Questions You Should Ask

Today, the National Institutes of Health announced that it is lifting a funding pause dating back to October 2014 on gain-of-function (GOF) experiments involving influenza, SARS, and MERS viruses. GOF research is important in helping us identify, understand, and develop strategies and effective countermeasures against rapidly evolving pathogens that pose a threat to public health. The funding pause was lifted in response to today’s release of the Department of Health and Human Services Framework for Guiding Funding Decisions about Proposed Research Involving Enhanced Potential Pandemic Pathogens (link is external)(HHS P3CO Framework). The HHS P3CO Framework describes a multi-disciplinary review process, involving the funding agency and a Department-level review group, that considers the scientific merits and potential benefits of the research, as well as the potential to create, transfer, or use an enhanced potential pandemic pathogen. This framework formalizes robust oversight for federally funded research with enhanced pathogens of pandemic potential. It is the product of an extensive deliberative process undertaken by experts throughout the public and private sectors, and is aligned with the Recommended Policy Guidance for Departmental Development of Review Mechanisms for Potential Pandemic Pathogen Care and Oversight (P3CO)(link is external).

We have a responsibility to ensure that research with infectious agents is conducted responsibly, and that we consider the potential biosafety and biosecurity risks associated with such research. I am confident that the thoughtful review process laid out by the HHS P3CO Framework will help to facilitate the safe, secure, and responsible conduct of this type of research in a manner that maximizes the benefits to public health.

I would especially like to acknowledge the efforts of the National Science Advisory Board for Biosecurity and the National Academies of Sciences, Engineering, and Medicine(link is external) for their thoughtful deliberations on the issues surrounding this important area of research. The work of these committees was instrumental in guiding the United States Government in its job of creating rigorous policy that allows vital research to move forward.

[https://www.nih.gov/about-nih/who-we-are/nih-director/statements/nih-lifts-funding-pause-gain-function-research]

Seven days before Donald Trump took office, his aides faced a major test: the rapid, global spread of a dangerous virus in cities like London and Seoul, one serious enough that some countries were imposing travel bans.

In a sober briefing, Trump’s incoming team learned that the disease was an emerging pandemic — a strain of novel influenza known as H9N2 — and that health systems were crashing in Asia, overwhelmed by the demand.

“Health officials warn that this could become the worst influenza pandemic since 1918,” Trump’s aides were told. Soon, they heard cases were popping up in California and Texas.

The briefing was intended to hammer home a new, terrifying reality facing the Trump administration, and the incoming president’s responsibility to protect Americans amid a crisis. But unlike the coronavirus pandemic currently ravaging the globe, this 2017 crisis didn’t really happen — it was among a handful of scenarios presented to Trump’s top aides as part of a legally required transition exercise with members of the outgoing administration of Barack Obama.

And in the words of several attendees, the atmosphere was “weird” at best, chilly at worst.

POLITICO obtained documents from the meeting and spoke with more than a dozen attendees to help provide the most detailed reconstruction of the closed-door session yet. It was perhaps the most concrete and visible transition exercise that dealt with the possibility of pandemics, and top officials from both sides — whether they wanted to be there or not — were forced to confront a whole-of-government response to a crisis. The Trump team was told it could face specific challenges, such as shortages of ventilators, anti-viral drugs and other medical essentials, and that having a coordinated, unified national response was “paramount” — warnings that seem eerily prescient given the ongoing coronavirus crisis.

But roughly two-thirds of the Trump representatives in that room are no longer serving in the administration. That extraordinary turnover in the months and years that followed is likely one reason his administration has struggled to handle the very real pandemic it faces now, former Obama administration officials said.

“The advantage we had under Obama was that during the first four years we had the same White House staff, the same Cabinet,” said former deputy labor secretary Chris Lu, who attended the gathering. “Just having the continuity makes all the difference in the world.”

Sean Spicer, Trump’s first White House press secretary, was among those who participated in the meeting. He said he understood the reasons such exercises could be useful, but described the encounter as a massive transfer of information that ultimately felt very theoretical. In real life, things are never as simple as what’s presented in a table-top exercise, he said.

“There’s no briefing that can prepare you for a worldwide pandemic,” added Spicer, who left the administration in mid-2017.

The outgoing Obama aides and incoming Trump aides gathered for roughly three hours on the afternoon of Friday, Jan. 13, 2017, in the Eisenhower Executive Office Building next to the White House.

