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Category Archives: Transhuman News

SNIPR BIOME Initiates First-in-Human Clinical Trial with SNIPR001 – PR Newswire

Posted: April 20, 2022 at 11:10 am

COPENHAGEN, Denmark, April 20, 2022 /PRNewswire/ --SNIPR BIOME ApS, a leading CRISPR and microbiome gene therapy biotechnology company, today announced dosing of the first human subjects in its phase 1 clinical trial with SNIPR001, an orally administered CRISPR-based therapeutic.

The purpose of the study is to investigate safety and tolerability of SNIPR001 in healthy volunteers and to evaluate the effect of SNIPR001 on reducing E. coli colonization in the gut. The study plans to enroll 36 healthy volunteers for multiple ascending dosing of SNIPR001 (NCT05277350). SNIPR001 has been granted Fast-Track designation by the FDA and is being developed in collaboration with the US non-profit organization CARB-X.

With the initiation of the First-in-Human study SNIPR BIOME becomes a clinical stage company. The experimental CRISPR therapeutic, SNIPR001, is designed to selectively target and eradicate E. coli in the gut, thus preventing translocation of these bacteria to the bloodstream, in a high-risk population of hematological cancer patients at risk for neutropenia. This precision approach could transform the wayE. coliinfections are prevented and treated, especially in the cancer ward. Today, there are no approved therapies for prophylactic therapy in this setting.

"Today, is a very special moment for SNIPR BIOME. For the first time ever, we are dosing a CRISPR-drug candidate in humans. Getting to this point is a major achievement and I am extremely proud of the whole SNIPR BIOME team, our collaborators, and advisors and especially our skilled CMC partner, Jafral, for their relentless effort in successfully bringing our first CRISPR-medicine into humans. However, this is only the beginning, and we truly believe that SNIPR001 could have the potential to help hematological cancer patients at increased risk of life-threatening bloodstream infections caused by multidrug resistant E. coli", says Dr. Christian Grndahl, Co-founder & CEO.

Dr. Milan Zdravkovic, Chief Medical Officer and Head of R&D at SNIPR Biome, comments: "We are excited about having brought our first asset into humans and expect top line results around year-end. We are in parallel pursuing our pipeline of CRISPR-medicines of exciting targets within oncology, immunology and cardio-metabolism, and have an ambition of selecting the next molecule from our pipeline to move into IND enabling studies also by the end of this year"

For more information, please contact:

Christian Grndahl, Dr.Med, Co-founder & CEOE-mail: [emailprotected] Mobile: +45 20202747www.sniprbiome.com

Please follow us on LinkedIn & Twitter: @sniprbiome

About SNIPR BIOME

SNIPR BIOME is a leadingCRISPR,and microbiome biotech company incorporated in Copenhagen, Denmark. SNIPR BIOME is engaged in the discovery and development of CRISPR/Cas-based medicines deploying its proprietary and patent-protected CRISPR/Casplatform. The company applies its CRISPR technologies to selectively target microbial pathogens and remodel the microbiome to address important unmet medical needs. SNIPR BIOME is pioneering a novel use of CRISPR/Castechnology to selectively and precisely eradicate target bacteria, while leaving the rest of the patient's microbial community intact. SNIPR BIOME was recently awarded a several million-dollar grant by CARB-X for CRISPR-based treatment ofhaematologicalcancer patients at risk of neutropenic fever and life-threating infections (SNIPR001). In addition, SNIPR BIOME and The University of Texas MD Anderson CancerCenterhas a strategic collaboration agreement to advance new CRISPR-based microbiome therapeutics to reduce immune-related adverse events (irAE) in patients being treated with combined immune checkpoint inhibitors. The company also develops proprietary technologies forin situproduction of therapeutics in the human microbiome. SNIPR BIOME and Novo Nordisk recently entered into a research agreement on an undisclosed target to evaluate this technology for gene therapy of the microbiome i.e.,in situproduction of therapeutics in the human microbiome. SNIPR BIOME holds an extensive portfolio of granted patents protecting CRISPR modification of microbiota as an adjunct to cancer therapy, vaccine therapy and other immunotherapies. In March 2019, SNIPR BIOME closed a $50 million Series A financing byLundbeckfondenEmerge (Copenhagen), Life Sciences Partners (Amsterdam), North-East Family Office (Copenhagen) and Wellington Partners (Munich).

For more details, please visit:www.sniprbiome.comand follow us on LinkedIn & Twitter: @sniprbiome

About CARB-X

CARB-X (Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator) is a global non-profit partnership dedicated to supporting early development antibacterial R&D to address the rising threat of drug-resistant bacteria. CARB-X is led by Boston University and funding is provided by the Biomedical Advanced Research and Development Authority (BARDA), part of the Office of the Assistant Secretary for Preparedness and Response (ASPR) in the US Department of Health and Human Services; the Wellcome Trust, a global charity based in the UK working to improve health globally; Germany's Federal Ministry of Education and Research (BMBF); the UK Department of Health and Social Care's Global Antimicrobial Resistance Innovation Fund (GAMRIF) funded by the UK Government Department of Health and Social Care (DHSC); the Bill & Melinda Gates Foundation, and with in-kind support from National Institute of Allergy and Infectious Diseases (NIAID), part of the US National Institutes of Health (NIH) within the US Department of Health and Human Services. CARB-X is investing up to US$480 million from 2016-2022 to support innovative therapeutics, preventatives and rapid diagnostics. CARB-X funds only projects that target drug-resistant bacteria highlighted on the CDC's Antibiotic Resistant Threats list, or the Priority Bacterial Pathogens list published by the WHO, with a priority on those pathogens deemed Serious or Urgent on the CDC list or Critical or High on the WHO list. CARB-X is headquartered at Boston University School of Law. https://carb-x.org/. Follow us on Twitter @CARB_X

Disclaimer

Research reported in this press release is supported by CARB-X. CARB-X's funding for this project is sponsored by the Cooperative Agreement Number IDSEP160030 from ASPR/BARDA and by an award from the Wellcome Trust. The content is solely the responsibility of the authors and does not necessarily represent the official views of CARB-X or any of its funders.

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https://news.cision.com/snipr-biome-aps/r/snipr-biome-initiates-first-in-human-clinical-trial-with-snipr001,c3548589

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SNIPR BIOME Initiates First-in-Human Clinical Trial with SNIPR001 - PR Newswire

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Urovant Sciences to Present Interim Data from Phase 2a Study of Potential Novel Gene Therapy, URO-902, and New Analyses of Data from Phase 3 EMPOWUR…

Posted: at 11:10 am

IRVINE, Calif. & BASEL, Switzerland--(BUSINESS WIRE)--Urovant Sciences, a wholly-owned subsidiary of Sumitovant Biopharma Ltd., announced that data from a Phase 2a trial of the investigational, novel gene therapy, URO-902, will feature as a late-breaker at the 2022 annual meeting of the American Urological Association (AUA2022), May 13-16, in New Orleans, Louisiana. The plenary presentation will include interim efficacy and safety data on URO-902 from the ongoing Phase 2a trial.

In addition, two podium presentations at AUA2022 will feature new analyses of data from the EMPOWUR 40-week extension trial of GEMTESA (vibegron) 75 mg, a Phase 3, randomized, double blind, active-comparator controlled multicenter study to evaluate long-term safety and efficacy in patients with symptoms of OAB. GEMTESA is approved by the U.S. Food and Drug Administration (FDA) for the treatment of OAB in adults with symptoms of UUI, urgency, and urinary frequency.

