187 new genetic variants linked to prostate cancer found in largest, most diverse study of its kind

An international collaboration led by USC explored the genomes of nearly 950,000 men, finding a total of 451 variants and refining what is known about genetic risk for prostate cancer.

Peer-Reviewed Publication

KECK SCHOOL OF MEDICINE OF USC

A globe-spanning scientific team has compiled the most comprehensive list of genetic variants associated with prostate cancer risk — 451 in all — through a whole-genome analysis that ranks as the largest and most diverse investigation into prostate cancer genetics yet. The research, led by the USC Center for Genetic Epidemiology, the Keck School of Medicine of USC and USC Norris Comprehensive Cancer Center, and in the United Kingdom by The Institute of Cancer Research, London, included major increases in representation among men from racial and ethnic groups that have often been left out of such research, revising what is known about genetic risk for the disease. 

With these findings, the researchers improved a system they developed for measuring genetic risk so that it was more effective in predicting who would or wouldn’t develop prostate cancer — even distinguishing between the likelihood of aggressive and less-serious cases among men of African descent. The finding that higher risk scores based on the 451 variants correlated with more-aggressive disease in men of African ancestry is a meaningful step toward improving early detection and making better informed decisions about screening.

The study, published in Nature Genetics, builds on 2021 research documented in the same journal that found 269 genetic variants correlating with prostate cancer risk, based on a sample of nearly 235,000 men. The new results were derived from genomic information from close to 950,000 men.

“We’re not going to learn everything there is to know about the genetics of prostate cancer by studying only white men,” said co-senior author Christopher Haiman, ScD, holder of the AFLAC Chair in Cancer Research and professor of population and public health sciences at the Keck School of Medicine. “Larger and larger studies, engaging a broader spectrum of populations, are important if we’re going to identify genetic markers of risk and develop risk prediction tools that are equally effective across populations.”

A substantial revision of what’s known about genetic risk for prostate cancer

The researchers compared genomic data from 156,319 prostate cancer patients with that of a control group totaling 788,443. From the previous study, there was an 87% increase in the number of prostate cancer cases included from men of African ancestry, 45% from Latino ethnicity, 43% from European ancestry and 26% from Asian ancestry.

Haiman and his colleagues found 187 new genetic variants associated with prostate cancer risk. They also found 150 genetic variants from earlier research that were replaced by variants in nearby spots on the DNA double helix that better correlated with prostate cancer risk through the lens of the larger, more diverse sample. 

“It’s an important refinement to find markers that are better at capturing risk across populations,” said Haiman, who is also director of the USC Center for Genetic Epidemiology and co-leader of the Cancer Epidemiology Program at USC Norris cancer center. “The idea of precision medicine and global medicine for all rely on including and integrating information across populations, because the best marker determined in whites might not be the best marker overall.”

Progress in assessing risk thanks to an international effort

In addition to fueling further research, the results have the potential to benefit human health by providing men with personalized risk information that they can use when having discussions with their doctors about screening and treatment. Ultimately the research could lay the ground work for genetic testing to identify those at greater risk for aggressive prostate cancer and enable early detection by screening them earlier and more often.

Because many prostate cancer cases diagnosed today might never reach the point where they are life-threatening — leading to unnecessary treatment that can degrade quality of life — differentiating between risk for aggressive disease is key. Up until now, the scientists’ system for calculating risk scores has correlated with likelihood of developing prostate cancer, but lacked predictive value about how serious a given case may be. 

“We’ll continue to improve this risk score, and look for markers that help to distinguish aggressive from less aggressive disease,” Haiman said. “Clinical trials will be required to evaluate the effectiveness of the risk score in helping doctors and patients make decisions about screening.”

This research combined the data from virtually every study to date examining DNA for genetic variants associated with prostate cancer risk. The U.S. Veterans Health Administration’s Million Veteran Program and Argonne National Laboratory proved to be essential partners [for including diverse populations in the study]. Bringing it all together required a team effort encompassing more than 300 researchers from well over 100 institutions, in 26 nations — from Barbados to Bulgaria, Nigeria to the Netherlands and Japan to Ghana. 

