Category Archives: Genetic Medicine

By Clare Wilson

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Plans for the National Health Service to sequence the DNA of every baby born in the UK, starting with a pilot scheme of 20,000 children, were announced by health minister Matt Hancock this week. It sounds like the UK is leading the way in high-tech healthcare but doctors are saying the idea is ethically questionable.

Babies are already tested for certain health conditions soon after birth, so it may seem as though sequencing their genome, their entire set of genes, is a simple upgrade of this routine screening, but that isnt the case.

UK babies are tested for nine carefully selected conditions, all of which can be avoided or lessened with pre-emptive treatment. For instance, the metabolic disorder phenylketonuria can cause brain damage, but this can be avoided through a low-protein diet.

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Unfortunately, most illnesses arent as simple or treatable. We are only at the beginning of our journey to understand the complexity of the human genome, and some of the information we have learned so far can create difficult dilemmas.

Take the genetic condition Huntingtons disease, which starts with mild symptoms in middle age, eventually progressing to severe disability and early death. There is no cure.

When people learn that Huntingtons is in their family, they may spend years deciding whether to take the test. Many choose not to. Parents who ask doctors to test their child are turned down, as set out in international guidelines. Deciding to learn if you have the gene responsible is such a personal choice that it must be left to the individual concerned once they turn 18.

Huntingtons is rare, but there are similar dilemmas over more common conditions such as genes that predispose people to Alzheimers disease and some types of cancer. There is currently little you can do to avoid dementia, and for women who learn they have a certain gene that increases cancer risk, the safest step is to have their breasts and ovaries removed.

Some people would rather not know about these risks before it is necessary. We have endless discussions about [the ethics of] testing children for conditions that dont manifest until later life, says Frances Elmslie of the British Society for Genetic Medicine.

Nor would it make sense to sequence children at birth then wait until they are 18 to give the results. In the intervening years, DNA sequencing is bound to become cheaper and more powerful. It would make more sense to offer it to every 18-year-old, says Martin Brunet, a family doctor in Surrey, UK.

There is a small group of children for whom genome sequencing can be useful: those with rare undiagnosed medical conditions. In one study, sequencing led to a diagnosis in a fifth of children in intensive care, and that figure is likely to improve over time. In these cases, parents can consent for their children because there is a medical benefit but that is very different to sequencing everyone out of curiosity.

A US group has begun a small trial of routine genome sequencing of healthy babies. The families are being monitored to see how they cope and to measure any harms and benefits.

No details are available about the UK plans and Hancock didnt respond to New Scientists requests for comment. But introducing sequencing for everyone is a massive step. It will require public consultation over the ethical questions not to mention on practical issues like how the data will be stored securely and the impact on doctors workloads, says Elmslie. We need to think really carefully about this.

More on these topics:

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Sequencing the genome of every UK baby would be an ethical minefield - New Scientist News

New testing at the University of Vermont Medical Center will help determine the role DNA plays in your health.

We want to improve peoples lives, said Dr. Debra Leonard, chair of Pathology and Laboratory Medicine at the University of Vermont Medical Center.

For the past year and a half, shes been working along with a team of physicians and specialists to develop Genomic DNA Testing.

It really is to integrate genetic information into routine medical care, she said.

Dr. Leonard said that information can be very helpful in improving outcomes for patients if they know their disease risk in advance. The testing will allow patients to learn about differences in their DNA that can make certain diseases more likely.

What we will be focusing on is diseases related to the heart and diseases related to cancer risk, Dr. Leonard said.

UVM Health Network is partnering with Invitae and LunaPBC on the project which will provide information on nearly 150 genes that are indicators for illnesses. The goal is to recognize if a patient is at risk for one of those diseases before they actually experience their first symptom, allowing doctors to intervene early and make informed decisions.

So we can use preventive strategies or close monitoring to catch the diseases earlier or even implement strategies to prevent the diseases, she said.