Overactive bladder remains a condition in need of additional treatment options. We look forward to sharing new data related to the use of GEMTESA in the OAB patient population as well as providing an initial read-out on the progress of our investigational gene therapy, URO-902, said Sef Kurstjens, M.D., Ph.D., Executive Vice President and Chief Medical Officer of Urovant Sciences. We believe that URO-902 could potentially offer a new treatment option for patients with overactive bladder who have been inadequately managed by oral pharmacologic therapy, if approved by the FDA. The two podium presentations on GEMTESA will also add to the scientific and medical communitys understanding of this important therapy.

Data on the potential novel gene therapy, URO-902, will be presented during Friday mornings plenary session:

Late-Breaking Abstract PLLBA-03, presented by Kenneth M. Peters, M.D., principal investigator, and Chief of the Department of Urology at Beaumont Hospital, Royal Oak; Medical Director of the Beaumont Womens Urology and Pelvic Health Center and professor and Chair of Urology of the Oakland University William Beaumont School of Medicine in Rochester, Michigan., titled, Efficacy and Safety of a Novel Gene Therapy (URO-902; pVAX/hSlo) in Female Patients with Overactive Bladder and Urge Urinary Incontinence: Results from a Phase 2a Trial. This presentation will take place on Friday, May 13, at 11:21 to 11:29 a.m. CDT during the plenary session in the Ernest N. Morial Convention Center, Great Hall A.

Data on GEMTESA will also be featured in two podium presentations at the conference on May 15, 2022:

Abstracts are available in the Journal of Urology at the following links:

URO-902: https://www.auajournals.org/doi/10.1097/JU.0000000000002671.03

EMPOWUR-EXT older adults: https://www.auajournals.org/doi/10.1097/JU.0000000000002596.11

EMPOWUR-EXT PRO: https://www.auajournals.org/doi/10.1097/JU.0000000000002596.12

About the Phase 2a Study of URO-902

This 48-week multicenter, randomized, double blind, placebo-controlled, dose-escalation study will evaluate the efficacy, safety, and tolerability of a single administration of URO-902, a novel gene therapy being developed for patients with OAB who have failed oral pharmacologic therapy. URO-902 is administered via direct intradetrusor injections via cystoscopy into the bladder wall under local anesthesia in patients who are experiencing OAB symptoms and UUI.

The Phase 2a trial includes 80 female patients in two cohorts. The first cohort received either a single administration of 24 mg of URO-902 or matching placebo into the bladder wall, and the second cohort received 48 mg of URO-902 or matching placebo into the bladder wall. Patients will be followed for up to 48 weeks after initial administration. Exploratory endpoints included change from baseline to week 12 in mean daily micturitions, urgency episodes, UUI episodes, and quality of life measures, as well as assessing the safety and tolerability of this investigational gene therapy for OAB.

About URO-902

URO-902 has the potential to be the first gene therapy for patients with OAB. If approved, this innovative treatment has the potential to address an unmet need for patients who have failed oral pharmacologic therapies.

About the EMPOWUR Trial

The EMPOWUR trial was an international, randomized, double-blind, placebo and active comparator-controlled Phase 3 clinical trial evaluating the safety and efficacy of investigational vibegron in men and women with symptoms of overactive bladder, including frequent micturition, urgency, and UUI. A total of 1,518 patients were randomized across 215 study sites into one of three groups for a 12-week treatment period with a four-week safety follow-up period: vibegron 75 mg administered orally once daily; placebo administered orally once daily; or tolterodine ER 4 mg administered orally once daily.

About the 40-Week EMPOWUR Extension

The EMPOWUR 40-week extension trial was a Phase 3, randomized, double blind, active-comparator controlled multicenter study to evaluate the long-term safety and efficacy of vibegron in patients with symptoms of overactive bladder. The extension study enrolled approximately 500 EMPOWUR completers. The primary endpoint was safety, measured by incidence of adverse events. Secondary endpoints were changes from EMPOWUR baseline at week 52 in average daily micturitions, UUI, urgency, and total urinary incontinence.

About Overactive Bladder

Overactive bladder (OAB) is a clinical condition that occurs when the bladder muscle contracts involuntarily. Symptoms may include urinary urgency (the sudden urge to urinate that is difficult to control), urgency incontinence (unintentional loss of urine immediately after an urgent need to urinate), frequent urination (usually eight or more times in 24 hours), and nocturia (waking up more than two times in the night to urinate).1

Approximately 30 million Americans suffer from bothersome symptoms of OAB, which can have a significant impairment on a patients day-to-day activities.1, 2

About GEMTESA

GEMTESA is a prescription medicine for adults used to treat the following symptoms due to a condition called overactive bladder:

It is not known if GEMTESA is safe and effective in children.

IMPORTANT SAFETY INFORMATION

Do not take GEMTESA if you are allergic to vibegron or any of the ingredients in GEMTESA.

Before you take GEMTESA, tell your doctor about all your medical conditions, including if you have liver problems; have kidney problems; have trouble emptying your bladder or you have a weak urine stream; take medicines that contain digoxin; are pregnant or plan to become pregnant (it is not known if GEMTESA will harm your unborn baby; talk to your doctor if you are pregnant or plan to become pregnant); are breastfeeding or plan to breastfeed (it is not known if GEMTESA passes into your breast milk; talk to your doctor about the best way to feed your baby if you take GEMTESA).

Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Know the medicines you take. Keep a list of them to show your doctor and pharmacist when you get a new medicine.

What are the possible side effects of GEMTESA?

GEMTESA may cause serious side effects including the inability to empty your bladder (urinary retention). GEMTESA may increase your chances of not being able to empty your bladder, especially if you have bladder outlet obstruction or take other medicines for treatment of overactive bladder. Tell your doctor right away if you are unable to empty your bladder.

The most common side effects of GEMTESA include headache, urinary tract infection, nasal congestion, sore throat or runny nose, diarrhea, nausea, and upper respiratory tract infection. These are not all the possible side effects of GEMTESA. For more information, ask your doctor or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Please click here for full Product Information for GEMTESA.

About Urovant Sciences

Urovant Sciences is a biopharmaceutical company focused on developing and commercializing innovative therapies for areas of unmet need, with a dedicated focus in Urology. The Companys lead product, GEMTESA(vibegron), is an oral, once-daily (75 mg) small molecule beta-3 agonist for the treatment of adult patients with overactive bladder (OAB) with symptoms of urge urinary incontinence, urgency, and urinary frequency. GEMTESA was approved by the U.S. FDA in December 2020 and launched in the U.S. in April 2021. GEMTESA is also being evaluated for the treatment of OAB in men with benign prostatic hyperplasia. The Companys second product candidate, URO-902, is a novel gene therapy being developed for patients with OAB who have failed oral pharmacologic therapy. Urovant Sciences, a wholly-owned subsidiary of Sumitovant Biopharma Ltd., intends to bring innovation to patients in need in urology and other areas of unmet need. Learn more about us at http://www.urovant.com or follow us on Twitter or LinkedIn.