“This shows what happens when the world research community comes together to make improvements for all,” Haiman said. “The fact that everyone was so willing to collaborate was enormously critical.”

About this study

The first author of the study is Anqi Wang, who earned her doctorate from the Keck School of Medicine in 2023. David Conti, professor of population and public health sciences at the Keck School and associate director of data science integration at USC Norris cancer center, was co-senior author. Among hundreds of co-authors, other study collaborators associated with the Keck School are Jiayi Shen, Fei Chen, Xin Sheng, Yili Xu, Alisha Chou, Ali Sahimi, Peggy Wan, Sue Ingles, Mariana Stern, Roberta McKean-Cowdin, Zeyun Lu and Nick Mancuso.

This study was supported by the National Institutes of Health (R01CA257328, U19CA214253, U01CA261339, P01CA196569, R00CA246063) and the Prostate Cancer Foundation (20CHAS03, 21YOUN11).

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JOURNAL

Nature Genetics

DOI

10.1038/s41588-023-01534-4 

METHOD OF RESEARCH

Meta-analysis

SUBJECT OF RESEARCH

People

ARTICLE TITLE

Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants

ARTICLE PUBLICATION DATE

9-Nov-2023

 

The autism-linked gene SYNGAP1 could impact early stages of human brain development, USC study reveals

New research shows that variants of SYNGAP1, a gene previously thought only to affect synapses between mature neurons, may disrupt early development in the brain’s cortex, a region involved in higher-order cognitive functions in humans.

Peer-Reviewed Publication

KECK SCHOOL OF MEDICINE OF USC

 

IMAGE: 

TWO SCULPTURES REPRESENTING A HUMAN NEURON AND A RADIAL GLIA CELL, INSPIRED BY THE FINDINGS PUBLISHED BY THE QUADRATO LAB IN NATURE NEUROSCIENCE.

 

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CREDIT: SCULPTURES BY JANE KWAK; PHOTO BY SERGIO BIANCO

The gene SYNGAP1, the variants of which are top risk factors for Autism Apectrum Disorder (ASD), has previously unappreciated effects on the developing brain, according to a new study published in Nature Neuroscience. The study shows how disease-causing variants of SYNGAP1, thought primarily to affect synapses between mature neurons, could disrupt early development in a key region of the brain known as the cortex. 

“Our findings reframe our understanding of the developmental role not only of SYNGAP1, but also of an entire category of ASD risk genes previously thought to be primarily involved in the function of synapses, which are the interfaces that allow nerve cells to communicate with each other,” said corresponding author Giorgia Quadrato, an assistant professor of stem cell biology and regenerative medicine at the Keck School of Medicine of USC. “Ultimately, this points to the importance of pursuing ASD therapies that target not only synapse function, but also early developmental defects.”

Disease-causing variants of SYNGAP1, a gene that provides instructions for making a protein that plays a critical role in the synapses, are associated with a variety of clinical manifestations. At least half of patients with a variant of the gene have been formally diagnosed with autistic features, and the majority of patients also experience intellectual disability, developmental delay, and epilepsy. 

Until now, most research in animal models related to the SYNGAP1 protein has focused on the synapses. To explore the functions of the SYNGAP1 protein during brain development, first authors Marcella Birtele and Ashley Del Dosso in the Quadrato lab and their colleagues analyzed organoids, which are brain structures grown from human stem cells in the lab. Some of these organoids were generated from the cells of a patient with a disease-causing variant in SYNGAP1.

“Organoids have created an opportunity to explore previously inaccessible aspects of human brain development,” said Quadrato.

By analyzing the organoids, the scientists found that the progenitor cells of the brain’s developing cortex, known as radial glia cells, contain the protein coded by the SYNGAP1 gene. Previously, it was thought that this SYNGAP1 protein was only found in the synapses of neurons within the cortex.