Right now, the testing is in its beginning phases. Last Friday, it was offered to the first patient, who agreed to have their blood drawn and sent out for testing, fully funded by the department. Over the next year, UVMMC is aiming to test 1,000 patients ages 18 and older.

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Genetic testing at UVMMC aims to improve patient care - Local 22/44 News

BRISBANE, Calif.--(BUSINESS WIRE)--Sangamo Therapeutics, Inc. (Nasdaq: SGMO), a genomic medicine company, announced today that is has established a new Scientific Advisory Board (SAB). The SAB comprises an eclectic group of industry and academic experts who will advise Sangamo on its current and future clinical programs and research and development strategy.

I am excited to be working with such a distinguished, diverse, and imaginative group of experts who have joined our Scientific Advisory Board to provide input into Sangamos research and clinical development strategy, with a view to helping us identify new opportunities for differentiation and innovation in the genomic medicine space, and to define and address future trends, said Adrian Woolfson, B.M., B.Ch., Ph.D., Head of Research and Development. As Sangamo continues to advance programs from our technology platforms into clinical programs, it is critical that we obtain input from individuals with diverse expertise across a broad range of relevant research and development areas."

The Sangamo SAB members are as follows:

For more information, please visit https://www.sangamo.com/about-us/leadership.

About Sangamo Therapeutics

Sangamo Therapeutics, Inc. is focused on translating ground-breaking science into genomic medicines with the potential to transform patients' lives using gene therapy, ex vivo gene-edited cell therapy, in vivo genome editing, and gene regulation. For more information about Sangamo, visit http://www.sangamo.com.

Forward-Looking Statements

This press release contains forward-looking statements regarding Sangamo's current expectations. These forward-looking statements include, without limitation, statements regarding the Company's ability to develop and commercialize product candidates to address genetic diseases with the Company's proprietary technologies and the timing of commencement or next stages of such programs and the anticipated benefits therefrom. These statements are not guarantees of future performance and are subject to certain risks, uncertainties and assumptions that are difficult to predict. Factors that could cause actual results to differ include, but are not limited to, the outcomes of clinical trials, the uncertain that members of the SAB will remain engaged with Sangamo and the uncertainties of the regulatory approval process. Actual results may differ from those projected in forward-looking statements due to risks and uncertainties that exist in Sangamo's operations and business environments. These risks and uncertainties are described more fully in Sangamo's Annual Report on Form 10-K for the year ended December 31, 2018 as filed with the Securities and Exchange Commission on March 1, 2019 and Sangamo's Quarterly Report on Form 10-Q for the quarter ended September 30, 2019 that it filed on November 6, 2019. Forward-looking statements contained in this announcement are made as of this date, and Sangamo undertakes no duty to update such information except as required under applicable law.

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Sangamo Therapeutics Announces New Scientific Advisory Board - Business Wire

[2][2] https://www.sciencedirect.com/science/article/pii/S0092867417311315?via%3Dihub

Notes to Editor:

The research findings described in this media release can be found in the scientific journal JAMA, under the title, Association of genetic variants with primary open angle glaucoma among individuals with African ancestry by The Genetics of Glaucoma in people of African Descent (GGLAD) consortium.

The authors of the paper are:

Michael A Hauser, PhD1,2,3+; R Rand Allingham, MD2,3+; Tin Aung, MD, PhD3,4+; Carly J Van Der Heide, MD5+; Kent D Taylor, PhD6,7+; Jerome I Rotter, MD6+; Shih-Hsiu J Wang, MD, PhD 8+; Pieter WM Bonnemaijer, MD9,10+; Susan E Williams, MD11+; Sadiq M Abdullahi, MD12; Khaled K Abu-Amero, PhD13; Michael G. Anderson, MD5; Stephen Akafo MD14; Mahmoud B Alhassan MD12; Ifeoma Asimadu, MD15; Radha Ayyagari, PhD16; Saydou Bakayoko, MD17,18; Prisca Biangoup Nyamsi, MD19; Donald W Bowden, PhD20; William C Bromley, MD21; Donald L Budenz, MD22; Trevor R Carmichael, MD, PhD11; Pratap Challa, MD2; Yii-Der Ida Chen, PhD6,7, Chimdi M Chuka-Okosa, MD23; Jessica N Cooke Bailey, PhD24,25; Vital Paulino Costa, MD26; Dianne A Cruz, MS27; Harvey DuBiner, MD28; John F Ervin, BA29; Robert M Feldman, MD30; Miles Flamme-Wiese, BSE5; Douglas E Gaasterland, MD31; Sarah J Garnai, BS32; Christopher A Girkin, MD33; Nouhoum Guirou, MD17,18; Xiuqing Guo, PhD6; Jonathan L Haines, PhD24,25; Christopher J Hammond, MD34; Leon Herndon, MD2; Thomas J Hoffmann, PhD35,36; Christine M Hulette, MD8; Abba Hydara, MD37; Robert P Igo, Jr, PhD24; Eric Jorgenson, PhD38; Joyce Kabwe, MD39; Ngoy Janvier Kilangalanga, MD39; Nkiru Kizor-Akaraiwe, MD 15,40; Rachel W Kuchtey, MD, PhD41; Hasnaa Lamari, MD42; Zheng Li, MD, PhD43, Jeffrey M Liebmann, MD44; Yutao Liu, PhD45,46,47; Ruth JF Loos, PhD48,49; Monica B Melo, PhD50; Sayoko E Moroi, MD, PhD32; Joseph M Msosa, MD51; Robert F Mullins, PhD5; Girish Nadkarni, MD48,52; Abdoulaye Napo, MD17,18; Maggie C Y Ng, PhD20; Hugo Freire Nunes, PhD50; Ebenezer Obeng-Nyarkoh, MA21; Anthony Okeke, MD53; Suhanya Okeke, MD15,40; Olusegun Olaniyi, MD12; Olusola Olawoye, MD54; Mariana Borges Oliveira, MD50; Louise R Pasquale, MD55,56; Rodolfo A. Perez-Grossmann, MD57; Margaret A Pericak-Vance, PhD58; Xue Qin, PhD59; Michele Ramsay, PhD60; Serge Resnikoff, MD, PhD61,62; Julia E Richards, PhD32,63; Rui Barroso Schimiti, MD64; Kar Seng Sim, MS43; William E Sponsel, MD65,66; Paulo Vinicius Svidnicki, PhD50; Alberta AHJ Thiadens; MD, PhD9; Nkechinyere J Uche, MD23,40; Cornelia M van Duijn, PhD9; Jos Paulo Cabral de Vasconcellos, MD, PhD 26; Janey L Wiggs, MD, PhD 67,68; Linda M Zangwill, PhD16; Neil Risch, PhD35,36,38+; Dan Milea, MD, PhD3+,; Adeyinka Ashaye, MD54+,; Caroline CW Klaver, MD, PhD 9,69+,; Robert N Weinreb, MD16+,; Allison E Ashley Koch, PhD1+,; John H Fingert, MD, PhD 5+,; & Chiea Chuen Khor, MD, PhD 3,43+