About Sumitovant Biopharma

Sumitovant is a global biopharmaceutical company leveraging data-driven insights to rapidly accelerate development of new potential therapies for unmet patient conditions. Through our unique portfolio of wholly-owned Vant subsidiariesUrovant, Enzyvant, Spirovant, Altavantand use of embedded computational technology platforms to generate business and scientific insights, Sumitovant has supported the development of FDA-approved products and advanced a promising pipeline of early-through late-stage investigational assets for other serious conditions. Sumitovant, a wholly-owned subsidiary of Sumitomo Pharma, is also the majority-shareholder of Myovant (NYSE: MYOV). For more information, please visit our website at http://www.sumitovant.com

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Urovant Sciences to Present Interim Data from Phase 2a Study of Potential Novel Gene Therapy, URO-902, and New Analyses of Data from Phase 3 EMPOWUR...

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CareDx Showcases Leadership with Over 25 Oral Presentations and Posters at the International Society for Heart and Lung Transplantation Meeting -…

Posted: at 11:10 am

Data Highlights Clinical Utility of CareDx Solutions, Including Findings from Surveillance HeartCare Outcomes Registry (SHORE) Demonstrating Power of Multimodality Assessment for More Precise Interventions

CareDx Symposia Feature Latest Advancements Including XenoSure and XenoMap

SOUTH SAN FRANCISCO, Calif., April 20, 2022 (GLOBE NEWSWIRE) -- CareDx, Inc. (Nasdaq: CDNA) The Transplant Company focused on the discovery, development, and commercialization of clinically differentiated, high-value healthcare solutions for transplant patients and caregivers today announced a leading presence at the International Society for Heart and Lung Transplantation (ISHLT) Annual Meeting and Scientific Sessions, with over 25 oral presentations and posters covering the latest innovations in heart and lung transplant surveillance and two symposia. ISHLT 2022 takes place on April 27-30 in Boston, Massachusetts.

CareDx showcases its leadership in heart and lung transplant patient care with a significant body of evidence highlighting the value of its diagnostic tools for heart and lung transplant recipients. Notably, oral presentations covering interim findings from the SHORE (Surveillance HeartCare Outcomes Registry) observational study will be presented, highlighting the value of multimodality assessment of heart transplant health for assessing the risk of rejection and de novo donor-specific antibodies (dnDSA). Additionally, CareDx symposia will spotlight leaders in the field delivering cutting-edge content using multimodality solutions, HeartCare, AlloMap gene-expression profiling, and AlloSure donor-derived cell-free DNA (dd-cfDNA).

CareDx is proud of its history of innovation in cardiothoracic transplantation, with many firsts, from multimodality molecular assessment of allograft health, to donor-derived cell-free DNA for lung transplantation, to recently introducing, XenoSure and XenoMap, for investigational use in xenotransplantation research, said Reg Seeto, CEO and President of CareDx. Its extremely rewarding to have another remarkable presence at this years ISHLT meeting with extensive data elucidating the clinical value of integrating CareDx solutions and multimodality assessments into clinical practice.

The initial findings from the SHORE study build upon a growing literature that supports non-invasive surveillance of heart transplant patients with AlloSure donor-derived cell-free DNA and AlloMap gene-expression profiling. These studies provide a more comprehensive assessment of the health of the transplanted heart, which will hopefully lead to better outcomes for our patients through more tailored management strategies and earlier detection of graft injury, said Dr. Jeffrey Teuteberg, MD, Cardiologist, and Associate Professor of Cardiovascular Medicine, Stanford Health Care. Multimodality surveillance using both dd-cfDNA and gene-expression profiling may prove to be a better marker of immune quiescence or activation than endomyocardial biopsy (EMB) and questioning the place of the EMB as the gold standard for cardiac allograft monitoring.

CareDx Lunch Symposia:

For more detailed agendas for the lunch symposia, please follow this link.

The following heart and lung transplant data will be presented:

About CareDx The Transplant CompanyCareDx, Inc., headquartered in South San Francisco, California, is a leading precision medicine solutions company focused on the discovery, development and commercialization of clinically differentiated, high-value healthcare solutions for transplant patients and caregivers. CareDx offers testing services, products, and digital healthcare solutions along the pre- and post-transplant patient journey and is the leading provider of genomics-based information for transplant patients. For more information, please visit: http://www.CareDx.com.

Forward Looking StatementsThis press release includes forward-looking statements related to CareDx, Inc., including statements regarding the potential benefits and results that may be achieved with CareDxs leading presence at the ISHLT Annual Meeting and Scientific Sessions, including oral presentations covering interim findings from the SHORE observational study and the CareDx symposia (the CareDx ISHLT Leadership). These forward-looking statements are based upon information that is currently available to CareDx and its current expectations, speak only as of the date hereof, and are subject to risks and uncertainties that could cause actual results to differ materially from those projected, including risks that CareDx does not realize the expected benefits of the CareDx ISHLT Leadership; risks that the findings of SHORE study may not be accurate; risks that ISHLT 2022 and the agendas of CareDx symposia fail to take place as planned; general economic and market factors; and other risks discussed in CareDxs filings with the SEC, including the Annual Report on Form 10-K for the fiscal year ended December 31, 2021 filed by CareDx with the SEC on February 24, 2022, and other reports that CareDx has filed with the SEC. Any of these may cause CareDxs actual results, performance or achievements to differ materially and adversely from those anticipated or implied by CareDxs forward-looking statements. CareDx expressly disclaims any obligation, except as required by law, or undertaking to update or revise any such forward-looking statements.

CONTACTS:CareDx, Inc.Sasha KingChief Marketing Officer415-287-2393sking@caredx.com

Investor RelationsIan Cooney(415) 722-4563investor@CareDx.com

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UCSC researcher completes human genome sequencing – The Mercury News

Posted: at 11:07 am

SANTA CRUZ After nearly 40 years of work, scientists have finally completed sequencing the human genome and UC Santa Cruz was at the center of it all.

The completion of the sequence gives an idea for the baseline of all human genetics. Humans are 99.9% identical genetically, according to UCSC Genomics Institute Director David Haussler. Therefore, while scientists have only sequenced the DNA of a human once, anyone can look at it and get a near indistinguishable snapshot of their own genetic code.

UCSC Chancellor Emeritus Robert Sinsheimer embarked on the quest in 1985. Karen Miga, an assistant professor in biomolecular engineering, completed the task at the end of March.

Its the greatest honor of my life, she said. What it turned out to be was this amazing walking with a whole group of people towards a historic moment. I feel lucky to be a part of that legacy.

The former chancellor had just finished sequencing the genome of a virus, which inspired him to gather a team to sequence the human genome in the mid-80s. However, that task would be much harder than the one he just completed.

The virus Sinsheimer sequenced only has a sequence of a few thousand DNA patterns, which is miniscule compared to the genome of human, according to Haussler. The human genome is comprised of 3 billion DNA sequences.

Haussler likened the task to a jigsaw puzzle, except this puzzle has 3 billion pieces and a corner piece is not as easy to find.

It gives you a feel for how hard this problem of putting together all the little snippets of DNA into the right orientation and figure out what the actual chromosome looks like how hard that problem is, said Haussler, who worked on the original Human Genome Project.

In fact, the puzzle is so complex that scientists from 20 different countries joined forces to sequence the human genome. That team became known as the Human Genome Project, and it officially launched in 1990.

Those scientists spent the next 10 years working on sequencing the human genome. Along the way, the Human Genome Project even faced competition against a private company, Solara Genomics, that sought to accomplish the same task but also find a way to monetize it.

That competition lead to further innovations in technology, which gave researchers the power to sequence the genome faster. While technology advanced, the task at hand still remained daunting.

That work was incredibly difficult because the genome was so huge and the technology could only read 1,000 bases at a time, Haussler said.

