Bioarctics läkemedel nekas registrering i Australien

Australiska myndigheten Therapeutic Goods Administration (TGA) har fattat beslutet att inte registrera lecanemab (Leqembi) för behandling av patienter med mild kognitiv störning på grund av Alzheimers sjukdom och mild Alzheimers demens (tidig Alzheimers sjukdom). Det framgår av besked på myndighetens hemsida.

”Alla mina ägodelar för ögonblick av tid”, ska Elizabeth I enligt myten ha sagt på sin dödsbädd. Och sedan 1500-talet har onekligen chanserna till ett längre liv förbättras avsevärt, skriver The Economist och dyker ner i den senaste forskningen. Nu är det istället kungligheterna inom tech som satsar stort på jakten efter längre och friskare liv. Från att den typen av forskning betraktats med skepsis av den traditionella medicinen börjar allt mer peka på att dagens alkemister gör reella fynd. Det handlar om allt från genteknik till nya sätt att använda redan etablerade läkemedel. And some of it is making progress, writes Geoffrey Carr By The Economist 25 September, 2023 ”All my possessions for a moment of time.” Those, supposedly, were the last words of Elizabeth I, who as queen of England had enough possessions to be one of the richest women of her era. Given her patronage of alchemists—who searched, among other things, for an elixir of life—she may have meant it literally. But to no avail. She had her last moment of time in March 1603, a few months short of the three score years and ten asserted by the Bible to be “the days of our years”. Things have improved since the reign of Good Queen Bess. People in the rich world can now reasonably assume that the days of their years will last well beyond 70. Those in poorer countries are catching up (see chart 1). In every year since 1950 average life expectancy around the world has risen by 18 weeks. There are, however, two catches. One is that the increases seem to have a limit. The number of centenarians has been growing and will grow more. The Pew Research Centre predicts there will be 3.7m worldwide by 2050, three times as many per head of population as in 2015. But only one in 1,000 of them lives beyond 110, and no one in history is reliably attested to have got past 120. The average is going up; the maximum, much less so (see chart 2). The other catch is that “healthspan”, the number of healthy, vital years, does not automatically keep pace with lifespan. Some of Elizabeth’s modern equivalents in wealth, if not majesty, are as desperate as she was for more moments than are currently on offer. In the hope of longer, healthier lives they are offering substantial down payments to today’s alchemists, the wizards of medicine and biotechnology trying to understand, decelerate and, ideally, reverse bodily ageing and its attendant ills. Peter Thiel, a co-founder of PayPal, Larry Page and Sergey Brin, co-founders of Google, and Jeff Bezos, founder of Amazon, have all invested in, and often been instrumental in the creation of, firms trying to prolong lifespan and healthspan. In March Sam Altman, the head of Openai, revealed that two years ago he had invested $180m in Retro Biosciences, a Silicon Valley firm founded with the goal of adding ten years to healthy human lifespans. Beneath the forest canopy of firms backed by tech royalty an undergrowth of more conventionally financed startups is working on drugs that might slow or stall some aspects of ageing. Even closer to the ground, the idea is catching on of prolonging lifespan and healthspan using pills and potions that are already available, in addition to (and sometimes instead of) the conventional approach of diet, exercise and early-to-bed. A culture of do-it-yourself lifespan extension is emerging, at least in affluent places endowed with the sort of technical expertise and technological hubris identified with Silicon Valley. Many in mainstream science and medicine look at all this slightly askance. That is understandable. It is an area which attracts chancers and charlatans as well as those with more decent motives, and its history is littered with “breakthroughs” that have led more or less nowhere. America’s Food and Drug Administration does not recognise “old age” as a disease state, and thus as a suitable target for therapy. Nevertheless, evidence has been accumulating that such research might have something to offer. Some established drugs really do seem to extend life, at least in mice. That offers both the possibility that they might do so in people and some insight into the processes involved. The ever-greater ease with which genes can be edited helps such investigations, as does access to large amounts of gene-sequence data. The ability to produce personalised stem cells, which stay forever young, has opened up new therapeutic options. And new diagnostic tools are now offering scientists means to calculate the “biological ages” of bodies and organs and compare them with actual calendar ages. In principle this allows longevity studies to achieve convincing results in less than a lifetime. Ageing seems quite simple. Bodies are machines, and machines wear out. But unlike most machines, bodies both make themselves and repair themselves. So why do they not do so perfectly? One answer is that the machines’ designer, evolution, is interested in reproduction, not longevity. Life is a matter of genes and environment, and the environment, in the form of accidents, predators and diseases, is what kills most creatures. Genes with benefits that show up only over a longer lifespan than the environment allows are not likely to do particularly well unless they provide other benefits. Genes that offer a successful and fertile youth are onto a winner. Indeed, evolution may be actively plotting against old age. If a gene helps an animal breed when young but endangers it when it is old, the odds are that it will spread. There is some evidence that one variant of a particular gene involved in Alzheimer’s disease provides reproductive advantages to young people. More generally, looked at from the evolutionary point of view of the genes involved, an individual is simply a way to make further copies of those genes, rather than an end in itself. Keeping the body’s repair mechanisms in tip-top condition is worthwhile only if it gets more genes into the next generation. If other uses of those resources do the job better, then repair will lose out. In this “disposable soma” approach, the individual is a means to an end abandoned when it is no longer fit for purpose. This sort of perspective explains why there are many conditions, such as Alzheimer’s and Parkinson’s diseases, retinal degeneration, type-2 diabetes and various cancers which are rare in early life but quite common in old age. But it also suggests that this need not be the case. The fact that evolution has no interest in keeping the repair systems going does not mean it cannot be done, just that some cunning may be required. Most genes have variants, known