Pancreatic Cancer Vaccine Shows Promise in Small Trial

Using mRNA tailored to each patient’s tumor, the vaccine may have staved off the return of one of the deadliest forms of cancer in half of those who received it.Five years ago, a small group of cancer scientists meeting at a restaurant in a deconsecrated church hospital in Mainz, Germany, drew up an audacious plan: They would test their novel cancer vaccine against one of the most virulent forms of the disease, a cancer notorious for roaring back even in patients whose tumors had been removed.The vaccine might not stop those relapses, some of the scientists figured. But patients were desperate. And the speed with which the disease, pancreatic cancer, often recurred could work to the scientists’ advantage: For better or worse, they would find out soon whether the vaccine helped.On Wednesday, the scientists reported results that defied the long odds. The vaccine provoked an immune response in half of the patients treated, and those people showed no relapse of their cancer during the course of the study, a finding that outside experts described as extremely promising.The study, published in Nature, was a landmark in the yearslong movement to make cancer vaccines tailored to the tumors of individual patients.Researchers at Memorial Sloan Kettering Cancer Center in New York, led by Dr. Vinod Balachandran, extracted patients’ tumors and shipped samples of them to Germany. There, scientists at BioNTech, the company that made a highly successful Covid vaccine with Pfizer, analyzed the genetic makeup of certain proteins on the surface of the cancer cells.Using that genetic data, BioNTech scientists then produced personalized vaccines designed to teach each patient’s immune system to attack the tumors. Like BioNTech’s Covid shots, the cancer vaccines relied on messenger RNA. In this case, the vaccines instructed patients’ cells to make some of the same proteins found on their excised tumors, potentially provoking an immune response that would come in handy against actual cancer cells.“This is the first demonstrable success — and I will call it a success, despite the preliminary nature of the study — of an mRNA vaccine in pancreatic cancer,” said Dr. Anirban Maitra, a specialist in the disease at the University of Texas MD Anderson Cancer Center, who was not involved in the study. “By that standard, it’s a milestone.”The study was small: Only 16 patients, all of them white, were given the vaccine, part of a treatment regimen that also included chemotherapy and a drug intended to keep tumors from evading people’s immune responses. And the study could not entirely rule out factors other than the vaccine having contributed to better outcomes in some patients.“It’s relatively early days,” said Dr. Patrick Ott of the Dana-Farber Cancer Institute.Beyond that, “cost is a major barrier for these types of vaccines to be more broadly utilized,” said Dr. Neeha Zaidi, a pancreatic cancer specialist at the Johns Hopkins University School of Medicine. That could potentially create disparities in access.But the simple fact that scientists could create, quality-check and deliver personalized cancer vaccines so quickly — patients began receiving the vaccines intravenously roughly nine weeks after having their tumors removed — was a promising sign, experts said.Since the beginning of the study, in December 2019, BioNTech has shortened the process to under six weeks, said Dr. Ugur Sahin, a co-founder of the company, who worked on the study. Eventually, the company intends to be able to make cancer vaccines in four weeks.And since it first began testing the vaccines about a decade ago, BioNTech has lowered the cost from roughly $350,000 per dose to less than $100,000 by automating parts of production, Dr. Sahin said.A personalized mRNA cancer vaccine developed by Moderna and Merck reduced the risk of relapse in patients who had surgery for melanoma, a type of skin cancer, the companies announced last month. But the latest study set the bar higher by targeting pancreatic cancer, which is thought to have fewer of the genetic changes that would make it ripe for vaccine treatments.In patients who did not appear to respond to the vaccine, the cancer tended to return around 13 months after surgery. Patients who did respond, though, showed no signs of relapse during the roughly 18 months they were tracked.Intriguingly, one patient showed evidence of a vaccine-activated immune response in the liver after an unusual growth developed there. The growth later disappeared in imaging tests.“It’s anecdotal, but it’s nice confirmatory data that the vaccine can get into these other tumor regions,” said Dr. Nina Bhardwaj, who studies cancer vaccines at the Icahn School of Medicine at Mount Sinai.Scientists have struggled for decades to create cancer vaccines, in part because they trained the immune system on proteins found on tumors and normal cells alike.Tailoring vaccines to mutated proteins found only on cancer cells, though, potentially helped provoke stronger immune responses and opened new avenues for treating any cancer patient, said Ira Mellman, vice president of cancer immunology at Genentech, which developed the pancreatic cancer vaccine with BioNTech.“Just establishing the proof of concept that vaccines in cancer can actually do something after, I don’t know, thirty years of failure is probably not a bad thing,” Dr. Mellman said. “We’ll start with that.”

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Scientist Looks Anew at Raccoon Dog Data, Stressing the Unknowns