To put that into perspective, the first chromosome in the human genome is 250 million bases long, Haussler noted. Subsequent chromosomes continue to get smaller, but there are still an additional 22 chromosomes adding up to more than 3 billion bases.

However, in July 2000, researchers at UCSC accomplished what seemed unachievable. A student at the university wrote a program that helped the Human Genome project complete a first draft of the sequence by July 7, 2000.

That was incredibly important to us because now scientists got a glimpse of our human heritage, Haussler said. In fact, regular people got a glimpse at our human heritage without having to pay a subscription.

That first draft displayed roughly 90% of the complete human genome. The remaining 10% of the human genome was just out of grasp with the state of technology at the time. As a result, many people in the project gave up, conceding that there is plenty of information for modern medicine in the 90% of the genome sequenced.

Technological advancements and perseverance would later help Miga, who was a grad researcher during the original project, catalogue the remaining 10% of the human genome.

Miga formally launched her international consortium in 2019, co-led by Evan Eichler from the University of Washington and Adam Phillippy from the National Institute of Health. Unlike the Human Genome Project, this consortium was independently funded and achieved its success on the free time of each of the associates.

Its completely grassroots. This is just a bunch of scientists from around the world using their spare time, using their own money that decided that this was something that needed to happen, Miga said.

The team really leaned into their research as the COVID-19 pandemic gripped the world.

While many people were learning to make banana bread, Miga and her team were completing the jigsaw puzzle of human genomics. However, what was left over from the Human Genome Project were some of the hardest pieces of the puzzle.

It was really difficult to sequence these, put them together or just reconstruct the puzzle, Miga said. When youre putting a puzzle together and you have all the blue-sky pieces that look the same, thats what we were up against.

But of course, the hardest pieces to solve were some of the most important parts of human genetics. The parts of the human genome that Miga cataloged are some of the fastest-changing genetics through history, Haussler said. They are also parts of genetics that are vital to human life.

The parts of the genome Miga focused on focused on the centromere of cells, which makes sure cells separate properly during mitosis. When this part of the cell does not function properly, it leads to cancer and birth defects.

With this portion of the genome sequenced, scientists can begin to work on sequencing cancer genomes, which will lead to further advancements in cancer research.

This is the first time we can study the sequences in these important regions, Miga said.

But that is not where this project ends. With the complete sequencing of the human genome which Miga and her finished in roughly three years scientists now look towards the pangenome project.

That project aims to further diversify the information in the sequenced genome. The idea is to represent at least 350 diverse people from around the world, Miga said. While scientists are celebrating the completion of a single human genome, it does not capture the full diversity of human genetics, she added.

We all have our own ties to human history. These variants distributed around the world give us an indication of how humans have migrated for the past 1,000 years, she said. Were hoping this project will identify even more of those complicated regions we know are present but havent been able to study in the past.

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UCSC researcher completes human genome sequencing - The Mercury News

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Polygenic risk, population structure and ongoing difficulties with race in human genetics – DocWire News

Posted: at 11:07 am

This article was originally published here

Philos Trans R Soc Lond B Biol Sci. 2022 Jun 6;377(1852):20200427. doi: 10.1098/rstb.2020.0427. Epub 2022 Apr 18.

ABSTRACT

The Apportionment of Human Diversity stands as a noteworthy intervention, both for the field of human population genetics as well as in the annals of public communication of science. Despite the widespread uptake of Lewontins conclusion that racial classification is of virtually no genetic or taxonomic significance, the biomedical research community continues to grapple with whether and how best to account for race in its work. Nowhere is this struggle more apparent than in the latest attempts to translate genetic associations with complex disease risk to clinical use in the form of polygenic risk scores, or PRS. In this perspective piece, we trace current challenges surrounding the appropriate development and clinical application of PRS in diverse patient cohorts to ongoing difficulties deciding which facets of population structure matter, and for what reasons, to human health. Despite numerous analytical innovations, there are reasons that emerge from Lewontins work to remain sceptical that accounting for population structure in the context of polygenic risk estimation will allow us to more effectively identify and intervene on the significant health disparities which plague marginalized populations around the world. This article is part of the theme issue Celebrating 50 years since Lewontins apportionment of human diversity.

PMID:35430888 | DOI:10.1098/rstb.2020.0427

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Greater diversity in genetic studies helps researchers uncover new insights – UNC Gillings School of Global Public Health

Posted: at 11:07 am

April 13, 2022

In genomic studies, researchers examine the DNA of a population to understand the influence of genetics on health and disease. Though genomic studies have been common for more than a decade, most participants in these studies have been of European descent.

Dr. Lindsay Fernndez-Rhodes

Dr. Misa Graff

A new study led by Lindsay Fernndez-Rhodes, PhD, assistant professor of biobehavioral health at Penn State and 2016 doctoral graduate of the UNC Gillings School of Global Public Health, and Mariaelisa Graff, PhD, associate professor of epidemiology at the Gillings School, has shown that increasing the diversity of genomic samples can improve researchers ability to identify important genetic markers for health conditions.

One of the goals of conducting genomic studies is to develop precision medicine, which is the delivery of the exact treatment or medication that a person needs exactly when they need it.

Precision medicine is a great idea, but it only works if we study the full diversity of the populations that we may see in the clinic, Fernndez-Rhodes explained. We cannot treat people with precision if we do not have the relevant data. Previous large-scale genomic studies have largely overlooked Hispanic/Latino people. Since the United States is becoming increasingly diverse, our ability to provide appropriate medical treatment will suffer if the gaps in our genomic data are not addressed.

Fernndez-Rhodes and Graff were joined by more than 100 researchers from around the world to form the Hispanic/Latino Anthropometry Consortium. The consortium pools research expertise and genetic data on people of Hispanic/Latino ethnicity in order to bolster the diversity in genomic studies.

Dr. Kari North

Our consortium fills a major research gap in genomic studies. Inclusion of individuals of diverse ancestral backgrounds is imperative, both from the perspective of scientific necessity and equity, said Kari E. North, PhD, professor of epidemiology at the Gillings School, one of the consortiums multiple principal investigators, and co-author of this research. By embracing diversity, we are discovering novel genomic associations and moving the field forward.

In anew article in Human Genetics and Genomics Advances, Fernndez-Rhodes and Graff led the examination of genomic data from more than 70,000 Hispanic/Latino individuals. The data were compiled from 18 smaller studies and combined with two other consortia to bring the total sample to over 470,000 adults. To date, the article is the largest published genomic study of body measures in Hispanic/Latino individuals.

The researchers identified regions of the genome that are associated with three body measurements: body mass index (BMI), height, and waste-to-hip ratio. BMI, a ratio of weight to height, is the most common assessment of obesity used by physicians. Waist-to-hip ratio indicates where on their bodies people are carrying excess weight.

Consortium researchers identified 42 previously unidentified regions of the human genome related to BMI, height and waist-to-hip ratio. These traits have been examined in previous genomic studies, but the unique ancestry and experiences of Hispanic/Latino people made the regions easier to identify using the consortiums combined data.

The newly identified regions of the genome may help scientists understand how people grow, develop and perhaps most importantly for human health develop obesity. Significantly, the regions appear to be relevant to the health and development of all people, regardless of their ancestry. The researchers say that the results indicate a widespread need to build larger, more diverse data sources.