The scientists also pinpointed specific ways in which a decreased level of the SYNGAP1 protein, which can result from different disease-causing SYNGAP1 gene variants in patients, disrupts early cortical development. Within the radial glia, a decreased level of the SYNGAP1 protein altered the cells’ cytoskeletons, which are networks of protein fibers that provide structure and support. 

The altered radial glia had a tendency to accelerate their differentiation into what are ultimately dysfunctional mature nerve cells, known as cortical projection neurons, which did not migrate properly to form well-organized neural circuits.

These results suggest that disease-causing SYNGAP1 variants can lead to the development of a disorganized cortex with disordered circuitry and altered neural activity in patients. The impaired neuronal excitability seen in SYNGAP1 patients could have its roots in these early developmental changes, in addition to synapse malfunction, as previously thought.

The findings could eventually lead to new ways to treat disorders caused by SYNGAP1 variants, according to Jonathan Santoro, an assistant professor of clinical neurology pediatrics at Children’s Hospital Los Angeles (CHLA).

“The Quadrato lab’s novel techniques and focus on neurogenetic disorders has begun to change our field’s understanding of neurodevelopmental disorders,” said Santoro. “Through continued collaborations between CHLA and USC, we hope to identify therapeutic targets for the treatment of these conditions in the future.”

“Every time somebody studies SYNGAP, we find out it does something else,” said Mike Graglia, whose son carries a SYNGAP1 variant, and who serves as the managing director of the SynGAP Research Fund, which provided support for the study. “The dogma is that all disease-causing variants have the same impact. In real life, it’s way more complicated. And what we’re starting to see is that these patients with different disease-causing variants have variable presentations. So, the depth of Giorgia’s work helps us understand these differences.”

About the study

Additional authors include Tiantian Xu from USC and Xiangya Hospital at Central South University in China; Tuan Nguyen, Brent Wilkinson, Negar Hosseini, Sarah Nguyen, Jean-Paul Urenda, Ilse Flores, Alexander Atamian, and Marcelo P. Coba from USC; Gavin Knight and Randolph S. Ashton from the University of Wisconsin-Madison; Camilo Rojas, Ritin Sharma, Patrick Pirrotte, and Gavin Rumbaugh from the University of Florida Scripps Biomedical Research Institute and Scripps Research; Roger Moore from City of Hope Comprehensive Cancer Center; and Eric J. Huang from City of Hope Comprehensive Cancer Center and the Translational Genomics Research Institute in Phoenix. 

The majority of the funding came from private sources, including the SynGAP Research Fund, the Donald D. and Delia B. Baxter Foundation, the Edward Mallinckrodt Jr. Foundation, and The Eli and Edythe Broad Foundation. Additional support came from federal funding from the National Science Foundation (grant 5351784498), the National Institute of Mental Health (grant MH115005), and the National Cancer Institute (grant P30CA033572).

Knight and Ashton are inventors on U.S. patent application number 16/044236 that describes methods for generating microarrayed single rosette cultures and are co-founders of Neurosetta LLC.

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JOURNAL

Nature Neuroscience

DOI

10.1038/s41593-023-01477-3 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

Lab-produced tissue samples

ARTICLE TITLE

The autism-associated gene SYNGAP1 regulates human cortical neurogenesis

ARTICLE PUBLICATION DATE

9-Nov-2023

COI STATEMENT

Gavin Knight and Randolph S. Ashton are inventors on U.S. Patent App. No. 16/044236 that describes methods for generating microarrayed single rosette cultures, and they are co-founders of Neurosetta LLC that is focused on commercializing the culture platform.

Publishersweekly.com

http://www.publishersweekly.com/9780061230943

The Last Oracle: A Sigma Force Novel - Publishers Weekly

 

The Last Oracle: A Sigma Force Novel. James Rollins, . . Morrow, $26.95 (448pp) ISBN 978-0-06-123094-3.

Fantasticfiction.com

https://www.fantasticfiction.com/r/james-rollins/last-oracle.htm

The Last Oracle (Sigma Force, book 5) by James Rollins

 

A master at combining historical and religious intrigue with edge-of-your-seat adventure, New York Times bestselling author James Rollins brings back SIGMA ...