After analyzing genetic data swabbed from a Wuhan market in early 2020, a virologist said it was unclear if animals for sale there had been infected.A new study of genetic data from a market in Wuhan, China, said the data did not support the case that the pandemic had started with illegally traded animals, touching off fresh debate about samples that other scientists see as critical pieces of the puzzle of how the coronavirus reached humans.The new study, which examined the relative amounts of animal and viral material in swabs taken from surfaces at the market in early 2020, said it was difficult to draw conclusions about whether given samples of the virus had come from infected live animals or were simply from incidental contamination.But several outside experts said the analysis, posted online this week by the study’s author, Jesse Bloom, a virologist at the Fred Hutchinson Cancer Center, could have been affected by a number of unknown variables and decisions about how to filter the data.For those reasons, they said, the findings did not do much to sway their impression of previous studies. Samples from the market containing animal and viral genetic material, they said, were consistent with the possibility that an animal there — perhaps a raccoon dog — had spread the virus to people, but did not prove that had happened.“I think there’s a pretty reasonable chance they picked up an infected raccoon dog, but that doesn’t prove that was the origin,” said Frederic Bushman, a microbiologist at the University of Pennsylvania who specializes in analyzing samples like those taken from the Wuhan market, but who was not involved in any of the market studies. “I don’t think the Bloom paper changes my thinking that much.”Chinese researchers wrote about the market data last year and then made the genetic sequences available this year, allowing a team of international scientists to study them. That team wrote in a report last month that based on the data, they could not conclusively identify an animal that had passed the virus to people.But they said the data confirmed that animals believed to be susceptible to the virus, like raccoon dogs and masked palm civets, a small Asian mammal implicated in the SARS outbreak two decades ago, were being sold at the market in late 2019. Many of the earliest Covid-19 patients also worked or shopped at the market.Because the market was one of only four places in Wuhan reported to be selling live animals of the sort that could plausibly spread the virus, the scientists said it was unlikely that so many early patients were linked to the market purely by chance. They said the genetic data also built on other evidence, including that two early lineages of the virus had been at the market.This week’s study took a different approach to analyzing the gene sequences.Dr. Bloom investigated whether the amount of genetic material from the virus correlated with the amount of genetic material from susceptible animal species in the samples. If one species at the market was overwhelmingly responsible for shedding the virus, he said in an interview, he would have expected to see a clear link between the amount of genetic material from the virus and the amount from that species.But the study found no clear correlations of that kind. Instead, the strongest correlations involved various fish sold at the market that could not have been infected, an indication that infected people had probably deposited viral material where the fish was.Dr. Bloom said that finding suggested that the virus, also known as SARS-CoV-2, was spread widely across the market by the time the swabs were collected in early 2020.“In the same way we shouldn’t read much of anything into the fact that there’s a bunch of SARS-CoV-2 mixed with largemouth bass and catfish samples, we also shouldn’t read much into the fact that there’s a raccoon dog sample with a SARS-CoV-2 read,” Dr. Bloom said.A common raccoon dog.Buschkind/AlamyBut outside experts said that various features of the samples could throw off efforts to correlate animal and viral material. The international scientists said in their report that they had considered running a similar analysis, but that it risked producing misleading results. Dr. Bloom acknowledged that “it’s an open question of whether that is an informative thing to calculate at all.”Genetic material from the virus degrades quickly, said Christopher Mason, a specialist in environmental sampling at Weill Cornell Medicine. Crucially, viral material may decay at a different rate than material from animals, making it difficult to compare them in samples collected over the course of weeks after the market’s closure.It could be that fish were most closely associated with the virus simply because the fish were likely to have been frozen or refrigerated, slowing the decay of viral material in those samples, said Tom Wenseleers, an evolutionary biologist at KU Leuven in Belgium.The latest analysis “confirms that looking at these sorts of correlations tells you next to nothing with respect to which host species could have been a plausible source of the pandemic,” Dr. Wenseleers said. This leaves scientists in the same situation as before, he said, with market data that doesn’t offer conclusive evidence of any particular origin scenario.The new study also looked closely at a swab from a cart at the market in which the international team had found a trace of the virus alongside genetic signatures of raccoon dogs, but no detectable genetic material from humans.Dr. Bloom wrote that the swab had only a minuscule amount of viral material, and that it was not clear why Chinese researchers had classified the swab as Covid-positive. His study said that swab was the only one that had substantial amounts of raccoon dog genetic material with any traces of the virus.Some scientists, though, said Dr. Bloom’s analysis risked dismissing other Covid-positive swabs by setting too high of a bar for the amount of animal genetic material in a sample.Dr. Bushman, of the University of Pennsylvania, said that the threshold used in the analysis was “aggressive” and that it was best to compare results obtained from a series of different cutoffs.Using a more sensitive threshold, the international team of scientists identified multiple Covid-positive samples containing raccoon dog genetic material, as well as others with genetic signatures of different animals thought to be susceptible to the virus.Alexander Crits-Christoph, a computational biologist formerly at Johns Hopkins University who helped lead the international team’s analysis, said the team also looked closely at whether the Chinese researchers had been right to describe the swab from the cart as positive for the virus.He noted that a number of other swabs from the same stall were clearly positive for the virus. He said results from sampling elsewhere in the market also indicated that unlike the swab from the cart, most of the truly negative swabs contained no traces of the virus at all.“This is environmental sampling of a virus that is a tiny needle in a haystack,” Dr. Crits-Christoph said.

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China Publishes Data Showing Raccoon Dog DNA at Wuhan Market