At least 30 representatives of Trump’s team — many of them soon-to-be Cabinet members — were present, each sitting next to their closest Obama administration counterpart. Incoming Commerce Secretary Wilbur Ross appeared to keep dozing off. Incoming Energy Secretary Rick Perry was getting along famously with Ernest Moniz, the man he was replacing, several fellow participants said.

But it was clear some on the Trump team had barely, if ever, spoken with the people they were replacing. News had broken that same day about national security adviser Michael Flynn’s unusual contacts with Russia’s ambassador to the United States, so his presence in the meeting added to the surrealness. Some members of both groups kept going in and out of the room, but most paid quiet attention to the presentations, which were led by top Obama aides.

Obama aides, in op-eds and essays ripping the Trump administration’s handling of the coronavirus, officially called COVID-19, have pointed to the Jan. 13, 2017, session as a key example of their effort to press the importance of pandemic preparedness to their successors.

In a Friday op-ed, Susan Rice, Obama’s national security adviser, blasted Trump for comments such as “you can never really think” that a pandemic like the coronavirus “is going to happen.” She mentioned the 2017 session as one of many instances of the Obama administration’s efforts to help its successor be ready for such a challenge. She also slammed the Trump team for dismantling the National Security Council section that would play a lead role in organizing the U.S. response to a global pandemic.

“Rather than heed the warnings, embrace the planning and preserve the structures and budgets that had been bequeathed to him, the president ignored the risk of a pandemic,” Rice wrote. (Trump’s former national security adviser John Bolton, who oversaw the dissolution of the NSC’s global health security and biodefense section, has defended it as necessary streamlining, countering that global health “remained a top NSC priority.” Trump, when recently asked about the reshuffling, called the question “nasty” and said, “I don’t know anything about it.”)

Lisa Monaco, Obama’s homeland security adviser, explained the thinking behind the January 2017 session in a recent essay for Foreign Affairs. “Although the exercise was required, the specific scenarios we chose were not,” she wrote. “We included a pandemic scenario because I believed then, and I have warned since, that emerging infectious disease was likely to pose one of the gravest risks for the new administration.”

None of the sources argued that one meeting three years ago could have dramatically altered events today. But Obama aides say the Trump administration’s fumbling of the coronavirus outbreak is partly rooted in how unprepared — and in some cases unwilling — it was to engage in transition exercises at all in late 2016 and early 2017.

David Shulkin, who was an Obama appointee at the time but had been nominated to be Veterans Affairs secretary in the Trump administration, said in an interview that with the exception of this exercise, which he didn’t recall well, he noticed that in his agency, there had been “little coordination” and “very little interest in working with the Obama appointees.”

“They had said we don’t really have a lot of need to talk to the Obama appointees,” he said.

That botched handoff sparked weeks of confusion, all the way up to Inauguration Day. “There was a frenzy before the transition where I was asked to consider staying because the [preparedness] mission was so important,” said Nicole Lurie, who served as Obama’s Health and Human Services assistant secretary for preparedness and response, where she worked on crises like the Ebola virus outbreak and attended the pandemic exercise. “Then through the HHS secretary’s office, the next day, I heard they changed their mind.”

The Trump campaign, like the rest of America, was shocked to win the November 2016 election. Soon afterward, Trump cast aside his team’s transition prep work that had happened already and started over; some of his aides described tossing carefully collected binders full of possible personnel picks into trash bins. It was days, sometimes weeks, before his nominees and their aides showed up to meet the people they were replacing — if they did so at all — or to engage in transition meetings. Obama aides said they left detailed memos for their successors, but that quite often it appeared those memos were never read. Many on the Obama side were genuinely surprised that so many actually showed up for the Jan. 13, 2017, exercise, and there were expectations that some would skip it. On the Obama side, several agencies were represented by their second-in-command at the meeting for reasons including a belief that Trump’s principals wouldn’t show.

The gathering was held to satisfy a requirement in a 2016 law that updated the procedures around presidential transitions to require, among other things, that the outgoing administration “prepare and host interagency emergency preparedness and response exercises.” Obama also mentioned it in a 2016 executive order laying out his transition goals.

[https://www.politico.com/news/2020/03/16/trump-inauguration-warning-scenario-pandemic-132797]

An experiment that created a hybrid version of a bat coronavirus — one related to the virus that causes SARS (severe acute respiratory syndrome) — has triggered renewed debate over whether engineering lab variants of viruses with possible pandemic potential is worth the risks.