Fantasybookcritic.blogspot.com

https://fantasybookcritic.blogspot.com/2008/06/last-oracle-by-james-rollins-wbonus-q.html

"The Last Oracle" by James Rollins w/Bonus Q&A...

 

Jun 23, 2008 ... “The Last Oracle” is the fifth entry in the Sigma Force series and like the others, the book is self-contained, although it does deal with a ...

AMERIKA PRISON NATION

Almost half of people who use drugs in rural areas were recently incarcerated

OHSU lead author of nationwide study says findings highlight prime opportunity to provide effective addiction treatment while people are in custody

Peer-Reviewed Publication

OREGON HEALTH & SCIENCE UNIVERSITY

New research finds that almost half of people who use illicit drugs in rural areas have been recently incarcerated.

Results from a survey of almost 3,000 people in eight rural areas nationwide who report using illicit drugs published today in the journal JAMA Network Open. The study found that 42% had been incarcerated, either in prison or local jails, in the preceding six months.

The study was conducted by researchers at Oregon Health & Science University and institutions across 10 states.

The findings suggest a prime opportunity to tackle the nation’s opioid crisis by expanding addiction treatment to people while they’re incarcerated. Currently, access to proven therapies such as medication to treat addiction is limited or unavailable in many jails.

“You have a reachable time in jails, and most jails are not providing this kind of addiction care,” said lead author Dan Hoover, M.D., assistant professor of medicine (general internal medicine and geriatrics) in the OHSU School of Medicine. “In a broader sense, our correctional institutions have a mandate to rehabilitate people who have entered the system — and treating addiction is a huge part of that.”

Effective treatment during incarceration can benefit communities overall, Hoover noted.

He cited a study in Rhode Island that measured a 12% decrease in all overdoses statewide after the state implemented medication-assisted therapy in its prison system in 2016. Conversely, Hoover noted that forcing incarcerated individuals to go through withdrawal without treatment leaves them more vulnerable to resuming drug use, criminal conduct and a heightened risk of overdose once they’re released.

“Many of these individuals are released back to the community within days,” Hoover said. “Their health is community health. That time in jail is the reachable moment to begin their path to treatment and recovery.”

Survey spans rural areas in 10 states

Researchers examined data from the Rural Opioid Initiative, a survey taken in eight rural U.S. regions from January 2018 to March 2020. The new study included 2,935 people who reported illicit drug use in the previous 30 days, inquiring about their substance use and treatment, and interactions with the criminal justice system.

The survey covered 65 rural counties across eight distinct regions spanning Oregon, Illinois, Wisconsin, North Carolina, Kentucky, West Virginia, Ohio, Massachusetts, New Hampshire and Vermont.

The study cited recent efforts in jurisdictions such as New Jersey and Seattle to develop pathways toward treatment and recovery for inmates while they’re incarcerated and when they’re released. For people with opioid use disorder, Food and Drug Administration-approved medications include methadone, buprenorphine and naltrexone, but the authors noted that those are rarely provided in American prison systems.

Oregon provides access to buprenorphine within the state prison system, but access remains spotty in local jails.

“Lack of criminal legal system funding apportioned for (substance use disorder, or SUD) treatment and lack of health insurance coverage during incarceration further contribute to poor SUD treatment access for this population,” the authors write.

Data were collected and methods developed through the Rural Opioid Initiative, a multi-site study developed collaboratively by investigators at eight research institutions and the National Institute on Drug Abuse of the National Institutes of Health, the Appalachian Regional Commission, the Centers for Disease Control and Prevention and the Substance Abuse and Mental Health Services Administration.