Scientists from the Chinese C.D.C. confirmed that DNA from raccoon dogs and other animals susceptible to the coronavirus was found at the market in early 2020.Chinese government scientists on Wednesday published a long-awaited study about a market in the city of Wuhan, acknowledging that animals susceptible to the coronavirus were there around the time the virus emerged. But the scientists also said that it remained unclear how the pandemic began.The study, published in the journal Nature, focused on swabs taken from surfaces in early 2020 at the Huanan Seafood Wholesale Market, a large market where many of the earliest known Covid patients had worked or shopped. The Chinese scientists had posted an early version of their genetic analysis of those samples in February 2022, but at the time downplayed the possibility of animal infections at the market.The scientists, many of whom are affiliated with the Chinese Center for Disease Control and Prevention, also wanted to publish their data in a peer-reviewed journal. And as part of that process, the scientists uploaded more genetic sequence data to a large international database, the administrators of the database said last month.A few weeks after the data became public, a team of international scientists who had been studying the origins of the pandemic said they stumbled upon the sequences. They found that samples testing positive for the coronavirus contained genetic material belonging to animals, including large amounts that were a match for the raccoon dog, a fluffy mammal sold for fur and meat that was known to be able to spread the coronavirus.That analysis, the subject of a report posted online in late March, did not prove that a raccoon dog itself was infected or that animals gave the virus to people. But it established that raccoon dogs deposited their genetic signatures in the same place where genetic material from the virus was left.Many virologists said that scenario was consistent with one in which the virus spilled into people from an illegally traded wild animal at the market.It appeared that the international team’s analysis sped up the release of the Chinese scientists’ study about the same data: The article appeared on Wednesday on Nature’s website with a note saying that it had been accepted for publication, but was still an “early version” and had not yet been edited.Several authors of the article affiliated with the Chinese C.D.C., William J. Liu, George Gao and Guizhen Wu, did not respond to requests for comment.In their first version of the article from February 2022, the Chinese authors did not mention finding any genetic material from raccoon dogs in the market swabs, which were taken from walls, floors, metal cages and carts. Beyond that, they said that the data did not point to any infected animals.But in Wednesday’s version a little more than a year later, they wrote that the study “confirmed the existence of raccoon dogs” and other animals susceptible to the coronavirus at the market.Many scientists believe that the existing evidence points to those animals likely acting as so-called intermediate hosts for the virus, which probably originated in bats. But they also say the evidence does not completely rule out a scenario in which people gave the virus to animals at the market.The Chinese authors stressed that uncertainty in the new study. They also raised the notion that the virus could have been ferried to the Wuhan market on packages of frozen food, also known as cold chain products. Many scientists consider that scenario highly improbable, but China has promoted it because it gives credence to the idea that the pandemic could have started outside of the country and arrived via imported foods.“The possibility of potential introduction of the virus to the market through infected humans, or cold chain products, cannot be ruled out yet,” the article said.The study included several other unlikely findings as well, outside scientists said in interviews on Wednesday. For example, it said that the swabs contained genetic material from a number of animals that were almost certainly not present at the market, including pandas, chimpanzees and mole-rats.Alice Hughes, an associate professor at the University of Hong Kong focused on conservation biology, said that the inclusion of those animals suggested either that the authors had incorrectly categorized the genetic material or that the samples were contaminated during sequencing in a lab.“This paper’s greatest asset is the fact that it releases a data set for other scientists to analyze more carefully and responsibly,” Dr. Hughes said. “Given the glaring errors in this analysis, the analysis has not been done in a way that’s careful enough to have confidence in any of the results.”Asked how Nature’s peer-review process had treated the species findings, a spokesman for the journal noted that the authors included a caveat that the list of species identified at the market was “not definitive” and more analysis was required.For the international scientists who had first reported finding signs of raccoon dogs in the Covid-positive swabs last month, the latest Nature study left a number of important questions unanswered about the methods used by the Chinese team to analyze the sequences.Still, the publication, as well as an earlier version of it posted online by the Chinese scientists last week, did supply critical new data, including the number of swabs taken from each stall in the market, said Alexander Crits-Christoph, a former postdoctoral researcher and computational biologist at Johns Hopkins University who helped lead the international team’s analysis.With that information, Dr. Crits-Christoph said that he and his collaborators were able to confirm an important finding: Swabs taken from a corner of the market selling wild animals were more likely to test positive for the virus, a result that could not be explained merely by Chinese researchers having taken more samples from that corner, he said.“It’s an extremely impressive data set and its importance is quite high,” Dr. Crits-Christoph said of the market samples. “And because of that, I think it’s a good thing this data has been published in the scientific record, even if I don’t agree with every interpretation.”

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Report of Wuhan Market Samples Found Covid and Animal Mixtures