There is a very large gap between who is experiencing obesity and who is being included in genomic studies. The consortium is working to close one part of that gap. Hopefully, this is the first step of many toward increased diversity in genomic studies, said Fernndez-Rhodes. Researchers need to ensure that all people are represented in our scientific knowledge base. We need to harness the power of diversity to uncover the genes that pattern human health and disease.

Read the original release from Penn State.

Contact the UNC Gillings School of Global Public Health communications team at sphcomm@unc.edu.

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Greater diversity in genetic studies helps researchers uncover new insights - UNC Gillings School of Global Public Health

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Still doubts over embryo selection based on PGT for polygenic conditions – ESHRE

Posted: at 11:07 am

Advances in genomic technologies continue to expand the possibilities of PGT. In a preclinical research study recently published in Nature Medicine, scientists from Silicon Valley-based genetic testing companies have examined the potential of using PGT to predict complex polygenically inherited conditions in human embryos. While the authors present interesting data, Mina Popovic and Susana Chuva de Sousa Lopes from ESHREs SIG Stem Cells here report that the study raises profound medical, technical and ethical concerns.

Coupled to technical developments in embryo genomic sequencing, advances in complex trait genetics and computational genomics have now enabled the introduction of PGT-P for embryo selection. Nevertheless, the predictive value, clinical utility and ethical implications of this test remain highly controversial. Given the lack of compelling evidence for its clinical application, several scientific societies, including ESHRE and the European Society of Human Genetics, have recently released statements against the use of PGT-P in clinical practice.(1,2)

Despite these concerns, commercial genetic testing companies, including Genomic Prediction (https://www.lifeview.com), Orchid Health (https://www.orchidhealth.com) and MyOme (https://myome.com), have already introduced the technology to the market, offering PGT-P to prospective parents for a variety of complex diseases all in one test. Marketed as the most comprehensive preimplantation genetic test available today, PGT-P is now being used to screen embryos for their genetic predisposition to cancers, diabetes, heart conditions, schizophrenia, Alzheimers, as well as other adult-onset diseases. Remarkably, the selection of embryos based on non-medical conditions - such as cognitive ability, education and household income - have also been proposed, with a tenuous health benefit already assigned to some of these traits.

The technology behind PGT-P draws on polygenic risk scores, derived from large-scale genome-wide association studies.(3) These studies employ high-throughput genomic technologies to scan thousands of genomes obtained from different individuals to uncover genetic variants, predominantly single nucleotide polymorphisms (SNPs), that are significantly associated with a particular complex trait. Such data can be used to generate polygenic risk scores which summarise a set of genetic variants in an individual to evaluate their risk of developing a certain condition. Polygenic risk scores have inherently gained intense interest for preventative medicine, to improve diagnoses and select optimal treatment for a variety of common diseases. Applying this concept in the context of preimplantation genetics has thus enabled PGT-P. Nevertheless, very few studies have examined the utility of polygenic risk scores for embryo selection and ultimately the extrapolation of such data to an IVF embryo cohort remains problematic.(4)

In their recent study, Kumar and colleagues from MyOme combined molecular and statistical techniques to infer the whole genome sequence of 110 embryos, using parental genome sequencing and embryo genotyping.(5) They suggest that this method, known as whole genome reconstruction, can be used to more accurately predict susceptibility to 12 common polygenic conditions in human embryos, including cancers, cardiometabolic and autoimmune diseases. The study used samples from couples who had previously had PGT-A or PGT-M, while DNA was also available from ten children who had prior PGT. The authors validated their technique by comparing the reconstructed genome and polygenic predictions for the embryos to those of the corresponding children. Genome-wide prediction accuracy ranged from 98-99%.

The findings suggest that whole genome reconstruction improves the accuracy of risk predictions by comprehensively profiling embryo genomes, whilst overcoming known technical limitations associated with the genetic analysis of small amounts of embryonic DNA. The paper touches on challenges regarding the statistical validity of polygenic risk scores for evaluating embryos in this setting, and discusses some ethical aspects of the procedure. Nevertheless, many questions remain unanswered.

Alongside the paper, Nature Medicine published two commentaries highlighting the technical, clinical and ethical dilemmas associated with PGT-P.(6,7) These questions are complex and wide-ranging, and while it is not possible to give them full justice in this report, they certainly deserve serious attention.(8)

Despite the growing interest in polygenic risk scores in biomedical research, limited guidelines for performing such analyses have ultimately led to inconsistent data and misinterpretations of results. Accordingly, several methodological limitations in prediction accuracy hinder the clinical utility of PGT-P. Ultimately, polygenic risk scores only capture parts of the relevant genetic component of a condition. Indeed, predicting the risk of adult-onset diseases cannot account for changes in environmental or lifestyle factors which might occur over time. Moreover, predictions only provide a relative risk compared to the specific study population they were generated in. As justly mentioned by Kumar and colleagues, polygenic risk scores exhibit limited predictive accuracy when extended to different populations, as they have been largely developed using genome-wide association studies of European ancestry.

Studies have further shown that the potential gain of quantitative traits, such as height or cognitive ability, remains relatively small.(9) In addition, a substantial number of embryos per cycle (>10) is required to increase the prediction accuracy of PGT-P. This is largely unfeasible for many couples undergoing IVF. Moreover, as PGT-P screens for multiple polygenic conditions simultaneously, it vastly complicates embryo selection.

Currently, the complex relationships between genetic variants and traits are not well understood, and it is uncertain whether a lower risk for one condition may in fact increase susceptibility to others. Indeed, PGT-P creates enormous challenges for clinical management and patient counselling. Prospective parents will face difficult decisions as they try to balance risks for multiple conditions. Complicated decision-making surrounding embryo selection may dimmish procreative autonomy, lead to additional cycles of ovarian stimulation, and ultimately elicit unwarranted disposal of viable embryos.

Adequate ethical oversight and societal discussion also remain imperative. Accessibility to the technology, the opportunity for using PGT-P for non-medical individual traits, discrimination and stigmatisation of certain conditions, and drawing attention away from individual responsibilities for managing disease risk, all present legitimate concerns. Yet, research on the perceptions and attitudes towards PGT-P, including those of its consumers, is sorely lacking. In this increasingly complex industry, clinical decision-making must rely on preclinical and clinical studies, controlled trials, as well as longterm followup. Such studies inherently demand time, and remain challenging to perform, particularly in the context of assisted reproduction. Nevertheless, balancing innovation with robust evidence surrounding the effectiveness, safety and ethical implications of newly emerging technologies is becoming more relevant than ever.