Funding support for the research reported in this press release was provided through grant awards U24DA048538, UG3DA044829/UH3DA044829, UG3DA044798/UH3DA044798, UG3DA044830/UH3DA044830, UG3DA044823/UH3DA044823, UG3DA044822/UH3DA044822, UG3DA044831/UH3DA044831, UG3DA044825, UG3DA044826/UH3DA044826, U24DA044801, and UL1TR002369 co-funded by NIDA, ARC, CDC and SAMHSA. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

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JOURNAL

JAMA Network Open

DOI

10.1001/jamanetworkopen.2023.42222 

METHOD OF RESEARCH

Survey

SUBJECT OF RESEARCH

People

ARTICLE TITLE

Recent Incarceration, Substance Use, Overdose, and Service Use Among People Who Use Drugs in Rural Communities

ARTICLE PUBLICATION DATE

9-Nov-2023

 

UChicago's Pritzker School of Molecular Engineering advances lithium-metal batteries, paving the way for safer, more powerful devices

In a study published in Matter, Professor Chibueze Amanchukwu charts a path toward better energy storage to combat climate change

Peer-Reviewed Publication

UNIVERSITY OF CHICAGO

The boom in phones, laptops and other personal devices over the last few decades has been made possible by the lithium-ion (Li-ion) battery, but as climate change demands more powerful batteries for electric vehicles and grid-scale renewable storage, lithium-ion technology might not be enough.

Lithium-metal batteries (LMBs) have theoretical capacities an order of magnitude greater than lithium-ion, but a more literal boom has stymied research for decades.

“A compounding challenge that further doomed the first wave of LMB commercialization in the late 1980s was their propensity to explode,” University of Chicago’s Pritzker School of Molecular Engineering Prof. Chibueze Amanchukwu wrote in a recent study.

The study to be published Nov. 9 in Matter, outlines a way around this decades-old problem, using solvent-free inorganic molten salts to create energy-dense, safe batteries, opening new possibilities for EVs and grid scale renewable energy storage.

“We have developed a non-flammable, non-volatile system that is safe and can actually improve energy densities by 2x (compared to Li-ion),” Amanchukwu said.

Conventional lithium-metal batteries rely on an electrolyte made by dissolving lithium salt in a solvent. Those volatile, flammable solvents – not the salt itself – caused those safety concerns.

To combat this, researchers have tried different solvents or phases or they tinkered with the salt concentration. It was always a trade-off: Batteries using solid-state inorganics for their electrolytes were safer; batteries using liquid electrolytes were more powerful. The results remained either unsafe batteries or batteries that didn’t live up to lithium-metal batteries’ massive theoretical capabilities. 

Amanchukwu’s team took a novel approach, questioning the conventional structure of the electrolyte itself.

“The question was what’s the solvent doing there in the first place? Just remove it,” Amanchukwu said.

Amanchukwu’s team made the lithium salt a liquid not by dissolving it, but by melting it. This required creating a new composition of salt that melts at low temperatures. The challenge was to hit a temperature where the lithium salt melts, but the lithium metal used elsewhere in the battery doesn’t.

To give a sense of the scope of the task, pure lithium chloride melts at just over 600° C. Lithium metal melts at 180° C, meaning any useful molten salt electrolyte would have to have a far lower melting point.

Amanchukwu and his team created a salt that melts at 45° C, resulting in a powerful battery that can operate safely at 80-100° C.

“That was a sweet spot to be in the middle, to still have all the safety benefits but operate at temperatures that allow it to be liquid,” Amanchukwu said.

Amanchukwu’s group is continuing to work on salt compositions with even lower melting points, with the final goal of a powerful lithium-metal battery that will operate safely at room temperature.

“How can you get this down to 25° C or 30° C? From a research and applied point of a view, there’s lots of excitement there,” Amanchukwu said. “We have the opportunity to create a very impactful battery that helps to solve a key global challenge – energy storage.”

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JOURNAL

Matter

DOI

10.1016/j.matt.2023.10.017 

ARTICLE TITLE

Low melting alkali-based molten salt electrolytes for solvent-free lithium metal batteries

ARTICLE PUBLICATION DATE

9-Nov-2023

 

Cornell chemists image basic blocks of synthetic polymers

Peer-Reviewed Publication

CORNELL UNIVERSITY

ITHACA, N.Y. -- Synthetic polymers are everywhere in our society – from nylon and polyester clothing to Teflon cookware and epoxy glue. At the molecular level, these polymers’ molecules are made of long chains of monomer building blocks, the complexity of which increases functionality in many such materials.