In a much-anticipated study, experts described a swab that contained loads of genetic material from the coronavirus and raccoon dogs.On Jan. 12, 2020, Chinese investigators combing a market for clues about the outbreak of a mysterious new illness in the city of Wuhan swabbed a cart. It was the kind typically used for transporting animal cages, and it came back positive for the coronavirus.Three years later, a team of international experts has sifted through the genetic contents of that swab, which were quietly uploaded to an international database and made public only this year. In a report released on Monday night, the scientists described in detail for the first time evidence from the swab that they say strengthens the case that illegally traded wild animals ignited the coronavirus pandemic.Chinese researchers who had originally uploaded the raw data had it removed from the database after they were contacted by the international team. Now administrators of the database itself have cut off access to the international scientists for what they said were rules violations, raising questions about the database’s own role in the tug of war over access to data that could shed light the origins of a virus that has killed seven million people.Along with genetic signatures of the coronavirus, the swab from the cart contained more than 4,500 lengthy fragments of genetic material from raccoon dogs, the report said. It had none from humans. Some Covid-positive swabs taken from other objects and surfaces at the market, the report said, also had more genetic material from animals than from humans.Finding genetic footprints from animals in the same place as genetic material from the virus does not prove that the animals themselves were infected. But some scientists who reviewed the report said that the dominance of genetic material from animals — and especially raccoon dogs — suggested that species known to be able to spread the coronavirus were indeed carrying infections at the market in late 2019.That scenario, they said, was consistent with the virus spilling into humans from market animals and touching off the pandemic, a set of circumstances similar to the one that gave rise to the first SARS outbreak in China two decades earlier.“You look at them and say those are probably infected animals,” Theodora Hatziioannou, a virologist at The Rockefeller University in New York who was not involved in the research, said of the latest findings. “If it was a human shedding the virus, one would expect to find human DNA there, too.”The swabs could yet hold more clues about where the virus in the samples had come from. The report said, for instance, that there was evidence of particular genes that could suggest the material had come from a raccoon dog’s upper respiratory tract.Even if an animal had been infected, however, it would not be clear that it had spread the virus to people. Someone infected with the virus could have gotten a market animal sick. And only by swabbing animals directly could scientists prove whether they had been carrying the virus, a step that was precluded by the market being cleared of animals soon after the outbreak began.The report has been the subject of intense speculation since the international experts presented their findings to the World Health Organization last week and then raced to compile their analyses. At the same time, the findings set off a battle for access to the genetic sequences at their heart.Chinese scientists had initially uploaded the raw sequences to a global database some time after publishing a study describing them last year. But once the international experts discovered the data in early March and alerted Chinese researchers to what they had found, the data was taken offline.Last week, the W.H.O. rebuked China for hiding such crucial information from the rest of the world for three years. Now the nonprofit organization based in Munich that runs the database, called GISAID, has come under scrutiny for its role in controlling access to the data.In the new report, the international team of scientists said that GISAID had “deviated from its stated mission” in allowing the Chinese researchers to withhold the data for so long.The database administrators responded to the report on Tuesday by cutting off the team members’ access to their online accounts and saying that they had violated its rules by getting out ahead of the Chinese scientists and posting their own analysis. The scientists said that they hewed to GISAID’s database-access agreement in downloading and studying the sequences, and noted that they had made multiple offers to work with the Chinese scientists.“The ramifications of cutting off access to this group of authors are huge,” said Michael Worobey, an evolutionary biologist at the University of Arizona and co-author of the new report, noting that GISAID also jeopardized work by team members related to coronavirus variants and flu preparedness. “They’re making false accusations.”The international team homed in on raccoon dogs — fluffy mammals related to foxes and sold for meat and fur — because of how much of the animals’ genetic material was found in the key swab from the cart and because they are known to spread the virus. They said their findings were consistent with that animal harboring the virus, which originated in bats, and passing it to humans at the market.“This isn’t an infected animal,” said Joel Wertheim, a virologist at the University of California, San Diego and a co-author of the report, referring to the new genetic data. “But this is the closest you can get without having the animal in front of you.”The report, though, also offered the most concrete evidence to date of other animals susceptible to the virus being sold at the market, noted Kristian Andersen, a virologist at the Scripps Research Institute in La Jolla, Calif., and a co-author of the report. Genetic material from those animals — like the masked palm civet, a small Asian mammal that was implicated in the SARS outbreak two decades ago — was also found in swabs that were positive for the coronavirus.“It’s literally Disney Land for zoonotic transfer,” said Joseph DeRisi, a professor of biochemistry at the University of California, San Francisco, and co-president of the Chan Zuckerberg Biohub, referring to the range of animals documented in the report.A number of other swabs at the market found large quantities of human genetic material — an indication, the report said, of certain virus samples likely being shed by infected people. Many of the earliest known Covid patients worked or shopped at the market.Still other positive swabs, the report said, were dominated by genetic material from animals that are not believed to be susceptible to the virus. A sample taken from a fish packaging surface, for example, contained a lot of fish genetic material. That virus was likely to have been deposited by a person, scientists said, illustrating that substantial amounts of animal genetic material did not necessarily mean that animals had produced the virus there.Citing those findings, some scientists said that the kinds of swabs analyzed in the report simply could not offer conclusive proof of an infected animal.“The report does contain useful information,” Sergei Pond, a virologist at Temple University in Philadelphia, said. But, he added, “Does it tell you anything about which animal was infected? It really doesn’t.”Dr. David Relman, a microbiologist at Stanford, said that it was difficult to assess the findings without more details about how the Chinese investigators had collected and analyzed their swabs. The Chinese paper last year, he noted, described using a kit to filter out human genetic material and make the tests more sensitive to the virus.But a number of swabs from the Chinese researchers described in the international team’s report contained substantial amounts of human genetic material, suggesting that those filtering methods had not depleted the samples of human material. Dr. DeRisi, who specializes in the type of analysis described in the report, said that such kits were generally ineffective at removing the genetic signatures of people.Frederic Bushman, a microbiologist at the University of Pennsylvania who also specializes in sequencing techniques, agreed that the report’s methods were sound.“I think the simplest explanation is that it’s an infected raccoon dog,” he said. “I don’t think it’s absolute proof.”

