetic diseases would be defined, and how future health services would be delivered.</p>
<p>Medical schools need to do a lot better preparing future physicians and health professionals if the dreams of personalized medicine are to be realized. </p>
<h2>Personalizing medicine</h2>
<p>Personalized medicine means treating patients based on the individual characteristics of their DNA. The information can be used either in direct intervention, as in cancer treatment, or in predictive medicine. </p>
<p>Different specializations would require varying levels of proficiency: for example, family physicians would need a sufficient background in genetics, while oncologists would need in-depth education.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/393882/original/file-20210407-23-f76x9k.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A doctor shows a patient information on a tablet" src="https://images.theconversation.com/files/393882/original/file-20210407-23-f76x9k.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/393882/original/file-20210407-23-f76x9k.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/393882/original/file-20210407-23-f76x9k.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/393882/original/file-20210407-23-f76x9k.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/393882/original/file-20210407-23-f76x9k.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/393882/original/file-20210407-23-f76x9k.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/393882/original/file-20210407-23-f76x9k.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">Family physicians will have increasing access to data and more detailed genetic information about their patients.</span>
<span class="attribution"><span class="source">(Shutterstock)</span></span>
</figcaption>
</figure>
<p>The HGP made two big promises. First, it promised personalized predictive medicine <a href="https://doi.org/10.1016/S0140-6736(16)00176-8">based on an individual’s genome sequences</a>. Disease-causing mutations at different locations on a gene would be identified, and an overall personalized risk score would be calculated that <a href="https://doi.org/10.1109/tbme.2017.2698602">would tell the individual his or her chances of developing that disease</a>.</p>
<p>The second promise was to develop a better and faster cures for complex diseases such as cancer.</p>
<p>The letdown came when genomic studies showed that genes affecting complex diseases were potentially large in number and individually of small effect, and worse still, <a href="https://dx.doi.org/10.1038/nrg2809">only a small number of all potential genes affecting a given disease could be identified</a>.</p>
<p>Even more problematic, it turned out that all individuals sharing the same risk factor for a given disease did not develop the disease. This creates a problem for predictive medicine if scientists cannot link a disease to a gene with any certainty.</p>
<h2>Evolution and genetic complexity</h2>
<p>The uncovered genomic complexity of diseases was contrary to expectations of the Mendelian model, which did not account for genetic variations beyond “<a href="https://doi.org/10.1161/CIRCULATIONAHA.118.035954">one gene — one disease</a>.”</p>
<p>This is where the work my collaborators and I carried out in our labs comes in. Our work in population genetics and evolutionary genomics relates to how these characteristics are calculated and combined into an overall score used in predictive medicine.</p>
<p>My lab specializes in the evolution of molecular complexity and its impact on precision medicine. We also study variation and evolution of sex and reproduction related genes and their role in the evolution of sexual dimorphism in complex diseases and mental disorders. We reviewed three decades of relevant work in genetics, genomics and molecular evolution and <a href="https://doi.org/10.1038/s41525-020-0128-1">drew the following conclusions</a>.</p>
<p>First, we showed that because of the blind nature of evolutionary forces and the role of chance in evolution in humans, many combinations of genes can lead to the same disease. This implies the existence of a considerable amount of redundancy in the molecular machinery of the organism.</p>
<p>Second, we showed that genes do not work alone: gene-gene and gene-environment interactions are a major part of any organism’s functional biology. This would explain, for example, <a href="https://dx.doi.org/10.1093/annonc/mdv022">why some women with breast cancer genes develop breast or ovarian cancer and some do not</a>.</p>
<p>Third, we showed that since males fight for mates and early reproduction, this would lead to an evolution of male-benefitting mutations even at the cost of them being harmful later, making males vulnerable to diseases in their old age. Male-benefitting mutations harmful to females would trigger a female-driven response leading to the evolution of increased female immunity, and possibly evolution of higher thresholds for complex diseases and mental disorders. </p>
<p>This would explain why many diseases such as <a href="https://doi.org/10.1007/s00239-021-09999-9">autism are more common in boys than girls</a>. In addition, some differences in disease prevalence, such as depression in women, is theorized to be the result of <a href="https://dx.doi.org/10.1007/s00213-019-05326-9">interaction between hormone fluctuation and social stress factors</a>.</p>
<h2>Physicians and personalized medicine</h2>
<p>If you have sought medical attention, it’s likely that your doctor may have asked you about your parents and your siblings. Your physician is interested in knowing if there are any health conditions, such as cardiovascular disease, diabetes or high blood pressure that run in the family and that might affect your health.</p>
<p>Future physicians will need to know <a href="https://dx.doi.org/10.1016/j.ccell.2008.01.004">a lot more than their patients’ family history</a>.</p>
<p>The number of situations that involve relevant genetic contributions will continue to increase with advances in molecular insights and precision medication. The medical research establishment is becoming increasingly aware of the importance of individual genetic differences and of sex and gender when assessing diseases and health-care proposals. Health professionals must have sufficient expertise in diversity, genomics and gene-environment (gene-drug) interaction.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/393875/original/file-20210407-15-7njvu.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Laptop with floating icons related to health care" src="https://images.theconversation.com/files/393875/original/file-20210407-15-7njvu.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/393875/original/file-20210407-15-7njvu.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/393875/original/file-20210407-15-7njvu.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/393875/original/file-20210407-15-7njvu.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/393875/original/file-20210407-15-7njvu.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/393875/original/file-20210407-15-7njvu.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/393875/original/file-20210407-15-7njvu.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">Medical schools need to develop their curriculums to include advances in genetic research.</span>
<span class="attribution"><span class="source">(Shutterstock)</span></span>
</figcaption>
</figure>
<p>Future physicians will be part of health networks involving medical lab technicians, data analysts, disease specialists and the patients and their family members. The physician would need to be knowledgeable about the basic principles of genetics, genomics and evolution to be able to take part in the chain of communication, information sharing and decision-making process. </p>
<p>This would require a more in-depth knowledge of genomics than generally provided in basic genetics courses.</p>
<p>Much has changed in genetics since the discovery of DNA, but much less has changed how genetics and evolution are taught in medical schools.</p>
<p>In 2013-14 a survey of course curriculums in American and Canadian medical schools showed that while most medical schools taught genetics, most respondents felt the amount of time spent was insufficient preparation for clinical practice as it did not provide them with sufficient knowledge base. The survey showed that <a href="https://doi.org/10.1038/gim.2014.208">only 15 per cent of schools covered evolutionary genetics in their programs</a>.</p>
<p>A simple viable solution may require that all medical applicants entering medical schools have completed rigorous courses in genetics and genomics.</p><img src="https://counter.theconversation.com/content/158280/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Rama Shankar Singh receives funding from McMaster University. </span></em></p>Medical education has not kept up with genetic discoveries — primary care physicians require more genetics and genomics training.Rama Shankar Singh, Professor of Biology, McMaster UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1421422020-09-01T18:00:14Z2020-09-01T18:00:14ZHow to use precision medicine to personalize COVID-19 treatment according to the patient’s genes<figure><img src="https://images.theconversation.com/files/348045/original/file-20200716-19-1td0whz.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C4868%2C3286&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A humorous message about actor Tom Hanks at the closed Las Vegas Mini Grand Prix amid the coronavirus pandemic.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/digital-billboard-displays-a-humorous-message-about-actor-news-photo/1224733683?adppopup=true"> Ethan Miller/Getty Images</a></span></figcaption></figure><p>Tom Hanks and his wife, Rita Wilson, were among the earliest celebrities to catch the novel coronavirus. In an interview at the beginning of July, <a href="https://www.theguardian.com/film/2020/jul/06/tom-hanks-on-surviving-coronavirus-i-had-crippling-body-aches-fatigue-and-couldnt-concentrate">Hanks described how differently COVID-19 had affected each of them</a> in March. </p>
<p>“My wife lost her sense of taste and smell, she had severe nausea, she had a much higher fever than I did. I just had crippling body aches,” he said. “I was very fatigued all the time and I couldn’t concentrate on anything for more than about 12 minutes.”</p>
<p>Why does COVID-19 present such different symptoms – or none at all – in different people?</p>
<p>Preexisting conditions can only be part of the story. Hanks is over 60 and is a Type 2 diabetic, putting him in a high-risk group. Nevertheless, he survived his brush with the virus with no pneumonia and apparently without any long-lasting effects. Knowing what causes variation in different patients could help physicians tailor their treatments to individual patients – an approach known as precision medicine.</p>
<p>In recent years, a gene-centric approach to precision medicine has been promoted as the future of medicine. It underlies the massive effort funded by the U.S. National Institutes of Health to collect over a million DNA samples under the <a href="https://allofus.nih.gov">“All of Us”</a> initiative that <a href="https://allofus.nih.gov/about/all-us-research-program-overview">began in 2015</a>. </p>
<p>But the imagined future did not include COVID-19. In the rush to find a COVID-19 vaccine and effective therapies, precision medicine has been insignificant. Why is this? And what are its potential contributions? </p>
<p>We are <a href="https://mirm-pitt.net/our-people/faculty-staff-bios/david-n-finegold-md/">a physician geneticist</a> and a <a href="https://www.hps.pitt.edu/people/colin-allen">philosopher of science</a> who began a discussion about the promise and potential pitfalls of precision medicine before the arrival of COVID-19. If precision medicine is the future of medicine, then its application to pandemics generally, and COVID-19 in particular, may yet prove to be highly significant. But its role so far has been limited. Precision medicine must consider more than just genetics. It requires an <a href="https://doi.org/10.1016/bs.adgen.2015.11.004">integrative “omic” approach</a> that must collect information from multiple sources – beyond just genes – and at scales ranging from molecules to society. </p>
<h2>From genetics to microbes</h2>
<p>Inherited diseases such as <a href="https://www.nhlbi.nih.gov/health-topics/sickle-cell-disease">sickle cell anemia</a> and <a href="https://ghr.nlm.nih.gov/condition/tay-sachs-disease">Tay-Sachs disease</a> follow a predictable pattern. But such direct genetic causes are perhaps the exception rather than the rule when it comes to health outcomes. Some heritable conditions – for instance, psoriasis or the many forms of cancer – depend on complex combinations of genes, environmental and social factors whose individual contributions to the disease are difficult to isolate. At best, the presence of certain genes constitutes a risk factor in a population but does not fully determine the outcome for an individual person carrying those genes.</p>
<p>The situation becomes yet more complicated for infectious diseases. </p>
<p>Viruses and bacteria have their own genomes that interact in complex ways with the cells in the people they infect. The <a href="https://www.ncbi.nlm.nih.gov/books/NBK554776/">genome of SARS-CoV-2 underlying COVID-19 has been extensively sequenced</a>. Its mutations are identified and traced worldwide, helping epidemiologists understand the spread of the virus. However, the interactions between SARS-CoV-2 RNA and human DNA, and the effect on people of the virus’s mutations, remain unknown.</p>
<h2>The importance of multi-scale data</h2>
<p>Tom Hanks and his wife caught the virus and recovered in a matter of weeks. Presumably each was infected over the course of a few minutes of exposure to another infected person, involving cellular mechanisms that operate on a timescale of milliseconds. </p>
<p>But the drama of their illness, and that of the many victims with far worse outcomes, is taking place in the context of a global pandemic that has already lasted months and may continue for years. People will need to adopt changes in their behavior for weeks or months at a time. </p>
<p>What should a precision medicine approach be in a pandemic? The gene-centric vision of precision medicine encourages people to expect individualized gene-targeted fixes. But, genes, behavior and social groups interact over multiple timescales.</p>
<p>To capture all the data needed for such an approach is beyond possibility in the current crisis. A nuanced approach to the COVID-19 pandemic will depend heavily on imprecise population level public health interventions: mask-wearing, social distancing and working from home. Nevertheless, there is an opportunity to begin gathering the kinds of data that would allow for a more comprehensive precision medicine approach – one that is fully aware of the complex interactions between genomes and social behavior.</p>
<h2>How to use precision medicine to understand COVID-19</h2>
<p>With unlimited resources, a precision medicine approach would begin by analyzing the genomes of a large group of people already known to be exposed to SARS-CoV-2 yet asymptomatic, along with a similar-sized group with identified risk factors who are dying from the disease or are severely ill.</p>
<p>An early study of this kind by <a href="https://precisionlife.com/wp-content/uploads/2020/06/precisionlife-COVID-19-Paper-68-genes-June-2020.pdf">Precisionlife Ltd data mined genetic samples of 976 known COVID-19 cases</a>. Of these, 68 high-risk genes were identified as risk factors for poor COVID-19 outcomes, with 17 of them deemed likely to be good targets for drug developments. But, as with all such statistical approaches, the full spectrum of causes underlying their association with the disease is not something the analysis provides. Other studies of this kind are <a href="https://www.scientificamerican.com/article/genes-may-influence-covid-19-risk-new-studies-hint/">appearing with increasing frequency, but there is no certainty in such fast-moving areas of science</a>. Disentangling all the relevant factors is a process that will take months to years.</p>
<p>To date, precision medicine has proven better suited to inherited diseases and to diseases such as cancer, involving mutations acquired during a person’s lifetime, than to infectious diseases. There are examples where susceptibility to infection can be caused by malfunction of unique genes such as the family of inherited immune disorders known as <a href="https://ghr.nlm.nih.gov/condition/x-linked-agammaglobulinemia">agammaglobulinemia</a>, but these are few and far between. </p>
<p>Many physicians assume that most diseases involve multiple genes and are thus not amenable to a precision approach. In the absence of the kind of information needed for a multi-omic approach, there is a clear challenge and opportunity for precision medicine here: If it is to be the future of medicine, in order to complement and expand our existing knowledge and approaches, it needs to shift from its gene-centric origins toward a broader view that includes variables like proteins and metabolites. It must consider the relationships between genes and their physical manifestations on scales that range from days to decades, and from molecules to the global society.</p><img src="https://counter.theconversation.com/content/142142/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>Precision medicine is often touted as the future of medicine. But so far, it hasn’t been helpful in the war against COVID-19. Here is how it could be used to tease apart the nuances of the disease.Colin Allen, Distinguished Professor of History & Philosophy of Science, University of PittsburghDavid Finegold, Professor, Department of Human Genetics, Pitt Public Health, University of PittsburghLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1319862020-02-18T15:51:52Z2020-02-18T15:51:52ZThese scientists are using DNA to target new drugs for your genes – Medicine made for you part 1<figure><img src="https://images.theconversation.com/files/315927/original/file-20200218-10995-1mbft4z.jpg?ixlib=rb-1.1.0&rect=23%2C112%2C2600%2C1607&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/laboratory-research-cancer-diseases-rack-rna-193672376">By Science Photo/Shutterstock</a></span></figcaption></figure><p>Welcome to the first episode of <a href="https://theconversation.com/uk/topics/medicine-made-for-you-82269"><em>Medicine made for you</em></a>, a brand new series from <a href="https://theconversation.com/uk/topics/the-anthill-podcast-27460">The Anthill</a>, a podcast from The Conversation. Across three episodes we’re taking a deep dive into the future of healthcare – and finding out how it could soon get a lot more personal.</p>
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<p>In part 1 of <em>Medicine made for you</em> we look at genes, clinical trials and how possible it might be for the NHS to take a more personalised view of our health. And we find out why Scotland, a country of 5.4 million people, with one of the lowest life expectancies in western Europe, is a pioneer of this kind of research.</p>
<p>Taking a much more precise approach to treatment means that for some diseases, doctors can prescribe drugs based on a person’s DNA. This so-called <a href="https://theconversation.com/uk/topics/precision-medicine-14622">precision medicine</a> is breaking new ground in the treatment of some diseases. And it could change medicine for good.</p>
<p>We start with a trip to Glasgow to find out why Scotland is leading the way in precision medicine. Anna Dominiczak, regius professor of medicine, vice principal and head of the College of Medical, Veterinary and Life Sciences at the University of Glasgow, talks about the massive potential precision medicine has to help diagnose, treat and prevent disease. </p>
<p>Next we take a tour of a lab to find out what happens behind the scenes.