as alleles, which all work, but may have somewhat different effects. Genetic manipulation of laboratory organisms and studies of the genes of human centenarians have identified alleles of particular genes that, in the former, have been proved experimentally to increase lifespan and, in the latter, are associated with longer lives. Such work helps illuminate the processes behind bodily ageing. It may, for example, lead to an understanding of why, as a study published in 2014 by researchers at King’s College London showed, centenarians are less likely to die of cancer or heart disease than people in their 80s are. This suggests that people who live a really long time may do so because they have some comparatively rare form of protection against things that kill younger old people. That may be very good news. Something does still kill them, though. The King’s College study found centenarians disproportionately vulnerable to general frailty and “the old man’s friend”, pneumonia. Another reason for hope in the face of evolution’s callousness is that the physiological details of ageing are becoming clearer. In particular, those researching the question have been able to divide the problem into bite-sized chunks that can, to some extent, be tackled individually. Some of these smaller (if often still huge) problems are attractive targets for intervention in their own right; chronic inflammation, for example, or the build-up of aberrant proteins seen in Alzheimer’s disease. George Church of Harvard University, a biotech guru unafraid of the unorthodox, thinks the approach could offer more than that: identify and deal with each of the components separately and you may find you have solved the problem in its entirety. Several groups have compiled lists of such chunks. One of the most widely consulted was devised by Carlos López-Otín of the University of Oviedo, in Spain, and his colleagues. They propose 12 hallmarks of ageing (see chart) chosen on the basis that they are all things which typically get worse with age, which accelerate ageing if stimulated and which seem to slow it down if treated. Deal with this dirty dozen (Dr Church would make it a baker’s dozen by adding cancer to the roll) and you might prolong life indefinitely and healthily. That, at least, is how the optimists look at it. Oncology is already a well-developed field of research. This report will not address it directly. Nor will it remark on diet, exercise and a good night’s sleep, other than to extol their value. They remain as necessary as ever. Instead, it will look at the progress being made with respect to each of the 12 hallmarks. The resulting picture is not as tidy as one might wish. Biology is a complex, networked affair and many of ageing’s hallmarks overlap. Sometimes that means an intervention may do good in more than one area. At other times there may be trade-offs. But even dealing with part of the list will bring people better lives. Deal with all of it and, well, who knows? © 2023 The Economist Newspaper Limited. All rights reserved.

En gris hjärta är ungefär rätt storlek. Med viss genmodifiering kan det också transplanteras till andra däggdjur utan att stötas bort, skriver MIT Technology Review. Redan i dag görs försök där grishjärtan opereras in i babianer. Nästa år kan det vara dags för mänskliga bebisar. eGenesis has started transplanting gene-edited pigs’ hearts into infant baboons—and humans may be next. By Jessica Hamzelou 17 July, 2023 The baby baboon is wearing a mesh gown and appears to be sitting upright. “This little lady … looks pretty philosophical, I would say,” says Eli Katz, who is showing me the image over a Zoom call. This baboon is the first to receive a heart transplant from a young gene-edited pig as part of a study that should pave the way for similar transplants in human babies, says Katz, chief medical officer at the biotech company eGenesis. The company, based in Cambridge, Massachusetts, has developed a technique that uses the gene-editing tool CRISPR to make around 70 edits to a pig’s genome. These edits should allow the organs to be successfully transplanted into people, the team says. As soon as next year, eGenesis hopes to transplant pig hearts into babies with serious heart defects. The goal is to buy them more time to wait for a human heart. Before that happens, the team at eGenesis will practice on 12 infant baboons. Two such surgeries have been performed so far. Neither animal survived beyond a matter of days. But the company is optimistic, as are others in the field. Many recipients of the first liver transplants didn’t survive either—but thousands of people have since benefited from such transplants, says Robert Montgomery, director of the NYU Langone Transplant Institute, who has worked with rival company United Therapeutics. Babies born with heart conditions represent “a great population to be focusing on,” he says, “because so many of them die.” Over 100,000 people in the US alone are waiting for an organ transplant. Every day, around 17 of them die. Researchers are exploring multiple options, including the possibility of bioprinting organs or growing new ones inside people’s bodies. Transplanting animal organs is another potential alternative to help meet the need. The idea of using organs and tissues from animals, known as xenotransplantation, is an old one—the first experiments were performed back in the 17th century. More recent attempts were made in the 1960s, and again in the 1990s. Many of these used organs from monkeys and baboons. But toward the start of the 1990s, a consensus emerged that pigs were the best donor candidates, says Montgomery. Primates are precious—they are intelligent animals that experience complex emotions. Only a small number can be used for human research, and at any rate, they reproduce slowly. They are also more likely to be able to pass on harmful viruses. On the other hand, people already know a lot about how to rear and farm pigs, and their organs are about the right size for humans. But transferring organs between animals of different species isn’t straightforward. Even organs from another human can be rejected by a recipient’s immune system, and animal tissues have a lot more components that our immune systems will regard as “foreign.” This can cause the organ to be attacked by immune cells. There’s also the possibility of transferring a virus along with the organ, for example. Even if a donor animal isn’t infected, it will have “endogenous retroviruses”—genetic code for ancient viruses that have long since been incorporated into its DNA. These viruses don’t cause problems for their animal hosts. But there’s a chance they could cause an infection in another species. “There’s a risk that viruses that are endemic to animals evolve in a human and become deadly,” says Chris Gyngell, a bioethicist at Murdoch Children’s Research Institute in Melbourne, Australia. The team at eGenesis is using CRISPR to address