1Department of Medicine, Duke University, Durham, NC, 2Department of Ophthalmology, Duke University, Durham, NC, 3Singapore Eye Research Institute, Singapore, 4Singapore National Eye Center, Singapore and Duke-NUS Medical School, Singapore, 5Department of Ophthalmology and Visual Sciences, Carver College of Medicine, University of Iowa, Iowa City, IA, 6The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, 7Department of Pediatrics, Harbor-University of California, Los Angeles Medical Center, Torrance, CA, 8Department of Pathology, Duke University, Durham, NC, 9Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands, 10Rotterdam Eye Hospital, Rotterdam, The Netherlands, 11Division of Ophthalmology, Department of Neurosciences, University of the Witwatersrand, Johannesburg, South Africa, 12National Eye Centre, Kaduna, Nigeria, 13Department of Ophthalmology, College of Medicine, King Saud University, Riyadh 11411, Saudi Arabia, 14Unit of Ophthalmology, Department of Surgery, University of Ghana Medical School, Accra, Ghana, 15Department of Ophthalmology, ESUT Teaching Hospital Parklane, Enugu, Nigeria, 16Department of Ophthalmology, Hamilton Glaucoma Center, Shiley Eye Institute, University of California, San Diego, La Jolla, CA, 17Institut d'Ophtalmologie Tropicale de l'Afrique, Bamako, Mali, 18Universit des sciences des techniques et des technologies de Bamako, Bamako, Mali, 19Service spcialis d'ophtalmologie, Hpital Militaire de Rgion No1 de Yaound, Yaound, Cameroun, 20Department of Biochemistry, Center for Diabetes Research, Wake Forest School of Medicine, Winston-Salem, NC, 21Center for Human Genetics, Bar Harbor, ME, 22Department of Ophthalmology, University of North Carolina, Chapel Hill, NC, 23University of Nigeria Teaching Hospital, Ituku Ozalla, Enugu, Nigeria, 24Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, 25Institute for Computational Biology, Case Western Reserve University, Cleveland, OH, 26Department of Ophthalmology, Faculty of Medical Sciences, University of Campinas, Campinas, Brazil, 27Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, 28Clayton Eye Care Center Management, Inc., Marrow, GA, 29Kathleen Price Bryan Brain Bank and Biorepository, Department of Neurology, Duke University, Durham, NC, 30Ruiz Department of Ophthalmology & Visual Science, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, 31The Emmes Corporation, Rockville, MD, 32Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI, 33Department of Ophthalmology and Visual Sciences, University of Alabama Birmingham, Birmingham, AL, 34Section of Academic Ophthalmology, School of Life Course Sciences, FoLSM, King's College London, London, United Kingdom, 35Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, 36Institute for Human Genetics, University of California San Francisco, San Francisco, CA, 37Sheikh Zayed Regional Eye Care Centre, Kanifing, The Gambia, 38Kaiser Permanente Northern California (KPNC), Division of Research, Oakland, CA, 39Department of Ophthalmology, Saint Joseph Hospital, Kinshasa, Limete, Democratic Republic of the Congo, 40The Eye Specialists Hospital, Enugu, Nigeria, 41Department of Ophthalmology and Visual Sciences, Vanderbilt University Medical Center, Nashville, TN, 42Clinique Spcialise en Ophtalmologie Mohammedia, Mohammedia, Morocco, 43Genome Institute of Singapore, Singapore, 44Bernard and Shirlee Brown Glaucoma Research Laboratory, Harkness Eye Institute, Columbia University Medical Center, New York, NY, 45Cellular Biology and Anatomy, Augusta University, Augusta, GA, 46James & Jean Culver Vision Discovery Institute, Augusta University, Augusta, GA, 47Center for Biotechnology & Genomic Medicine, Augusta University, Augusta, GA, 48The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, 49The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 50Center for Molecular Biology and Genetic Engineering, University of Campinas, Campinas, Brazil, 51Lions Sight-First Eye Hospital, Kamuzu Central Hospital, Lilongwe, Malawi, 52Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, 53Nigerian Navy Reference Hospital, Ojo, Lagos, Nigeria, 54Department of Ophthalmology, University of Ibadan, Ibadan, Nigeria, 55Icahn School of Medicine at Mount Sinai, Department of Ophthalmology, New York, NY, 56Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, 57Instituto de Glaucoma y Catarata, Lima, Peru, 58John P Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, 59Duke Molecular Physiology Institute, Duke University, Durham, NC, 60Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa, 61Brien Holden Vision Institute, Sydney, Australia, 62School of Optometry and Vision Science, University of New South Wales, Sydney, Australia, 63Department of Epidemiology, University of Michigan, Ann Arbor, MI, 64Hoftalon Hospital, Londrina, Brazil, 65San Antonio Eye Health, San Antonio, TX, 66Eyes of Africa, Child Legacy International (CLI) Hospital, Msundwe, Malawi, 67Harvard University Medical School, 68Massachusetts Eye and Ear Hospital, Boston, MA, 69Department of Ophthalmology, Radboud University Medical Center, Nijmegen, The Netherlands

+ Drs. Hauser, Allingham, Aung, Van Der Heide, Taylor, Rotter, Wang, Bonnemaijer, Williams, Risch, Milea, Ashaye, Klaver, Weinreb, Ashley Koch, Fingert, and Khor contributed to the work equally.