In an article published in Nature Medicine¹ on 9 November, scientists investigated a virus called SHC014, which is found in horseshoe bats in China. The researchers created a chimaeric virus, made up of a surface protein of SHC014 and the backbone of a SARS virus that had been adapted to grow in mice and to mimic human disease. The chimaera infected human airway cells — proving that the surface protein of SHC014 has the necessary structure to bind to a key receptor on the cells and to infect them. It also caused disease in mice, but did not kill them.

Although almost all coronaviruses isolated from bats have not been able to bind to the key human receptor, SHC014 is not the first that can do so. In 2013, researchers reported this ability for the first time in a different coronavirus isolated from the same bat population².

The findings reinforce suspicions that bat coronaviruses capable of directly infecting humans (rather than first needing to evolve in an intermediate animal host) may be more common than previously thought, the researchers say.

But other virologists question whether the information gleaned from the experiment justifies the potential risk. Although the extent of any risk is difficult to assess, Simon Wain-Hobson, a virologist at the Pasteur Institute in Paris, points out that the researchers have created a novel virus that “grows remarkably well” in human cells. “If the virus escaped, nobody could predict the trajectory,” he says.

Creation of a chimaera

The argument is essentially a rerun of the debate over whether to allow lab research that increases the virulence, ease of spread or host range of dangerous pathogens — what is known as ‘gain-of-function’ research. In October 2014, the US government imposed a moratorium on federal funding of such research on the viruses that cause SARS, influenza and MERS (Middle East respiratory syndrome, a deadly disease caused by a virus that sporadically jumps from camels to people).

The latest study was already under way before the US moratorium began, and the US National Institutes of Health (NIH) allowed it to proceed while it was under review by the agency, says Ralph Baric, an infectious-disease researcher at the University of North Carolina at Chapel Hill, a co-author of the study. The NIH eventually concluded that the work was not so risky as to fall under the moratorium, he says.

But Wain-Hobson disapproves of the study because, he says, it provides little benefit, and reveals little about the risk that the wild SHC014 virus in bats poses to humans.

Other experiments in the study show that the virus in wild bats would need to evolve to pose any threat to humans — a change that may never happen, although it cannot be ruled out. Baric and his team reconstructed the wild virus from its genome sequence and found that it grew poorly in human cell cultures and caused no significant disease in mice.

“The only impact of this work is the creation, in a lab, of a new, non-natural risk,” agrees Richard Ebright, a molecular biologist and biodefence expert at Rutgers University in Piscataway, New Jersey. Both Ebright and Wain-Hobson are long-standing critics of gain-of-function research.

In their paper, the study authors also concede that funders may think twice about allowing such experiments in the future. “Scientific review panels may deem similar studies building chimeric viruses based on circulating strains too risky to pursue,” they write, adding that discussion is needed as to “whether these types of chimeric virus studies warrant further investigation versus the inherent risks involved”.

Useful research

But Baric and others say the research did have benefits. The study findings “move this virus from a candidate emerging pathogen to a clear and present danger”, says Peter Daszak, who co-authored the 2013 paper. Daszak is president of the EcoHealth Alliance, an international network of scientists, headquartered in New York City, that samples viruses from animals and people in emerging-diseases hotspots across the globe.

Studies testing hybrid viruses in human cell culture and animal models are limited in what they can say about the threat posed by a wild virus, Daszak agrees. But he argues that they can help indicate which pathogens should be prioritized for further research attention.

Without the experiments, says Baric, the SHC014 virus would still be seen as not a threat. Previously, scientists had believed, on the basis of molecular modelling and other studies, that it should not be able to infect human cells. The latest work shows that the virus has already overcome critical barriers, such as being able to latch onto human receptors and efficiently infect human airway cells, he says. “I don’t think you can ignore that.” He plans to do further studies with the virus in non-human primates, which may yield data more relevant to humans.

[https://www.nature.com/news/engineered-bat-virus-stirs-debate-over-risky-research-1.18787]

Nearly a year has passed since the Obama administration announced a moratorium on controversial “gain-of-function” (GOF) research, and the advisory board charged with coming up with guidance for how the government funds such projects and weighs the risks and benefits met this week to hear updates from working groups and receive more input on their deliberations.

The National Science Advisory Board for Biosecurity (NSABB) is playing the lead role in formulating policies for work on studies that enhance pathogenicity, transmissibility, or host range of a pathogen with the goals of better understanding disease and developing vaccines and drugs.