this risk. “You can use CRISPR-Cas9 to inactivate the 50 to 70 copies of retrovirus in the genome,” says Mike Curtis, president and chief executive officer at eGenesis. The edits prevent retroviruses from being able to replicate, he says. Scientists at the company perform other gene edits, too. Several serve to “knock out” pig genes whose protein products trigger harmful immune responses in humans. And the team members insert seven human genes, which they believe should reduce the likelihood that the organ will be rejected by a human recipient’s immune system. In all, “we’re producing [organ] donors with over 70 edits,” says Curtis. The team performs these edits on pig fibroblasts—cells that are found in connective tissue. Then they take the DNA-containing nuclei of edited cells and put them into pig egg cells. Once an egg is fertilized with sperm, the resulting embryo is implanted into the uterus of an adult pig. Eventually, cloned piglets are delivered by C-section. “It’s the same technology that was used to clone Dolly back in the ’90s,” says Curtis, referring to the famous sheep that was the first animal cloned from an adult cell. eGenesis has around 400 cloned pigs housed at a research facility in the Midwest (he is reluctant to reveal the exact location because facilities have been targeted by animal rights protesters). And early last year, the company set up a “clean” facility to produce organs fit for humans. Anyone who enters has to shower and don protective gear to avoid bringing in any bugs that might infect the pigs. The 200 pigs currently at this center live in groups of 15 to 25, says Curtis: “It’s basically like a very clean barn. We control all the feed that comes in, and we have waste control and airflow control.” There’s no mud. The pigs that don’t end up having their organs used will be closely studied, says Curtis. The company needs to understand how the numerous gene edits they implement affect an animal over the course of its life. The team also wants to know if the human genes continue to be expressed over time. Some of the pigs are over four years old, says Curtis. “So far, it looks good,” he adds. When it comes to organ transplants, size is important. Surgeons take care to match the size of a donor’s heart to that of the recipient. Baby baboons are small—only hearts taken from pigs aged one to two months old are suitable, says Curtis. Once they are transplanted, the hearts are expected to grow with the baboons. The first baboon to get a pig heart, which was just under a year old, died within a day of surgery. “It was a surgical complication,” says Curtis. The intravenous tube providing essential fluids to the baboon became blocked, he says. “The animal had to be euthanized.” A second baboon was operated on a few months later. The team encountered another surgical complication: this time, the surgeons couldn’t get the baboon’s blood vessels to stay attached to those in the pig’s organs. The baboon died nine days after the operation. In both cases, “the heart itself was beating well,” says Curtis. “So far, the first two are very encouraging from cardiac performance … the hearts look good.” The surgeons who performed the operations are confident they’ll be able to avoid the surgical complications in the future, he says. Once the baboon trial is completed, the team at eGenesis wants to offer the pig hearts to babies under the age of two who were born with severe heart conditions. Such children have limited treatment options—human hearts of the right size are few and far between, and some of the devices used to treat heart conditions in adults aren’t suitable for little children with small hearts. Curtis hopes the pig hearts could initially be used as a temporary measure for such children—essentially buying them more time to wait for a donated human heart. Once a potential recipient has been found, the company can seek approval for the surgery from the US Food and Drug Administration. Ethicists will point out that babies won’t be able to give informed consent for surgery. That decision will come down to their caregiver, who will likely be in a dire situation, says Syd Johnson, a bioethicist at Upstate Medical University in Syracuse, New York. “These are parents who are desperate for anything that might save their child’s life,” she says. But Gyngell thinks the focus should be on who has the most to gain from an experimental procedure like this. “The fact is that pediatric patients have a greater clinical need, because there are far fewer other options available to them,” he says. Montgomery, who is himself the recipient of a donated human heart, agrees. He says he supports eGenesis’s goals. “These babies that have congenital heart disease … have a 50% mortality rate,” he says. “It’s a flip of a coin whether that kid is going to live or not.” That reasoning doesn’t wash with Johnson. The procedure is risky, and a child whose immune system rejects the organ could suffer, she says: “One hundred percent of the patients who’ve been transplanted with an animal organ have died [soon after the procedure]—that’s just an inescapable fact.” David Bennett Sr., who was the first living person to receive a gene-edited pig heart, in 2022 died two months later. There are more risks when using organs from gene-edited animals, says Johnson. We still don’t know if these genetic modifications might affect human recipients, especially in the long term. “The desire to do something to save these babies [with heart conditions] is obviously very strong for everyone who is involved,” she says. “But we still need to be honest and transparent about what the risks are—and they are, to some extent, unknown.” Montgomery himself has transplanted gene-edited pig organs into adults who have been declared brain dead. Those organs—which include kidneys and, in unpublished work, hearts—were from pigs bred by the rival company Revivicor, which was acquired by United Therapeutics. The experiments ran for just two or three days, but Montgomery plans to run a similar experiment in individuals who will be studied for a month after the transplant. So far, he says, “we’ve got very good results.” He believes young children may be better candidates for pig organs than adults, because their immune systems are still developing and therefore might be less likely to reject the organ. “They may well have some level of tolerance,” he says. A third baboon is due to receive a pig heart in August. The company plans to perform at least one such operation a month until 12 animals have been operated on. The team members hope they’ll be able to fix the surgical issues and enable the baboons to live longer. Some other non-human primates that have received kidneys from the gene-edited pigs have already survived over a year, says Curtis. “When you’re pioneering something new, there’s a steep learning curve,” Montgomery says. © 2023 Technology Review, Inc. Distributed by Tribune Content Agency.