Susie Cooke, head of medical genomics at Glasgow Precision Oncology Laboratory, shows us the sequencing process – allowing us to see first hand how DNA is tested and analysed. </p>
<p>Cooke is trying to improve treatment outcomes, since 90% of the top selling drugs only work for 30-50% of patients. The current so-called “trial and error” method of medicine results in only 25% of cancer patients responding to drugs – as Cooke explains:</p>
<blockquote>
<p>Every year 165,000 people in the UK die from cancer and the UK is lagging behind other countries in terms of cancer outcomes … there needs to be a really big shift to improve these statistics. This is all going to be about finding out who does respond to drugs and who doesn’t – and for those people who don’t respond let’s stop giving them those treatments because they don’t work, they have side effects and they cost the NHS a lot of money. And instead let’s find something that does work for those patients that aren’t responding.</p>
</blockquote>
<p>Clinical trials are crucial to this process as they can help scientists work out which groups of people respond to treatment and which don’t. Andrew Biankin, regius chair of surgery and director of the Translational Research Centre at the University of Glasgow, explains why he believes patients should be offered a clinical trial at the start of treatment, not at the end. Biankin believes this move would help to remove some of the stigma in clinical trials as it would seem much less like a “last option”. </p>
<p>Lesley Stephen, from Edinburgh, is one such patient who has benefited from clinical trials. She has been living with advanced breast cancer for five years:</p>
<blockquote>
<p>My clinical trial has given me a really good quality of life for the last four years. Prior to that I was just on chemotherapy and given months to live. Although with stage four cancer it can’t be cured, the hope is that you can extend your life and live well – but chemo doesn’t give you that. Just by luck, by pure chance, I got onto a clinical trial and have had an amazing response to it.</p>
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<p>But she also tells us how hard it can be to find out about clinical trials. There are quite strict rules about who can and can’t go on a trial – the sicker you are, the less likely you are to be accepted. She says many patients don’t even know clinical trials exist. So it seems there is a long way to go before everyone has the choice to join one at the start of cancer treatment.</p>
<p>Despite this, Iain McInnes, professor of experimental medicine and director of the Research Institute at the University of Glasgow, believes that ten years from now, precision medicine will be the new normal. He thinks this way of doing things will simply be part of the infrastructure and integral to the development of new drugs:</p>
<blockquote>
<p>The application of an effective precision medicine tool will significantly reduce the cost of care. You’re reducing the likelihood of a non response, you’re reducing the poorer quality of life that is suffered by a person who doesn’t respond to drugs. You’re reducing the likelihood of side effects – which costs money to manage. And most of the long-term predictions indicate that a precision medicine approach could save substantial sums of money for the NHS and the health budgets in many counties beyond.</p>
</blockquote>
<p>Not everyone is so optimistic. Stephen MacMahon, principal director of The George Institute for Global Health at the University of Oxford, worries that the current enthusiasm for precision medicine may blind us to the benefits of <a href="https://theconversation.com/in-defence-of-imprecise-medicine-the-benefits-of-routine-treatments-for-common-diseases-128440">“imprecise” medicine</a> which saves millions of lives every year. He also has concerns that rolling out a precision medicine approach far and wide could result in some patients taking liberties with their health:</p>
<blockquote>
<p>I hear people say that they might not need to change their lifestyle because by the time they’re at risk of heart disease there’ll probably be a cure that will target their genes and they’ll be ok. And I think [in that sense], there are risks about getting the balance and message on this wrong. </p>
</blockquote>
<p>It’s clear then that for precision medicine to work more widely it would require a complete shift in the way the health system currently operates. This isn’t to say it’s not possible, but for the NHS to catch up with what the research shows is available, there will need to be a fundamental change in the way medicine is practised.</p>
<p>In our second episode, out on February 25, we’ll delve further into the personalisation of healthcare – looking at the role it could play in our diets and nutrition.</p>
<p><em>The music in this episode is <a href="https://freemusicarchive.org/music/Chris_Zabriskie/Reappear/04_-_Is_That_You_or_Are_You_You">Is That You or Are You You?</a> by Chris Zabriskie. Medicine made for you is produced and reported by Holly Squire and Gemma Ware, and hosted by Annabel Bligh for The Anthill podcast. A big thanks to City, University of London, for letting us use their studios.</em></p><img src="https://counter.theconversation.com/content/131986/count.gif" alt="The Conversation" width="1" height="1" />
PODCAST: The first episode of a new series from The Anthill focuses on precision medicine.Annabel Bligh, Business & Economy Editor and Podcast Producer, The Conversation UKGemma Ware, Head of AudioHolly Squire, Special Projects Editor, The Conversation UKLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1314202020-02-11T13:00:15Z2020-02-11T13:00:15ZMedicine made for you: introducing a new series from The Anthill podcast<figure><img src="https://images.theconversation.com/files/314451/original/file-20200210-109901-1j5hdi.jpg?ixlib=rb-1.1.0&rect=15%2C62%2C5160%2C3274&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/horizontal-image-collection-prescription-capsules-tablets-1226220355">Katy Pack/Shutterstock</a></span></figcaption></figure><p>In <em>Medicine made for you</em>, a new series from <a href="https://theconversation.com/uk/topics/the-anthill-podcast-27460">The Anthill podcast</a>, we’ll be taking a deep dive into the future of healthcare – and find out how it could soon get a lot more personal. </p>
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<p>We’ll hear from leading academics about the <a href="https://theconversation.com/personalised-medicine-how-science-is-using-the-genetics-of-disease-to-make-drugs-better-30747">personalisation of healthcare</a>, how it’s changing the way we think about our bodies, and the choices we might make about our health in the future.</p>
<p>For much of history, if you had an ailment you’d probably visit an apothecary who’d mix up a medicine for you, based on your symptoms. But that personalised service fell away as the pharmacy profession became more sophisticated and regulated. </p>
<p>Today, if your doctor prescribes you a drug, it’s pretty likely to be designed for an “average” patient, based on how a group of people have responded to a clinical trial. But now advances in medical research mean that for some diseases, doctors are able to prescribe drugs based on a person’s DNA. Known as precision medicine, this kind of approach is breaking new ground in the treatment for some diseases. And it could change medicine for good. </p>
<p>In <a href="https://theconversation.com/these-scientists-are-using-dna-to-target-new-drugs-for-your-genes-medicine-made-for-you-part-1-131986">the first episode of <em>Medicine made for you</em></a> we’ll be looking at genes, clinical trials and how possible it might be for the NHS to take on a more personalised approach when it comes to our health. And we’ll find out why Scotland, a country of 5.4 million people, with one of the lowest life expectancies in western Europe, is one of the pioneers of this kind of research. </p>
<p>The second episode joins the <a href="https://theconversation.com/how-personal-will-nutritional-advice-become-in-the-future-medicine-made-for-you-part-2-132387">search for personalised nutrition</a> to find out how close researchers are getting to designing diets based for our own bodies. And in the third episode we explore other ways that healthcare is becoming more personalised, including the growth of <a href="https://theconversation.com/from-3d-printing-drugs-to-social-prescribing-medicine-made-for-you-part-3-132817">social prescribing schemes</a> in which patients are offered help to access specific services and activities to help improve their health and wellbeing. We’ll also look at how else the delivery of healthcare is being made more personal, from the delivery of drugs, to who gets screened for particular conditions. </p>
<p>Throughout this series we’ll also explore what’s stopping us from getting a truly personalised form of medicine – and ask <a href="https://theconversation.com/in-defence-of-imprecise-medicine-the-benefits-of-routine-treatments-for-common-diseases-128440">whether we’d want this anyway</a> if we consider ethical and economic challenges. </p>
<p>You can listen via <a href="https://theconversation.com/uk/topics/medicine-made-for-you-82269">The Conversation</a>, or subscribe wherever you get your podcasts from by clicking the links below.</p>
<p><em>The music in this trailer is <a href="https://freemusicarchive.org/music/Chris_Zabriskie/Reappear/04_-_Is_That_You_or_Are_You_You">Is That You or Are You You?</a> by Chris Zabriskie. Medicine made for you is produced by Holly Squire and Gemma Ware, and hosted by Annabel Bligh for The Anthill. A big thanks to City, University of London, for letting us use their studios.</em> </p>
<p><a href="https://itunes.apple.com/gb/podcast/the-anthill/id1114423002?mt=2"><img src="https://images.theconversation.com/files/233721/original/file-20180827-75984-1gfuvlr.png" alt="Listen on Apple Podcasts" width="268" height="68"></a> <a href="https://open.spotify.com/show/265Bnp4BgwaEmFv2QciIOC?si=-WMr1ecDTsO_6avrkxZu8g"><img src="https://images.theconversation.com/files/237984/original/file-20180925-149976-1ks72uy.png?ixlib=rb-1.1.0&q=45&auto=format&w=268&fit=clip" width="268" height="82"></a> </p>
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<p><a href="https://tunein.com/podcasts/Technology-Podcasts/The-Anthill-p877873/"><img src="https://images.theconversation.com/files/233723/original/file-20180827-75984-f0y2gb.png" alt="Listen on TuneIn" width="318" height="125"></a> <a href="https://radiopublic.com/the-anthill-GOJ1vz"><img class="alignnone size-medium wp-image-152" src="https://images.theconversation.com/files/233717/original/file-20180827-75990-86y5tg.png?ixlib=rb-1.1.0&q=45&auto=format&w=268&fit=clip" alt="Listen on RadioPublic" width="268" height="87"></a></p><img src="https://counter.theconversation.com/content/131420/count.gif" alt="The Conversation" width="1" height="1" />
Introducing a new series from The Anthill podcast on the future of personalisation in healthcare.Annabel Bligh, Business & Economy Editor and Podcast Producer, The Conversation UKGemma Ware, Head of AudioHolly Squire, Special Projects Editor, The Conversation UKLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1284402020-01-09T10:27:19Z2020-01-09T10:27:19ZIn defence of ‘imprecise’ medicine: the benefits of routine treatments for common diseases<figure><img src="https://images.theconversation.com/files/307954/original/file-20191219-11891-1dulpuc.jpg?ixlib=rb-1.1.0&rect=0%2C386%2C5491%2C3268&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Statins are imprecise and rather brilliant. </span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/generic-pack-controversial-cholesterol-preventative-drug-199388345">roger ashford/Shutterstock</a></span></figcaption></figure><p>The NHS <a href="https://www.england.nhs.uk/genomics/">states that</a> it “will be the world-leading healthcare system in its use of cutting-edge genomic technologies to predict and diagnose inherited and acquired disease, and to personalise treatments and interventions”. As all diseases are either inherited or acquired, this is no modest claim.</p>
<p>This approach to medical care is known as “precision medicine”, and given the hype that surrounds the model, you might be forgiven for thinking that the usual practice of “imprecise” medicine is greatly inferior. And yet it has been the routine and, in many respects, indiscriminate use of effective treatments for a range of common diseases that has improved the health of large numbers of patients over the past few decades.</p>
<h2>Targeting genes</h2>
<p>Precision medicine assumes that genes play a big role in causing diseases and that new treatments targeting genes and their processes can have significant benefits. The government is so enthusiastic about this new approach that in 2019 it offered gene sequencing to the entire UK population, albeit for a fee. In <a href="https://www.bbc.co.uk/news/uk-47013914">announcing this initiative</a>, Health Secretary Matt Hancock said “there are huge benefits to sequencing as many genomes as we can – every genome sequenced moves us a step closer to unlocking life-saving treatments”.</p>
<p>But just how big are the benefits likely to be? How relevant is precision medicine to preventing and treating the diseases responsible for most premature deaths and hospital admissions in the UK, such as heart disease, stroke, hip fracture and dementia – diseases where genetic links are not clear.</p>
<p>In a <a href="http://www.onlinejacc.org/content/72/16/1883">study</a> of half a million participants in the UK Biobank project, 1.7 million separate gene variants were shown to be associated with heart disease. Yet in combination, these variants accounted for less than 3% of heart disease after considering known causes such as smoking and high cholesterol.</p>
<p>Precision medicine seems likely to offer most promise for preventing and treating less common diseases, as they are more likely to have a major genetic cause. The poster child for precision medicine is the drug trastuzumab (also known as Herceptin), which was developed following the discovery of HER2, a genetic factor implicated in about 20% of breast cancer cases.</p>
<p>Trastuzumab targets a specific biological mechanism that is involved in HER2 positive cancer, and treatment with this drug improves survival and reduces cancer recurrence. But the effects are not quite as remarkable as has been sometimes suggested. A meta-analysis of <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6799843/">clinical trials</a> reported that after ten years, 74% of patients treated with trastuzumab remained alive and recurrence-free compared with 62% of those who did not receive trastuzumab. A worthwhile effect for sure, but only for about 10-15% of patients. </p>
<h2>Stark contrast</h2>
<p>Comparing these important but small gains with the impact of an “imprecise” approach taken to other diseases offers a stark contrast. For example, HIV used to be a death sentence. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220799/">Today, 94%</a> of people with the disease are still alive after 30 years, thanks to antiretroviral drugs. Similarly, deaths in the five-year period following a heart attack <a href="https://heart.bmj.com/content/102/24/1945">declined by 70% between 1979 and 2013</a>, largely due to the <a href="https://www.ncbi.nlm.nih.gov/pubmed/17554120/">routine use of drugs</a> such as aspirin, ACE inhibitors and statins.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/307962/original/file-20191219-11919-el8q01.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/307962/original/file-20191219-11919-el8q01.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=397&fit=crop&dpr=1 600w, https://images.theconversation.com/files/307962/original/file-20191219-11919-el8q01.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=397&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/307962/original/file-20191219-11919-el8q01.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=397&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/307962/original/file-20191219-11919-el8q01.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=499&fit=crop&dpr=1 754w, https://images.theconversation.com/files/307962/original/file-20191219-11919-el8q01.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=499&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/307962/original/file-20191219-11919-el8q01.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">Thanks to antiretrovirals HIV is no longer a death sentence for most people.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/sample-blood-collection-tube-hiv-test-304165361">Room's studio/Shutterstock</a></span>
</figcaption>
</figure>
<p>Interestingly, for both heart attacks and HIV, when efforts have been made to personalise treatment, it has <a href="https://www.ncbi.nlm.nih.gov/pubmed/20201758?dopt=Abstract">generally led</a> to worse outcomes; in large part as a consequence of doctors withholding treatments they believe may not be beneficial or could be dangerous for a particular person. Unfortunately, such clinical insights are more often wrong than right.</p>
<p>It’s hard not to conclude that the nation’s health would be better served by the NHS if it aspired to be a global leader in the standardisation of care for common serious diseases. Let’s not let the current enthusiasm for precision medicine blind us to the benefits of the “imprecise” medicine we know saves millions of lives every year.</p><img src="https://counter.theconversation.com/content/128440/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Stephen MacMahon has received funding from the National Health and Medical Research Council of Australia for clinical research on the effects of treatments for diabetes, stroke and congestive heart failure.</span></em></p>Precision medicine is all the rage, but it may only be effective at treating less common diseases.Stephen MacMahon, Professor of Medicine, University of OxfordLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1273112019-11-21T11:44:31Z2019-11-21T11:44:31ZOmega-3 fish oil as effective as drugs for some children with ADHD<figure><img src="https://images.theconversation.com/files/302674/original/file-20191120-547-16o5byy.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/fish-white-enamel-bowl-iron-vitamins-292698929">IKasparus/Shutterstock</a></span></figcaption></figure><p>Attention deficit hyperactivity disorder (ADHD) is quite common. It affects about one in 20 children and is three or four times more common in boys than in <a href="https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2698633">girls</a>. Children with ADHD, which is <a href="https://www.nhs.uk/conditions/attention-deficit-hyperactivity-disorder-adhd/">characterised by</a> inattention, hyperactivity and impulsivity, are more likely to drop out of school. Fortunately, drugs to treat the condition work well for <a href="https://www.sciencedirect.com/science/article/abs/pii/S0890856709612223?via%3Dihub">60-80% of children who take them</a>. But that leaves 20-40% of children who have a poor response to the drugs or who suffer from side effects.</p>
<p>Some studies have shown that <a href="https://www.nature.com/articles/npp2017160">omega-3 fish oil may help with ADHD symptoms</a>. What’s more, they’re safe and well-tolerated. However, the results of these studies have been mixed – some children get better, others get worse. We wanted to know whether these results depended on whether or not the children had enough omega-3 in their body to begin with. </p>
<p>Omega-3 fatty acids, such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), are important for our brain, body, immune system and heart. We can only get them from food, such as oily fish, spinach and nuts. </p>
<p>Previous studies have found that children with ADHD eat less omega-3-containing food and have less omega-3 <a href="https://journals.sagepub.com/doi/full/10.1177/2167702616637820">in their bodies than children without ADHD</a>, so they are also more likely to show symptoms indicating a lack of omega-3, such as eczema, brittle nails, and dry and scaly <a href="https://academic.oup.com/ajcn/article-abstract/62/4/761/4651115?redirectedFrom=fulltext">skin</a>. But in previous studies, omega-3 fatty acids were given to children with ADHD without checking if they were deficient in omega-3 in the first place.</p>
<p>In our study, published in the journal <a href="https://www.nature.com/articles/s41398-019-0633-0">Translational Psychiatry</a>, we examined 92 children, aged six to 18, diagnosed with ADHD. Half were randomly assigned to a group taking omega-3, EPA. The other half (the control group) were given a placebo. The trial lasted 12 weeks.</p>
<p>We measured the children’s progress with a continuous performance test (CPT), an objective cognitive assessment of attention, vigilance and impulsivity at the beginning and at the end of the trial. We found that children who were deficient in omega-3, measured in the blood, became more attentive and vigilant at the end of the 12 weeks when taking EPA. The difference was statistically significant, that is, unlikely to be the result of chance.</p>
<p>In contrast, we found that children in the EPA group with little or no omega-3 deficiency had a worsening in some ADHD symptoms, especially impulsivity. This further suggests that you can have “too much of a good thing”, and that an adequate amount of omega-3 is needed for optimal results. </p>
<p>Currently, there is no recommended dosage for pure EPA, but a <a href="https://journals.sagepub.com/doi/full/10.1177/0260106018772170?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub%3Dpubmed">panel of experts</a> suggested that the patients who prefer omega-3 supplementation over stimulants (such as Ritalin) should take a combination of DHA and EPA at doses greater than or equal to 750mg a day for at least 12 weeks.</p>