The experiments have triggered “dual-use” worries—that methods could be used not only for beneficial purposes but also to engineer bioterror threats. Some experts have also raised concerns about an intentional or accidental release of the experimental pathogens, especially in light of recent safety lapses involving federal facilities.

The Obama administration first announced the moratorium on Oct 17, and early indications were that it would take about a year for the NSABB to hammer out a federal funding policy and a risk-benefit assessment. However, the latest estimate is for the recommendations and risk assessment to be finalized in the spring of 2016.

Last December the administration allowed a handful of GOF studies to resume, some involving Middle East respiratory syndrome coronavirus (MERS-CoV) and influenza. An NSABB working group is tackling the funding policy recommendations, and in March the government awarded a $1.1 million contract to Gryphon Scientific to formally assess the risks and benefits of GOF work.

The NSABB’s meeting on Oct 28 was streamed live online and will soon be available in an online audio archive. Christopher Viggiani, PhD, the NSABB’s executive director at the National Institutes of Health (NIH), said the group was briefed on the progress of funding policy development and received an update on Gryphon’s work so far on the risk-benefit assessment. He said members also discussed a host of related ethical, legal, and policy issues and heard input from the public.

Timeline for next steps

During the meeting the NSABB also aired a timeline for the next steps, Viggiani said. The working group is expected to start reviewing the preliminary risk-benefit assessment in November. And at its next meeting on Jan 7 and 8, the NSABB is expected to review the final version of the risk-benefit assessment and the working group’s draft funding policy recommendations.

Viggiani said both items will also be discussed at a National Academy of Sciences (NAS) meeting on Mar 10 and 11, and the NSABB tentatively expects to present its final recommendation tentatively in the spring of 2016. The NAS meeting will be the second devoted to discussing GOF issues. The first debate was held in December 2014.

In a blog post on the latest NSABB developments, Carrie Wolinetz, PhD, the NIH’s associate director for science policy, wrote that the GOF debate is about public trust in science. She added that new discoveries and technology are promising, but they test policy frameworks. “It is an exciting time, but also a sobering one for those in science policy. It is our job to help ensure that science can advance rapidly as well as safely, ethically, and responsibly.”

Discussions in the medical literature

Meanwhile, scientists continue to weigh in on the GOF debate in two reports in the Sep 27 online edition of Journal of Infectious Diseases. One group of authors built a case for including clinicians in GOF discussions, while the others detailed six recommendations from an Infectious Diseases Society of America (IDSA) working group.

In the first report, two scientists with military labs and one from the University of Pittsburgh Medical Center’s Center for Health Security wrote that microbiologists and policy specialists have guided much of the GOF discussion, but more input is needed from medical and public health practitioners, because they are often the “end users” of the products of such research.

In the debate that’s transpired so far, the ramifications for the research on practicing clinicians hasn’t been clarified, the group wrote.

They said GOF research helps ensure that clinicians have the tools to respond to outbreaks, and that decisions affecting what type of research is allowed to continue directly affect clinicians’ work. They added, howver, that clinicians will also need to be acutely aware of the risks posed by the work.

The second editorial is from the IDSA’s working group on dual-use research of concern and lists six key recommendations for the NSABB as it conduct its GOF work. The group first shared its recommendations with the NSABB in an Aug 10 letter.

Their recommendations include focusing on experiments of special concern, and they worried that under the NSABB’s current framework, work to produce high-growth vaccine virus strains would likely be hampered. They also urged the group to address uncertainties and seek a wide array of expertise in weighing risks and benefits.

Other recommendations included accounting for public perception of science during risk discussions, considering the framework’s impact on science in the face of potential GOF limits, and finding ways to improve the safety of GOF.

[https://www.cidrap.umn.edu/news-perspective/2015/10/work-continues-policies-gain-function-research]

The US government surprised many researchers on 17 October when it announced that it will temporarily stop funding new research that makes certain viruses more deadly or transmissible. The White House Office of Science and Technology Policy is also asking researchers who conduct such ‘gain-of-function’ experiments on influenza, severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) to stop their work until a risk assessment is completed — leaving many unsure of how to proceed.

“I think it’s really excellent news,” says Marc Lipsitch, an epidemiologist at the Harvard School of Public Health in Boston, Massachusetts, who has long called for more oversight for gain-of-function research. “I think it’s common sense to deliberate before you act.”