Den globala coronapandemin har förändrat vårt sätt att tänka kring biosäkerhet. Allt fler forskare ser nu över farorna med att forska på nya virus och andra patogener, skriver The Washington Post. Enligt tidningen har forskningen på nya sjukdomsframkallande ämnen och organismer de senaste årtiondena utvecklats snabbare än vad säkerheten kring forskningen gjort. Ingen vet exakt hur många farliga patogener som finns runt om i värdens laboratorier, men enligt uppskattningarna rör det sig om tusental. – Det är ett nationellt säkerhetsproblem och ett globalt folkhälsoproblem, säger infektionsexperten James Le Duc till tidningen. (Svensk översättning av Omni). The covid-19 epidemic has challenged conventional thinking about biosafety, leading a growing number of scientists to reconsider the danger of prospecting for unknown viruses and other research with pathogens. By David Willman and Joby Warrick April 11, 2023 BANGKOK - When the U.S. government was looking for help to scour Southeast Asia's rainforests for exotic viruses, scientists from Thailand's Chulalongkorn University accepted the assignment and the funding that came with it, giving little thought to the risks. Beginning in 2011, Thai researchers made repeated treks every year to remote caves and forests inhabited by millions of bats, including species known to carry diseases deadly to humans. The scientists collected saliva, blood and excrement from the wriggling, razor-fanged animals, and the specimens were placed in foam coolers and driven to one of the university's labs in Bangkok, a metropolis of more than 8 million people. The goal was to identify unknown viruses that might someday threaten humans. But doubts about the safety of the research began to simmer after the virus hunters were repeatedly bitten by bats and, in 2016, when another worker stuck herself with a needle while trying to extract blood from an animal. Some of the workers received booster shots to prevent infection by common rabies, and none of them reported illness, according to their supervisor. But the incidents raised disturbing questions about the research: What if they encountered an unknown virus that killed humans? What if it spread to their colleagues? What if it infected their families and neighbors? As if to underscore the risks, in 2018 another lab on the same Bangkok campus - a workspace built specifically to handle dangerous pathogens - was shut down for months because of mechanical failures, including a breakdown in a ventilation system that guards against leaks of airborne microbes. Then, in a catastrophe that began in Wuhan, a Chinese city 1,500 miles away, the coronavirus pandemic swept the globe, becoming a terrifying case study in how a single virus of uncertain origin can spread exponentially. In spring 2021, the Thai team's leader pulled the plug, deciding that the millions of dollars of U.S. research money for virus hunting did not justify the risk. "To go on with this mission is very dangerous," Thiravat Hemachudha, a university neurologist who supervised the expeditions, told The Washington Post. "Everyone should realize that this is hard to control, and the consequences are so big, globally." Three years after the start of the coronavirus pandemic, a similar reckoning is underway among a growing number of scientists, biosecurity experts and policymakers. The global struggle with covid-19, caused by the novel coronavirus, has challenged conventional thinking about biosafety and risks, casting a critical light on widely accepted practices such as prospecting for unknown viruses. A Post examination found that a two-decade, global expansion of risky research has outpaced measures to ensure the safety of the work and that the exact number of biocontainment labs handling dangerous pathogens worldwide, while unknown, is believed by experts to be in the thousands. In scores of interviews, scientific experts and officials - including in the Biden administration - acknowledged flaws in monitoring the riskiest kinds of pathogen research. While the pandemic showcased the need for science to respond quickly to global crises, it also exposed major gaps in how high-stakes research is regulated, according to the interviews and a review of thousands of pages of biosafety documents. The source of the coronavirus pandemic remains uncertain. While many scientists and experts suspect it may have been caused by a natural spillover from animals to humans, the FBI, including Director Christopher A. Wray, and a recent Energy Department assessment concluded with varying degrees of confidence that its likely source was an accidental release from a lab in Wuhan. Within the United States, government regulation has also failed to keep step with new technologies that allow scientists to alter viruses and even synthesize new ones. The Biden administration is expected this year to impose tighter restrictions on research with the kinds of pathogens that could trigger an outbreak or a pandemic, according to officials familiar with the matter who spoke on the condition of anonymity to discuss internal deliberations. Governments and private researchers continue building high-containment laboratories to work with the most menacing pathogens, despite a lack of safety standards or regulatory authorities in some countries, science and policy experts said. Meanwhile, U.S. agencies continue to funnel millions of dollars annually into overseas research, such as virus hunting, that some scientists say exposes local populations to risks while offering few tangible benefits. "If you stand back and look at the big picture, the science is rapidly outpacing the policy and the guardrails,'' said James Le Duc, an infectious-disease expert who led research for the U.S. Army and the Centers for Disease Control and Prevention before founding a maximum-containment lab complex at the University of Texas at Galveston. "This is a national security concern," he said. "It's a global public health concern." A few hours' drive outside Bangkok are lush rainforests and craggy highlands that are home to dense swarms of bats - ranging from palm-sized insect eaters to foot-long species that feast on fruit. Thai researchers had long monitored the bats for deadly strains of viruses known to infect humans, including rabies and severe acute respiratory syndrome, called SARS. But the virus hunting performed there over the past decade at U.S. government expense included a different goal - to discover pathogens unknown to science. Chulalongkorn University, Thailand's oldest and one of Southeast Asia's top-ranked biomedical institutions, became a hub for U.S.