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<img alt="" src="https://images.theconversation.com/files/302691/original/file-20191120-491-1kdv7g4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/302691/original/file-20191120-491-1kdv7g4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=423&fit=crop&dpr=1 600w, https://images.theconversation.com/files/302691/original/file-20191120-491-1kdv7g4.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=423&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/302691/original/file-20191120-491-1kdv7g4.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=423&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/302691/original/file-20191120-491-1kdv7g4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=531&fit=crop&dpr=1 754w, https://images.theconversation.com/files/302691/original/file-20191120-491-1kdv7g4.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=531&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/302691/original/file-20191120-491-1kdv7g4.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=531&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="caption">Drugs that treat ADHD are effective in 60-80% of children.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/w/index.php?curid=379025">Wikimedia</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
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<h2>First of its kind</h2>
<p>Our study is the first to use the concept of personalised medicine (also known as “precision medicine”) applied to nutritional studies. It is also the first study to point out the omega-3 may not provide benefits for all children with ADHD, and in some cases, may even be detrimental. For this reason, children with ADHD should only take a supplement with omega-3 under the supervision of their doctors. And children shouldn’t switch from their medication to fish oil supplements, especially if they are doing well on the medication. </p>
<p>Of course, eating more oily fish should be a priority for these children, too.</p><img src="https://counter.theconversation.com/content/127311/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jane Chang does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>The first personalised medicine trial for a nutritional supplement has just reported its results.Jane Chang, Visiting Researcher, Child and Adolescent Psychiatry, King's College LondonLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1226712019-09-26T16:34:56Z2019-09-26T16:34:56ZWhy drug trials are only part of the answer to making sure medicines work<figure><img src="https://images.theconversation.com/files/293658/original/file-20190923-54775-g5cdx6.jpg?ixlib=rb-1.1.0&rect=5%2C0%2C992%2C666&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Clinical trials are important, but can't get us to medicine prescribing that is 100% effective.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/clinical-trial-174168614">Image Point Fr/Shutterstock.com</a></span></figcaption></figure><p>There was a moment when, as a pharmacist, I realised that a lot of people to whom I gave medicine were going to receive little benefit, or even none at all. Healthcare staff make clinical decisions of when to use one medicine or another based upon evidence drawn from clinical trials. Clinical trials give us the data that show the probability that a medicine will have the desired effect – but there is also the chance that it will not.</p>
<p>Clinical trials are a good way of identifying drugs that, on the whole, are effective at achieving a specific outcome. But “on the whole” doesn’t take into account the wide variation among humans that means patients may react very differently to the drugs they’re given. The promise of <a href="https://theconversation.com/personalised-medicine-how-science-is-using-the-genetics-of-disease-to-make-drugs-better-30747">personalised medicine</a> is that through a more accurate understanding of a patient’s genetic makeup, alongside factors such as their lifestyle, diet and environment, they can be prescribed different drugs depending on what we know about how those drugs will affect them personally, rather than “on the whole”.</p>
<h2>Clinical trial mathematics</h2>
<p>Clinical trial data are <a href="https://bestpractice.bmj.com/info/toolkit/learn-ebm/how-to-calculate-risk/">based on probabilities</a>. Most controlled trials test a drug against a placebo or an existing drug, and the outcomes – such as not having a heart attack, or experiencing a side effect – are counted up to compare. </p>
<p>The likelihood that a patient will experience an event is known as <em>absolute risk</em>. This <a href="https://academic.oup.com/ndt/article/32/suppl_2/ii13/3056571">is calculated</a> by dividing the number of events by the number of people. For example, if eight of a group of 100 people have a heart attack in a single year, the absolute risk is 8/100 = 0.08 (or 8%). Say that during a drug trial the absolute risk for those given the drug is 0.03, and for the placebo group it is 0.08, the drug on trial would be said to have achieved an <em>absolute risk reduction</em> of 0.05 (or 5%). </p>
<p>However, there is a risk that people experience an event whether or not they are taking the drug. This <em>relative risk</em> is calculated by dividing the absolute risk of the group taking the drug by the absolute risk of the control group given the placebo. The drug’s efficiency taking into account background risk – the <em>relative risk reduction</em> – is calculated by dividing the absolute risk reduction by the absolute risk of the placebo group. Using the same example above, it would be 0.05/0.08, or 0.625 (or 62.5%). </p>
<p>Crucially, if you are in the business of manufacturing and selling medicines, expressing a drug’s effectiveness by its relative risk reduction offers a better impression than by its absolute risk: let’s face it, a reduction of 62.5% sounds much more impressive than a reduction of 5%.</p>
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<img alt="" src="https://images.theconversation.com/files/294361/original/file-20190926-51438-1582u4s.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/294361/original/file-20190926-51438-1582u4s.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/294361/original/file-20190926-51438-1582u4s.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/294361/original/file-20190926-51438-1582u4s.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/294361/original/file-20190926-51438-1582u4s.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/294361/original/file-20190926-51438-1582u4s.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/294361/original/file-20190926-51438-1582u4s.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">Side effects are common, but those that don’t benefit from the drug shouldn’t have to put up with them.</span>
<span class="attribution"><span class="source">Sherry Yates Young/Shutterstock</span></span>
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<em>
<strong>
Read more:
<a href="https://theconversation.com/personalised-medicine-how-science-is-using-the-genetics-of-disease-to-make-drugs-better-30747">Personalised medicine: how science is using the genetics of disease to make drugs better</a>
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<h2>Patients as individuals</h2>
<p>Using these methods on clinical trial data help us gauge the effectiveness of medicines, but they don’t take into account the differences among the patients taking them. Through genetic variation, <a href="https://theconversation.com/how-your-genes-influence-what-medicines-are-right-for-you-46904">human bodies vary considerably in the way they interact with drugs</a>, potentially making them more effective, less effective, or something else entirely. For example, people with high cholesterol, something that runs in families, are in the UK currently <a href="https://www.nice.org.uk/guidance/cg71/chapter/Recommendations#case-finding-and-diagnosis">offered DNA testing</a> to confirm their diagnosis, and start treatment much earlier. </p>
<p>To see how much these factors affect how medicines work: an estimate of the number of people that must take a drug for one person to get the desired outcome is known as the <a href="https://www.bmj.com/content/310/6977/452"><em>number needed to treat</em></a>. Using the same example of a drug trial with an absolute risk reduction of 0.05 (5%), this means that, statistically, 20 people (20x5%=100%) would need to be given the drug for one to feel the benefits. As we don’t know which of the 20 will benefit from taking the drug, we must give it to all of them.</p>
<p>This is a problem because medicines are not without harms: almost all have side effects, which the other 19 may suffer even without experiencing the drug’s benefits. This is known as <a href="https://www.bmj.com/content/347/bmj.f4869"><em>number needed to harm</em></a>, where harm could be anything from headaches and rashes to internal bleeding or even death. Clearly, if taking a medicine you would want to know that the benefit outweighs the harm.</p>
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Read more:
<a href="https://theconversation.com/why-i-donated-my-entire-genome-sequence-to-the-public-83741">Why I donated my entire genome sequence to the public</a>
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<h2>Minimising medicines</h2>
<p>As an example, statins are drugs commonly used to lower cholesterol and reduce the risk of having heart attacks and strokes. The drug will reduce the relative risk of heart attack or stroke by about 25%, but may also generate side effects. The patient and prescriber need to balance the benefit versus the harm. This decision can be guided using <a href="https://www.nice.org.uk/guidance/cg181/resources/patient-decision-aid-pdf-243780159">patient decision aids</a>, developed to help patients understand the balance of benefits and harms in the context of how they may have to change their lifestyle while taking the medicine.</p>
<p>There has been interest in a recent trial of the <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)31791-X/fulltext">polypill</a>, a tablet containing blood pressure-lowering medicine and a statin, which was given to around 3,400 people over the age of 50 in Golestan province, Iran. At a population level it led to a reduction in cardiovascular events, but the same approach will also mean more people will experience side effects compared to an approach that targets only those at high risk. In low and middle-income countries that lack the resources to diagnose and target many individuals, this may be a price worth paying.</p>
<p>Which brings us back to the promise of personalised medicine: ideally we would be able to identify the hypothetical one in 20 patients given a drug that benefit from it, and prescribe the medicine to them alone. Beyond the benefit to the patient, there are cost benefits to the health service and to society, but chiefly there are benefits for the other 19 who need not take a drug that won’t benefit them and may cause them side effects or adverse drug interactions. Better understanding of our genome and how it affects our risk of disease will provide the tools to <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(14)61730-X/fulltext">identify those most at risk</a>, and target them alone.</p>
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<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/315932/original/file-20200218-11040-p9wweg.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/315932/original/file-20200218-11040-p9wweg.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=112&fit=crop&dpr=1 600w, https://images.theconversation.com/files/315932/original/file-20200218-11040-p9wweg.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=112&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/315932/original/file-20200218-11040-p9wweg.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=112&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/315932/original/file-20200218-11040-p9wweg.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=140&fit=crop&dpr=1 754w, https://images.theconversation.com/files/315932/original/file-20200218-11040-p9wweg.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=140&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/315932/original/file-20200218-11040-p9wweg.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>This article is part of a series tied to Medicine made for you, a series by The Anthill podcast on the future of healthcare and how it could soon get a lot more personal. <a href="https://theconversation.com/uk/topics/medicine-made-for-you-82269">Read more here</a>.</em></p><img src="https://counter.theconversation.com/content/122671/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Alison Astles 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>Clinical trials are used to establish that medicines work. But these don’t take into account the genetic differences between us that can mean very different outcomes for different patients.Alison Astles, Subject Leader in Pharmacy, University of HuddersfieldLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1186632019-06-12T21:04:53Z2019-06-12T21:04:53ZRapid DNA analysis helps diagnose mystery diseases<figure><img src="https://images.theconversation.com/files/279009/original/file-20190611-32317-1tby3hy.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Decoding all the DNA in a patient's biological sample can reveal whether an infectious microbe is causing the disease.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/3d-illustration-method-dna-sequencing-430949605?src=tcYoS2adFzk6wi7ipNkRFA-1-2">ktsdesign/Shutterstock.com</a></span></figcaption></figure><p>As doctors, we deal with a lot of uncertainty. Often, it is difficult to diagnose what is making a patient sick because symptoms from both infectious and non-infectious diseases can be indistinguishable from each other. </p>
<p>The tried-and-true method for clinicians has been to formulate a list of the most likely possibilities – and narrow that list down by ordering a series of tests. However, despite extensive, state-of-the-art testing in hospitals today, we still can’t diagnose approximately 50% of cases of <a href="http://doi.org/10.1056/NEJMoa1500245">respiratory infection</a> (pneumonia), <a href="http://doi.org/10.1186/cc12896">bloodstream infection</a> (sepsis), and <a href="https://doi.org/10.1212/WNL.0000000000000086">neurological infection</a>.</p>
<p>I am an infectious diseases physician and microbiologist at University of California, San Francisco. But in college I specialized in computer science and bioengineering. Because so many of my current patients never end up with a definitive diagnosis, I became interested in applying my skills to leverage emerging sequencing technology and develop a <a href="https://doi.org/10.1101/gr.171934.113">computational pipeline</a> for analysis of DNA sequencing data, with the ultimate goal of providing more accurate diagnoses.</p>
<h2>What is next-generation sequencing?</h2>
<p><a href="https://chiulab.ucsf.edu">My colleagues and I</a> have developed a novel clinical diagnostic test that allows millions of DNA sequences to be decoded from a single clinical sample; for example, a tube of cerebrospinal fluid collected from a hospitalized patient via a lumbar puncture, also known as a “spinal tap.” The aim of this test, called “metagenomic next-generation sequencing” (mNGS), is to diagnose mysterious infections in acutely ill patients. </p>
<p>So far, the bulk of our experience is using this test to diagnose the most severely ill patients with life-threatening infections. However, I envision that as sequencing costs fall, this test could be performed routinely for all patients with suspected infectious syndromes.</p>
<p>This test is called “metagenomic” because DNA from all potential pathogens – bacteria, viruses, fungi and parasites – as well as the patient are simultaneously sequenced. We diagnose likely causes of infection by searching for tell-tale traces of DNA from the causative pathogen. </p>
<p>Currently, the overall turnaround time for the test is 48-72 hours. <a href="https://blogs.biomedcentral.com/on-medicine/2015/09/29/metagenomic-sequencing-diagnose-infectious-diseases/">New sequencing devices</a> may soon make it possible to run this test in less than six hours.</p>
<h2>Precision diagnosis of acute infectious diseases</h2>
<p>For <a href="http://opr.ca.gov/ciapm/projects/2015/Acute_Infectious_Diseases.html">our study</a>, published in the <a href="http://www.nejm.org/doi/full/10.1056/NEJMoa1803396">New England Journal of Medicine</a>, we enrolled 204 children and adults from eight different hospitals across the U.S. All of these patients had a mysterious, undiagnosed neurological illness – <a href="https://nextgendiagnostics.ucsf.edu/for-patients/#neurological-conditions">meningitis, encephalitis and/or myelitis</a> – of unknown origin. </p>
<p>To identify the cause we used clinical mNGS testing to identify the pathogens causing the patient’s acute illness.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/279004/original/file-20190611-32327-361ug4.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/279004/original/file-20190611-32327-361ug4.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=316&fit=crop&dpr=1 600w, https://images.theconversation.com/files/279004/original/file-20190611-32327-361ug4.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=316&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/279004/original/file-20190611-32327-361ug4.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=316&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/279004/original/file-20190611-32327-361ug4.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=397&fit=crop&dpr=1 754w, https://images.theconversation.com/files/279004/original/file-20190611-32327-361ug4.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=397&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/279004/original/file-20190611-32327-361ug4.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=397&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="caption">mNGS testing for diagnosis of neurological infections.</span>
<span class="attribution"><span class="source">Charles Chiu</span></span>
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<p>We ran the mNGS test on cerebrospinal fluid samples from these patients. After analyzing the data we found that in a surprisingly large proportion of infections – 13 of 58, or 22.4% – mNGS testing was necessary to make a timely and accurate diagnosis. </p>
<p>In eight of these infections identified by mNGS only, the diagnosis directly guided doctors to a targeted and appropriate antibiotic treatment. In <a href="https://doi.org/10.1093/ofid/ofx121">one neurological infection caused by hepatitis E virus</a>, the mNGS diagnosis likely spared the patient from a liver transplant. That’s because her hepatitis E infection was treatable with an antiviral drug: ribavirin. Without knowing that the patient’s infection was caused by the hepatitis E virus, this effective drug would not have been considered.</p>
<p>Overall, our study demonstrates the clinical usefulness of metagenomic testing in diagnosing neurological infections. The approach can be used for other types of clinical samples and infections, such as analysis of respiratory samples to diagnose infectious pneumonia. </p>
<p>It is my hope and expectation that this powerful new diagnostic tool will transform the way that we as physicians manage infections in our critically ill patients. This would ultimately lower health care costs and saving lives by virtue of earlier and more accurate diagnoses.</p>
<p>[ <em>Like what you’ve read? Want more?</em> <a href="https://theconversation.com/us/newsletters?utm_source=TCUS&utm_medium=inline-link&utm_campaign=newsletter-text&utm_content=likethis">Sign up for The Conversation’s daily newsletter</a>. ]</p><img src="https://counter.theconversation.com/content/118663/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Charles Chiu's research is supported the California Initiative to Advance Precision Medicine, NIH grant R01HL105704, a UC Center for Accelerated Innovation grant funded by NIH grant U54HL119893 and NIH/NCATS UCSF-CTSI grant UL1TR000004, the Charles and Helen Schwab Foundation, the George and Judy Marcus Innovation Fund, and the Sandler and William K. Bowes, Jr. Foundations.</span></em></p>Superfast DNA analysis is now being used to crack medical mysteries when physicians can’t figure out whether an infectious microbe is causing the disease.Charles Chiu, Professor of Laboratory Medicine, University of California, San FranciscoLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1163312019-05-02T21:53:54Z2019-05-02T21:53:54ZCanadian health care needs agile leaders and bold visions for the future<figure><img src="https://images.theconversation.com/files/272096/original/file-20190501-113858-136wdmt.jpg?ixlib=rb-1.1.0&rect=148%2C0%2C6927%2C3552&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Rapidly advancing technologies, including artificial intelligence, robotics, 3D-printing, smart-phones, smart-homes, precision medicine and diagnostics, promise to disrupt health care as we know it. </span> <span class="attribution"><span class="source">(Shutterstock)</span></span></figcaption></figure><p>The way we live and work is being disrupted like never before. Various technological, demographic, economic, political and environmental forces are forcing us to rethink the way we run society’s key institutions.</p>
<p>Our <a href="https://www.forbes.com/sites/williamhaseltine/2018/04/02/aging-populations-will-challenge-healthcare-systems-all-over-the-world/#185fcd0a2cc3">global population is aging</a>, the <a href="https://unfccc.int/news/climate-change-impacts-human-health">effects of climate change</a> are more deeply felt with each passing day and industry must adjust its processes given the <a href="https://medium.com/swlh/how-emerging-technologies-are-impacting-industries-b85afc14b5d">pace of technological advances</a>.</p>