Critics of such work argue that it is unnecessarily dangerous and risks accidentally releasing viruses with pandemic potential — such as an engineered H5N1 influenza virus that easily spreads between ferrets breathing the same air^1, 2. In 2012, such concerns prompted a global group of flu researchers to halt gain-of-function experiments for a year (see Nature http://doi.org/wgx; 2012). The debate reignited in July, after a series of lab accidents involving mishandled pathogens at the US Centers for Disease Control and Prevention in Atlanta, Georgia.

The White House’s abrupt move seems to be a response to renewed lobbying by gain-of-function critics who wanted such work suspended and others who sought to evaluate its risks and benefits without disrupting existing research.

Arturo Casadevall, a microbiologist at the Albert Einstein College of Medicine in New York City, calls the plan “a knee-jerk reaction”. “There is really no evidence that these experiments are in fact such high risk,” he says. “A lot of them are being done by very respectable labs, with lots of precautions in place.”

Some researchers are confused by the moratorium’s wording. Viruses are always mutating, and Casadevall says that it is difficult to determine how much mutation deliberately created by scientists might be “reasonably anticipated” to make a virus more dangerous — the point at which the White House states research must stop. The government says that this point will be determined for individual grants in discussions between funding officers and researchers.

One of the most prominent laboratories conducting gain-of-function studies is run by Yoshihiro Kawaoka, a flu researcher at the University of Wisconsin–Madison. In 2012, Kawaoka published a controversial paper¹ reporting airborne transmission of engineered H5N1 flu between ferrets. He has since created an H1N1 flu virus using genes similar to those from the 1918 pandemic strain³, to show how such a dangerous flu could emerge. The engineered H1N1 was transmissible in mammals and much more harmful than the natural strain.

Kawaoka says that he plans to comply with the White House directive to halt current research once he understands which of his projects it affects. “I hope that the issues can be discussed openly and constructively so that important research will not be delayed indefinitely,” he says.

But it seems that the freeze could be lengthy. The White House says that it will wait for recommendations from the US National Science Advisory Board for Biosecurity (NSABB) and the National Research Council before deciding whether and how to lift the ban. The groups are expected to finish their work within a year. As Nature went to press, the NSABB was set to convene on 22 October, its first meeting in two years. Lipsitch, who will speak at the event, says that he will advocate for the development of an objective risk-assessment tool to evaluate individual research projects. In particular, he says, decision-makers should consider whether a gain-of-function study makes a contribution to a public-health goal, such as the prevention and treatment of flu, that could justify both the risk and the use of money that could be spent on safer research.

“There clearly are going to be instances where gain-of-function research is necessary and appropriate, and there are others where the opposite applies,” says Ian Lipkin, a virologist at Columbia University in New York City. The need to understand the ongoing Ebola outbreak in West Africa and control its spread, for instance, emphasizes the importance of infectious-disease research — as well as the regulation of such work, Lipkin says. Although public worry about Ebola being transferred through the air is unfounded, researchers could make a case for the need to determine how the virus could evolve in nature by engineering a more dangerous version in the lab. “I think we should have some sort of guidelines in place before such experiments are even proposed,” says Lipkin. Yet Ebola is not included in the White House’s research-funding ban, and a spokesperson says that there are no plans to include it on the list.

One thing is certain, says Casadevall: the NSABB meeting is certain to see heated debate as scientists from all sides convene. “I hope they have enough room,” he adds.

[https://www.nature.com/news/us-suspends-risky-disease-research-1.16192]

An international research team has identified two novel coronaviruses (CoVs) in Chinese horseshoe bats that are closely related to the SARS-CoV and can infect human cells, which supports the hypothesis that the SARS virus originated in bats and suggests that it may have the capacity to jump directly from bats to humans, instead of passing through another animal first.

The new findings, reported today in Nature, come from a genetic analysis of samples taken from a horseshoe bat colony, a year-long effort that took place in Kunming, China, in the southwestern part of the country in Yunnan province. The team, which included investigators from China, Australia, Singapore, and the United States, found at least seven different strains of SARS-like viruses circulating in the bats.

Genetic sequencing revealed that two of the novel viruses were more closely related to SARS-CoV than any virus seen before. And for the first time, the research team was able to isolate a SARS-like virus from a bat fecal sample, which allowed them to run a series of tests to see if it could infect different human and animal cells.

During the SARS outbreak a decade ago, Chinese researchers concluded that civets were the immediate source of the virus in human infections, which led the government to order the slaughter of all civets in captivity and ban killing and cooking the animals. However, researchers haven’t determined if they are the virus’s natural reservoir. In previous studies, Chinese researchers had found CoV sequences similar to the SARS virus in bats, monkeys, snakes, and civets.