-funded projects that called for the collection and study of viruses on a vastly larger scale. Rather than focusing on pathogens that had made the jump to humans, the goal was to find and genetically evaluate viruses still circulating principally among animals, project documents show. By building extensive databases of these viruses, U.S. sponsors of the research - including the Pentagon's Defense Threat Reduction Agency and the U.S. Agency for International Development - hoped to forecast which of the microbes might threaten humans. Thiravat, the physician who oversaw the work with wildlife pathogens, recalled that he initially welcomed the chance in 2011 to partner with American scientists in the Pentagon-funded virus-hunting program called Prophecy. The following year, the visitors from the United States were touting a similar project, called PREDICT, with an overall $200 million budget administered by USAID. The goal was to identify pathogens "most likely to become pandemic" and prevent such events. The virus hunting typically started with flights or difficult drives to remote provinces where clusters of trees and networks of caverns provided sanctuary for bat colonies. The Thai researchers would approach the caves and roosting trees at dusk, just as the nocturnal inhabitants were beginning to stir, and work until dawn, catching some in nets and grasping them with gloved hands so that the bodily fluids could be collected on swabs for analysis. Sometimes, Thiravat removed his cumbersome rubber gloves to make the task easier. "In the early days, we didn't think it was that harmful," he said. Humans can become infected through direct contact with the bats' secretions, including their droppings, which are mined as fertilizer in parts of Southeast Asia. "We were really lucky," Thiravat said, that no one died. Over time, Thiravat said he grew worried about the risk of accidental infection - in the field, and as the vials of bat material were transported back to his campus lab in Bangkok - where workers clad in protective masks and coats genetically sequenced the viruses using a technique called polymerase chain reaction. Before those analyses began on the lab's cramped ninth floor, technicians in the field sought to "inactivate" the specimens to prevent the viral material from infecting anyone. For more than a decade, the process of collection, transportation and analysis played out several times a year. One misstep could invite trouble: a virus-contaminated needle piercing latex and skin in the field, a spill in transit or an equipment malfunction in the lab. In China, where a separate virus-cataloguing effort has been underway for years, scientists have described being bitten or scratched by bats or having bat urine or blood splashed into their eyes and faces. A 25-year-old American researcher became ill with a Sosuga virus in 2012 after a research expedition to Sudan and Uganda to collect blood and tissue from bats and rodents. She survived after being hospitalized for 14 days upon returning to the United States, suffering from fever, malaise, headache and muscle and joint pain, according to CDC scientists. The virus, rarely detected in humans, is endemic among the African region's jumbo-sized fruit bats. In 2018, at Chulalongkorn, the scientists were shaken when technicians discovered malfunctioning safety equipment at another lab operating on the same floor as the one used by the virus hunters, according to Thiravat. The technicians found a fault in an air-pressure system designed to keep dangerous microbes from infecting lab workers, and a broken autoclave, a high-pressure steam sterilizer necessary to inactivate and safely dispose of viruses or other contaminated materials. No sicknesses were reported. Repairs were ordered, and the lab was shut down for six months, Thiravat and two colleagues who help operate the facility, Chanida Ruchisrisarod and Teerada Ponpinit, told The Post. The deficiencies have not previously been publicized. In early 2021, with Thailand's death toll in the coronavirus pandemic topping 22,000, Thiravat began informing his U.S. contacts and others that he was finished with virus hunting. A decade of work, he said, had produced no discernible benefit for Thailand while exposing his researchers to life-threatening risk. Thiravat told American officials that the U.S. money - about $10 million of it had flowed to his team's operations - would be better spent on mosquito nets and other conventional public health measures proven to save lives. The field workers' earlier bat bites also weighed on him. In an email to a Pentagon grants official and others, he described a "paradigm shift" in his decision to move away from virus hunting. "Instead of wildlife surveillance that revealed hundreds of viruses belonging to many families - including coronaviruses that may or may not jump to humans,'' Thiravat wrote on April 14, 2022, "we focus on attempting to identify what is responsible for illness in humans and animals." A copy of the correspondence was obtained by The Post. The associate dean for research at Chulalongkorn, Vorasuk Shotelersuk, acknowledged Thiravat's decision while saying that university policy does not prohibit collecting wildlife viruses. "I see that it has some risks," Vorasuk said. "But I see that it's possible that . . . the risks can be handled properly." A spokeswoman for the Pentagon's Defense Threat Reduction Agency, Andrea Chaney, said it now funds "no active bio-surveillance studies in Thailand" but "would be eager to partner with Thailand on future projects." On Friday, Thiravat said he had ordered destruction of the thousands of bat specimens collected during virus hunting expeditions and stored at the university. Until the early 21st century, research into the most lethal pathogens - including the Ebola and Marburg viruses - was typically the domain of a handful of fortresslike laboratories around the world, such as those at Fort Detrick, Md., where scientists performed their tasks with elaborate protective gear, including air-purifying respirators and full-body pressurized suits. But the 2001 American anthrax-letter attacks and later outbreaks of biological threats such as Ebola sparked a construction boom. Funded in part by millions of U.S. dollars, governments worldwide built additional maximum containment labs, which some officials promoted as bulwarks against bioterrorism that would also help diagnose newly emerged human infections, and speed research that could deliver lifesaving vaccines or therapeutics. The number of labs continues to soar. Of the most restrictive, known as Biosafety Level (BSL) 4 labs, some 69 exist or are under construction in 27 countries. Half were built in the past decade, including 10 last year, according to data gathered for a newly released report by Global Biolabs, a British-U.S. consortium that advocates for vigorous oversight of pathogen research. The growth in research also has driven construction of a slightly less-restrictive