<p>While nearly all professional fields must adapt, health care, in particular, will need strong leadership to withstand these forces. Is the Canadian health-care system ready? Does it have the leadership capacity to bring about adaptive system-level changes?</p>
<p>At <a href="https://healthleadershipacademy.ca/">McMaster University’s Health Leadership Academy</a>, we just published new research in answer to this question.</p>
<p><a href="https://healthleadershipacademy.ca/files/2019/04/Alternative-Futures-of-Health.pdf">Our white paper</a> identifies key disruptive forces impacting the health-care sector. The paper imagines alternative plausible futures and identifies the attributes that will be required of tomorrow’s leaders in any of these future scenarios.</p>
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<strong>
Read more:
<a href="https://theconversation.com/3d-printers-a-revolutionary-frontier-for-medicine-83031">3D printers: A revolutionary frontier for medicine</a>
</strong>
</em>
</p>
<hr>
<h2>Disruptive forces in health care</h2>
<p>Our team carried out a full review of academic research in the field and also conducted a stakeholder dialogue with 60 experts from across the Canadian health system. We identified several driving forces that stand to impact Canadian health care:</p>
<ol>
<li><p>Exponential advances in technology are fuelling an ever-expanding knowledge economy and widespread job displacements. Examples include <a href="https://www.theglobeandmail.com/opinion/article-how-artificial-intelligence-can-completely-revolutionize-canadian/">artificial intelligence</a>, <a href="https://sencanada.ca/content/sen/committee/421/SOCI/reports/RoboticsAI3DFinal_Web_e.pdf">robotics</a>, <a href="https://toplink.weforum.org/knowledge/insight/a1Gb00000038pHMEAY/explore/summary">3D-printing, smart phones, smart homes</a>, precision medicine and diagnostics.</p></li>
<li><p>Economic disparities between the rich and the poor are growing and contributing to the populist movement and nationalism worldwide, with <a href="https://toplink.weforum.org/knowledge/insight/a1Gb00000038pHMEAY/explore/summary">health care becoming increasingly inaccessible</a> to the economically disadvantaged.</p></li>
<li><p><a href="https://www.forbes.com/sites/williamhaseltine/2018/04/02/aging-populations-will-challenge-healthcare-systems-all-over-the-world/#185fcd0a2cc3">An aging population</a>, coupled with <a href="https://www.massmedic.com/wp-content/uploads/2018/03/Ontario-Office-of-the-Chief-Health-Innovation-Strategist.pdf">other demographic shifts</a> (such as the growth of a more multicultural population across Canada), places heavy demands on an economically stretched health-care system. The growing challenges of mental health, addiction, <a href="https://canadiancentreforaddictions.org/drug-use-and-abuse-in-canada/">drug trafficking</a> and <a href="https://theconversation.com/how-the-opioid-crisis-is-disrupting-hospital-care-103600">the opioid crisis</a> add further pressures.</p></li>
<li><p>The rapidity and magnitude of climate change threatens the environment, but also the <a href="https://unfccc.int/news/climate-change-impacts-human-health">health and well-being of individuals</a>. Not only does climate change bring heatwaves, flooding and other extreme events, it also impacts food security and increases the transmission season and the geographical range of many diseases.</p></li>
</ol>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/272089/original/file-20190501-113867-1f6rarf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/272089/original/file-20190501-113867-1f6rarf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/272089/original/file-20190501-113867-1f6rarf.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/272089/original/file-20190501-113867-1f6rarf.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/272089/original/file-20190501-113867-1f6rarf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/272089/original/file-20190501-113867-1f6rarf.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/272089/original/file-20190501-113867-1f6rarf.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">More than 500 wildfires burned in British Columbia in August 2018. Wildfires cause many health problems, from anxiety and PTSD to asthma and low birth weight in children.</span>
<span class="attribution"><span class="source">THE CANADIAN PRESS/Darryl Dyck</span></span>
</figcaption>
</figure>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/climate-change-will-increase-deaths-by-suicide-102156">Climate change will increase deaths by suicide</a>
</strong>
</em>
</p>
<hr>
<h2>Agility, integrity, ‘big picture’ thinking</h2>
<p>Our research underscores the growing importance of <a href="https://doi.org/10.1186/s12960-016-0171-2">transformational</a> and <a href="https://doi.org/10.1186/s12913-019-3883-x">shared leadership</a> within health care.</p>
<p>No matter what the future holds, emerging health leaders must be able to identify, and have the courage to act upon, opportunities that present risk but also offer transformational change — to improve the patient experience.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/272091/original/file-20190501-113861-17mylv8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/272091/original/file-20190501-113861-17mylv8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=410&fit=crop&dpr=1 600w, https://images.theconversation.com/files/272091/original/file-20190501-113861-17mylv8.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=410&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/272091/original/file-20190501-113861-17mylv8.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=410&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/272091/original/file-20190501-113861-17mylv8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=515&fit=crop&dpr=1 754w, https://images.theconversation.com/files/272091/original/file-20190501-113861-17mylv8.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=515&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/272091/original/file-20190501-113861-17mylv8.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=515&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">How will Canada’s health-care leaders develop health solutions for our aging society?</span>
<span class="attribution"><span class="source">(Shutterstock)</span></span>
</figcaption>
</figure>
<p>For example, robots are now widely used in <a href="https://www.reuters.com/article/us-japan-ageing-robots-widerimage/aging-japan-robots-may-have-role-in-future-of-elder-care-idUSKBN1H33AB">elder-care facilities throughout Japan.</a> These robots take on human characteristics and help stem the loneliness of residents. There are even “<a href="https://www.theverge.com/2018/12/20/18149817/lovot-groove-x-home-robot-japan-designed-to-be-loved">cat bots</a>,” as proxies for pets, in these elder-care facilities. </p>
<p>Here, advanced technologies are being harnessed to deal with a demographic crisis in Japan — a rapidly aging population with fewer young people to provide elder care. It took bold leadership to spearhead these initiatives (and overcome resistance grounded in the perceived emotional coldness of non-human caregivers). Here, one driving change (technology) was used to deal with the issues emanating from another of the driving changes (demographics).</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/how-robots-are-helping-doctors-save-lives-in-the-canadian-north-104462">How robots are helping doctors save lives in the Canadian North</a>
</strong>
</em>
</p>
<hr>
<p>Our health-care leaders will need to be resilient, agile, fast learners, smart and adaptable. They will need to be of high integrity and have a systems-wide, “big picture” mindset.</p>
<p>They will also need to cultivate a dynamic community of shared leadership that includes patients and their families. For example, <a href="https://www.ideou.com/blogs/inspiration/creative-confidence-series-design-thinking-in-healthcare">health-care professionals might use design thinking</a> as part of a broad and inclusive consultation. </p>
<p>The design thinking process builds empathy and a more nuanced understanding of how patients and their families feel, think and see their care experience. An example would be consulting directly with patients, family and care providers concerning their experiences on a palliative care unit, and implementing their ideas for bettering these experiences and improving well-being for all parties.</p>
<h2>Diversity within leadership ranks</h2>
<p>As for current system readiness, our research identified several deficiencies. There is little coordinated effort, for example, across provincial and territorial health-care systems to pursue leadership development.</p>
<p>Without a collective, shared vision for what effective health-care leadership should look like, navigating the disruptive forces at play will be quite challenging.</p>
<p>The <a href="https://www.forbes.com/sites/williamhaseltine/2018/04/02/aging-populations-will-challenge-healthcare-systems-all-over-the-world/#185fcd0a2cc3">global patient population is aging,</a> but so too is the <a href="https://www.modernhealthcare.com/article/20180505/NEWS/180509944/building-the-bench-hospitals-and-health-systems-prepare-for-boomer-retirement-wave">health-care leadership workforce</a>. Our research revealed that succession planning is not consistent, nor are selection practices for emerging health leaders.</p>
<p>The increase in <a href="https://canadianimmigrant.ca/guides/moving-to-canada/diversity-in-canada-an-overview">cultural diversity across Canada</a> must be considered in the design and administration of our future health system, given that the number of foreign-born immigrants now represent <a href="https://www12.statcan.gc.ca/nhs-enm/2011/as-sa/99-010-x/99-010-x2011001-eng.cfm.">around a fifth of the Canadian population</a>. </p>
<p><div data-react-class="Tweet" data-react-props="{"tweetId":"1118885850710888452"}"></div></p>
<p>We must also integrate the unique health-care and social needs of Indigenous populations as part of our collective responsibility towards <a href="http://www.trc.ca/">Truth and Reconciliation</a>. The health system must make culturally appropriate services more readily available. </p>
<p><a href="https://healthleadershipacademy.ca/files/2019/04/Alternative-Futures-of-Health.pdf">Many of our research participants</a> anecdotally shared that they still observe a significant lack of diversity within leadership ranks.</p>
<h2>Bold and ambitious visions</h2>
<p>Perhaps most pressing is the lack of incentives and available budgets for leaders to build bold and ambitious visions for health-care organizations.</p>
<p>Bureaucratic institutional systems leave leaders with little autonomy and encourage them to make incremental low-risk changes instead. Priority allocations go to first-line health services, often forgoing “nice to have” items such as leadership development for employees.</p>
<p>While no one can predict the future, we call for action to cultivate environments within the health system for emerging leaders to develop.</p>
<p>For our part, McMaster University’s Health Leadership Academy will use the results of this research to update and adjust our <a href="https://healthleadershipacademy.ca/education/emerging-health-leaders/emerging-health-leaders-application/">leadership development programs</a> — to better prepare leaders to navigate the disruptive forces ahead.</p>
<p>As budgets shrink, resources are constrained and patient needs sharply increase, the development of effective leaders is anything but “nice to have.” In fact, leadership development in health care has never been more important.</p><img src="https://counter.theconversation.com/content/116331/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Rick Hackett 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>In an era of rapid technological advance, devastating climate change, increasing inequality and a steadily aging society, health-care leadership development is vital.Rick Hackett, Canada Research Chair, Organizational Behaviour & Human Performance, McMaster UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1121252019-03-26T22:34:28Z2019-03-26T22:34:28ZA new drug promises to lower risks of asthma attack<figure><img src="https://images.theconversation.com/files/265940/original/file-20190326-36267-183atex.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Research published in Science Translational Medicine in February 2019 used a virtual patient to test the drug, Fevipiprant.</span> <span class="attribution"><span class="source">(Shutterstock)</span></span></figcaption></figure><p>A <a href="http://stm.sciencemag.org/content/11/479/eaao6451">recent study</a> shows that a gamechanger drug called Fevipiprant <a href="https://www.theguardian.com/society/2016/aug/06/fevipiprant-asthma-drug-trial-treatment">promises to lower patients’ risks of suffering an asthma attack and being admitted to a hospital</a>. </p>
<p>This is the <a href="https://www.eurekalert.org/pub_releases/2019-02/uol-apt021119.php">first time a drug reducing airway smooth muscle mass</a> — a key clinical indicator of disease severity that increases the likelihood of more frequent asthma attacks and even deaths — has been reported.</p>
<p>Along with <a href="https://www.sheffield.ac.uk/dcs/people/academic/rsmallwood">Rod Smallwood,</a> fellow of the British Royal Academy of Engineering, I developed computer models that allowed us to simulate results from a <a href="https://doi.org/10.1016/S2213-2600(16)30179-5">Phase 2 clinical trial</a> — to predict therapy outcomes in patients.</p>
<p>The original trial was led by <a href="https://www2.le.ac.uk/departments/iii/people/brightling">Christopher Brightling</a>, clinical professor in respiratory medicine at the University of Leicester and the principal co-ordinator of the European Lung Foundation <a href="https://www.europeanlung.org/en/projects-and-research/projects/airprom/home">AirPROM</a>. </p>
<h2>Asthma is increasingly common</h2>
<p>Asthma affects around 339 million people worldwide, killing as many as 1,000 people every day, according to the <a href="http://www.globalasthmareport.org/Global%20Asthma%20Report%202018.pdf">Global Asthma Report 2018</a>. </p>
<p>The prevalence of asthma is on the rise, with low- and middle-income countries suffering most — in part, because essential medicines are unavailable, unaffordable or are of unreliable quality.</p>
<p>Asthma is caused by complex set of interactions between a patient’s genes, cells and environment that lead to an increase in airway smooth muscle mass: a process referred to as “remodelling.”</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/265935/original/file-20190326-36256-1ha1vsh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/265935/original/file-20190326-36256-1ha1vsh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=338&fit=crop&dpr=1 600w, https://images.theconversation.com/files/265935/original/file-20190326-36256-1ha1vsh.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=338&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/265935/original/file-20190326-36256-1ha1vsh.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=338&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/265935/original/file-20190326-36256-1ha1vsh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=424&fit=crop&dpr=1 754w, https://images.theconversation.com/files/265935/original/file-20190326-36256-1ha1vsh.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=424&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/265935/original/file-20190326-36256-1ha1vsh.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">
<figcaption>
<span class="caption">A man wears a health mask on the skytrain in Bangkok, Thailand, in February 2019, to guard against air and dust pollution.</span>
<span class="attribution"><span class="source">(Shutterstock)</span></span>
</figcaption>
</figure>
<p>Our airways are composed of <a href="http://stm.sciencemag.org/content/11/479/eaao6451.full">several different cell types</a> that exist together in a highly ordered state. The airway lumen is lined by epithelial cells and, further inside, the mesenchyme. The latter contains muscle cells that increase in mass during asthma. Another crucial feature of the airway are the inflammatory cells that are recruited in the event of a foreign challenge (such as an allergen or virus).</p>
<p>In health, these three elements work in harmony to ensure effective airflow and appropriate response to external challenges. In asthma, these harmonic interactions are compromised, resulting in increased muscle mass.</p>
<p>Developing a sound strategy to treat asthma requires a precise understanding of the factors that contribute to the emergence of the disease. We cannot achieve this through experimentation alone because so many factors contribute to the disease. With mathematical models, we can use hypotheses to help reduce the complexity of the system. </p>
<h2>We made a ‘virtual patient’</h2>
<p>In the clinical trial, Fevipiprant was observed to <a href="https://doi.org/10.1016/S2213-2600(16)30179-5">reduce the number of inflammatory cells</a> and muscle mass. </p>
<p>To understand how, <a href="https://leicester.figshare.com/articles/Clinical_level_agent-based_model_of_pathological_airway_remodeling_in_asthma/7610933">I developed a mathematical model</a> that combined the epithelial, mesenchymal and inflammatory elements — to understand what is responsible for airway remodelling during asthma. </p>
<p>I used something called <a href="https://doi.org/10.1093/bib/bbt077">“agent-based modeling”</a> — a mathematical approach that relies on rule-sets governing interactions between various model elements.</p>
<p>I developed a “virtual patient” with severe asthma and gave them virtual drugs. I made sure that the model was capturing biological reality by first administering virtual Mepolizumab, which killed inflammatory cells in the airways. The virtual patient performance was <a href="https://doi.org/10.1164/rccm.200208-789OC">consistent with clinical results</a>. </p>
<p>I then gave the virtual patient Fevipiprant. While it showed the same amount of reduction in inflammatory cells as the clinical trial, it failed to show the same amount of reduction in muscle mass as observed clinically.</p>
<p>This led to the conclusion that Fevipiprant acted not by reducing the inflammation alone, but by also directly impacting muscle mass. Experiments conducted by <a href="https://www2.le.ac.uk/departments/iii/existing-staff-and-students/researcher-forum/biographies/dr-ruth-saunders">Ruth Saunders</a> at the University of Leicester, with muscle cells taken from patients suggested that Fevipiprant reduced the recruitment of cells called myofibroblasts, which add to muscle mass during remodelling. </p>
<p>When this secondary feature was added to the model, the observed reduction in the muscle mass of the virtual patient was consistent with clinical data.</p>
<h2>Reduced dependence on steroids</h2>
<p>Fevipiprant could be a potential therapy to improve airway remodelling in asthma. </p>
<p>Using this drug could allow patients to reduce their dependence on high-dose steroids, whose side-effects include weight gain, diabetes and high blood pressure. </p>
<p>Secondly, the “virtual patient” can play a role in drug design and optimization, potentially lowering drug-development costs. </p>
<p>While this does need more testing with other therapies, it is a milestone in patient-specific models and promises a new era of precision within respiratory medicine.</p><img src="https://counter.theconversation.com/content/112125/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>The research discussed in this article was funded by Airway Disease Predicting Outcomes through Patient Specific Computational Modelling (AirPROM) via the Seventh European Union Framework, the National Institute for Health Research (NIHR) Leicester Biomedical Research Centre and the Swiss pharmaceutical company, Novartis.</span></em></p>Asthma affects around 339 million people worldwide. A new drug promises to lower risks of asthma attack and may eventually allow patients to reduce their dependence on steroids.Himanshu Kaul, Postdoctoral Fellow, University of British ColumbiaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/904592018-02-02T05:07:08Z2018-02-02T05:07:08ZFour ways precision medicine is making a difference<figure><img src="https://images.theconversation.com/files/204367/original/file-20180201-123829-1rvxlpc.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Identification of genetic mutations has led to the development of effective drugs.</span> </figcaption></figure><p><em>This article is part of a <a href="https://theconversation.com/au/topics/precision-medicine-series-49226">package on precision medicine</a>, where we explore genomic sequencing and what it means for better diagnosis and treatment of many conditions including cancer and rare diseases.</em></p>
<hr>
<p>All human characteristics are profoundly influenced by genetic factors, including <a href="http://www.annualreviews.org/doi/abs/10.1146/annurev-genom-091212-153448">susceptibility to infectious and complex diseases</a> such as tuberculosis and cancer. Until now it has been virtually impossible to target medicine to a specific individual’s genetic makeup, and medicine has been aimed at the average.</p>
<p>But now “precision medicine” is allowing us to analyse a person’s genetic makeup and target treatments based on their specific needs. A report released this week by the Australian Council of Learned Academies, <a href="https://acola.org.au/wp/pmed/">The Future of Precision Medicine in Australia</a>, notes the cost of sequencing individual genomes has plummeted from more than US$1 billion to US$1,000 over the past 15 years, and continues to fall.</p>
<p>Here are four areas in which precision medicine is making a difference in health care, and some of the ways we hope it will improve health care in the future.</p>
<h2>1. Diagnosing and preventing genetic disease</h2>