Global health officials suspect that bats might be the reservoir of the Middle Eastern respiratory syndrome coronavirus (MERS-CoV), especially after researchers in August reported finding a virus fragment in a bat that appeared to match the one infecting people in a handful of Middle Eastern countries. Also, diverse SARS-like CoVs have also been reported in bats in China, Europe, Africa, and North America.

Same receptor as SARS virus

In the new study, researchers found that the virus they isolated and cultured from bat guano uses the same human receptor as SARS-CoV to infect human cells. The angiotensin-converting enzyme 2 (ACE2) receptor is mainly found in pneumocytes, deep in human lungs.

In a series of lab tests using different species’ cell lines, researchers found that the virus they isolated can infect human alveolar epithelial cells, pig kidney cells, and the bats’ own kidney cells, but cannot infect six other cell lines that they used.

In cross-neutralizing antibody tests using nine blood samples collected from SARS patients in 2003, the team found that seven were able to completely neutralize an infectious dose of the bat SARS-like virus.

The team wrote that, in view of the findings of diverse CoVs in bats, they wouldn’t be surprised if further surveillance found some that are even more closely matched to the SARS virus. Bat coronavirus findings in the Middle East, China, and other parts of the world suggest that the viruses remain a substantial global public health threat, they added.

Evidence of SARS origin

Vincent Racaniello, PhD, a Columbia University virologist who writes Virology Blog, told CIDRAP News that the findings are the best evidence yet that SARS-CoV originated in bats.

“The hypothesis has been that a bat progenitor to the SARS-CoV that could bind ACE2 initiated the SARS outbreak, but as that virus had never been isolated, the hypothesis was just that,” he said. “Clearly an ACE2-binding CoV that circulates in bats is a prime candidate to start the SARS epidemic.”

Another main message from the findings is that there are clearly SARS-CoV-like viruses circulating in bats that could infect humans, Racaniello said. “How many are out there, and their threat to humans, is a good question. All of this shows why it is important to know the viruses infecting the animals around us.”

Peter Daszak, PhD, senior coauthor of the study and president of EcoHealth Alliance, a New York City–based nonprofit group that studies emerging infectious diseases, said in a statement that the findings are a reminder of the need to protect bats from human-driven environmental changes and to devise public health measures to reduce the risk of disease transmission.

He said the risk is substantial, because it’s not unusual for bats to be used as a food source in China and other parts of Asia.

The study was funded in large part by grants from US government agencies, including the US Agency for International Development (USAID) PREDICT project, geared toward pathogen discovery in high-risk wildlife species in emerging disease hotspots.

Ian Lipkin, MD, a well-known virus researcher based at Columbia University’s Center for Infection and Immunity, said in an EcoHealth Alliance statement that the study hasn’t resolved the definitive source of the SARS virus. “Nonetheless, it does provide compelling evidence that an intermediate host was not necessary,” he said.

Caution about infection assumptions

One infectious disease expert, however, cautioned that the new findings don’t draw a direct connection between infected bats and infected humans.

Michael Osterholm, PhD, MPH, director of the University of Minnesota’s Center for Infectious Disease Research and Policy, publisher of CIDRAP News, said there is little doubt that bats are a natural reservoir for this virus and play a role in human CoV infections, but the biology and natural history of an infectious agent are two different issues.

Transmission typically involves a complex chain of events, beyond the basic ability of an infectious agent to infect a cell in lab culture, he said. For example, the mode of transmission, such as saliva from a bite as the key factor in rabies transmission from bats, affects how a pathogen spreads to humans.

Osterholm said that if bats shed the virus primarily in their feces, scientists need to explore the dynamics of how the pathogen might reach and infect humans.

The new study adds to the understanding of how humans are infected with SARS, he said. “It’s like piecing together the origin of the human species. Each year we learn new pieces about how it happened.”

[https://www.cidrap.umn.edu/news-perspective/2013/10/close-relative-sars-virus-found-chinese-bats]

NEW YORK/CHICAGO (Reuters) – To reach his office in Galveston National Laboratory, where scientists study deadly pathogens such as the Ebola and Marburg viruses, director James Le Duc swipes his key card at the building’s single entrance, which is guarded 24/7 by Texas state police.

As he walks the hallways, more than 100 closed-circuit cameras watch him. Seven more locked doors stand between him and his destination. Entering a research lab requires another card swipe and, for labs housing especially dangerous microbes, a fingerprint scan.