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WHO Accuses China of Withholding Data on Covid’s Origins

Genetic research from China suggests to some experts that the coronavirus may have sprung from a market in Wuhan. Now the data are missing from a scientific database.The World Health Organization rebuked Chinese officials on Friday for withholding research that may link Covid’s origin to wild animals, asking why the data had not been made available three years ago and why it is now missing.Before the Chinese data disappeared, an international team of virus experts downloaded and began analyzing the research, which appeared online in January. They say it supports the idea that the pandemic could have begun when illegally traded raccoon dogs infected humans at a Wuhan seafood market.But the gene sequences were removed from a scientific database once the experts offered to collaborate on the analysis with their Chinese counterparts.“These data could have — and should have — been shared three years ago,” Dr. Tedros Adhanom Ghebreyesus, the W.H.O.’s director general, said. The missing evidence now “needs to be shared with the international community immediately,” he said.According to the experts who are reviewing it, the research offers evidence that raccoon dogs, fox-like animals known to spread coronaviruses, had left behind DNA in the same place in the Wuhan market that genetic signatures of the new coronavirus also were discovered.To some experts, that finding suggests that the animals may have been infected and may have transmitted the virus to humans.With huge amounts of genetic information drawn from swabs of animal cages, carts and other surfaces at the Wuhan market in early 2020, the genetic data had been the focus of restless anticipation among virus experts since they learned of it a year ago in a paper by Chinese scientists.A French biologist discovered the genetic sequences in the database last week, and she and a team of colleagues began mining them for clues about the origins of the pandemic.That team has not yet released a paper outlining the findings. But the researchers delivered an analysis of the material to a W.H.O. advisory group studying Covid’s origins this week in a meeting that also included a presentation by Chinese researchers regarding the same data.“These data could have — and should have — been shared three years ago,” Dr. Tedros Adhanom Ghebreyesus, the W.H.O.’s director general, said. Cyril Zingaro/EPA, via ShutterstockThe analysis seemed to clash with earlier contentions by Chinese scientists that samples taken in the market that were positive for the coronavirus had been ferried in by sick people alone, said Sarah Cobey, an epidemiologist and evolutionary biologist at the University of Chicago who was not involved in the latest analysis.“It’s just very unlikely to be seeing this much animal DNA, especially raccoon dog DNA, mixed in with viral samples, if it’s simply mostly human contamination,” Dr. Cobey said.Questions remain about how the samples were collected, what precisely they contained and why the evidence had disappeared. In light of the ambiguities, many scientists reacted cautiously, saying that it was difficult to assess the research without seeing a complete report.The idea that a lab accident could have accidentally set off the pandemic has become the focus of renewed interest in recent weeks, thanks in part to a fresh intelligence assessment from the Department of Energy and hearings led by the new Republican House leadership.But a number of virus experts not involved with the latest analysis said that what was known about the swabs gathered in the market buttressed the case that animals sold there had sparked the pandemic.“It’s exactly what you’d expect if the virus was emerging from an intermediate or multiple intermediate hosts in the market,” Dr. Cobey said. “I think ecologically, this is close to a closed case.”Dr. Cobey was one of 18 scientists who signed an influential letter in the journal Science in May 2021 urging serious consideration of a scenario in which the virus could have spilled out of a laboratory in Wuhan.On Friday, she said lab leaks continued to pose enormous risks and that more oversight of research into dangerous pathogens was needed. But Dr. Cobey added that an accumulation of evidence — relating to the clustering of human cases around the Wuhan market, the genetic diversity of viruses there, and now the raccoon dog data — strengthened the case for a market origin.The new genetic data do not appear to prove that a raccoon dog was infected with the coronavirus. Even if it had been, the possibility would remain that another animal could have passed that virus to people, or even that someone infected with the virus could have transmitted it to a raccoon dog.Some scientists stressed those points on Friday, saying that the new genetic data did not appreciably shift the discussion about the pandemic’s origins.“We know it’s a promiscuous virus that infects a bunch of species,” said David Fisman, an epidemiologist at the University of Toronto, who also signed the May 2021 letter in Science.Chinese scientists had released a study in February 2022 looking at the market samples. Some scientists speculated that the Chinese researchers might have posted the data in January because they were required to make them available as part of a review of their study by a scientific journal.The Chinese study had suggested that samples that were positive for the virus had come from infected people, rather than from animals sold in the market. That fit with a narrative long promulgated by Chinese officials: that the virus sprang not only from outside the market, but also from outside the country altogether.But the Chinese report had left clues that viral material at the market had been jumbled together with genetic material from animals. And scientists said that the new analysis by the international team illustrated an even stronger link with animals.“Scientifically, it doesn’t prove that raccoon dogs were the source, but it sure smells like infected raccoon dogs were at the market,” said Jeremy Kamil, a virologist at Louisiana State University Health Sciences Center Shreveport.He added, “It raises more questions about what the Chinese government really knows.”Scientists cautioned that it was not clear that the genetic material from the virus and from raccoon dogs had been deposited at the same time.Depending on the stability of genetic material from the virus and the animals, said Michael Imperiale, a virologist at the University of Michigan, “they could have been deposited there at potentially widely different times.”Still, Dr. Arturo Casadevall, an immunologist at the Johns Hopkins Bloomberg School of Public Health who co-authored a recent study with Dr. Imperiale examining the origin of the coronavirus, said that linking animal and viral material nevertheless added to the evidence of a natural spillover event.“I would say it strengthens the zoonotic idea,” he said, “that is, the idea that it came from an animal at the market.”In the absence of the actual animal that first spread the virus to people, Dr. Casadevall said, assessing the origins of an outbreak would always involve weighing probabilities. In this case, animals sold at the market were removed before researchers began taking samples in early 2020, making it impossible to find a culprit.Tim Stearns, the dean of graduate and postgraduate studies at the Rockefeller University in New York, said that the latest finding was “an interesting piece of the puzzle,” though he said it was “not in itself definitive and highlights the need for a more thorough investigation.”For all the missing elements, some scientists said that the new findings highlighted just how much information scientists had managed to assemble about the beginnings of the pandemic, including home addresses for early patients and sequence data from the market.Theodora Hatziioannou, a virologist at the Rockefeller University, said that it was critical that the raw data be released. But, she said, “I think the evidence is overwhelming at the moment toward a market origin.”And the latest data, she said, “makes it even more unlikely that this started somewhere else.”Felicia Goodrum, an immunobiologist at the University of Arizona, said that finding the virus in an actual animal would be the strongest evidence of a market origin. But finding virus and animal material in the same swab was close.“To me,” she said, “this is the next best thing.”

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Why the Odds Are Stacked Against a Promising New Covid Drug