<p>The precision medicine revolution is transforming the diagnosis and prevention of genetic disease. Tragically, <a href="http://www.kumc.edu/GEC/prof/prevalnc.html">at least 2% of all children</a> are afflicted by a severe developmental or intellectual disability, which can result from damage to any one of thousands of genes that encode the proteins we need to function. </p>
<p>Genome sequencing can now identify <a href="https://www.nature.com/articles/nature13394">40-60% of the affected genes</a>, giving parents and doctors the answers they need to improve treatment.</p>
<p>This information also improves the confidence of parents to have more children, as the problem can be avoided by IVF. For these reasons, the UK National Health Service has <a href="https://www.genomeweb.com/molecular-diagnostics/100k-genomes-project-returns-patient-reports-nhs-prepares-commission-wgs">recently announced</a> genome sequencing will be used to determine the cause in cases of severe unexplained disability. Hopefully Australia will soon follow suit.</p>
<p>This is just the beginning. The use of genome sequencing for preconception screening of prospective parents is just around the corner, and has the potential to reduce the incidence of genetic disability in our community.</p>
<hr>
<p><strong><em>Read more:</em></strong></p>
<ul>
<li><p><strong><em><a href="https://theconversation.com/explainer-what-is-pre-pregnancy-carrier-screening-and-should-potential-parents-consider-it-79184">What is pre-pregnancy carrier screening and should potential parents consider it?</a></em></strong></p></li>
<li><p><strong><em><a href="https://theconversation.com/what-prospective-parents-need-to-know-about-gene-tests-such-as-prepair-87083">What prospective parents need to know about gene tests such as ‘prepair’</a></em></strong></p></li>
</ul>
<hr>
<h2>2. Cancer diagnosis and treatment</h2>
<p>Cancer is caused by a wide range of cell mutations, but traditional tests do not make clear which of these is driving a particular cancer. </p>
<p>Identification of these mutations has led to the development of effective drugs such as <a href="http://www.cancerresearchuk.org/about-cancer/cancer-in-general/treatment/cancer-drugs/drugs/imatinib">Imatinib</a>, with many more in late stage development. But these are expensive and can be applied only if the precise target is known. </p>
<p>Countries such as the United States, United Kingdom and France are trialling sequencing the cancer’s DNA in order to better target treatment. Unpublished, emerging evidence indicates a substantial improvement in survival, but surprisingly, an overall reduction in costs. This appears to be due to fewer episodes of patients requiring acute care.</p>
<p>Some of the outcomes of genomically-informed cancer treatment are spectacular. I am aware of two children locally with lethal cancers, one of whom was close to death, who have been apparently cured as a result of prescribing the correct drug (which had never before been indicated in the cancers concerned) following genome analysis.</p>
<p>We can also increasingly predict an individual’s risk of getting cancer by analysing genes known to be involved in cancer. A <a href="https://jamanetwork.com/journals/jamaoncology/article-abstract/2646798?redirect=true">recent study using MRIs</a> of people judged at high risk of cancer because of an inherited mutation in a cancer-causing gene showed 10% already had tumours that weren’t yet causing symptoms. These could then be readily removed. </p>
<h2>3. The suitability of medicines</h2>
<p>A <a href="https://www.mja.com.au/journal/2006/184/11/incidence-and-cost-adverse-events-victorian-hospitals-2003-04">high proportion</a> of hospital admissions in Australia and other countries are <a href="http://www.bmj.com/content/329/7456/15">due to toxic reactions</a> to prescribed medications. And many medications are useless in some people. </p>
<p>The main reason for this is we have different forms of the liver enzymes that clear chemicals from our bloodstream, which in turn affects their concentration and how long they last. By necessity, prescriptions are directed at the average. </p>
<p>There are also rare gene mutations that make some medications lethal for some people. Genome analysis can predict and avoid many of these adverse reactions or unproductive prescriptions, saving enormous amounts of money and making medication more personal and precise.</p>
<h2>4. Population health data</h2>
<p>Given the benefits of genome sequencing for individual health, it’s assumed most people will consent, and have the results incorporated into their personal medical records. Amalgamation of this information with clinical records will provide rich data that can be mined for biomedical discovery, as well as for better management of medical systems and resource allocation.</p>
<p>Personal wearable and implantable devices that can monitor physiological responses (sleep, blood sugar, blood pressure, medication compliance, etc.) will contribute the other half of the personal picture by providing real-time information to assist diagnosis, helping people find the best strategies for improving their health. </p>
<p>Medicine will become one of the most data-intensive industries on the planet, changing from the art of crisis management to the science of good health. This will have a transformative effect on health, both individually and systemically, with enormous implications for national economies.</p><img src="https://counter.theconversation.com/content/90459/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>John Mattick is the Executive Director of the Garvan Institute of Medical Research, the owner of Genome.One, which is clinically accredited to undertake whole genome sequencing and analysis.</span></em></p>“Precision medicine” is allowing us to analyse a person’s genetic makeup and target treatments based on their specific needs.John Stanley Mattick, Executive Director, Garvan Institute of Medical Research, Garvan InstituteLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/905272018-02-01T05:25:30Z2018-02-01T05:25:30ZNot all genetic tests should be publicly funded – here’s why<figure><img src="https://images.theconversation.com/files/204368/original/file-20180201-123862-1tw7bjj.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">More knowledge about your genetic makeup enables you to make better-informed choices – but at what cost?</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/download/confirm/1012409287?src=IFDhfMXejh9L_mVp9K-Z_g-1-70&size=huge_jpg">Shutterstock</a></span></figcaption></figure><p><em>This article is part of a <a href="https://theconversation.com/au/topics/precision-medicine-series-49226">package on precision medicine</a>, where we explore genomic sequencing and what it means for better diagnosis and treatment of many conditions including cancer and rare diseases.</em></p>
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<p>New genetic technologies hold great promise in their potential to treat patients based on their individual genetic information. Advances in mapping the human genome mean the cost of doing a genetic test has fallen dramatically, though the costs of these tests – and subsequent treatment – are still high.</p>
<p>It’s exciting to think we’re on the brink of a genomic revolution in health care. But just because new technology becomes available, it doesn’t mean it should automatically be funded by the government through Medicare or the Pharmaceutical Benefits Scheme (PBS). </p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/its-2030-and-precision-medicine-has-changed-health-care-this-is-what-it-looks-like-90539">It's 2030, and precision medicine has changed health care – this is what it looks like</a>
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<p>A number of types of genetic tests are currently available, including those for: </p>
<ul>
<li>a person’s whole genome sequence</li>
<li>a particular gene that carries the certainty of a diagnosis</li>
<li>a gene that increases the person’s risk of developing a disease</li>
<li>a patient who already has a diagnosis, to test whether a particular medicine will be effective.<br></li>
</ul>
<p>Each genetic test, each disease and each treatment pathway must be analysed to determine the balance of costs and benefits. We need to apply the same principles we do for any test, procedure or new medicine to determine whether it should be publicly funded: it must represent good value for money and be likely to improve health outcomes.</p>
<h2>Gene-based therapies</h2>
<p>Let’s consider the example of cancer treatment. Some medicines work only on tumours with particular genetic markers. By using a test to target the medicine only to cancer patients who have the marker, we can be more confident that the medicine is effective for those who are treated, thus avoiding unnecessary costs and possible side-effects. This could make the new medicine more affordable. </p>
<p>But for the seller of the medicine, greater effectiveness means they can ask a higher price. Indeed, they <a href="http://www.oecd-ilibrary.org/science-and-technology/pharmacogenetics-opportunities-and-challenges-for-health-innovation/business-models-for-pharmacogenetics_9789264076808-6-en;jsessionid=15bo09hn8l46w.x-oecd-live-03">need to</a>, because now there is a smaller target “market”. </p>
<p>The cystic fibrosis drug Ivacaftor, for instance, <a href="http://www.abc.net.au/news/2014-10-26/cystic-fibrosis-patients-to-benefit-from-drug-listing/5842332">cost patients around A$250,000 a year</a> before it was subsidised on the PBS. The clinical trials had only demonstrated effectiveness in patients with a G551D mutation, which is only <a href="http://www.pbs.gov.au/info/industry/listing/elements/pbac-meetings/psd/2013-11/ivacaftor">8.6% of the population</a> with the disease. </p>
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Read more:
<a href="https://theconversation.com/how-cancer-doctors-use-personalised-medicine-to-target-variations-unique-to-each-tumour-47349">How cancer doctors use personalised medicine to target variations unique to each tumour</a>
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<p>The challenge for the government is whether we can afford to pay higher prices for each of these targeted medicines. Then there’s the issue of who will pay for the test, which will need to be done for everyone who might have the genetic marker. Should it be the government, private health insurers or individuals?</p>
<p>Without public funding of genetic testing, access to the effective treatment depends on whether you can afford to pay for the test, which undermines the equity principles of Medicare. </p>
<p>To overcome this challenge, Australia now requires <a href="http://www.health.gov.au/internet/hta/publishing.nsf/content/co-1">integrated submissions of “co-dependent” technologies</a>. This means, for instance, that if access to a new medicine on the PBS depends on the results of a test, the test should be publicly funded, and at a price that represents good value for money. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/204379/original/file-20180201-123829-1hiwy9s.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/204379/original/file-20180201-123829-1hiwy9s.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/204379/original/file-20180201-123829-1hiwy9s.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/204379/original/file-20180201-123829-1hiwy9s.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/204379/original/file-20180201-123829-1hiwy9s.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/204379/original/file-20180201-123829-1hiwy9s.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/204379/original/file-20180201-123829-1hiwy9s.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">Gene-based therapy is more expensive but more targeted.</span>
<span class="attribution"><a class="source" href="https://unsplash.com/photos/Q4eWnth5S74">Thought Catalog</a></span>
</figcaption>
</figure>
<h2>Testing for known diseases</h2>
<p>More knowledge about your genetic makeup enables you to make better-informed choices: whether to seek preventive treatment; to change your behaviour to reduce risks; or to plan for the future. </p>
<p>In the context of specific known diseases, such testing is best done in a setting with genetic counselling, so the person can fully understand the implications of the knowledge and the decisions that may need to be made. </p>
<p>For a woman who has had breast cancer, a BRCA gene test can inform her choice about, for example, mastectomy to prevent a second breast cancer. Testing of immediate family members can determine if they carry the gene, allowing them to seek preventive treatment or more frequent screening. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/angelina-jolie-has-had-a-double-mastectomy-so-what-is-brca1-14227">Angelina Jolie has had a double mastectomy, so what is BRCA1?</a>
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<p>But sometimes nothing can be done with the knowledge you obtained from your gene test. Knowing you have a higher risk of, say, dementia, could improve your well-being by giving you the chance to plan. Or it could just make you feel worse. </p>
<p>The costs and benefits of a genetic test depend greatly on whether there is effective prevention or treatment available, and what that treatment is. </p>
<h2>Value for money</h2>
<p>Australia assesses whether any test in health care represents good value for money by mapping out the treatment pathways that are available for each test result, and evaluating the costs and health benefits of each of these. </p>
<p>Based on such an assessment, the <a href="https://www.bcna.org.au/news/2017/10/bcna-welcomes-new-medicare-rebates-for-genetic-testing/">Medical Services Advisory Committee recently recommended</a> a Medicare rebate of A$1,200 for genetic testing for hereditary mutations for breast and ovarian cancer, including the BRCA1 and 2 genes. This would cover most, if not all, of the cost of the test. The committee also recommended Medicare pay a A$400 rebate for predictive testing for family members. </p>
<p>The <a href="http://www.msac.gov.au/internet/msac/publishing.nsf/content/1411.1-public">committee concluded</a> the test would be good value for money, at around A$18,000 per <a href="http://www.health.gov.au/internet/publications/publishing.nsf/Content/illicit-pubs-needle-return-1-rep-toc%7Eillicit-pubs-needle-return-1-rep-5%7Eillicit-pubs-needle-return-1-rep-5-2">Quality Adjusted Life Year</a> (QALY) gained (from breast and ovarian cancers avoided). A QALY is a way of quantifying the additional survival and quality of life from the test compared with not having the test available. </p>
<p>For a test for a single gene or genes that are a certain marker for specific diseases, assessment of cost effectiveness is relatively straightforward, particularly if there is an effective treatment available. </p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/new-cancer-drugs-are-very-expensive-heres-how-we-work-out-value-for-our-money-44014">New cancer drugs are very expensive - here's how we work out value for our money</a>
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<h2>Predicting future diseases</h2>
<p>For a test that indicates increased risk of developing diseases in the future, such as whole genome sequencing, the options are less clear. </p>
<p>The committee would ask: can the person reduce their risk by exercising more and eating better? And will the information increase their motivation to do so over and above medical advice already received? Or will it motivate them to seek more treatment over time? And how effective is this treatment?</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/204377/original/file-20180201-123859-1ekbi9v.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/204377/original/file-20180201-123859-1ekbi9v.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/204377/original/file-20180201-123859-1ekbi9v.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/204377/original/file-20180201-123859-1ekbi9v.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/204377/original/file-20180201-123859-1ekbi9v.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/204377/original/file-20180201-123859-1ekbi9v.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/204377/original/file-20180201-123859-1ekbi9v.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">It’s not always best to know.</span>
<span class="attribution"><a class="source" href="https://unsplash.com/photos/CTAbgDbm2Bw">Eric Didier</a></span>
</figcaption>
</figure>
<p>Whole genome sequencing and genetic counselling is available privately in Australia now <a href="https://www.genome.one/post/oneome-and-genome-one-team-up-to-provide-powerful-genetic-insights">for around A$6,000</a> (including a health assessment) – so affordable only to the rich. It is not publicly funded because the benefits are uncertain. </p>
<p>It could just be “nice to know” (as such tests are marketed in the US); it could motivate the person to change their behaviour and thus lead to better health outcomes; or it could create anxiety and unnecessary intervention, and thus ultimately increase health care costs, not just for the individual but for the society. </p>
<p>There is no blanket answer to whether genomic testing is cost-effective. Each test, each disease and each treatment pathway must be analysed to determine the balance of costs and benefits, following the same approach as for other new medical technologies.</p>
<hr>
<p><em>Read the other articles in our <a href="https://theconversation.com/au/topics/precision-medicine-series-49226">precision medicine package here</a>.</em></p><img src="https://counter.theconversation.com/content/90527/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Rosalie Viney receives funding from NHMRC and ARC. She was formerly a member of the Pharmaceutical Benefits Advisory Committee. </span></em></p><p class="fine-print"><em><span>Jane Hall receives funding from the NHMRC and the ARC. </span></em></p><p class="fine-print"><em><span>Grattan Institute began with contributions to its endowment of $15 million from each of the Federal and Victorian Governments, and $4 million from BHP Billiton. In order to safeguard its independence, Grattan Institute’s board controls this endowment. The funds are invested and Grattan uses the income to pursue its activities</span></em></p>It’s exciting to think we’re on the brink of a genomic revolution in health care. But just because new technology becomes available, it doesn’t mean it should automatically be publicly funded.Rosalie Viney, Professor of Health Economics, University of Technology SydneyJane Hall, Professor of Health Economics and Director, Centre for Health Economics Research and Evaluation, University of Technology SydneyStephen Duckett, Director, Health Program, Grattan InstituteLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/845912018-01-31T19:04:52Z2018-01-31T19:04:52ZWhat is CRISPR gene editing, and how does it work?<figure><img src="https://images.theconversation.com/files/203941/original/file-20180130-170442-4m9ea.png?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Scientists discovered some bacteria can cut the DNA of invading viruses as a defence mechanism. They realised they could use this to cut human DNA. </span> </figcaption></figure><p><a href="https://www.technologyreview.com/s/608967/arming-bodies-with-crispr-to-fight-huntingtons-disease-and-als/">You’ve probably read</a> <a href="http://www.bionews.org.uk/page_894685.asp">stories</a> about <a href="https://futurism.com/crispr-is-on-the-cusp-of-eradicating-a-host-of-diseases/">new research</a> using the <a href="https://motherboard.vice.com/en_us/article/pakxem/scientists-used-crispr-to-edit-a-gene-that-causes-miscarriages">gene editing technique</a> CRISPR, also called CRISPR/Cas9. The scientific world is captivated by this revolutionary <a href="https://theconversation.com/explainer-what-is-genome-editing-25072">technology</a>, since it is easier, cheaper and more efficient than previous strategies for modifying DNA. </p>
<p>The term CRISPR/Cas9 stands for Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR associated protein 9. The names reflect <a href="https://www.broadinstitute.org/what-broad/areas-focus/project-spotlight/crispr-timeline">important features identified during its discovery</a>, but don’t tell us much about how it works, as they were coined before anyone understood what it was.</p>
<p><iframe id="tc-infographic-229" class="tc-infographic" height="580px" src="https://cdn.theconversation.com/infographics/229/1e1ccd9abbd9a92604e144561050c08a9c49d8b3/site/index.html" width="100%" style="border: none" frameborder="0"></iframe></p>
<h2>What does CRISPR/Cas9 do?</h2>
<p>CRISPR/Cas9 is a system found in bacteria and involved in immune defence. Bacteria use CRISPR/Cas9 to cut up the DNA of invading bacterial viruses that might otherwise kill them. </p>
<p>Today we’ve adapted this molecular machinery for an entirely different purpose – to change any chosen letter(s) in an organism’s DNA code. </p>
<p>We might want to correct a disease-causing error that was inherited or crept into our DNA when it replicated. Or, in some cases, we may want to enhance the genetic code of crops, livestock or <a href="https://theconversation.com/the-future-of-genetic-enhancement-is-not-in-the-west-63246">perhaps even people</a>.</p>
<p>So do we just snip the unwanted gene out and replace it with a good one? </p>
<hr>
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Read more:
<a href="https://theconversation.com/explainer-what-is-genome-editing-25072">Explainer: what is genome editing?</a>
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<p>We first have to remember that animals and plants are composed of millions of cells, and each cell contains the same DNA. There is no point editing just one cell: we would have to edit the same gene in every single cell. We’d have to snip out millions of genes and paste in millions of new ones. </p>