In particular, copolymers, which consist of different types of monomers in the same chain, allow for fine-tuning of the material’s properties, said Peng Chen, the Peter J.W. Debye Professor of Chemistry in the College of Arts and Sciences (A&S). The monomer sequence plays a critical role in a material’s properties, but scientists until now have lacked a method for sequencing synthetic copolymers.

Chen and colleagues have developed CREATS (Coupled REaction Approach Toward Super-resolution imaging), which allows them to image polymerization catalysis reactions at single-monomer resolution and, through fluorescent signaling, to differentiate monomers from one another. Both are important steps in discovering the molecular composition of a synthetic polymer.

They describe the technique and the first discoveries they’ve made with it in “Optical Sequencing of Single Synthetic Polymers,” published Nov. 9 in Nature Chemistry.

Co-lead authors are Rong Ye, Xiangcheng Sun and Xianwen Mao, all former postdoctoral researchers in the Chen group. Co-authors are former Chen group postdoctoral researchers Susil Baral and Chunming Liu, current postdoctoral researcher Felix Alfonso, and Geoffrey Coates, the Tisch University Professor in chemistry and chemical biology (A&S).

“Synthetic polymers are made of monomer units linked together like a string of beads,” Chen said. In the simplest polymers, the monomers are identical, but more complex properties arise when polymers contain monomers of different sorts – called copolymers. The precise arrangement of the monomers in a copolymer plays an important role in its properties, such as stiffness or flexibility.

Sequence plays a role in the properties of natural polymers, too, Chen said. A protein, for example, is made of 20 amino acid monomers arranged in a very specific sequence.

“In a natural polymer, nature has control,” Chen said. “In synthetic polymers, humans are making the arrangements, and the chemists generally don’t have that precise control.”

Sequencing copolymers is so difficult in large part because of heterogeneity in synthetic polymers, Chen said. Individual chains differ in length, composition and sequence, which requires single-polymer sequencing methods that can resolve and identify individual monomers.

Some modern methods allow scientists to control the arrangement of monomers in a chain, Chen said, but only for very short polymers – 10 to 20 monomers long.

Using CREATS, the researchers can determine the sequence of a polymer as it is made, one monomer at a time, by imaging and identifying every single monomer as it is added to the polymer. To make the monomers visible, CREATS couples the polymerization reaction with another reaction that produces fluorescent signals.

“Every monomer that goes in gives off a puff of light,” Chen said. “The light is induced by a laser, and the puff of light has a color. In our case, it’s either green or yellow. By seeing whether it’s yellow or green, we see what monomer goes in.”

The lab is already equipped to measure synthetic polymer properties. Now that they can determine the sequence of an individual polymer, a next step is to combine the two experiments to correlate structure and function, ultimately providing guiding principles for polymer design to achieve certain properties.

“If you know how sequence controls property, you can really think about designing whatever sequence you want to achieve a certain property,” Chen said. “This knowledge presumably can help people tailor their materials for a desired application.”

The research was funded by the Polymer Chemistry program of Army Research Office, a directorate of the U.S. Army Combat Capabilities Development Command Army Research Laboratory.

-30-

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JOURNAL

Nature Chemistry

DOI

10.1038/s41557-023-01363-2 

 

Is the US reporting system for vaccine safety broken?

Investigation raises concerns that the system is not operating as intended and signals are being missed

Peer-Reviewed Publication

BMJ

A US reporting system designed to detect potential safety issues with vaccines is supposed to be user-friendly, responsive, and transparent. But an investigation published by The BMJ today finds it’s not meeting its own standards.

The Vaccine Adverse Event Reporting System (VAERS), co-managed by the US Centers for Disease Control and Prevention (CDC) and the Food and Drug Administration (FDA), collects reports of symptoms, diagnoses, hospitalisations, and deaths following vaccination that might indicate a possible safety concern about a vaccine, explains journalist Jennifer Block. 