1. See https://www.focusonreproduction.eu/article/ESHRE-News-PRS and https://www.eshre.eu/Europe/Position-statements/PRS2. Forzano F, Antonova O, Clarke A, et al. The use of polygenic risk scores in pre-implantation genetic testing: an unproven, unethical practice. Eur J Hum Genet 2021; doi.org/10.1038/s41431-021-01000-x3. Tam V, Patel N, Turcotte M, et al. Benefits and limitations of genome-wide association studies. Nat Rev Genet 2019; 20: 46784. doi.org/10.1038/s41576-019-0127-14. Turley P, Meyer MN, Wang N, et al. Problems with using polygenic scores to select embryos. N Eng J Med 2021; 385: 7886. doi.org/10.1056/NEJMsr21050655. Kumar A, Im K, Banjevic M, et al. Whole-genome risk prediction of common diseases in human preimplantation embryos. Nat Med 2022; 28: 513516.doi.org/10.1038/s41591-022-01735-06. Gleicher N, Albertini DF, Patrizio P, Orvieto R, Adashi EY. The uncertain science of preimplantation and prenatal genetic testing. Nat Med 2022; 28: 442444. doi.org/10.1038/s41591-022-01712-77. Johnston J, Matthews LJ. Polygenic embryo testing: understated ethics, unclear utility. Nat Med 2022; 28(3): 446448. doi.org/10.1038/s41591-022-01743-08. Siermann M, Tuiko O, Vermeesch JR, et al. A review of normative documents on preimplantation genetic testing: Recommendations for PGT-P. Genet Med 2022: S1098-3600(22)00678-5. doi.org/10.1016/j.gim.2022.03.0019. Karavani E, Zuk O, Zeevi D, et al. Screening human embryos for polygenic traits has limited utility. Cell 2019; 179: 1424-1435.e8. doi.org/10.1016/j.cell.2019.10.033

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Viewpoint: E.O. Wilson’s legacy under fire in some quarters after donated papers underscore fascination with racial differences and human diversity -…

Posted: at 11:07 am

Did Edward O. Wilson Harvard professor, iconic biologist, champion of global biodiversity promote racist ideas? For years, some scientists have suggested the very question is rooted in smear campaigns and misreadings of Wilsons work. Other scholars have argued that racism and sexism are apparent in Wilsons writing on human evolution.

Since Wilsons death in late December 2021, at the age of 92, the question has been subject to renewed debate, after an opinion piece in Scientific AmericandescribingWilsons dangerous ideas set off a backlash from some scientists.

Now, two separate pairs of researchers, drawing from Wilsons papers at the Library of Congress, have published details of correspondence in which Wilson privately supports a psychologist known for his racist work. It doesnt surprise me at all, said Joseph Graves, Jr., an evolutionary biologist at North Carolina Agricultural and Technical State University who haswrittenextensivelyabout scientific racism, and who reviewed some of the new archival work before it was published. Whats important about the new research, he added, was coming up with the smoking gun.

Not everyone agrees the new evidence is so definitive, but the revelations promise to prolong the reckoning over Wilsons legacy and to add to an ongoing discussion about how racism and sexism may have shaped entire fields of study.

Wilson may be best known for his widely praised research on ants, and for his push to protect biodiversity. But the scientists work on human evolution has been contested since 1975, when he published Sociobiology: The New Synthesis, a sweeping study of the evolution of social behavior in animals. The books final chapter, which aims to consider man in the free spirit of natural history, as though we were zoologists from another planet, touches on the evolutionary origins of language, territoriality, and other behaviors. In the chapter, Wilson wonders whether there could be marked genetic differences between socioeconomic classes. (He concludes theres little evidence thats the case.) And he speculates that some of the differences between human cultures could be rooted in genetic differences, calling for a discipline of anthropological genetics to explore the question further.

Wilson was touching on questions that remain deeply polarizing: To what extent are certain features of human societies, like xenophobia, altruism, or inequality, dictated by our genes? And can some of the complex variation among human groups, from IQ scores to incarceration rates, be explained by genetic differences, rather than by environmental and social forces? Many racist projects from the eugenics movement to Nazism to present-day White nationalism have argued that racial differences have deep genetic roots. Such pseudoscientific ideas continue to fuel popular racist canards, such as theideathat Black people have genes predisposing them to violence.

Today, theres a broad consensus among experts in human evolution that that race is a social construct, not a biological category, and that it is extraordinarily difficult to link specific genes to complex human behaviors. And some researchers and advocates warn that, absent better data, explorations of those questions often just reproduce old stereotypes or offer thin cover for bigoted ideas.

After the publication of Sociobiology, Wilson was subject to fierce criticism, including from some of his Harvard colleagues, who argued he had gotten out ahead of the scientific evidence and that his conclusions about the way biology shapes human behavior veered into dangerous territory.

Wilson pushed back against those charges, arguing that his work had been misunderstood and, in some cases, distorted. (To keep the record straight, I am happy to point out that no justification for racism is to be found in the truly scientific study of the biological basis of social behavior, he wrote in 1981, stressing his belief in a single human nature.) Despite the criticisms, Sociobiology was enormously influential: The book helped launch the field of evolutionary psychology, and it had a profound influence on the study of animal behavior and biological anthropology.

Less than a week after Wilson died, Monica McLemore, a health researcher at the University of California, San Francisco, published the op-ed in Scientific American describing Wilsons work as problematic, and calling on scientists to reckon with his legacy. In response, the science blogger Razib Khan wrote anopen letterchallenging the way McLemores piece characterized Wilsons work, including baseless accusations of racism. Dozens of prominent scientists signed the letter.

The open letter pitted a group of mostly White scientists against a Black colleague who had raised concerns about racism. McLemore, who has received threats and hate mail since her piece was published, questioned the judgment of the researchers who signed it. That reputable scientists would be sloppy enough to sign a letter that would bring that kind of hate to my stance in this current moment to me the naivete is huge, she told Undark in a recent Zoom conversation. (Khan did not reply to requests for comment.)

Some of the letters initial signatories retracted their names after learning of Khanspast connectionswith figures associated with white nationalism, including alt-right figurehead Richard Spencer and publisher Ron Unz.

Soon after, Wilsons own connections to the right-wing fringe upended the conversation again.

One pair ofresearchers who surfaced those connections, Howard University evolutionary biologist Stacy Farina and her husband, Matthew Gibbons, began reading sections of Sociobiology while stuck at home during the Covid-19 pandemic. They were taken aback by what they found.

I had read some chapters of Sociobiology as a grad student, said Farina. And theres a lot of really great science in there. Its a very interesting book. And I had no idea that the last chapter had any of that stuff in it. Part of her motivation for digging into Wilsons work, she continued, was a sense of gaps in her own training. I am frustrated with the lack of education about these issues in evolutionary biology.

Later, during a Library of Congress workshop for Howard faculty, Farina asked if the Library had archival material on Wilson. Sure enough, the institution holds his personal papers including boxes of documents related to the sociobiology wars. When she and Gibbons perused the collection, they were drawn to four folders labeled with the name of J. Philippe Rushton, a Canadian psychologist who, starting in the 1980s, published studies arguing that substantial genetic differences existed between racial groups.

Population differences exist in personality and sexual behavior such that, in terms of restraint, Orientals > whites > blacks, begins one 1987 Rushton paperpublished in the Journal of Research in Personality. His work would eventually be dogged by accusations of statistical flaws and ethics violations, and key papers were retracted.

In 2002, Rushton took the helm of the Pioneer Fund, an organization founded in the 1930s to promote eugenics, the idea that humanity can be improved by manipulating which people reproduce. He led the nonprofit until his death in 2012.

On weekends, Farina and Gibbons began returning to the Library of Congress. It was a nice little escape during the pandemic, said Gibbons, who works as a business development specialist for a public health organization. Head out in the morning, go to an early session, grab some lunch, and sort of freak out over what the morning session revealed, race the clock and try to document as much as we could before they kicked us out at the end.

The letters, Farina said, demonstrate a warm relationship between Wilson and the psychologist. In the correspondence, which dates from the 1980s and 90s, Wilson expressed support for Rushtons work, and lamented a stifling culture that, he suggested, had prevented him from speaking more freely, referring in one note to a leftward revival of McCarthyism. When Rushtons university seemed poised to sanction him for academic misconduct, Wilson sent letters in his defense. He also sent letters to drum up support for Rushton from colleagues at Harvard and at the conservativeNational Association of Scholars.