<p>And not all cells are easy to get to – how could we reach cells buried in our bones or deep within a brain? </p>
<p>A better approach is to start at the beginning and edit the genome while there is only one cell – a very early embryo.</p>
<p>So, all we need is a giant microscope and a tiny pair of scissors. And that is basically what we use. </p>
<p>Cas9 is the technical name for the virus-destroying “scissors” that evolved in bacteria. The CRISPR part of the name comes from repeat DNA sequences that were part of a complex system telling the scissors which part of the DNA to cut.</p>
<h2>Find, cut and then paste</h2>
<p>In order to target our Cas9 scissors, we link them to an artificial guide that directs them to the matching segment of DNA.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/204121/original/file-20180130-38198-1tfi88o.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/204121/original/file-20180130-38198-1tfi88o.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/204121/original/file-20180130-38198-1tfi88o.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/204121/original/file-20180130-38198-1tfi88o.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/204121/original/file-20180130-38198-1tfi88o.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/204121/original/file-20180130-38198-1tfi88o.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/204121/original/file-20180130-38198-1tfi88o.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/204121/original/file-20180130-38198-1tfi88o.png?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">We give the scissors a copy of the DNA we’re after so they know where to cut.</span>
<span class="attribution"><a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<p>Remember, DNA comes in two strands, with one strand fitting alongside the other. We make a guide with a code that will line up with only one part of our 3 billion base pair long genome – it’s like a “Google” search. It’s truly possible for our guide to comb through vast amounts of genetic material to find the one section it matches exactly. Then our “scissors” can make the cut in exactly the right place.</p>
<p>Once the Cas9 scissors cut the DNA just where we intend, the cell will try to repair the break using any available DNA it can find. So, we also inject the new gene we want to insert. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/204125/original/file-20180130-38203-1mwwt0p.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/204125/original/file-20180130-38203-1mwwt0p.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/204125/original/file-20180130-38203-1mwwt0p.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/204125/original/file-20180130-38203-1mwwt0p.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/204125/original/file-20180130-38203-1mwwt0p.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/204125/original/file-20180130-38203-1mwwt0p.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/204125/original/file-20180130-38203-1mwwt0p.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/204125/original/file-20180130-38203-1mwwt0p.png?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">If we inject new DNA it will take the place of the DNA we have cut.</span>
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<p>
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Read more:
<a href="https://theconversation.com/now-we-can-edit-life-itself-we-need-to-ask-how-we-should-use-such-technology-68821">Now we can edit life itself, we need to ask how we should use such technology</a>
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<p>You can use a microscope and a tiny needle to inject the CRISPR/Cas9 together with the guide and the donor DNA, the new gene. Or, you can punch holes in cells with electric currents and let these things just float in, use guns to shoot them in stuck-on tiny bullets, or introduce them encapsulated in bubbles of fat that fuse with the cell membrane and release their contents inside. </p>
<p>But how does the new gene find the right place to embed itself? Imagine you wanted to put in the last piece of a jigsaw puzzle with 3 billion pieces, and it’s inside a cell, filled with goop like a passionfruit.</p>
<p>What you’d do is fabricate a jigsaw piece of precisely the right shape and inject it into the passionfruit. Then it’s just a case of jiggling around until eventually the piece finds its way to the correct part of the puzzle and slots into the only place it fits.</p>
<p>You don’t need to be able to see the DNA in our genome through the microscope – it’s too small. And you don’t really have to jiggle either – random diffusion (called <a href="https://www.britannica.com/science/Brownian-motion">Brownian motion</a>) will always deliver the jigsaw piece to the place where it fits in the end. </p>
<p>First, the guide will jiggle along and find the right place for the scissors to cut, and then the new donor DNA will similarly line up where it fits and will be permanently stitched into the DNA strand via natural DNA repair mechanisms.</p>
<p>Recently, though, <a href="https://www.nature.com/news/crispr-hacks-enable-pinpoint-repairs-to-genome-1.22884">new CRISPR editing systems</a> have been created that don’t even require a cut through the DNA. In this case, the CRIPSR/Cas and guide system can deliver an enzyme to a particular gene and alter it, changing perhaps an A to a G or a C to a T, rather than cutting anything out or putting anything in.</p>
<h2>What are we doing with CRISPR/Cas9?</h2>
<p>Most experiments use mouse embryos or cells grown in petri dishes in artificial liquid designed to be like blood. Other researchers are modifying stem cells that may then be re-injected into patients to repopulate damaged organs. </p>
<p>Only a few labs around the world are actually working with <a href="https://theconversation.com/genome-editing-of-human-embryos-broadens-ethics-discussions-84888">early human embryos</a>. This research is highly regulated and carefully watched. Others work on plant cells, as whole plants can be grown from a few cells. </p>
<p>As we learn more, the scope of what we can do with CRISPR/Cas9 will improve. We can do a lot, but every organism and every cell is different. What’s more, everything in the body is connected, so we must think about unexpected side effects and <a href="https://theconversation.com/human-embryo-crispr-advances-science-but-lets-focus-on-ethics-not-world-firsts-81956">consider the ethics of changing genes</a>. Most of all we, as a society, should discuss and agree what we wish to achieve.</p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/why-we-can-trust-scientists-with-the-power-of-new-gene-editing-technology-51480">Why we can trust scientists with the power of new gene-editing technology</a>
</strong>
</em>
</p>
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<p><strong><em>Read the other articles in our <a href="https://theconversation.com/au/topics/precision-medicine-series-49226">precision medicine series here</a>.</em></strong></p><img src="https://counter.theconversation.com/content/84591/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Merlin Crossley receives funding from the Australian Research Council and National Health and Medical Research Council. He is a Trustee of the Australian Museum, on the Board of the Australian Science Media Centre, and the Editorial Board of The Conversation.</span></em></p>CRISPR harnesses the natural defence mechanisms of some bacteria to cut human DNA strands. Then the DNA strand either heals itself or we inject new DNA to mend the gap. This is gene editing.Merlin Crossley, Deputy Vice-Chancellor Academic and Professor of Molecular Biology, UNSW SydneyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/905392018-01-30T23:30:15Z2018-01-30T23:30:15ZIt’s 2030, and precision medicine has changed health care – this is what it looks like<figure><img src="https://images.theconversation.com/files/203929/original/file-20180130-170419-1eah061.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">In 2030, some diseases are defined more specifically than in the past with a focus on their molecular makeup. This is known as precision medicine.</span> <span class="attribution"><span class="source">from shutterstock.com</span></span></figcaption></figure><p><em>This article is part of a <a href="https://theconversation.com/au/topics/precision-medicine-series-49226">package on precision medicine</a>, where we explore genomic sequencing and what it means for better diagnosis and treatment of many conditions including cancer and rare diseases.</em></p>
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<p>Imagine it is 2030. Ten-year-old Amy is wheeled into a children’s hospital clinic by her mother and, across town, 45-year-old Anh is visiting his oncologist one week after leaving hospital for his lung cancer operation. </p>
<p>Amy is slowly losing her ability to walk due to a muscle disorder that has only recently been given a name. Many diseases of muscle in children such as muscular dystrophy are caused by gene mutations (muscle disorders in adults are less likely to have a genetic mutation basis). In 2018, <a href="https://www.ncbi.nlm.nih.gov/pubmed/25380242">only around 40%</a> of these mutations were known. </p>
<p>In 2030, we know 99% of mutations causing inherited muscle diseases worldwide. Because the costs of genetic sequencing are so much lower, more people have had their genomes scanned. Researchers have spent the last 20 years gathering information about various genetic markers and mutations into massive biobanks. This data is now globally accessible, which has led to international collaboration and better understanding of diseases.</p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/personalised-medicine-has-obvious-benefits-but-has-anyone-thought-about-the-issues-59158">Personalised medicine has obvious benefits but has anyone thought about the issues?</a>
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</em>
</p>
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<p>So, 2030 is seeing a boom in precision medicine – where some diseases are defined more specifically than in the past with a focus on their molecular makeup. That is, the genes related to the DNA of the disease and other molecular elements. Precision medicine has vastly improved the ability to diagnose rare inherited diseases; to diagnose and treat cancers; and to aid in diagnosis and management of infectious diseases, dementia, heart disease and diabetes, among many others.</p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/203743/original/file-20180129-100915-eipqys.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/203743/original/file-20180129-100915-eipqys.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/203743/original/file-20180129-100915-eipqys.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=798&fit=crop&dpr=1 600w, https://images.theconversation.com/files/203743/original/file-20180129-100915-eipqys.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=798&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/203743/original/file-20180129-100915-eipqys.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=798&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/203743/original/file-20180129-100915-eipqys.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1003&fit=crop&dpr=1 754w, https://images.theconversation.com/files/203743/original/file-20180129-100915-eipqys.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1003&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/203743/original/file-20180129-100915-eipqys.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1003&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Scientists have been able to pinpoint exactly which gene mutation caused Amy’s disease.</span>
<span class="attribution"><span class="source">from shutterstock.com</span></span>
</figcaption>
</figure>
<h2>Amy’s story</h2>
<p>At Amy’s fifth gene test during her life, performed using the seventh version of specialist software for mutation detection associated with muscle disease, she was finally told which mutation led to her disability.</p>
<p>Some rare neuromuscular diseases are limited to very few families in the world. When only one family member is affected, and particularly if they are the first in the family, the responsible defect in the gene can be extremely difficult to determine among all the normal variations in the human genome.</p>
<p>Through access to global repositories of genomic data, Amy’s specialist has been able to download all known cases of this disease in the world. She has summarised information on the likely health outcomes of other patients and available treatment options or trials. </p>
<p>Amy’s disease is so newly diagnosed that there has been no funded research in this specific area. But there are similarities with other better known muscle disorders. Using international databases, the specialist finds a potential trial applicable to Amy. The trial has shown promise in preventing continued decline of muscle function. </p>
<p>Amy’s mother is relieved she finally has an answer to the cause of her daughter’s disability. Putting a name to it and knowing there are others with this disease comforts her. Of course, knowing potential trials might help stabilise her daughter’s condition leaves her with some hope that continued decline in Amy’s muscle strength is not inevitable.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/203741/original/file-20180129-100912-1axgper.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/203741/original/file-20180129-100912-1axgper.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/203741/original/file-20180129-100912-1axgper.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/203741/original/file-20180129-100912-1axgper.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/203741/original/file-20180129-100912-1axgper.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/203741/original/file-20180129-100912-1axgper.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/203741/original/file-20180129-100912-1axgper.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/203741/original/file-20180129-100912-1axgper.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">Amy’s mother is relieved doctors know what has caused her daughter’s disease.</span>
<span class="attribution"><span class="source">from shutterstock.com</span></span>
</figcaption>
</figure>
<p>That night, after putting Amy to bed, Amy’s mother contemplates trying for a second child. There has been a public debate in Australia about preconception screening, which would allow a mother to abort her fetus if it’s known to be carrying a gene mutation that causes a severe debilitating disease. The debate has concluded that preconception screening is allowed under certain circumstances. </p>
<p>Now that Amy’s mutation is known, preconception screening is an option. Amy’s mother will discuss this with her husband in the morning. </p>
<hr>
<p><strong><em>Read more:</em></strong></p>
<ul>
<li><p><strong><em><a href="https://theconversation.com/explainer-what-is-pre-pregnancy-carrier-screening-and-should-potential-parents-consider-it-79184">What is pre-pregnancy carrier screening and should potential parents consider it?</a></em></strong></p></li>
<li><p><strong><em><a href="https://theconversation.com/what-prospective-parents-need-to-know-about-gene-tests-such-as-prepair-87083">What prospective parents need to know about gene tests such as ‘prepair’</a></em></strong></p></li>
</ul>
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<h2>Anh’s story</h2>
<p>Anh, a 45-year-old web designer, wants to know more about the prognosis and management of his cancer now that he has had the operation to remove it. </p>
<p>Before the operation, he was examined with the latest nuclear-medicine-based imaging technologies. This includes imaging at the molecular level with state-of-the-art scans that have been subsidised through Medicare. Specialist radiologists examined the results using high-resolution smart sensing imaging software to look for any spread of tumour (the software can sense known tumour markers).</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/203740/original/file-20180129-100899-j2zghk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/203740/original/file-20180129-100899-j2zghk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/203740/original/file-20180129-100899-j2zghk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/203740/original/file-20180129-100899-j2zghk.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/203740/original/file-20180129-100899-j2zghk.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/203740/original/file-20180129-100899-j2zghk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/203740/original/file-20180129-100899-j2zghk.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/203740/original/file-20180129-100899-j2zghk.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">Ahn’s cancer has been completely removed and the doctors are confident it hasn’t spread anywhere else.</span>
<span class="attribution"><span class="source">from shutterstock.com</span></span>
</figcaption>
</figure>
<p>Anh had also had his blood examined by molecular pathologists who looked for any tiny bits of tumour DNA circulating in his blood. In 2018, this technology (known as a liquid biopsy) was only just starting out and used in very few places as it required specialist molecular knowledge. It was purely a research tool, unfunded by Medicare and not approved for use in a diagnostic laboratory setting.</p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/a-new-blood-test-can-detect-eight-different-cancers-in-their-early-stages-90221">A new blood test can detect eight different cancers in their early stages</a>
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</em>
</p>
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<p>Anh’s treating team used a combination of information to feel reasonably confident there was no evidence of any tumour spread prior to his operation. Unfortunately, the sensitivity of these tests is still not yet at 100%, so ongoing follow-up will be required.</p>
<p>At the time of the operation, specialist hospital pathologists examined part of Ahn’s lung affected by the tumour. They performed tests that looked at the entire makeup of the tumour, which yielded lots of information to compare with the world literature and international database for the same tumour, including its specific markers. </p>
<p>Tumour markers are the unique aspects of DNA and proteins that make the tumour “signature”. Drugs can then target and block some of these specific markers to prevent the tumour from progressing, or even to destroy the tumour. </p>
<p>Mutation of the tumour over time and changes in the molecular markers remain a problem. This has been an ongoing area of research, central to government funding policy, for the past ten years. It takes many years and a large amount of expertise and money from the time of finding a target to developing and trialling drugs. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/203932/original/file-20180130-170410-17809mh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/203932/original/file-20180130-170410-17809mh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/203932/original/file-20180130-170410-17809mh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/203932/original/file-20180130-170410-17809mh.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/203932/original/file-20180130-170410-17809mh.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/203932/original/file-20180130-170410-17809mh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/203932/original/file-20180130-170410-17809mh.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/203932/original/file-20180130-170410-17809mh.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">Anh had a number of state-of-the-art scans that his team used to make more precise decisions on his condition.</span>
<span class="attribution"><span class="source">from shutterstock.com</span></span>
</figcaption>
</figure>
<p>In 2018 only 10-15% of patients with lung cancer had a <a href="http://www.nejm.org/doi/full/10.1056/NEJMoa1713137">tumour molecular target</a> that had an available drug that could work on it. In 2030, that rate is much higher.</p>
<p>Anh asks his oncologist what he expects will happen to him in the future. The doctor explains each individual needs to be seen in his own right despite the collective world of data about his tumour. He says the presence of this new gene marker will be fed into a research and trials database to find what is happening in the world in relation to drugs targeting this novel marker.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/how-cancer-doctors-use-personalised-medicine-to-target-variations-unique-to-each-tumour-47349">How cancer doctors use personalised medicine to target variations unique to each tumour</a>
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</em>
</p>
<hr>
<p>For now, Anh has a good outlook. The results of the analysis of his lung tumour in the pathology department – which looked at key issues like the tumour type and size and whether it has been removed completely or entered small vessels – and the examination of the molecular signature of the tumour are all entered into the diagnostic algorithm based on global data. It has suggested the chances of Anh’s tumour coming back within five years are around 5-10%. Pretty low.</p>
<p>The oncologist tells Anh he is free to go back to work. He will monitor him with regular blood checks aimed at markers for his specific tumour. Now that these are known, the specific test can be individualised to Anh’s tumour. The hand-held screening gadget can send the information straight to the specialist’s office, so he will be notified automatically in the event of change. </p>