Author contributions: Drs Hauser (mike.hauser@duke.edu) and Khor (khorcc@gis.a-star.edu.sg) had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis

For media queries and clarifications, please contact:

Lyn LaiOfficer, Office of Corporate CommunicationsGenome Institute of Singapore, A*STARTel: +65 6808 8258Email: laiy@gis.a-star.edu.sg

Ravi ChandranCorporate CommunicationsSingapore National Eye CentreTel: +65 8121 8569Email: ravi.chandran@snec.com.sg

About A*STARs Genome Institute of Singapore (GIS)

The Genome Institute of Singapore (GIS) is an institute of the Agency for Science, Technology and Research (A*STAR). It has a global vision that seeks to use genomic sciences to achieve extraordinary improvements in human health and public prosperity. Established in 2000 as a centre for genomic discovery, the GIS will pursue the integration of technology, genetics and biology towards academic, economic and societal impact.

The key research areas at the GIS include Human Genetics, Infectious Diseases, Cancer Therapeutics and Stratified Oncology, Stem Cell and Regenerative Biology, Cancer Stem Cell Biology, Computational and Systems Biology, and Translational Research.

The genomics infrastructure at the GIS is utilised to train new scientific talent, to function as a bridge for academic and industrial research, and to explore scientific questions of high impact.

For more information about GIS, please visit http://www.a-star.edu.sg/gis.

About the Agency for Science, Technology and Research (A*STAR)

The Agency for Science, Technology and Research (A*STAR) is Singapore's lead public sector agency that spearheads economic oriented research to advance scientific discovery and develop innovative technology. Through open innovation, we collaborate with our partners in both the public and private sectors to benefit society.

As a Science and Technology Organisation, A*STAR bridges the gap between academia and industry. Our research creates economic growth and jobs for Singapore, and enhances lives by contributing to societal benefits such as improving outcomes in healthcare, urban living, and sustainability.

We play a key role in nurturing and developing a diversity of talent and leaders in our Agency and research entities, the wider research community and industry. A*STARs R&D activities span biomedical sciences and physical sciences and engineering, with research entities primarily located in Biopolis and Fusionopolis. For ongoing news, visit http://www.a-star.edu.sg/.

About Singapore Eye Research Institute (SERI)

Established in 1997, SERI is Singapores national research institute for ophthalmic and vision research. SERIs mission is to conduct high impact eye research with the aim to prevent blindness, low vision and major eye diseases common to Singaporeans and Asians. SERI has grown from a founding team of five in 1997 to a faculty of 220, encompassing clinician scientists, scientists, research fellows, PhD students and support staff. This makes SERI one of the largest research institutes in Singapore and the largest eye research institute in Asia-Pacific. In addition, SERI has over 250 adjunct faculties from various eye departments, biomedical institutes and tertiary centres in Singapore.

SERI has amassed an impressive array of more than 3,585 scientific papers as of July 2019, and has secured more than $314 million in external peer-reviewed competitive grants. To date, SERIs faculty has been awarded more than 568 national and international prizes and filed more than 130 patents. Serving as the research institute of the Singapore National Eye Centre and affiliated to the Duke-NUS Medical School, National University of Singapore, SERI undertakes vision research in collaboration with local clinical ophthalmic centres and biomedical research institutions, as well as major eye centres and research institutes throughout the world. Today, SERI is recognized as a pioneering centre for high quality eye research in Asia, with breakthrough discoveries that has translated to significant paradigm shift in eye care delivery. For more information, visit http://www.seri.com.sg

About Singapore National Eye Centre (SNEC)

Singapore National Eye Centre was incorporated in 1989 and commenced operations in 1990. It is the designated national centre within the public sector healthcare network, and spearheads and coordinates the provision of specialised ophthalmological services with emphasis on quality education and research. Since its opening in 1990, SNEC has achieved rapid growth and currently manages an annual workload of 400,000 outpatient visits and 40,000 major eye surgeries and lasers.