A new drug quashes all coronavirus variants. But regulatory hurdles and a lack of funding make it unlikely to reach the U.S. market anytime soon.Over the past year, America’s arsenal of Covid treatments has shrunk as new variants of the coronavirus have eroded the potency of drug after drug. Many patients are now left with a single option, Paxlovid. While highly effective, it poses problems for many people who need it because of dangerous interactions with other medications.But a new class of variant-proof treatments could help restock the country’s armory. Scientists on Wednesday reported in The New England Journal of Medicine that a single injection of a so-called interferon drug slashed by half a Covid patient’s odds of being hospitalized.The results, demonstrated in a clinical trial of nearly 2,000 patients, rivaled those achieved by Paxlovid. And the interferon shots hold even bigger promise, scientists said. By fortifying the body’s own mechanisms for quashing an invading virus, they can potentially help defend against not only Covid, but also the flu and other viruses with the potential to kindle future pandemics.“It doesn’t matter if the next pandemic is a coronavirus, an influenza virus, or another respiratory virus,” said Eleanor Fish, an immunologist at the University of Toronto who was not involved in the new study. “For all the viruses we’re seeing that are circulating now, there’s utility to using interferon.”For all of its promise, though, the drug — called pegylated interferon lambda — faces an uncertain road to the commercial market. Regulators at the Food and Drug Administration late last year told the drug’s maker, Eiger Biopharmaceuticals, that they were not prepared to authorize it for emergency use. Eiger executives said part of the problem seemed to be that the clinical trial did not include an American site, but rather only sites in Brazil and Canada, and that it was initiated and run by academic researchers, rather than the company itself.The regulators suggested that only a large clinical trial conducted at least in part in the United States and with more involvement from the company would suffice, Eiger executives said, a scenario that would require several years and considerably more funding. An F.D.A. spokeswoman said disclosure laws prevented the agency from commenting.Those barriers are indicative of problems that some experts worry are threatening the development of a wide range of next-generation Covid treatments and vaccines — products that may help address the ongoing toll from Covid and also give scientists a head start in preparing for the next pandemic.More on the Coronavirus PandemicCovid Vaccine Mandate: New York City will end its aggressive but contentious coronavirus vaccine mandate for municipal workers, Mayor Eric Adams announced, signaling a key moment in the city’s long battle against the pandemic.End of an Era: The Biden administration plans to let the coronavirus public health emergency expire in May, a sign that federal officials believe the pandemic has moved into a new, less dire phase.Canceled Doses: As global demand for Covid-19 vaccines dries up, the program responsible for vaccinating the world’s poor has been negotiating to try to get out of its deals with pharmaceutical companies for shots it no longer needs.Mask Rules: Many countries dropped pandemic mask requirements months ago. But in places like South Korea, which only recently got rid of its rule, masks remain common. This is why.As it stands, Eiger executives said that they might seek authorization for the interferon shot outside of the United States. China, for example, has been looking for new treatment options.Some scientists involved in the research expressed frustration that doctors could not already prescribe the shots. Despite vaccines and previous infections helping to contain the damage from the virus, Covid is still killing roughly 450 Americans daily.“I think it is a crazy situation that we’re still here now, three years into the pandemic, and I have one drug that I can prescribe with confidence to people who are getting infected,” said Dr. Jeffrey Glenn, a virologist and director of a pandemic preparedness initiative at Stanford University, who helped lead the study of the interferon shot. “We need more options.”Dr. Glenn founded Eiger, holds shares in Eiger and sits on its board of directors, but no longer works for the company.A participant in the interferon drug trial took a Covid test in Montes Claros, Brazil.CardResearch, Belo Horizonte, BrazilInterferons are a group of proteins that alert neighboring cells to fortify themselves in the hours after a virus invades. The coronavirus, like other viruses, is good at defusing the body’s natural interferon response. A drug that delivered extra interferons, researchers believed, could potentially help patients outmaneuver the virus.In targeting patients’ immune responses, rather than the virus itself, those treatments potentially offered another advantage over existing treatments, reducing the chance that a variant would evolve that could resist the drug, said Vineet Menachery, an immunologist at the University of Texas Medical Branch.A number of monoclonal antibodies have fallen out of use because they stopped working against new variants. Paxlovid has remained effective because it is much more difficult for the virus to get around, but new variants could one day render it less useful, too.“I don’t know of any virus that can navigate a cell where interferon got there first,” said Benjamin tenOever, a microbiologist at N.Y.U. Grossman School of Medicine.Harnessing those capabilities in a drug, though, is not easy. Interferons can trigger wide-ranging side effects, including inflammation, a risk in Covid cases because some patients have an overactive immune response.“You basically tell your body you’re being highly infected by a virus, and to fight, fight, fight at all costs,” said Juliet Morrison, a microbiologist at the University of California, Riverside.Previous studies had tested interferon treatments only on patients who were already sick and in the hospital. That meant that the drugs were often administered too late, leading to mixed or disappointing results.The scientists behind the Eiger drug envisioned a clever workaround.With hepatitis treatments in mind, they had previously acquired a drug based on lambda interferons, a lesser-known type of interferon whose receptors are largely restricted to specific areas, like the respiratory tract. That happened to be precisely where the coronavirus was replicating. And it meant that the side effects would theoretically be less intense than those from the more commonly used class of interferons, whose receptors are throughout the body.Those hopes were borne out in the latest trial. After administering the shot to about 900 patients and giving another 1,000 patients a placebo, the researchers found no appreciable difference in the incidence of side effects, they said.Vaccination kept the vast majority of patients in both groups safe from hospitalization or a prolonged emergency department visit. But treating patients with interferon within a week after they noticed symptoms halved their chances of being hospitalized: Twenty-five people given the shot were hospitalized, compared with 57 who had not been treated.The effects were even more pronounced when the drug was given within three days of symptoms developing, and when it was given to unvaccinated people. Most of the patients in the study were at relatively high risk from Covid — either because they were 50 or older, or because they had an underlying condition or a weakened immune system.And the drug appeared to work across variants, showing even more potency when Omicron was dominant, the study found.“Despite the pandemic being less of an emergency than it was at its peak, we’re still seeing people coming into the hospital and getting very sick with Covid,” said Dr. Jordan Feld, a specialist in viral hepatitis at the University of Toronto, who is a co-author of the study and has received funding from Eiger. “Having treatment options to try to prevent that from happening would be really helpful.”Some researchers said they envisioned testing interferon drugs in people who were seeking treatment for a range of respiratory viruses, including the flu and R.S.V., or respiratory syncytial virus, which put considerable pressure on hospitals this winter. Doctors could even treat patients before they knew which virus was causing them problems.Some studies have also suggested that the same class of drugs, if used quickly enough, could prevent people exposed to the virus from getting infected in the first place.“I suspect the greatest utility of all these interferons will be in prophylactic treatment,” said Dr. Fish of the University of Toronto, “especially in outbreak settings for high-risk individuals to protect them from infection.”

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New Covid Booster Shots Cut Risk of Hospitalization by Half, CDC Reports