<p>Precision medicine has truly made a difference in the lives of millions of people around the world. While there are still many issues to be fixed, including adequate funding for further research continuing on from the new information provided, appropriate drug trial funding and ethical issues, the future is looking brighter.</p>
<hr>
<p><strong><em>Read the other articles in our <a href="https://theconversation.com/au/topics/precision-medicine-series-49226">precision medicine package here</a>.</em></strong></p><img src="https://counter.theconversation.com/content/90539/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Catriona McLean 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>In 2030, there is a boom in precision medicine, where diseases – from cancer to dementia – are defined and targeted more specifically with a focus on their molecular makeup.Catriona McLean, Professor, Central Clinical School, Monash UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/840242017-11-26T23:46:19Z2017-11-26T23:46:19ZStudying circadian rhythms in plants and their pathogens might lead to precision medicine for people<figure><img src="https://images.theconversation.com/files/195885/original/file-20171122-6020-15wox5s.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Though not this obvious from the outside, plants are keeping time.</span> <span class="attribution"><span class="source">Hua Lu</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span></figcaption></figure><p>At dusk, the leaves of the tamarind tree close, waiting for another dawn. Androsthenes, a ship captain serving under Alexander the Great, made the first written account of these leaf movements in the fourth century B.C.</p>
<p>It took centuries longer to discover that he was describing the effects of the circadian clock. This internal time-sensing mechanism allows many living organisms to keep track of time and coordinate their behaviors along 24-hour cycles. It follows the regular day/night and seasonal cycles of Earth’s daily rotation. Circadian research has advanced so far that the <a href="https://www.nobelprize.org/nobel_prizes/medicine/laureates/2017/">2017 Nobel Prize</a> in physiology or medicine was awarded for the groundbreaking work that <a href="https://theconversation.com/nobel-winners-identified-molecular-cogs-in-the-biological-clocks-that-control-our-circadian-rhythms-85061">elucidated the molecular basis underlying circadian rhythms</a>.</p>
<p>Biologists like us are studying the circadian clocks in plants for insights into how they affect the health and well-being of all life on Earth. As researchers continue to untangle more about how these clocks work – including how they influence interactions between hosts and their invading pathogens and pests – new forms of specially timed precision medicine could be on the horizon.</p>
<h2>Our hidden pacemaker</h2>
<p>Organisms from all three domains of life possess an amazing diversity of circadian rhythms. Seemingly simple <em>Cyanobacteria</em> <a href="https://doi.org/10.1038/nrmicro.2016.196">alternate photosynthetic activity between day and night</a>. The fungus <em>Neurospora crassa</em> produces <a href="https://www.ncbi.nlm.nih.gov/pubmed/21707668">spores every morning just before dawn</a>. Migratory monarch butterflies use a delicate <a href="https://doi.org/10.1016/j.celrep.2016.03.057">sun compass in their annual migration</a>. Almost <a href="https://www.nigms.nih.gov/education/pages/Factsheet_CircadianRhythms.aspx">every aspect of human activity</a> is influenced by the circadian clock – you can easily see this in yourself if you fly across time zones or engage in shift work.</p>
<p>The driving force behind circadian rhythms is what scientists call the <a href="https://doi.org/10.1038/nsmb.3327">circadian clock’s central oscillator</a>, an elaborate network of genes that turn each other’s activity on and off. Together, they form complex feedback loops that accurately calibrate time.</p>
<p>Although individual clock genes are not always the same across domains of life, the feedback mechanism of the central oscillator is. This mechanism acts as a switch to synchronize an organism’s daily activities with day and night fluctuations and other environmental changes. Such amazing balancing acts reflect organisms’ abilities to anticipate changing environment throughout the day. </p>
<h2>Precise timekeeping and health</h2>
<p>A well-calibrated circadian clock is critical for growth and fitness, which is why misalignment of the circadian clock with environmental cues causes diverse and far-reaching health issues. Some human diseases, including <a href="https://doi.org/10.1126/scitranslmed.3003200">diabetes</a>, <a href="https://doi.org/10.1073/pnas.1008734107">obesity</a>, <a href="https://doi.org/10.1515/hmbci-2013-0057">cardiovascular disease</a> and <a href="https://doi.org/10.1007/s11920-014-0483-7">some psychiatric disorders</a> such as depression and bipolar disorder, are likely linked to circadian clocks being out of sync with the environment. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/195917/original/file-20171122-6016-ewil30.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/195917/original/file-20171122-6016-ewil30.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/195917/original/file-20171122-6016-ewil30.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=236&fit=crop&dpr=1 600w, https://images.theconversation.com/files/195917/original/file-20171122-6016-ewil30.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=236&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/195917/original/file-20171122-6016-ewil30.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=236&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/195917/original/file-20171122-6016-ewil30.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=297&fit=crop&dpr=1 754w, https://images.theconversation.com/files/195917/original/file-20171122-6016-ewil30.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=297&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/195917/original/file-20171122-6016-ewil30.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=297&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">After infection by a fungus, plants with a mutant circadian clock (right) showed much more damage than the normal plants (left).</span>
<span class="attribution"><span class="source">Hua Lu</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<p>Increasing evidence also links the circadian clock to plant health. In particular, plant scientists have shown that a properly tuned <a href="https://doi.org/10.1146/annurev-phyto-080516-035451">circadian clock is important for plant disease resistance</a> to arrays of pathogens and pests. Although plants do not produce antibodies or use specialized immune cells to ward off invaders, some aspects of their immune system are similar to ours. Because of how easy it is to grow and genetically manipulate them, some plants, like <em>Arabidopsis</em>, serve as ideal systems to investigate how the circadian clock influences the outcome of diseases in plants once infected.</p>
<h2>Plant-pathogen interactions around the clock</h2>
<p>Plants, being immobile, must strategically allocate their limited energy and resources when faced with pathogens and pests. They have the sophisticated ability to <a href="https://doi.org/10.1146/annurev-phyto-080516-035451">time their defense</a>, which allows them to anticipate likely attacks before they occur and modulate defense responses to real attackers.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/196307/original/file-20171124-21838-1fowi5t.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/196307/original/file-20171124-21838-1fowi5t.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/196307/original/file-20171124-21838-1fowi5t.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=323&fit=crop&dpr=1 600w, https://images.theconversation.com/files/196307/original/file-20171124-21838-1fowi5t.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=323&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/196307/original/file-20171124-21838-1fowi5t.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=323&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/196307/original/file-20171124-21838-1fowi5t.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=405&fit=crop&dpr=1 754w, https://images.theconversation.com/files/196307/original/file-20171124-21838-1fowi5t.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=405&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/196307/original/file-20171124-21838-1fowi5t.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=405&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Stomata are little pores on the plant’s surface that can open and close.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-vector/opening-closing-stomata-411951568">Valentina Moraru/Shutterstock.com</a></span>
</figcaption>
</figure>
<p>The forefront of plant defense is on the surface. Physical features like trichomes, little hairs that stick out, protectively cover a plant, and wax coatings deter invaders from clinging onto the surface. The plant surface also has numerous mouth-like pores called stomata. Normally, <a href="https://doi.org/10.1038/nrg3976">stomata rhythmically open in the day and close at night</a>, a process regulated by the circadian clock in anticipation of light and humidity changes. While this process is important for photosynthesis and water exchange, opening stomata can be used by some pathogens as portals to access nutrients and space inside the plant tissue and closing stomata restrict pathogen invasion. </p>
<p>Beyond frontline physical barriers, plants have evolved complex surveillance systems to detect pathogens and pests as intruders. When cell surface receptors recognize a pathogen, the plant immediately closes its stomata at the invasion site. <a href="https://doi.org/10.1371/journal.ppat.1003370">Dysfunctional circadian clocks impair stomatal closure</a>, resulting in more severe disease.</p>
<p>Further pathogen recognition sends alert signals deep into the plant tissue, activating an arsenal of defense responses, including reprogramming of gene expression, production of antimicrobial compounds and enhancement of defense signaling. Even in the absence of pathogens, many of these responses show low but rhythmic changes that are influenced by the circadian clock. When a real attack arrives, the plants’ daily rehearsal of their defense systems ensures a <a href="https://doi.org/10.1146/annurev-phyto-080516-035451">strong and concerted timely defense</a>. Plants with misaligned clocks succumb to the attack. </p>
<p>One excellent example of a plant timing its defense comes from <a href="https://sites.duke.edu/donglab/">Xinnian Dong’s group</a> at Duke University. <em>Hyaloperonospora arabidopsidis</em> is a pathogen that disseminates its virulent spores in the morning and causes disease in <em>Arabidopsis</em> plants. Dong’s group elegantly showed that <em>Arabidopsis</em> anticipates this attack by expressing a set of defense genes at dawn that gives resistance against the pathogen. When the researchers disrupted the <em>Arabidopsis</em> circadian clock, it abolished this <a href="https://doi.org/10.1038/nature09766">morning defense</a> and made the plant more susceptible. </p>
<p>Plants also rely on timely defense to fight off insects. For instance, cabbage loopers have peak feeding activity before dusk. Beautiful work by <a href="http://www.bioc.rice.edu/%7Ebraam/">Janet Braam’s group</a> at Rice University showed that <em>Arabidopsis</em> produces the defense signaling hormone jasmonic acid with a peak at noon in anticipation of this attack. When the insects actually strike, the circadian clock <a href="https://doi.org/10.1073/pnas.1116368109">boosts this noon defense</a>, producing more jasmonic acid to inhibit insect feeding. </p>
<h2>Do clocks dance in pairs?</h2>
<p>As seen from these examples, pathogens and pests have their own circadian clocks and use them to determine the best time to be active. How does this ability affect their invasions of hosts? So far, researchers aren’t sure whether pathogen and pest clocks are coordinated to that of the host. If they are, then how in sync they are could determine the outcome of their interactions.</p>
<p>Current evidence indicates that some eukaryotic microbes, such as <a href="https://doi.org/10.1038/nature09766"><em>Hyaloperonospora arabidopsidis</em></a> and <a href="https://doi.org/10.1105/tpc.112.102046"><em>Botrytis cinerea</em></a>, are able to manipulate the <em>Arabidopsis</em> circadian clock. Even prokaryotic pathogens, like <a href="https://doi.org/10.1371/journal.ppat.1003370"><em>Pseudomonas syringae</em></a>, in spite of lacking a canonical central oscillator, can interfere with plant clocks in various ways.</p>
<p>In humans and mice, <a href="https://doi.org/10.1016/j.cell.2014.09.048">some populations of gut microbiota oscillate daily</a>, depending on the host circadian clock. Interestingly, <a href="https://doi.org/10.1177/0748730417729066">gut microbiota are capable of reprogramming the host clock</a>. How does this transkingdom communication occur? How can it influence the outcome of host and microbe interactions? Research in this area represents a fascinating and unexplored level of host-invader dynamics.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/196308/original/file-20171124-21801-qcc5qi.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/196308/original/file-20171124-21801-qcc5qi.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/196308/original/file-20171124-21801-qcc5qi.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/196308/original/file-20171124-21801-qcc5qi.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/196308/original/file-20171124-21801-qcc5qi.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/196308/original/file-20171124-21801-qcc5qi.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/196308/original/file-20171124-21801-qcc5qi.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/196308/original/file-20171124-21801-qcc5qi.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">Well-timed actions in plants – like the tamarind tree’s closing leaves noticed by Androsthenes millennia ago – could eventually help us design more precise medicines.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/young-tamarind-leaves-blur-background-481065826">oraphan_nan/Shutterstock.com</a></span>
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<h2>The clock as healer and helper</h2>
<p>The ability to integrate time cues with development and responses to environmental assaults is an evolutionary adaptation. Plants have taught biologists much about circadian rhythms and their role in modulating everything from development to defense.</p>
<p>Clock research has opened an opportunity to apply this knowledge to other systems, including humans. How can we modify the daily cycling of certain defense features to enhance immunity without causing developmental stress? What times of day are we most susceptible to certain pathogens? What are the most invasive times of day for various pathogens and pests?</p>
<p>Answers to questions like these will help unravel host-pathogen/pest interactions, not just in plants but also in people. Ultimately, this knowledge could contribute to the design of precision medicines that are tailored to boost timely defense in individual people to fight against various pathogens and pests. In addition, our understanding of plant disease resistance will aid agricultural control of pathogens and pests, mitigating the global challenge of crop loss.</p>
<p>Ongoing research continues to reveal how the influence of circadian rhythms extends as boundlessly as the sun’s rays.</p><img src="https://counter.theconversation.com/content/84024/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Hua Lu receives funding from National Science Foundation. </span></em></p><p class="fine-print"><em><span>Linda Wiratan receives funding from the UMBC Undergraduate Research Award.</span></em></p>Precisely calibrated timekeepers are found in organisms from all domains of life. Biologists are studying how they influence plant/pathogen interactions – what they learn could lead to human medicines.Hua Lu, Associate Professor of Biological Sciences, University of Maryland, Baltimore CountyLinda Wiratan, B.S. Student of Biochemistry and Molecular Biology, University of Maryland, Baltimore CountyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/831462017-10-24T02:58:28Z2017-10-24T02:58:28ZWhy we should test everyone’s genes to predict disease<figure><img src="https://images.theconversation.com/files/189942/original/file-20171012-31375-rl66b8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">If we could test the genome of all Australians we could better target preventive health campaigns. </span> <span class="attribution"><span class="source">from www.shutterstock.com</span></span></figcaption></figure><p>If you could take a test that would reveal the diseases you and your family might be more likely to get, would you want to do it? </p>
<p>Rapid developments in gene testing technologies have sparked debate about whether healthy Australians should undergo genetic testing.</p>
<h2>A bit about genetic testing</h2>
<p>First we have to understand the difference between the genetic tests we’re talking about. There are three key applications of genetic tests and they’re often confused.</p>
<p>The first application is a diagnostic test – where someone is ill and we use a genetic test to try to find out what’s wrong with them. </p>
<p>The second type is when a family member has a genetic disease and you want to know if you carry the same mutation that made them ill (predictive test).</p>
<p>The third type of genetic test is for genetic “risk prediction”. This can be used on anyone, in the absence of illness, to find out whether they carry genes that could lead to illness later.</p>
<p>The first two types are typically available for a small number of diseases and each test is for a faulty copy of a single gene. Most of these <a href="https://www.rarevoices.org.au/page/15/what-is-a-rare-disease">diseases are very rare</a> and many start in childhood. For diseases where diagnostic tests are available these are valuable to confirm diagnosis. </p>
<p>Predictive tests are worth conducting when they could lead to direct action to avoid disease (for example, removing breast tissue in the presence of a faulty copy of the <a href="https://www.cancer.gov/about-cancer/causes-prevention/genetics/brca-fact-sheet">BRCA1 gene</a>).</p>
<p>Diagnostic and predictive genetic tests for some very rare diseases have been available for decades. These tests could have implications for coverage and cost of <a href="https://theconversation.com/australians-can-be-denied-life-insurance-based-on-genetic-test-results-and-there-is-little-protection-81335">health and life insurance</a>.</p>
<h2>The case for testing the healthy</h2>
<p>Genetic tests that predict your risk for more common diseases may soon become readily available in the healthcare industry. These could help doctors diagnose disease, and could prompt lifestyle changes in patients in the same way a cholesterol test serves as a risk predictor for heart disease. </p>
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Read more:
<a href="https://theconversation.com/genetic-testing-isnt-a-crystal-ball-for-your-health-66906">Genetic testing isn't a crystal ball for your health</a>
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<p>Obtaining the DNA blueprint for an individual is cheap, costing no more than A$50 per person. </p>
<p>The results from large-scale disease studies are then applied to this blueprint and we can estimate a person’s genetic risk for many common diseases. Despite inaccuracy in the genetic risk predictor for any one individual, these predictors can be informative at a group level. This is where genetic risk prediction becomes very attractive.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/190336/original/file-20171016-27705-1o0zp47.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/190336/original/file-20171016-27705-1o0zp47.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/190336/original/file-20171016-27705-1o0zp47.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=338&fit=crop&dpr=1 600w, https://images.theconversation.com/files/190336/original/file-20171016-27705-1o0zp47.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=338&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/190336/original/file-20171016-27705-1o0zp47.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=338&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/190336/original/file-20171016-27705-1o0zp47.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=425&fit=crop&dpr=1 754w, https://images.theconversation.com/files/190336/original/file-20171016-27705-1o0zp47.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=425&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/190336/original/file-20171016-27705-1o0zp47.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=425&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">If we knew from their genome who was at risk of what disease, we could target campaigns and interventions.</span>
<span class="attribution"><span class="source">from www.shutterstock.com</span></span>
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</figure>
<p>Imagine we have the genetic blueprint for all Australians. We could then stratify people into high-risk versus low-risk groups for numerous common diseases. Disease prevention programs such as mass screening for <a href="http://www.cancerscreening.gov.au/internet/screening/publishing.nsf/Content/breast-screening-1">breast cancer</a> and <a href="http://www.cancerscreening.gov.au/internet/screening/publishing.nsf/Content/bowel-screening-1">bowel cancer</a> are currently targeted at defined age groups, with age being the only indicator of risk. Using genetic risk prediction, these programs could be aimed at those who are at high genetic risk for the disease. </p>