To keep deadly viruses from escaping, each lab uses negative air flow and dedicated exhaust systems. Workers wear full-body air-supplied suits. To test its security, Galveston ran an exercise with the Federal Bureau of Investigation simulating a would-be intruder and another, with the University of Texas, war-gaming a campus shooter. The facility passed both tests.

Galveston’s strict security underlines a little-known fact about hundreds of labs working with bacteria and viruses that could make the 1918-19 Spanish flu epidemic – when as many as 40 million people died – seem like a summer cold. Many of the precautions it takes are not required by law.

“A lock on the door is the only specified requirement,” said Rutgers University virologist Richard Ebright. “There is no explicit requirement for guards, bio-identity checks, or video monitoring like 7-Elevens have. The rules require very strict paperwork but no real physical security.”

Labs whose experiments on dangerous pathogens are funded by the U.S. government must follow specific rules to keep the microbes from escaping, but those rules are not enforceable for researchers working with private funds. Outside the country, security and safety requirements vary widely, experts say.

“It’s all subject to interpretation,” said a scientist close to the U.S. National Science Advisory Board for Biosecurity, which monitors research that might pose a bioterrorism threat.

If a lab receiving U.S. government funding violates the guidelines, the Centers for Disease Control and Prevention can cut off the flow of money, “but it can’t shut you down,” the scientist said. “I don’t have a lot of confidence in our biosafety right now.”

IMMEDIATE CONCERN OVER BIRD FLU RESEARCH

Questions about biosafety – keeping dangerous microbes from escaping labs – and biosecurity – keeping out bad actors intent on releasing or stealing the pathogens – are front and center for global health officials due to a growing controversy over experiments with the bird flu virus.

Scientists and government officials will meet on Thursday and Friday at the World Health Organization in Geneva to hash out the safest way to deal with the studies and address fears that lab-engineered viruses could either escape or be used as a bioterror weapon.

Last year, labs at the University of Wisconsin, Madison, and Erasmus MC in Rotterdam independently created mutant forms of avian influenza, known as H5N1, that can be transmitted directly among mammals. The natural strain can be caught only through close contact with infected birds.

One immediate question is what level of safety should be required for that research. So far, it has been conducted at biosafety-level 3 labs. Under U.S. guidelines, BSL-3 applies to agents that cause “serious or lethal disease” but do not ordinarily spread between people and for which treatments or preventives exist. BSL-4 applies to agents with no preventives or treatment.

The Wisconsin and Erasmus scientists received approval to conduct their experiments under BSL-3 conditions because, they argued, antiviral drugs can treat avian flu. Erasmus was subject to U.S. guidelines because its experiments were funded by the National Institutes of Health.

“The viruses generated here are sensitive to influenza antivirals” so they fit the BSL-3 criteria, said Rebecca Moritz of the University of Wisconsin’s Office of Biological Safety. There are “multiple physical barriers and the facilities are monitored at all times.”

All lab workers there wear disposable jumpsuits and powered respirators in addition to scrubs, shoes, shoe covers, and double gloves, she said. Each time scientists leave the lab, they must remove their protective equipment and shower before putting on their street clothes. Erasmus does the same.

The labs said they have emergency and security plans for a wide variety of threats. Neither would provide specifics on those security measures on the grounds the details could aid any would-be attackers.

Such precautions are not foolproof, however. According to a 2009 report by the Government Accountability Office, there were 400 accidents at BSL-3 labs in the United States in the previous decade.

Some scientists therefore argue that the experiments creating contagious H5N1 mutants should be done only at BSL-4 facilities.

“An escape would still produce the worst pandemic in history,” said Michael Osterholm of the University of Minnesota and a member of the NSABB, at a symposium at the New York Academy of Sciences this month.

“The risk of this agent, if in fact it can be readily transmitted between humans, is catastrophic,” he told Reuters. “Until we know how this virus actually acts in humans, I think you have no choice but to move this (research) to BSL-4.”

SPACE SUITS

BSL-4 labs, like the one in Galveston, have all the BSL-3 precautions and are also in isolated facilities with dedicated exhaust, vacuum, and other systems to prevent escape. In addition, workers must wear what are essentially space suits.

But the BSL guidelines relate to biosafety, not security.

The debate over H5N1 experiments has also raised the question of how secure BSL-3 and BSL-4 labs are. It has assumed a greater urgency as the number of known U.S. BSL-3 labs has surged from 415 in 2004 to 1,495 in 2010.