The research was conducted in part when older variants of the coronavirus were spreading. Other factors may have influenced the conclusions.Updated booster shots have bolstered Americans’ defenses against serious Covid, reducing the risk of hospitalization by roughly 50 percent compared with certain groups inoculated with the original vaccines, the Centers for Disease Control and Prevention reported in a pair of studies published on Friday.The research represents the agency’s first look at how the reformulated boosters, tailored to protect against recent Omicron variants, are performing in the prevention of severe consequences of infection with the virus, including emergency department visits and hospitalizations.Federal health officials are urging Americans to get the updated booster shots, hoping to revive a lagging vaccination campaign. So far, though, fewer than a fifth of American adults and only a third of people ages 65 and older have received updated shots, reflecting a retreat in many parts of the country from the more aggressive vaccination drives earlier in the pandemic.New virus variants that are better able to dodge the immune system have gained traction, and Covid cases and hospitalizations have climbed in recent weeks. About 375 Americans are dying each day on average, an increase of 50 percent over the past two weeks. Older people have been hit especially hard.The virus has exacerbated the difficulties facing a health care system already under strain from resurgences of the flu and respiratory syncytial virus after two years of reductions in those infections.Read More on the Coronavirus PandemicFree at-Home Tests: With cases on the rise, the Biden administration restarted a program that has provided hundreds of millions of tests through the Postal Service.Updated Shots: The Food and Drug Administration expanded eligibility for the updated coronavirus boosters to children as young as 6 months old.Contagion: Like a zombie in a horror film, the coronavirus can persist in the bodies of infected patients well after death, even spreading to others, according to two startling studies.Pregnant Women: Even though studies have shown that the Covid vaccine is safe for expectant women, many have avoided getting the shots, unaware of the risks that the virus poses.Even as federal health officials encourage testing and mask use in certain settings, precautions have become far less common in practice. Antiviral medication for Covid remains difficult to find for many who are infected.“We probably won’t see waves of Covid like we have in the past, which is a good thing, but it doesn’t mean people aren’t still dying and that those lives couldn’t still be saved if we got more shots in arms,” said Dr. David Dowdy, an epidemiologist at the Johns Hopkins Bloomberg School of Public Health.One C.D.C. study released on Friday examined how the updated shots protected people from Covid-related emergency department visits and hospitalizations in seven health systems.The study, which looked at about 15,000 hospitalizations, stretched from mid-September to mid-November, when Covid cases were largely being caused by the BA.5 Omicron variant — the target, in part, of the reformulated shots.Since then, however, more evasive versions of Omicron known as BQ.1 and BQ.1.1 have become more common, and it’s not clear how relevant the conclusions are to the newer variants.During the BA.5 period, people who had received the updated boosters had a 57 percent lower risk of hospitalization compared with unvaccinated people, a 38 percent lower risk compared with people who had recently received doses of the original vaccine, and a 45 percent lower risk compared with people whose last dose of the original vaccine was at least 11 months earlier.But the C.D.C.’s study did not account for whether patients had previously been infected with the virus, potentially making the updated vaccines appear less effective than they are. And the research did not take into account whether certain groups were more likely to have received treatments like Paxlovid, which might have skewed the results.A second study reported on the benefits of updated boosters for older Americans in 22 hospitals from early September to late November.Among people ages 65 and older, the updated vaccines reduced the risk of Covid hospitalization by 84 percent compared with unvaccinated people, and by 73 percent compared with people who had received at least two doses of the original vaccines.C.D.C. scientists said that the higher estimates of vaccine effectiveness in older age groups might reflect a variety of differences in the particular groups of patients being studied.

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Nobel Prize in Physiology or Medicine to Be Awarded Today

It will be the first Nobel Prize awarded this year, with more announcements being made over the coming week.The Nobel Prize in Physiology or Medicine will be awarded by the Nobel Assembly in Sweden on Monday — the first of several prizes to be given over the next week. The Nobel Prizes, among the highest honors in science, recognize groundbreaking contributions in a variety of fields.Who won the Nobel Prize in Physiology or Medicine in 2021?The prize was awarded jointly to David Julius and Ardem Patapoutian for their discoveries about key mechanisms of how people sense heat, cold, touch and body movements.When will the other Nobel Prizes be announced?The Nobel Prize in Physics will be awarded on Tuesday by the Royal Swedish Academy of Sciences in Stockholm. Last year, Syukuro Manabe, Klaus Hasselmann and Giorgio Parisi won for their work detailing humanity’s role in climate change.The Nobel Prize in Chemistry will be awarded on Wednesday by the Swedish Academy in Stockholm. Last year, Benjamin List and David W.C. MacMillan won for their development of a new tool that spurred research into new drugs and reduced the chemistry’s effect on the environment.The Nobel Prize in Literature will be awarded on Thursday by the Swedish Academy in Stockholm. Last year, Abdulrazak Gurnah won for “his uncompromising and compassionate penetration of the effects of colonialism and the fate of the refugee in the gulf between cultures and continents.”The Nobel Peace Prize will be awarded on Friday by the Norwegian Nobel Institute in Oslo. Last year, Maria Ressa and Dmitri A. Muratov, both journalists, won for their efforts in the struggle to protect press freedoms.Next week, the Nobel Memorial Prize in Economic Sciences will be awarded on Oct. 10 by the Swedish Academy in Stockholm. Last year, the prize went to David Card, Joshua D. Angrist and Guido W. Imbens.All of the prize announcements will also be streamed live by the Nobel Prize organization. Prize winners will receive their awards at a ceremony in Stockholm in December.

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Lasker Award Honors Development of Noninvasive Prenatal DNA Test