type of laboratory, known as the BSL-3. These labs are designed to handle sometimes-fatal pathogens such as plague and anthrax and the viruses that cause covid-19 and West Nile fever. The Bangkok laboratory that was shut down over safety concerns in 2018 is rated BSL-3. Although no reliable totals exist for the number of BSL-3 labs globally - scientists suspect there are perhaps thousands - the federal Government Accountability Office has listed 1,362 in the United States alone, most of those operated by the federal government, state governments or academic institutions. But the GAO noted that its number is an incomplete count. "We found that there are entities that have high-containment labs but have not registered" with the federal government, Kelly L. DeMots, a GAO assistant director for health care, told The Post. Labs are required to register if they are working with dangerous microbes, including Ebola, anthrax and more than 60 other pathogens and toxins. The CDC inspects the registered labs, which are supposed to disclose accidents or mishaps. From 2009 to 2018, such labs reported an average of 98 incidents annually, ranging from minor problems with protective gear to exposures from accidental jabs with contaminated needles, according to CDC records. A separate accounting, based on National Institutes of Health records obtained by private researchers through the Freedom of Information Act, identified 184 incidents between 2004 and 2018. They all occurred in labs rated at BSL-2 or higher and included spills of contaminated wastes, bites from infected animals and label mix-ups that resulted in workers unknowingly handling live viruses, according to an analysis by Lynn Klotz, a senior science fellow at the Center for Arms Control and Non-Proliferation in D.C. The BSL-2 labs handle infectious pathogens or toxins that pose a moderate risk if inhaled, swallowed or exposed to the skin. Labs designated BSL-1 should have some personal protective equipment and an autoclave for decontaminating materials. Several lab workers identified in NIH records tested positive for exposure to dangerous pathogens, Klotz's research showed, although there were no reports of serious illnesses or exposures to people outside the labs, according to his analysis, which he provided to The Post. A GAO report released in January revealed multiple gaps in the federal government's policing of the riskiest kinds of experiments. The report, which identified no labs by name, said the Department of Health and Human Services is providing "subjective and potentially inconsistent" oversight of U.S.-funded research. Additionally, "HHS does not conduct oversight" of research funded by foundations and other nongovernment groups, even when the work involves "enhancement of potential pandemic pathogens." Far less is known about labs outside the United States. Regulation falls to each individual country, and there are no enforced international standards. Global Biolabs, the advocacy group, found that nearly 1 in 10 BSL-4 labs operating in other countries score poorly in international rankings for lab safety. In some cases, labs were constructed without local regulations or meaningful oversight of the handling of dangerous pathogens, or "even a well-established culture of responsible research," said Gregory Koblentz, a co-author of the Global Biolabs report and the director of the biodefense graduate program at George Mason University's Schar School of Policy and Government. Most countries lack the sophisticated controls needed to prevent dangerous viruses or bacteria from being misused or diverted for illicit purposes, he said. "This is a major blind spot in global surveillance for future biological threats," Koblentz said. Neither are there reliable sources of information on research accidents, especially in developing countries, where laboratories often struggle to pay the bills and sometimes are forced to contend with blackouts and shortages of clean water, according to interviews with scientists and other experts. "In some parts of the world, they just don't have the people, the money or the need" for the research performed at the high containment labs, said Thomas Inglesby, a biosecurity adviser to multiple U.S. administrations who also is the director of the Johns Hopkins Center for Health Security in Baltimore. Scientists and officials contacted in Southeast Asia and Africa, for instance, described constant struggles to fund salaries and the training of lab personnel, along with paying for protective gear, replacement parts and other upkeep of safety systems. "My worry is the maintenance and the costs," Oyewale Tomori, a virologist and former president of the Nigerian Academy of Science, said in an interview from Lagos. Tomori is "very concerned" with the several BSL-3 labs operating in Nigeria, he said, "because the funding to maintain and sustain" biosafety is lacking. At the World Health Organization, epidemiologist Kazunobu Kojima has for more than a decade led its efforts to encourage countries to reduce the risks, revising, for example, a biosafety manual that labs are encouraged to adopt. The WHO, Kojima said by email, has found that poorer countries - which he declined to name - "struggle to attain the necessary capacities and capabilities to manage biosafety and biosecurity challenges." The U.S. National Academy of Sciences also has sought for more than a decade to promote safety by inviting international lab specialists to conferences and asking them privately to share their concerns. Interviews with participants and conference summaries reviewed by The Post reveal long-standing deficiencies. "Major gaps in biosafety implementation'' were reported in the Caribbean region, "where a survey of 13 major labs found that only about half the respondents indicated that respirators were used correctly," according to the summary of a conference held in 2011 in Istanbul. Of about 45 BSL-3 facilities operating in Southeast Asia, "questions exist about standards, management, training and security for most labs in the region,'' according to the summary. Many lab safety cabinets - intended to contain pathogenic material aerosolized during experiments - were "neither functional nor regularly inspected,'' according to a second account of the meeting prepared by the National Academy of Sciences, which added: "For some labs, the availability of electricity and water was severely limited." In 2016, scientists who gathered again warned of systemic lab deficiencies in Asia. In Malaysia, "adequate resources are needed to improve basic biosafety infrastructure, facilities and equipment." In Vietnam, of the country's more than 5,000 BSL-1 and BSL-2 labs, "only 600 of them are certified" by the government and "most facilities do not yet meet the biosafety conditions." In India, "awareness about bio-risk management at . . . many national laboratories is inadequate and . . . trained staff on biosafety issues is needed." Micah Lowenthal, the director of the National Academy's committee on international security and arms control, said the conferences sought to "reduce the possibility of an outbreak." "We want to improve the practices at the laboratories," said Lowenthal, who is a physicist. The presentations helped demonstrate, he said, "how hard it is to build and run these facilities. They're expensive; there's a lot of care that has to go into it." The United States has allocated more than $400 million to virus hunting worldwide since 2009, according to grant documents and other federal records. Proponents contend that this effort could help develop the medicines to counter future spillovers of deadly viruses from animals to humans, and two of the U.S.