It relies on a mixture of voluntary adverse event reports from doctors and patients and mandatory reporting from vaccine manufacturers, which are required by law to report all adverse events of which they are aware.

According to VAERS’ standard operating procedure for covid-19, reports must be processed quickly, within days of receipt.

But The BMJ has learned that in the face of an unprecedented 1.7 million reports since the rollout of the covid-19 vaccines, VAERS staffing was likely not commensurate with the demands of reviewing serious reports submitted, including reports of death. 

Freedom of Information Act (FOIA) documents seen by The BMJ suggest that Pfizer has more than 1,000 more full time employees than the CDC, despite the latter’s responsibility for handling adverse event reports for all manufacturers.

What’s more, other countries have acknowledged deaths “likely” or “probably” related to mRNA vaccination, whereas the CDC, which says it has reviewed nearly 20,000 reports (far more than other countries) hasn’t acknowledged a single death linked to mRNA vaccine.

The BMJ has spoken to more than a dozen people, including a number of physicians and a state medical examiner, who have filed VAERS reports of a serious nature on behalf of themselves or patients and were never contacted by clinical reviewers, or were contacted months later. 

Some were told conflicting information about updating their report or discouraged from making a report altogether.

A group of physicians and advocates have met multiple times with representatives of the FDA between 2021 and 2022 to express their concerns that the system is not operating as intended and signals are being missed. 

In response to several questions about these meetings and the issues raised therein, the FDA responded by email that the agency “is actively engaged in safety surveillance of these vaccines to identify and address potential safety concerns” and that “physicians and epidemiologists from the FDA and CDC continuously screen and analyse data from VAERS for covid-19 vaccines to identify potential signals that would indicate the need for further study.”

The BMJ has also found that the FDA and CDC essentially maintain two separate VAERS databases - a public-facing database containing only initial reports, and a private, backend system containing all updates and corrections - for example, a formal diagnosis, recovery, or a death.

CDC told The BMJ that this was to protect patient confidentiality. Yet, interestingly, Block notes that the FDA’s adverse event reporting system (FAERS), which collects reports on drugs, does maintain a publicly accessible database that gets updated, as does the Medical Device Reporting system, raising the question of why VAERS can’t do the same.

Neither the CDC nor the FDA provided an explanation. An FDA spokesperson told The BMJ that “patients can submit formal requests under FOIA to obtain the full record of their report.”

For serious cases, reporters to VAERS are supposed to receive emails prompting them for updates. It includes a code and upload link, but reporters The BMJ spoke with didn’t get confirmation emails, and if they search for their report in the database it will remain unchanged. Similarly, if a reporter successfully treated their diagnoses and improved, or confirmed that the cause for their illness was unrelated to a vaccine, that would not be reflected in the public database.

Narayan Nair, the FDA division director who oversees VAERS, acknowledged in a meeting with advocates that people get frustrated when they look for an updated report, find the original untouched, and feel like they’re “being ignored.” “They never see it on the front end, because we don't alter that initial report.”

[Ends]

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JOURNAL

The BMJ

DOI

10.1136/bmj.p2582 

ARTICLE TITLE

Investigation: Is the US’s Vaccine Adverse Event Reporting System broken?

ARTICLE PUBLICATION DATE

10-Nov-2023

The enigma of embryonic development: How certain animals trim their genomes

New research is underway to decipher a fascinating biological puzzle—how some animals can naturally discard more than half of their genetic information during embryonic development.

Grant and Award Announcement

UNIVERSITY OF WARWICK

 

IMAGE: 

GENOME COMPARISON WITH ANNOTATIONS

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CREDIT: CREDIT UNIVERSITY OF WARWICK

 

New research is underway to decipher a fascinating biological puzzle—how some animals can naturally discard more than half of their genetic information during embryonic development.

 

This radical natural phenomenon has captivated scientists for over 130 years, presenting a tantalizing question in the field of developmental biology and genetics.