Unbeknownst to Farina and Gibbons, a pair of historians were also exploring the Wilson archive. In 2018, University of Illinois historian of science David Sepkoski began working with Wilsons papers while researching abookon biodiversity. Like Farina and Gibbons, he noticed and gravitated toward the Rushton folders.

Struck by what he was reading, Sepkoski began dropping scanned images of letters into a Dropbox folder he shares with Mark Borrello, a historian of biology at the University of Minnesota. Im sure I called you from the archives, and was like, Youre not gonna believe this, Sepkoski told Borrello during a recent Zoom conversation with Undark. The two began sketching out a book project on Wilson.

The correspondence, Sepkoski and Borrello now say, suggests that Wilson was carefully managing his public persona even as he quietly continued his dispute with his left-wing critics.

Providing comments on one Rushton paper which applied a famous Wilson theory, meant to examine reproductive differences between different species, to argue that Black and non-Black people pursue different reproductive strategies Wilson was effusive. This is a brilliant paper, he wrote, one of the most original and heuristic written on human biology in recent years.

Whether it can even be published in this or some other journal devoted to human sociobiology, Wilson wrote later in his comments, will be a test of our courage and fidelity to objectivity in science.

Earlier this month, spurred by the backlash against McLemore, Farina and Gibbonspublishedtheir findings in Science for the People Magazine, a left-wing outlet linked to the activist group thatprominently opposedWilsons work in the 1970s.

Days later, Sepkoski and Borrello published their ownessayin The New York Review of Books, with more details from the Wilson archives.

The reaction to the letters among the scientific community has been mixed. Some researchers suggested the revelations do not necessitate a substantial reevaluation of Wilsons legacy. Asked about the new letters, sociologist Ullica Segerstrale referred back to her influential 2000 book, Defenders of the Truth, which covers the dispute between Wilson and his antagonists. In thebook, Segerstrale challenges characterizations of Wilson as a racist thinker, and argues that his critics often failed to engage with the actual substance of his work. I stand by my general analysis in that book regarding the thinking and behavior of both E.O. Wilson and Science for the People, she wrote in an email to Undark.

At the blog Why Evolution is True, biostatistician Gregory MayerdescribedFarina and Gibbons findings as small beer. Wilson, he wrote, appeared to be primarily defending Rushtons academic freedom, not endorsing his ideas. To do so does not imply an identity of views, Mayer wrote. In a phone interview, he suggested that historians should focus on more pressing historical topics, such as Wilsons role in the development of a key concept in ecology, rather than his correspondence with a discredited Canadian psychologist.

For other scientists, though, the letters felt significant. Writing for Small Pond Science, a science and teaching blog, biologist Terry McGlynnreflectedon the letters impact. When navigating the whiter parts of the cultural landscape of biology, the general party line has often been that Ed was mostly right about sociobiology, but his ideas had been twisted by racists, and there wasnt anything he could do about that, he wrote.

But, he continued, its indubitable that the party line I have passively received over the decades simply does not comport with reality.

Not everyone found the content of the letters especially surprising. Indeed, close attention to Wilsons work and public statements, some scholars said, already provided ample evidence that he was sympathetic to ideas that most biologists now consider not just morally questionable, but scientifically unfounded.

In 2014, Wilson gave a warm blurb to then-New York Times science journalist Nicholas Wades book A Troublesome Inheritance. The book argues that Black people may be, on average, more impulsive and less hardworking than White or East Asian people, and that basic differences in human society why Haiti is poor, for example, and European countries wealthy are attributable to genetic differences among groups. Inreviews,debates, andpublic statements, experts in human evolution pilloried the book for misrepresenting the science. A notable exception was Wilson, who, in his blurb, praised Wade for exemplifying the virtues of truth without fear and celebrating human genetic diversity.

Thats pretty much out in the open, said Princeton University biological anthropologist Agustn Fuentes, who describes A Troublesome Inheritance as awful, racist, horribly unscientific. What has changed, he said, is the scientific community itself. The field, he said, is really hitting a peak moment of reflection, of engagement with the complexities of racism and sexism, and how its structured some of the basic ideas.

Indeed, a recentpaperin the journal Nature Ecology and Evolution, authored by faculty, staff, and graduate students in the Department of Ecology and Evolutionary Biology at UC-Santa Cruz, is titled Anti-racist interventions to transform ecology, evolution, and conservation biology departments. Recently, biologists have mobilized to change species names that honorConfederate officersand other figures with troubling histories.

Even just in the last two or three years, it feels like something has shifted, said Ambika Kamath, a behavioral and evolutionary ecologist at the University of Colorado-Boulder. Among other factors driving that change, she said, is that biologists from more diverse backgrounds are coming into the field.

Kamath is hopeful that the conversation around Wilson will spark broader introspection among her colleagues. The problem, she and some other researchers argue, goes far beyond Wilson. I dont really care that Wilson had racist ideas, because I know pretty much all of the people that I dealt with, when I was coming up through the science system, had racist ideas, said Graves, who in 1988 became the first Black American to receive a Ph.D. in evolutionary biology. Wilson was just one of many.

For now, more work from the archives may continue to flesh out a fuller picture of Wilsons life and thought. Speaking last week, McLemore, the author of the Scientific American op-ed on Wilson, said she was still getting hate mail and threats. All I wanted to do, she said, was to have a more nuanced discussion about the work.

Michael Schulson is a contributing editor for Undark. His work has also been published by Aeon, NPR, Pacific Standard, Scientific American, Slate, and Wired, among other publications.

A version of this article was originally posted at Undark and is reposted here with permission. Undark can be found on Twitter @undarkmag

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Viewpoint: E.O. Wilson's legacy under fire in some quarters after donated papers underscore fascination with racial differences and human diversity -...

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COVID immunity: Why some people are never infected – Torrington Register Citizen

Posted: at 11:07 am

There are many people who have never gotten COVID-19, despite repeated exposure. At the other extreme, there are lots whove gotten sick from the coronavirus more than once, despite being vaccinated and even boosted.

A lot of factors are at play, experts said, including genetics and variations in immune response. Scientists are working towards finding a clear answer.

Theres a difference between people who can never catch COVID, despite exposure, and those who are able to clear it out of their systems without ever knowing they had it. If this second category of people tested regularly, they might show positive for a day or two. Different factors are likely at play between the two groups.

Its so messy, Dr. Julie Parsonnet, an infectious disease specialist at Stanford University. We dont know how to differentiate between whether youre just lucky, really careful or if genetically something is different.

In one study, conducted in early 2021 and known as the human challenge study, 36 healthy young adult volunteers none of whom had been vaccinated or previously infected were deliberately given the virus that causes COVID-19 in their noses and tested frequently afterward to track infection. Remarkably, nearly half never got infected at all.

Researchers dont yet know why some of those participants didnt get COVID, and it remains to be seen whether the pattern holds for more infectious but milder variants like omicron.

People have different immune responses to COVID: Despite exposure, some dont seem to catch the coronavirus at all, while others, even vaccinated people, are getting infected several times. A Yale New Haven Health nurse administers a COVID-19 vaccine in this file photo.

Dr. Monica Gandhi, an infectious disease expert at UCSF, said its important to note that with many infectious diseases, including HIV, which she studies and treats, there are instances where people are exposed over and over but never get the virus.