Ten subspecialties in Cataract and Comprehensive Ophthalmology, Corneal and External Eye Disease, Glaucoma, Neuro-Ophthalmology, Oculoplastics, Pediatric Ophthalmology and Strabismus, Refractive Surgery, Ocular Inflammation and Immunology, Medical Retina and Surgical Retina have been established to provide a full range of eye treatments from comprehensive to tertiary levels for the entire spectrum of eye conditions.

SNEC was accorded the Excellence for Singapore Award in 2003 for achieving excellence in the area of Ophthalmology, thrusting Singapore into international prominence. In 2006, SNEC received the first Minister for Health Award for public health. Clinician scientists from Singapore National Eye Centre and Singapore Eye Research Institute were awarded the prestigious President's Science and Technology Award in 2009, 2010 and 2014 for their outstanding contributions in translational, clinical and epidemiological research in cornea, retina and glaucoma. Visit us at http://www.snec.com.sg.

Excerpt from:
Researchers Find Link Between Eye Disease And Degeneration Of The Brain - BioSpace

Summary

A study reports on a new way to determine who is most likely to benefit from immunotherapy. It may help explain why immunotherapy works differently in people around the world.

Since 2011, the immunotherapy drugs called checkpoint inhibitors have become an increasingly important treatment for certain cancers. This is especially true for people with melanoma and lung cancer.

Early on, investigators observed that these drugs are extremely effective for some people, even eliminating their cancer entirely. Unfortunately, they dont work at all for many others. Considerable research has tried to understand why this is the case and exactly how these drugs work.

Checkpoint inhibitors work by releasing a natural brake on your immune system so that immune cells called T cells recognize and attack tumors.

Memorial Sloan Kettering physician-scientist Timothy Chan has focused on these efforts. He is one of the corresponding authors of a study published November 7, in Nature Medicine that reports a new way to determine who is most likely to benefit from immunotherapy. The findings may help explain why immunotherapy works differently in people around the world.

Our results help solve part of the mystery of why there is such a large variation in the effectiveness of immune checkpoint drugs, says Dr. Chan, who leads the Immunogenomics and Precision Oncology Platform at MSK. Its important that future clinical trials of immune checkpoint drugs take our discovery into account. This is especially important for international phase III trials.

For decades, the human leukocyte antigen (HLA) genes have been known to govern how the immune system responds to foreign substances in the body. Over thousands of generations, as early humans migrated out of Africa and around the planet, they evolved variations in their HLA genes. These changes protected them from infectious organisms that were found in different parts of the world.

The classic battle between pathogens and the human immune system plays out in the HLA genes, Dr. Chan says. A 2017 study from Dr. Chan was the first to show that HLA genes are important for the bodys ability to see cancer after immunotherapy as well. That study reported that people who had a greater number of different copies, or alleles, in their HLA-1 genes responded better to immunotherapy compared with those whose HLA-1 genes had fewer alleles. The new study builds on this previous work.

To quantify how efficient the immune system is at detecting cancer, the researchers looked at the HLA genes from more than 1,500 people who had received immune checkpoint drugs as part of clinical trials at MSK and other hospitals. Most of those included in the study had melanoma or non-small cell lung cancer, but other kinds of cancer were also represented.

Study Uncovers Genetic Reasons Why Some People Respond to Immunotherapy Better than Others

Immunotherapy drugs called checkpoint inhibitors have been a game changer for some people with cancer. But for most patients, these drugs have been disappointing. Researchers are trying to figure out why.