 

Equipped with the latest in genetic engineering tools, the team at The University of Warwick is working to dissect the mechanisms behind this selective genomic editing. By uncovering the processes that allow some nematode worms to abandon up to 60% of the genetic material of some of their cells, the researchers hope to develop biotechnological tools that could enable large-scale, precise genomic alterations. These can be applied in different areas – from engineering models of hereditary diseases, helping to drive medical advancements and treatments, to improving crop resilience to harsh environmental conditions in the agricultural industry.

 

The new study is part of the Biotechnology and Biological Sciences Research Council’s (BBSRC) Pioneer Awards, which could revolutionise our understanding of the rules of life. Sixty two  researchers across the UK, including Professor Andre Pires da Silva at the University of Warwick, are to receive a share of £12 million to pursue visionary bioscience research.

 

By drawing upon unconventional thinking and approaches, the investigators hope to make exciting discoveries with the potential to transform our understanding of the fundamental rules of life. These new investigations aim to radically change the way we think about important biological phenomena covering plant, microbial and animal sciences.

 

The investment by the Biotechnology and Biological Sciences Research Council’s (BBSRC) Pioneer Awards enables the pursuit of unique ideas that challenge current thinking and paradigms or open up entirely novel areas of exploration altogether.

 

Professor Andre Pires da Silva, School of Life Sciences, University of Warwick, said: “Funding opportunities for curiosity-driven studies have led to several important discoveries with practical applications. This includes the development of the polymerase chain reaction (PCR) technique, which is now widely used in biomedical research for amplifying DNA. The BBSRC is giving us a tremendous chance to explore a unique way of genome regulation, which may also help in building new tools to help areas such as medicine and agriculture.”

 

Professor Guy Poppy, Interim Executive Chair at BBSRC, added: “Understanding the fundamental rules of life, such as the principles governing genetics, evolution and biological processes, is essential for advancing scientific knowledge. It is also imperative to societal progress.

 

“Many of the challenges faced by today's society, such as global food security, environmental sustainability and healthcare, are deeply rooted in biological processes.

 

“BBSRC is committed to understanding the rules of life and by investing in cutting-edge discovery research through schemes such as the Pioneer Awards pilot, we are expanding the horizons of human knowledge while helping to unlock innovative bio-based solutions to some of the world's most pressing challenges.”

 

Notes to Editors

 

About the Pioneer Awards

BBSRC’s pilot pioneer awards scheme aimed to support original and potentially transformative research at an early stage of development. The scheme was designed to stimulate creativity within the bioscience research community by providing funding that encourages a ‘high-risk, high-reward’ research culture. The funded projects represent either a significant departure from existing lines of investigation within the research field or an entirely new line of inquiry.

Focused on BBSRC’s understanding the rules of life theme, the projects open up new research directions relevant to fundamental bioscience questions and have the potential to substantially shift current and future thinking about key topics.

 

The projects:

 

• are original and visionary, challenging current thinking and paradigms
• focus on exploring and revealing novel insights and theories relating to our fundamental understanding of biological systems
• are early stage and untested, lacking preliminary data and perhaps involving creative or unconventional approaches to the research challenge
• may involve a high level of uncertainty or require a range of exploratory investigations, such that while there are clear aims to explore, the outcomes are neither predictable nor guaranteed
• involve any combination of experimental, analytical and theoretical work, potentially crossing disciplinary boundaries, including non-bioscience fields

 

A review of the pilot call is underway. 

About BBSRC

BBSRC is part of UK Research and Innovation (UKRI) and invests in world-class bioscience research and training on behalf of the UK public. Our aim is to further scientific knowledge, to promote economic growth, wealth and job creation and to improve quality of life in the UK and beyond. 

 

Funded by government, BBSRC invested £451 million in world-class bioscience in 2019-20. We support research and training in universities and strategically funded institutes. BBSRC research and the people we fund are helping society to meet major challenges, including food security, green energy and healthier, longer lives. Our investments underpin important UK economic sectors, such as farming, food, industrial biotechnology and pharmaceuticals.