-funded programs are aimed explicitly at preventing human pandemics. The Biden administration initially backed the research, announcing on Oct. 5, 2021, a USAID initiative called DEEP VZN (short for "Discovery & Exploration of Emerging Pathogens - Viral Zoonoses") in Africa, Asia and Latin America. The program would "detect, prevent and respond to future biological threats," USAID said at the time. "DEEP VZN will build and expand on previous work by significantly scaling up USAID's efforts to understand where, when, and how viruses spillover from animals to humans,'' said an agency news release, promoting the $125 million program. But in December 2021, officials with the White House National Security Council and the Office of Science and Technology Policy privately advocated to end DEEP VZN and another USAID program called "STOP Spillover," a $100 million effort to analyze disease threats from animals and prevent outbreaks or pandemics. According to interviews with people familiar with the matter, who spoke on the condition of anonymity to discuss internal administration deliberations, the officials made their recommendation personally and in emails to USAID Administrator Samantha Power and her top aides. Power pledged a review of the programs, but USAID continues to fund the research, the officials said. Power declined through a spokeswoman to comment. The White House recommendation was based in part on classified warnings about the possibility that foreign adversaries could use the programs' data to advance bioweapons programs, said those familiar with the events. Critics of virus hunting contend that the programs create unacceptable risks and have generated vast amounts of genetic data of limited usefulness. They note that the harvesting of bat viruses failed to predict the coronavirus pandemic or yield new vaccines. The work provides researchers with a snapshot in time of viruses that are continuously evolving, but "there is no way to know, based on the identification of a virus in an animal, whether it's going to pose a threat to humans, to livestock or to wildlife," said W. Ian Lipkin, an epidemiologist at Columbia University. Lipkin said his New York City lab analyzed viruses collected abroad for the U.S. government's PREDICT program. Prominent biosecurity specialists also have warned of the appeal to terrorists. Kevin Esvelt, a Massachusetts Institute of Technology biotechnologist who helped develop the pioneering gene-editing technology known as CRISPR, told members of Congress in December 2021 that posting the genetic sequences of viruses could lead to a global pandemic. Doing so, he said, is like publicly revealing the instructions for making a nuclear bomb. "If someone were to assemble pandemic-capable viruses from a publicly available list and released them in airports worldwide," Esvelt told The Post, "that might be a civilization-level threat." The rapid changes in technology have left regulators a step behind, experts say. That gap became apparent after an NIH-funded researcher named Ron Fouchier in the Netherlands shocked his peers by revealing in 2011 that he had created a mutant strain of a particularly lethal kind of avian flu, H5N1. The resulting pathogen, Fouchier reported, had for the first time spread through respiratory droplets among caged ferrets. The experiment, approved in advance by the NIH, sought to anticipate what might happen if such mutations threaten humans through natural evolution. Reached by email, Fouchier said his work "filled crucial gaps in knowledge . . . about what makes an influenza virus transmissible in the air via mammals." His facilities in Rotterdam, he said, are inspected regularly by Dutch and U.S. government officials, and were "specifically built to work safely and securely with airborne viruses." As for what controls are needed globally, Fouchier said: "Authorities should ensure that this type of work can only occur in safe and secure labs, to ensure negligible risk to humans and the environment." Fouchier's work, and several high-profile research mishaps in the United States - including the discovery in 2014 of six vials of virulent smallpox on NIH's central campus in Bethesda, Md. - alarmed the Obama White House. That fall, officials imposed a moratorium on government-funded experiments with some viruses that would result in a "gain of function," a change that made the pathogen more lethal, more transmissible or more resistant to drugs or vaccines. In late 2017, the Trump administration lifted the moratorium and announced new guidelines and an HHS-appointed expert panel to provide oversight. The new system was meant to ensure that U.S.-funded experiments - including those conducted overseas - that could yield more-dangerous viruses would first undergo high-level federal review to assess such projects' overall risks and potential benefits. But the policy change applies only to research funded by the HHS and its components, including the NIH. The rules do not encompass experiments that might be backed by the Pentagon, other federal agencies or private companies and institutions. The 2017 revisions also included an overlooked loophole that exempted experiments from the expert panel's review unless a lab-created pathogen was "reasonably anticipated'' to be both "highly transmissible" and "highly virulent." In a report in January, the HHS inspector general faulted NIH's oversight of a project that was launched in China and funded by agency grants from 2014 to 2019 to EcoHealth Alliance, a nonprofit organization based in New York City. According to the report, EcoHealth failed to promptly disclose safety concerns about lab work conducted with coronavirus strains by a subgrantee, the Wuhan Institute of Virology, in the Chinese city where the coronavirus pandemic began. The NIH "did not effectively monitor or take timely action to address EcoHealth's compliance," the report said. In