People inherit one copy of HLA-1 from each parent. For each person analyzed, the team found that the more molecularly diverse, or different from each other, the two copies of each of their HLA-1 genes were, the more likely someone was to respond to treatment and survive their cancer. The investigators developed a novel way to measure this difference, which they call HLA evolutionary diversity (HED).

Dr. Chans co-corresponding author on the Nature Medicine paper, Tobias Lenz of the Max Planck Institute for Evolutionary Biology in Germany, is an expert in the evolution of the human immune system and the HLA genes. Research fellow Diego Chowell and graduate student Chirag Krishna from Dr. Chans lab and graduate student Federica Pierini from Dr. Lenzs lab were the co-first authors.

Dr. Chan has also looked at other factors that make immune checkpoint drugs more effective. In 2014, he led the first studies finding that patients who responded to these drugs tended to have a large number of gene mutations in their tumors. This is known as having a high tumor mutational burden (TMB). When tumors have a greater number of mutations, it is more likely that they will produce proteins that the immune system hasnt seen before.

For checkpoint inhibitor drugs to be effective, the immune system needs to be able to recognize cancer cells as foreign, Dr. Chan says. High TMB and diverse HLA genes are two sides of the same coin. Both make it more likely that the immune system will see the cancer.

The researchers note in their study that high TMB and high HED are independent of each other, but the combined outcome of the two led to benefits from immunotherapy drugs that were greater than either of these effects on their own. These are the yin and yang of T cellbased immune checkpoint treatment, Dr. Chan says. High TMB is less useful if a person is unable to present the mutations to the immune system. Having a high HED allows that to happen.

Our results help solve part of the mystery of why there is such a large variation in the effectiveness of immune checkpoint drugs.

Recent immunotherapy clinical trials have begun to include TMB in their evaluation of how effective checkpoint inhibitors are, Dr. Chan notes. But among different trials, there is great variation in the role that TMB plays. No one has been able to figure out whats going on, he says. It turns out, we should also be looking at HLA diversity. This finding may account for the unexplained variation thats seen in the role of TMB in immunotherapy trials.

He adds that it may also account for the different response rates that have been observed in different parts of the world. HED can vary dramatically depending on where someone lives.

The investigators are now working to develop a standardized way to report HED, so that it can be incorporated into future clinical studies. Dr. Chans team is in the process of evaluating HED with industry partners using global phase III trial data. They hope that this measure can eventually become a regular part of cancer diagnosis and be used to match people with cancer with the most personalized treatments.

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Genetic Variations Help Explain Why Immunotherapy Works Differently in Different People - On Cancer - Memorial Sloan Kettering

Somewhere along the road from sickness to health, the American medical system took a wrong turna big one.

The cost of care in our country is sky-high, yet our population health outcomes tend to be worse than those of other developed countries (many of which have universal health care). Major surgeries, treatments for long-term illnesses like cancer, and medical attention for catastrophic injuries are so expensive that people can lose their homes or be forced to declare bankruptcy. Even a routine visit to a general practitioner can cost hundreds of dollars. Yet Americans have some of the highest rates of heart disease, diabetes, and obesity in the world.

How did we get here?

In a talk at Singularity Universitys Exponential Medicine summit this week in San Diego, Dr. Jordan Shlain shared his thoughts on that question, as well as a framework for moving American healthcare forward. The first step, he believes, is a new Hippocratic oath, one thats been updated for our high-tech age.

It was the fifth century BC when Hippocrates put forth the idea that physicians should try to help people and do no harm (a pretty intuitive concept, one would think), among other ethical standards. The Hippocratic oath was born, and over time its been modified to reflect shifts in medicine and society. But the field of medicine has changed even more than the oath has, and Shlain believes its time for another overhaul.

He pointed to the beginning of early modern medicine as pivotal to the field. As new technologies came along that had potential to treat people more effectively, everyone wanted access to those technologies, so someone had to start manufacturing themand the incentive to do so was a profit.