<p>Imagine a disease that affects 1% of the population. Let’s say the genetic risk predictor indicates only 20% of the population is at increased genetic risk and we invite those people for clinical screening. In this scenario, still the vast majority of those screened will not get the disease. But of those who will get the disease, most are expected to have been selected for the screening program based on their genetic risk prediction test. </p>
<p>This example shows how screening only those at high genetic risk following a genetic risk prediction test will lead to more cost-effective mass screening programs and could prevent overdiagnosis and over-treatment.</p>
<p>Genetic risk prediction becomes even more useful when linked to other sources of health data – such as medical history, family medical history and lifestyle factors such as smoking. Ongoing research is expected to <a href="http://www.nejm.org/doi/full/10.1056/NEJMp1500523#t=article">improve accuracy</a> of genetic predictors for common diseases. </p>
<p>The potential for applying these predicted risks in public health programs and clinical settings is huge. This means we could base our healthcare system on prevention rather than treatment. And, when someone does fall ill, we could more accurately target their specific causes and symptoms using <a href="https://allofus.nih.gov/">precision medicine</a>.</p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/personalised-medicine-has-obvious-benefits-but-has-anyone-thought-about-the-issues-59158">Personalised medicine has obvious benefits but has anyone thought about the issues?</a>
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<h2>What needs to be addressed first?</h2>
<p>A major impediment of a genetic risk prediction test for common diseases is that it can’t be used as a diagnostic instrument because it has low accuracy. Existing tests for rare genetic diseases are straightforward and accurate because they test for a faulty copy of a single gene. The presence of a faulty copy is often conclusive.</p>
<p>In common diseases, not one but thousands of genes are involved. Each single gene has a small individual contribution to disease risk. Also, non-genetic factors, such as lifestyle habits, contribute to the risks of common diseases.</p>
<p>Predicting risk from the small individual contributions of thousands of genes in combination with non-genetic factors is much more complex. This complexity makes it impossible to predict an individual’s risk for disease with high accuracy. </p>
<p>Over the past ten years, accuracy of genetic risk predictors for common diseases has improved and further improvement is expected. But due to the complex nature of common diseases, the genetic predictor will never be entirely accurate. </p>
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<strong>
Read more:
<a href="https://theconversation.com/australians-can-be-denied-life-insurance-based-on-genetic-test-results-and-there-is-little-protection-81335">Australians can be denied life insurance based on genetic test results, and there is little protection</a>
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<p>A large number of technical and social challenges need to be addressed for smooth implementation of genetic risk prediction in the healthcare system. In particular, there are concerns about privacy and insurance. </p>
<p>And all genetic testing should come with detailed explanation to ensure people properly understand the risks facing them and can cope with them. Awareness of increased risk for developing a disease can be stressful. On the other hand, people may become proactive in trying to avoid the disease by living a healthier life to reduce their chance of getting sick. </p>
<p>Australia is not alone in facing the challenges of regulation of genetic testing. Once genetic risk prediction is implemented in one country, others will likely follow.</p><img src="https://counter.theconversation.com/content/83146/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Naomi Wray receives funding from the National Health and Medical Research Council. </span></em></p><p class="fine-print"><em><span>Anna Vinkhuyzen 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>If you could take a test that would reveal the diseases you and your family might be more likely to get, would you want to do it?Anna Vinkhuyzen, Research Fellow, Institute for Molecular Bioscience, The University of QueenslandNaomi Wray, Professor, The University of QueenslandLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/820072017-08-13T08:37:10Z2017-08-13T08:37:10ZMonitoring outcomes is key to improving mental health treatment in South Africa<figure><img src="https://images.theconversation.com/files/181430/original/file-20170808-13761-2396uy.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Precision medicine matches patients with interventions, rather than just matching treatments to illnesses.</span> <span class="attribution"><span class="source">Shutterstock</span></span></figcaption></figure><p>The traditional way of understanding medical treatment is that a doctor matches a particular treatment to a particular illness. The problem is that people with the same illness can respond differently to the same treatment. </p>
<p><a href="http://www.nejm.org/doi/full/10.1056/nejmp1500523#t=article">Precision medicine</a> – or personalised medicine – is a relatively new approach that takes account of individual differences when planning treatments. Here, doctors individualise interventions by matching patients with appropriate treatments. This entails using evidence to select the most effective intervention for a patient based on their genetic makeup, circumstances, lifestyle and collection of symptoms. </p>
<p>To do this doctors need to collect detailed information about how different patients respond to different treatments. </p>
<p>Many health related disciplines are moving towards the practice of precision medicine. For example, <a href="https://bmcpsychiatry.biomedcentral.com/articles/10.1186/s12888-017-1230-5">research</a> suggests that about 55% of people who are diagnosed with depression will respond well to antidepressant medication. In precision medicine, doctors try to understand what individual factors predict these different treatment responses. This enables doctors to make evidence based decisions about which patients with depression should be prescribed medication and which should receive other kinds of treatment. Using this approach could help patients recover quicker and can save time and resources</p>
<p>But this approach to collecting and using evidence to plan interventions is not being widely used when it comes to psychological treatments. This is particularly true in developing countries like South Africa where psychologists aren’t routinely monitoring their treatment outcomes and using evidence to improve their practice. </p>
<p>This is a serious problem. A precision approach would enable psychologists to use scarce mental health resources more efficiently, select the most appropriate treatments, and provide better care to the <a href="http://www.scielo.org.za/scielo.php?pid=S0256-95742009000500022&script=sci_arttext&tlng=pt">high number</a> of South Africans suffering from mental health problems. </p>
<p>It was in this context that we embarked on a <a href="http://journals.sagepub.com/doi/abs/10.1177/0081246317720853">project</a> to implement a routine outcome monitoring system in a community psychology clinic in the Western Cape Province of South Africa. Our results showed that it’s possible to monitor treatment outcomes as part of routine psychological care, although the tools used to achieve this need to be refined.</p>
<h2>Giving evidence-based approaches a chance</h2>
<p>So why has psychology been so slow to move towards precision medicine? </p>
<p><a href="http://journals.sagepub.com/doi/abs/10.1177/0081246317720853">Research</a> published recently in the South African Journal of Psychology highlights the fact that many psychologists are reluctant to use empirical evidence when treating individual patients. It seems that many psychologists also resist objectively monitoring how their patients respond to psychological interventions and measuring treatment outcomes. </p>
<p>Part of the problem is that many psychologists don’t believe that <a href="https://journals.co.za/content/sapsyc/42/1/EJC98673">psychological functioning</a> can be quantified. </p>
<p>It’s true that it can be difficult to measure psychological change and it’s impossible to use a single measure of treatment outcome for all patients. But there are a number of tools that have been developed that can provide useful information about how patients respond to psychotherapy. These tools are more widely used in developed countries and their use is <a href="http://psycnet.apa.org/record/2009-24214-002">advocated</a> by the American Psychiatric Association as a way of improving standards of care. But this isn’t the case in most developing countries.</p>
<p>We believe that it’s not enough for psychologists to <a href="https://journals.co.za/content/sapsyc/42/1/EJC98673">rely heavily</a> on theories which are unsupported by evidence or subjective accounts of recovery. Psychologists in South Africa have a duty to begin thinking about how they can adapt and apply tools that have been developed elsewhere to collect information about treatment outcomes. This will move the practice of psychology in South Africa closer to an evidence-based approach. </p>
<p>Based on this understanding, we implemented a treatment monitoring system at a community psychology clinic. We asked all patients at the clinic to give us regular feedback about their level of emotional and social functioning. Patients were asked to complete short questionnaires about changes in their symptoms, perceptions of their emotional well-being and changes in the quality of their relationships. We encouraged the clinicians working in the clinic to use this patient feedback to monitor patient responses and refine their treatments. </p>
<p>The goal was to see whether a system that has been used to monitor treatment outcomes in other countries, such as the US and Australia, could be usefully incorporated into routine care in a South African context. We found that it is possible to monitor treatment responses as part of routine psychological care and that the tools that currently exist could be used in South Africa. But we may still need to do some work to make sure that these tools are easily understood by patients and correctly used by psychologists. </p>
<h2>More work to be done</h2>
<p>Monitoring systems like the one we implemented normally rely on patients to self-report their symptoms and level of functioning. One of the challenges we experienced is that patients didn’t always understand what they were being asked. This meant that their responses could not always be accurately interpreted. </p>
<p>More work is clearly needed to refine the system to make it more user-friendly for patients. This will entail more than just directly translating the instruments into local languages. We need to make sure that the words and ideas used are culturally appropriate and meaningful in different South African contexts. </p>
<p>But even if the system is perfected, this will be of little value if psychologists don’t use it. In our research we found that some clinicians did not use the system consistently or correctly, even when they were trained to do so. </p>
<p>More work with practising psychologists is needed to understand their reluctance to monitor treatment outcomes as part of routine patient care. Maybe there are good reasons for their resistance. But it might also simply be that some psychologists need to make an ideological shift in the way they think about their work and the way they understand the importance of evidence-based practice.</p><img src="https://counter.theconversation.com/content/82007/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jason Bantjes receives funding from South African Medical Research Foundation.</span></em></p><p class="fine-print"><em><span>Mark Tomlinson and Xanthe Hunt 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>People with the same condition can respond differently to the same treatment. This is why personalised treatment is so important in all fields of medicine, including psychology.Jason Bantjes, Senior Lecturer in the Psychology Department, Stellenbosch UniversityMark Tomlinson, Professor in the Department of Psychology, Stellenbosch UniversityXanthe Hunt, Researcher in Psychology, Stellenbosch UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/797572017-06-22T05:24:48Z2017-06-22T05:24:48ZGene testing for the public: a way to ward off disease, or a useless worry?<figure><img src="https://images.theconversation.com/files/175076/original/file-20170621-30161-18owo4w.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">If you were destined for dementia in your 60s, but there was nothing you could do about it, would you want to know?</span> <span class="attribution"><span class="source">shutterstock.com</span></span></figcaption></figure><p>The launch in Australia of a <a href="http://www.smh.com.au/national/health/australianfirst-whole-genome-sequencing-and-health-testing-open-to-public-20170619-gwtsgm.html">genomic testing service</a> aimed at healthy people heralds a new era of individual patient care. A scan of your genome, which is the complete set of your genes, to find out if you are at risk of particular diseases, can mean you can then go on to take preventive measures against them.</p>
<p>The CEO of the Garvan Institute’s Genome.One lab, which is offering the testing, <a href="https://www.garvan.org.au/genome-one-news-australia2019s-first-whole-genome-and-health-assessment-service-to-provide-an-unprecedented-insight-into-our-current-and-future-health">said</a> it would transform the health system, making it more focused on prevention than treatment of disease.</p>
<p>Genomic testing can have tremendous benefits, as in the case of diagnosing <a href="http://www.nature.com/gim/journal/vaop/ncurrent/full/gim20161a.html">children with rare diseases</a>. When applied to the right patients, genomic testing can provide a diagnosis for <a href="http://www.nature.com/gim/journal/vaop/ncurrent/full/gim20161a.html">more than half</a> of patients with unusual symptoms. And the cost of this to the health system is much lower than for traditional diagnostic tests.</p>
<p>Certainly that all sounds like a good thing, but genomic testing is not yet the precision diagnostic and treatment tool we hope it will one day be. And all genetic knowledge is not necessarily helpful. As with any medical intervention, genomic testing carries risks as well as benefits.</p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/175077/original/file-20170621-14473-18glw29.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/175077/original/file-20170621-14473-18glw29.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/175077/original/file-20170621-14473-18glw29.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=600&fit=crop&dpr=1 600w, https://images.theconversation.com/files/175077/original/file-20170621-14473-18glw29.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=600&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/175077/original/file-20170621-14473-18glw29.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=600&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/175077/original/file-20170621-14473-18glw29.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=754&fit=crop&dpr=1 754w, https://images.theconversation.com/files/175077/original/file-20170621-14473-18glw29.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=754&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/175077/original/file-20170621-14473-18glw29.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=754&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">Genomic testing scans all your 23,000 genes at once.</span>
<span class="attribution"><span class="source">from shutterstock.com</span></span>
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<h2>Why genomic testing?</h2>
<p>Genomic testing takes advantage of recent advances in our knowledge of genetic causes of disease, as well as technology. It’s a test of all 23,000 genes in the body at once. </p>
<p>The success of genomic testing in diagnosing rare disorders has raised the question of whether these tests should be performed in healthy people before they become sick. The potential benefits of testing healthy people are obvious, especially when it comes to conditions that have a proven treatment or prevention.</p>
<p>Cancer is a good example of where genomic testing can save lives. A person found to carry a genetic predisposition to bowel cancer can choose to have regular colonoscopies, which can detect and remove pre-cancerous growths before they cause harm. </p>
<p>And because genetic disorders run in families, potential health benefits can extend to other family members who may have the same genetic predisposition.</p>
<p>The ultimate goal of genomic testing, as part of personalised medicine, is that it will be available to everyone, allowing each person’s health care to be tailored to their individual genetic make-up. In the future, this “lifetime health resource” <a href="https://ses.library.usyd.edu.au//bitstream/2123/15602/1/genomic-testing-as-a-lifetime-pdf-2016.pdf">promises to improve health care</a> from conception to death.</p>
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<p><strong><em>Further reading: <a href="https://theconversation.com/how-cancer-doctors-use-personalised-medicine-to-target-variations-unique-to-each-tumour-47349?sr=1">How cancer doctors use personalised medicine to target variations unique to each tumour</a></em></strong></p>
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<h2>Are we ready for this?</h2>
<p>A considerable challenge of genomic testing is the extraordinary complexity of each person’s genome. To try to interpret a single human genome is to grapple with literally millions of genetic variants, or points where the person’s genetic code differs from the average person’s.</p>
<p>Perhaps a handful of these variants will cause disease, but the rest will most likely be harmless. Determining which is which is far from straightforward.</p>
<p>Another problem is that even when specific genetic variants are judged to be harmful, the benefits of knowing this information are not always as clear cut as in the case of bowel cancer. It is an unfortunate reality that most disorders detectable by genomic testing have <a href="https://www.ncbi.nlm.nih.gov/books/NBK56184/">no proven treatment</a> or means of prevention.</p>
<p>For instance, particular gene variants may put you at risk of developing dementia in your 60s. But if there was nothing you could do to prevent it, would you want to know?</p>
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<p><em><strong>Further reading: <a href="https://theconversation.com/genetic-testing-isnt-a-crystal-ball-for-your-health-66906?sr=1">Genetic testing isn’t a crystal ball for your health</a></strong></em></p>
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<p>Even when treatments are available, the benefits of knowing you have a certain genetic predisposition may not outweigh the disadvantages. </p>
<p>Consider that genomic testing finds you carry a predisposition to sudden heart death, <a href="https://www.betterhealth.vic.gov.au/health/conditionsandtreatments/long-qt-syndrome">such as Long QT syndrome</a>. This is an outcome you would certainly wish to avoid. But what if knowing this information caused you to worry more, and the treatment required you to give up sport and take a medication that caused you to feel lethargic every day? </p>
<p>And what if, in the absence of symptoms, your risk of actually dying was <a href="http://circgenetics.ahajournals.org/content/5/2/183.long">only slightly increased</a> compared to the general population? Would you still want to know this information, or perhaps prefer to remain ignorant?</p>
<h2>Should we get the test?</h2>
<p>The Genome.One clinic at the Garvan Institute in Sydney has addressed some of these concerns by taking a cautious approach. </p>
<p>Genetic counselling is provided before and after testing, and although the whole genome is sequenced, analysis and reporting is limited to just 1% of all genes. Most of these selected genes are associated with heart conditions and cancers, and have been chosen because these diseases are well understood, with treatment strategies available. </p>
<p>Genes that cause untreatable diseases, such as dementia, have deliberately been excluded from analysis. This strategy minimises the risk of harm that may come from the test, but the trade-off is that the likelihood of actually finding something useful is greatly diminished. In fact, <a href="http://www.smh.com.au/national/health/australianfirst-whole-genome-sequencing-and-health-testing-open-to-public-20170619-gwtsgm.html">Genome.One reportedly estimates</a> only 5-10% of people tested will receive an abnormal result; that is, one that will show them to be at risk of disease.</p>
<p>While it is hard to argue against a test that just might save your life, currently there is insufficient evidence that the benefits of genomic testing outweigh the risks. Even for those who can afford the price tag of A$6,400, there are probably more effective targets for our health-related spending. Like many years of gym membership, for example.</p><img src="https://counter.theconversation.com/content/79757/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>David Amor receives funding from the NHMRC and is an employee of the Murdoch Children's Research Institute, which provides clinical genomic testing through its subsidiary, VCGS. </span></em></p>A test of all your genes for disease risk is not yet the precision diagnostic and treatment tool we hope it will one day be.David Amor, Lorenzo and Pamela Galli Chair in Developmental Medicine, Murdoch Children's Research InstituteLicensed as Creative Commons – attribution, no derivatives.