written remarks to the inspector general, EcoHealth's president, Peter Daszak, disputed that his company had been required to immediately notify NIH of the concerns that the agency later identified. But Daszak also said that EcoHealth had "corrected certain procedures" and aims for "even better compliance" with federal rules. Asked for comment, EcoHealth reiterated by email the points that Daszak made to the inspector general. Officials at NIH did not contest the conclusions and told the inspector general that corrective actions were underway, including tighter monitoring of foreign subgrantees. Anthony S. Fauci, who was the director of the NIH institute that funded the work in Wuhan, has told Congress that none of those experiments amounted to gain-of-function research. Fauci, 82, retired on Dec. 31. Le Duc, the infectious-disease expert, and other scientists said the coronavirus pandemic has shown that the federal review standards need to be tightened because even a pathogen that kills at a modest rate can inflict devastation if it is highly transmissible. In September, the National Science Advisory Board for Biosecurity said the existing definition of pandemic-risk pathogens "should be modified to include potentially highly transmissible pathogens having low or moderate virulence." That would open more U.S.-funded work to the scrutiny of the HHS panel of experts. In January, the federal board detailed its recommendation in a 29-page report. Kenneth W. Bernard, a member of the board, told The Post that the proposed change would close "the loophole" and enable stricter scrutiny of high-stakes research. But he said that tighter controls may prompt some virologists to move experiments to less-regulated labs overseas. "We need to develop incentives for people to put safety and carefulness at the same level as scientific advance,'' said Bernard, a physician who was a biodefense assistant to President George W. Bush. "The [Biden] administration should move on this quickly." The White House expects to address the matter in its planned policy revision, officials said. Some bioengineering firms, acutely aware of the potential for harm if their technology is misused, have chosen not to wait for tighter federal rules. They have introduced their own safeguards and oversight systems, voluntarily taking on responsibilities and costs that normally fall to governments. One of them is the San Francisco company Twist Bioscience. The 10-year-old firm is among about two dozen globally that synthesize DNA at scale; Twist manufactures artificial genetic sequences to sell to other scientists in labs around the world. Twist's synthetic DNA is used by researchers to create "designer" bacteria and viruses that can attack cancer cells or clean up oil spills. In theory, it also could be used for malicious purposes, such as tweaking a disease strain to make it more virulent or drug-resistant. Every day, from inside Twist's glass office tower near San Francisco International Airport, a machine resembling a 3D printer deposits microscopic strands of genetic code on a silicon wafer as workers in protective gear keep watch. New orders arrive over the internet, and the finished products are sent out the door by courier or mail truck in as little as six days. Concealed within the jumble of coding that makes up a typical order could be the keys to a lifesaving cure - or the biological equivalent of a powerful bomb. The synthetic-DNA industry is new, and few federal regulations govern it. Asked by The Post about the technology, HHS officials said the department this year is likely to issue "updated guidance'' for "the gene and genome synthesis enterprise." Twist executives, however, say they have already introduced their own safeguards. In the company's security department, computers scan each order to see whether the requested DNA matches up with known pathogens, including restricted microbes that cannot legally be acquired without a license. A different team investigates the individuals behind each order. What's the history and track record of the buyer? Do names and shipping addresses match up? What's the intended use of the DNA? On a few occasions, a suspicious order has prompted a call to the FBI, company officials said. "We're being asked to manufacture this thing, so we have to make sure we truly understand who the ordering party is and whether they have a legitimate use," said James Diggans, Twist's head of biosecurity. The extra steps are costly and time-consuming for a company that has to compete with other synthetic-DNA producers, including in Europe and China. Twist has tried to turn this perceived liability into an asset, marketing itself to customers as a company that sees biosecurity as an essential value that all responsible researchers should share. Some vendors are less willing to spend the money, particularly in markets overseas, said Emily Leproust, a French-born organic chemist and the company's co-founder and CEO. Twist has pushed its competitors to abide by the same standards. But with few regulations and no international enforcement, biosecurity remains, for now, a premium feature - an option, for the purveyors of a new science who are sufficiently worried about the risks to take an extra step. "The majority in the industry are good players, but there a few who don't participate, and I think it's wrong," Leproust said. "Every invention is like a coin, with a side that's positive and a side that is negative. With dynamite you build a canal. But you can also kill." - - - Warrick reported from San Francisco. The Washington Post's Alice Crites in Washington and Emmanuel Martinez in San Diego contributed to this report. About this project To track spending on pathogen research, The Post analyzed data from ForeignAssistance.gov, which details money provided by the U.S. government to other countries, international organizations and foreign groups for them to acquire goods, services or technical assistance. Reporters identified money allocated since 2012. To isolate work related to infectious microbes as well as zoonotic viruses, which can spread between animals and people, reporters searched for keywords in the project name and description fields. Keywords included: zoonotic, spillover, influenza, pathogen H5N1, and others. Reporters also specifically searched for projects and programs, such as PREDICT and DEEP VZN. Because of the lack of detail in the programs and activities, spending includes training, seminars and overall work that supports the identification, prevention, and surveillance of zoonotic viruses and infectious diseases. To calculate the funding by country, reporters used the "Constant Dollar Amount" field, which is adjusted for inflation. © 2023 The Washington Post. Sign up for the Today's Worldview newsletter here.