The prestigious medical prizes also recognized the creator of a global Covid dashboard and discoveries of proteins and cell bindings to fight disease.It was a startling discovery: Tiny pieces of an unborn baby’s DNA were found floating through its mother’s bloodstream — not inside the mother’s cells, where genetic material is usually found, but rather outside them.But when Dr. Yuk Ming Dennis Lo, a researcher in Hong Kong, described the finding in 1997, it was greeted with something of a shrug. Industry experts were so indifferent that after Dr. Lo’s team licensed the fetal DNA detection technology to a British company, he said, the company turned around and gave the license back.Two decades later, the significance of the technique is no longer in doubt. Dr. Lo eventually helped turn his discovery into a noninvasive prenatal test for Down syndrome that has been performed tens of millions of times and adopted in more than 60 countries.His work was recognized on Wednesday with a Lasker Award, which is among the most prestigious prizes in medicine, coming with $250,000 in winnings and a reputation for preceding a Nobel Prize. Dr. Lo won in the clinical medical research category.The Lasker Foundation also awarded prizes in two other categories. Lauren Gardner, who created the Johns Hopkins University Covid-19 Dashboard, was given the public service award. A group of three researchers whose work relates to how cells interact with their surroundings received the basic medical research award, which goes to a fundamental discovery that opens new scientific territory.Dr. Lo, of the Chinese University of Hong Kong, published his signature discovery in 1997, shortly after he moved back to Hong Kong, his birthplace, from Britain, where he had done his graduate studies. It was several months before Hong Kong would be returned to China, and a resulting exodus of professionals from the city had created plum university openings for young scientists like him.For eight years, Dr. Lo had been trying to find reasonably high concentrations of fetal DNA in the mother’s bloodstream. Such a discovery, he hoped, could help to obviate the need for risky prenatal testing methods, which relied on sampling fetal tissue, and could open the door to noninvasive screenings instead.Read More on the Coronavirus PandemicA Persistent Variant: Ten months have passed since Omicron’s debut. Since then it has displayed a remarkable capacity to evolve new tricks.A Blunted Response: Major data gaps, the result of decades of underinvestment in public health, have undercut the U.S. government’s response to Covid — and now to monkeypox.Biden’s Comments: In an interview that aired on CBS’s “60 Minutes,” President Biden said that “the pandemic is over.” But 400 to 500 Americans are still dying every day of Covid-19.Updated Boosters: As masks have fallen away and quarantines have diminished, the new vaccines are one of the last remaining weapons in America’s arsenal against the coronavirus. So far, the rollout is methodical, but muted.Dr. Lo had been looking in the mother’s blood cells for the unborn baby’s genetic material. But he had also come across reports describing how DNA from a tumor had been found circulating not in blood cells, but in the watery portion of cancer patients’ blood, the plasma. If tumor DNA could be found in that portion of the bloodstream, why not fetal DNA, too?“I had the strange thought that the cancer growing in the patients is a little bit like the placenta that has implanted into the uterus,” he said.He started searching for traces of fetal DNA in the plasma. “That was a good guess,” he said. Homing in on fetal DNA in the mother’s plasma remained tricky. Dr. Lo needed a way to detect the extra copy of chromosome 21 that causes Down syndrome. Separating out the mother’s DNA from the baby’s in tests did not work well enough. Instead, in 2008, Dr. Lo alighted on a technique in which he looked at a large sample of randomly chosen DNA fragments from the mother’s plasma and investigated whether those from chromosome 21 were very slightly elevated.Dr. Lo likened the task to trying to figure out whether someone had one or two coins in their wallet. Unable to look inside the wallet, he could study their overall weight instead and, using an extremely finely tuned balance, could look for telltale extra fractions of a pound.“I started to actually build that molecular balance,” he said.Lauren Gardner, a civil and systems engineer at Johns Hopkins University, created a Covid-19 dashboard that she said has remained the most detailed global snapshot of the pandemic.Lasker FoundationThe other Lasker awardees, too, managed improbable technical feats, albeit in different fields.Lauren Gardner, a civil and systems engineering professor at Johns Hopkins University, received the public service award for leading the creation of a Covid-19 dashboard that she has said still offers the most detailed global picture of the pandemic.On Jan. 21, 2020, a doctoral student of hers, Ensheng Dong, approached her about tracking cases of a novel pneumonia in his home country, China. Mr. Dong had the tools: He could mine Chinese websites for early case data, and he knew how to build online maps. Dr. Gardner said that she remembered the costs of not having access to timely data during outbreaks of Zika and Middle Eastern respiratory syndrome, or MERS, and she wanted to ensure that would not be the case again.“I was thinking it would be mostly of interest to the research community,” she said.Within a couple of months, the dashboard was receiving tens of millions of page views and more than 4.5 billion requests for data per day. In the absence of similarly fast or comprehensive case data from public health bodies like the World Health Organization or the Centers for Disease Control and Prevention, the university dashboard became a go-to source for policymakers, scientists and ordinary citizens alike.It became so visible, Dr. Gardner said, that she later received calls from the U.S. State Department voicing concerns about how certain geopolitically sensitive countries were represented on their map.Dr. Gardner said that the dashboard drew some of its power from being run out of a university, rather than the government. That feature stood in good stead during periods in 2020 when the Trump administration was downplaying case counts. But she said they were ultimately filling a void in public data that should have been addressed by the government.“We were doing for the U.S. what the C.D.C. should’ve been doing, and for the world what the W.H.O. should’ve been doing,” she said. “But they didn’t have the resources to do it, and that needs to change.”With governments reducing investments in detecting and reporting Covid cases, the future of the dashboard may be dictated more by the loss of high-quality data than by the direction of the pandemic itself, Dr. Gardner said.However, she said she hoped that public demand for accessible health data would outlive the dashboard, even if there remained major challenges, such as a deficit of funding and an absence of national standards for how to report infectious disease cases.“The best thing we’ve done is create this expectation for access to this type of data among the people that are affected,” Dr. Gardner said. Similar maps and dashboards, she said, could be useful well before the next pandemic: “Influenza data exists, but not in an accessible format that’s easy to digest, where I can see as a Marylander or Texan if there’s flu coming my way.”From left, Richard O. Hynes of the Massachusetts Institute of Technology, Timothy A. Springer of Boston Children’s Hospital and Dr. Erkki Ruoslahti of the Sanford Burham Prebys Medical Discovery Institute.Lasker FoundationThe Lasker Award for basic medical research went to three scientists who described how cells bind to their surrounding networks of proteins and other molecules — findings that pointed the way toward treatments for a number of diseases.Two of the winners — Richard O. Hynes, of the Massachusetts Institute of Technology, and Dr. Erkki Ruoslahti, of the Sanford Burham Prebys Medical Discovery Institute in San Diego — independently identified a protein that helps to fasten cells to that surrounding network.The third, Timothy A. Springer, of Boston Children’s Hospital, found proteins that guided immune cells in the body and helped them recognize foreign antigens. That work, in the 1980s, drew skepticism from some scientists. Dr. Springer recalled a professor once passing a napkin down the bar at a scientific conference that read simply, “It doesn’t work.”But it did. The research later formed the basis for treatments for dry eye disease and multiple sclerosis, as well as ulcerative colitis and Crohn’s disease, two types of inflammatory bowel disease.As the three scientists, each in their own labs, homed in on the structure of the proteins they were studying, which are now known as integrins, it became clear that they were all part of the same molecular family. Dr. Springer recalled Dr. Hynes inviting him to his lab, where they compared the sequences of their respective proteins. He eventually met Dr. Ruoslahti at a conference organized by Dr. Hynes.“It was like different kinds of apples — a Gala apple to a Fuji apple,” Dr. Springer said.Despite their achievements, the Lasker awardees are still honing their findings. For Dr. Lo in Hong Kong, that has meant trying to use his critical insight from the 1990s — that tumors and unborn babies both leave genetic signatures in the bloodstream — to develop tests that screen for cancers. The tests are best at detecting bigger tumors but can find some early-stage cancers, too.“If your method is sensitive enough,” he said, “it can actually save lives.”

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