When X-rays and penicillin were invented, we could see things wed never seen before and treat things wed never been able to treat before, Shlain said. Someone had to make X-ray machines and someone had to form a pharmaceutical company. But the convergence of medicine and business fed mounting costs, conflicts of interest, bureaucracy, and a focus on profits over patients.

Medical technology companies and pharmaceutical companies are now massive and complex, as are the medical and regulatory systems. Theres a lot standing between physicians and patients, Shlain said. It leads us to reactive medicine, and theres physician burnout.

The root of this problem, he believes, is that a corporate oath has superseded the Hippocratic oath in healthcare. The corporate oath says to increase shareholder value, generate profits, and constantly grow margins. But they dont know the outcomes on the other side, Shlain said. Exhibit A? The opioid crisis.

Since 1970, the costs of medications and medical devices have only gone upand so have corporate revenues. went up, cost of devices went up. But despite spending all this money and having all this expensive technology and medications, were not doing too well, Shlain said, pointing to a graph that shows life expectancy in the US falling since 2014. We need to differentiate between consumers and patients.

Shlains new oath consists of nine different statements.

1. I shall endeavor to understand what matters to the patient and actively engage them in shared decision making. I do not own the patient, nor their data. I am a trusted custodian.

Shlain pointed out that rather than asking patients What matters to you? physicians ask, Whats the matter with you? But to get the right answer, it should be a combination, and not just between doctors and patients, but in every interaction in the healthcare system.

2. I shall focus on good patient care and experience to make my profits. If I cant do well by doing good and prove it, I dont belong in the field of the healing arts.

We need to have some version of transparency for our outcomes, Shlain said.

3. I shall be transparent and interoperable. I shall allow my outcomes to be peer-reviewed.

Silicon Valley has gotten better at embracing a culture of learning from failure and even encouraging failure as a path to eventual advancement, but the medical field hasnt done the sameand perhaps rightfully so, since failure can mean a life lost. However, Shlain added, a byproduct of failure is almost always some sort of lesson.

4. I shall enable my patients the opportunity to opt in and opt out of all data sharing with non-essential medical providers at every instance.

Data privacy should be respected both as a path to trust and as a basic patient right.

5. I shall endeavor to change the language I use to make healthcare more understandable; less Latin, less paternal language; I shall cease using acronyms.

I would rename type two diabetes the over-consumption of processed food disease, because thats what it is, Shlain said. You dont get it, you participate in its process. But you didnt know it, because the language obfuscates that. So we really need to dig into language here, because language does tie to the metaphors we live by.

6. I shall make all decisions as though the patient was in the room with me and I had to justify my decision to them.

7. I shall make technology, including artificial intelligence algorithms that assist clinicians in medical decision making, peer-reviewable.

Everyone has proprietary technology and were supposed to use it despite not knowing how it works, Shlain said. Its in the interest of both practitioners and patients for this to change.

8. I believe that health is affected by social determinants. I shall incorporate them into my strategy.

Someones zip code can tell you more about their health than their genetic code, Shlain said. We need to focus on community.

9. I shall deputize everyone in my organization to surface any violations of this oath without penalty. I shall use open-source artificial intelligence as the transparency tool to monitor this oath.

Shlain pointed out that feedback loops in big corporations often arent productive, because people worry about losing their jobs. We need to create some mechanism of a feedback loop to ensure that this happens, he said.

This new oath isnt just for clinicians, Shlain emphasized. Its for everyone who touches the healthcare system in any way. That includes pharmaceutical companies, device manufacturers, medical suppliers, hospitals, and so on.

Given how fast new technologies are changing the healthcare landscape, we may need a totally new oath in ten years; what happens when robots are performing surgery, AI systems have taken over diagnosis, and gene editing can cure almost any congenital disease? Well need to continuously stay aware of how doctors roles are evolving, and update the ethical codes they practice by accordingly.

What we need is a culture of care, at every level, Shlain said. In order to change our paradigm, we need to have a set of principles that get us there.

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Why Medicine Needs a New Hippocratic Oathand What It Should Be - Singularity Hub