In the case of HIV, this is because these people lack the receptors for the virus. That means no matter how much they are exposed, theyll never become infected because its physically impossible. Scientists say this is likely true with COVID, as well.

But for those who seem to be able to clear the virus so quickly they never knew they had it, differences in the behavior of the immune system could be the reason.

One study on health care workers who repeatedly tested negative found that these people had high levels of memory T cells the long-lasting cells of the immune system that remember a virus and protect against severe disease from previous, non-COVID coronavirus infections, which may have helped them fight off infection more quickly. But another study found that, especially in older patients, high levels of memory T cells can actually be a risk factor for severe COVID-19, as they can trigger a more severe immune response to the virus that overwhelms their systems.

Both situations could be true, and scientists dont yet know exactly why cross-reactive T cells may be helpful for some and detrimental for others, Gandhi said, though this mechanism is less important for people who are vaccinated, as vaccines generate COVID-specific T cells.

Part of what makes COVID so weird is our own immune system, Gandhi said. Were all just really different.

A prominent example of that is the way the virus behaves in children, she said. Children tend to have a different immune response to new pathogens than adults, she said, which means their lungs and immune system are less likely to get inflamed.

Another mystery, she said, is that only some people, especially children, seem to be able to produce effective cross-immunity T cells from other, non-COVID coronavirus infections. Doctors still dont know why some peoples systems do this and others dont.

We need to still look for other genetic factors, Gandhi said.

There also could be physiological factors, like the shape of the nose, how people breathe and what kind of mucus they produce, Parsonnet said, which have not yet been widely studied.

On the flip side, scientists dont yet understand why some people end up getting COVID several times, even after being vaccinated. Some people may have never fully cleared the virus, even if symptoms go away, causing them to test positive repeatedly. Others may just have more reactive immune systems.

Gandhi said that outside factors such as stress or pregnancy can play a role in how likely you are to become infected and sick from the virus, in much the same way that college students get ill around the time of stressful final exams.

People have different immune responses to COVID: Despite exposure, some dont seem to catch the coronavirus at all, while others, even vaccinated people, are getting infected several times.New Haven Fire Department Chief John Alston, Jr., gets the first dose of a Moderna COVID-19 vaccine from APRN Grace Grajales in front of the New Haven Health Department in this file photo.

We can be more or less susceptible throughout our lives, she said. Its multifactorial. All of these reasons could be at play.

But really understanding the nuances between whats genetic, whats a quickly cleared virus and whats just lucky will take intensive scientific studies, Parsonnet said. One such effort to discover exactly how genes affect the severity of COVID infection or whether you get it at all is underway, through a collaborative project called the COVID Human Genetic Effort. But the research is still in its early stages.

Right now, we just dont know the answer, she said. But people are really interested in looking at it.

Danielle Echeverria is a San Francisco Chronicle staff writer. Email: danielle.echeverria@sfchronicle.com Twitter: @DanielleEchev

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Coronavirus Found in Human Feces Up to 7 Months After Infection – WebMD

Posted: at 11:07 am

By Dennis Thompson HealthDay Reporter

MONDAY, April 18, 2022 (HealthDay News) -- COVID-19 is mainly known as a respiratory ailment, but a new study suggests the coronavirus can infect your intestinal tract for weeks and months after you've cleared the bug from your lungs.

In the study about 1 out of 7 COVID patients continued to shed the virus' genetic remnants in their feces at least four months after their initial diagnosis, long after they've stopped shedding the virus from their respiratory tract, researchers found.

This could explain why some COVID patients develop GI symptoms like abdominal pain, nausea, vomiting and diarrhea, said senior researcher Dr. Ami Bhatt, an associate professor of medicine and genetics at Stanford University.

"We found that people who had cleared their respiratory infection -- meaning they were no longer testing positive for SARS-CoV-2 in their respiratory tract -- were continuing to shed SARS-CoV-2 RNA in their feces," Bhatt said. "And those people in particular had a high incidence of GI symptoms."

A long-term infection of the gut also might contribute to long COVID symptoms in some people, Bhatt and her colleagues theorized.

"Long COVID could be the consequence of ongoing immune reaction to SARS-CoV-2, but it also could be that we have people who have persistent infections that are hiding out in niches other than the respiratory tract, like the GI tract," Bhatt said.

For this study, the research team took advantage of an early clinical trial launched in May 2020 at Stanford to test a possible treatment for mild COVID infection. More than 110 patients were monitored to follow the evolution of their symptoms, and regular fecal samples were collected as part of an effort to track their viral shedding.

Many other studies have focused on viral shedding in patients with severe cases of COVID, but this is the first to assess the presence of viral RNA in fecal samples collected from people with mild to moderate COVID, researchers said.

About half of the patients (49%) had COVID RNA remnants in their stool within the first week after diagnosis, researchers found.

But at four months following diagnosis, when no more COVID remained in their lungs, nearly 13% of patients continued to shed viral RNA in their feces.

About 4% still were shedding viral RNA in their feces seven months out from their initial diagnosis, researchers found.

Bhatt was quick to note that the RNA constituted genetic remnants of the coronavirus, and not actual live virus -- so it's unlikely a person's poop could be contagious.

"While there have been isolated reports of people being able to isolate live SARS-CoV-2 virus from stool, I think that that's probably much less common than being able to isolate live virus from the respiratory tract," Bhatt said. "I don't think that our study suggests that there's lots of fecal-oral transmission."

But the lingering presence of COVID in the gut does suggest one potential influence for long-haul disease, she said.

"SARS-CoV-2 might be hanging out at the gut or even other tissues for a longer period of time than it sticks around in the respiratory tract, and there it can basically continue to kind of tickle our immune system and induce some of these long-term consequences," Bhatt said.

Long COVID has become such an established problem that many major medical centers have established their own long COVID clinics to try to suss out symptoms and potential treatments, said Dr. William Schaffner, medical director of the National Foundation for Infectious Diseases.

"A very substantial proportion of individuals who recover from COVID acutely nonetheless have lingering symptoms, and they can involve an array of different organ systems," Schaffner said.

"These data add to the notion that the cells in the intestine may themselves be involved with COVID viral infection, and they could potentially be contributors to some of the symptoms -- abdominal pain, nausea, kind of just intestinal distress -- that can be one aspect of long COVID," he said.

Bhatt said the findings also have implications for public health efforts to predict emerging COVID outbreaks by testing a community's wastewater for evidence of the virus, and Schaffner agrees.

"If, as they say, about 4% of people seven or eight months later are still excreting viral remnants in their stool, it complicates the assessment of the density of new infections in a community," Schaffner said. "It's another thing we have to take into consideration and start looking at going forward."

But Dr. Amesh Adalja, a senior scholar with the Johns Hopkins Center for Health Security, doesn't agree that such long-term shedding in stool should affect the accuracy of wastewater COVID surveillance.

"I dont think that these findings change the value of wastewater surveillance, as weve already seen its value in real life," Adalja said. "Whats valuable about wastewater surveillance is the trend if it is increasing or decreasing, which isnt really impacted by this phenomenon."

The new study appears in the online journal Med.

More information

The U.S. Centers for Disease Control and Prevention has more about wastewater surveillance for COVID-19.

SOURCES: Ami Bhatt, MD, PhD, associate professor, medicine and genetics, Stanford University, Stanford, Calif.; William Schaffner, MD, medical director, National Foundation for Infectious Diseases; Amesh Adalja, MD, senior scholar, Johns Hopkins Center for Health Security; Med, April 12, 2022

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