Hundreds or thousands of BSL-3 laboratories may be unknown, however, because “no federal agency is required to track the number of biocontainment labs,” found a 2011 report by the National Research Council, an arm of the U.S. National Academy of Sciences.

Globally, BSL-3 labs have recently been built or are under construction in Bangladesh, India, Indonesia, China, Brazil, and Mexico, among others, the NRC found. Yet “many countries have few or no regulations,” the NRC concluded.

BSL-4 labs are also proliferating. A 2011 workshop in Istanbul organized by the NRC was told that there are 24 BSL-4 facilities, including in Germany, Gabon, Sweden, Russia, South Africa and Canada. The United States has six, including Le Duc’s, which is part of the University of Texas Medical Branch.

“We are now in a proliferation race for BSL-3 and 4 labs,” said Laurie Garrett, the senior fellow for global health at the Council on Foreign Relations in New York. “Having such a facility is a mark of national sophistication. But the spread of these labs allows the unfettered proliferation of the world’s most dangerous microbes.”

Indeed, deadly microbes have escaped high-security labs. Between 1978 and 1999, just over 1,200 people acquired infections from BSL-4 labs around the world; 22 were fatal. Since then, lab workers have been killed by Ebola and SARS, or severe acquired respiratory syndrome. Thieves tried to steal animal pathogens from an Indonesian lab in 2007, the NRC workshop was told.

GUIDELINES, NOT LAW

U.S. research on dangerous human pathogens must follow safety guidelines set by the CDC. They may or may not be followed at labs elsewhere in the world, concluded the NRC workshop.

In part, that is because BSL-3 and BSL-4 designations “have very wide interpretations,” said Ren Salerno, senior manager for cooperative threat reduction programs at Sandia National Laboratories, part of the U.S. Department of Energy.

Although U.S. government-funded research must adhere to biosafety guidelines, they “do not have the force of law,” said Ebright. “If you’re a private lab, privately funded, there is no requirement that you comply.” The CDC declined to make a spokesperson available to discuss biosafety and biosecurity.

Many labs in developing countries say they adhere to guidelines as tough as those applied to U.S. facilities. If they receive U.S. funding, lab personnel must pass an FBI security risk assessment, for instance.

In Thailand, police check the background of all staff members and require fingerprints to access freezers containing microbes.

A BSL-4 lab in Australia employs a security staff of 10. It is housed in a fenced, isolated building and has infrared cameras to detect intruders. Gabon’s BSL-4 lab is surrounded by electric fences and has a guard on duty at all times. Only three people know the code to the freezer holding Ebola.

U.S. biosecurity requirements are laid out in the 2001 Patriot Act, which says that facilities storing “select agents” – microbes and toxins that could be used as bioweapons – must develop and implement a plan to keep them secure. Such labs must also provide the government the names of everyone with access to the pathogens; none can be on a terrorism watch list.

Experts dismiss Hollywood’s nightmare scenarios such as bombing a BSL-4 lab or crashing a 737 jumbo jet into one.

“The one nice thing about pathogens is that they’ll self-destruct under intense heat,” said Salerno.

What Salerno does give credence to is either an accidental escape or a plot to steal a pathogen by lab employees acting on their own or under duress.

“As more of this kind of research occurs, and it will, especially internationally, the risks of both accidental release or potential theft and misuse will increase as well,” Salerno said. “The science is way ahead of governments’ ability to regulate the science.”

[https://www.reuters.com/article/us-health-biosecurity-idUSTRE81E0R420120215]

ROTTERDAM, Holland Jan. 20, 2012— — It is the stuff of science fiction: scientists tamper with a killer bird flu virus and create something much worse. But what has been created in a Rotterdam laboratory is not fiction. It is deadly real.

So deadly that the U.S. government – which funded the Rotterdam research – asked scientists to omit key details of their research when they are published to keep the formula out of the hands of bio-terrorists. And today, researchers announced a self-imposed 60-day “voluntary pause” on any research involving highly transmissible form of bird flu that they have created.

The researchers are responding to the worldwide furor that erupted after word of their work became public. There are serious public health reasons for the research and they want to lower the temperature of the discussion while they explain what they have done and why they have done it.

The lead author of today’s announcement is Dr. Ron Fouchier, a respected molecular virologist. He heads at Erasmus Medical Centre in Rotterdam, in the Netherlands, that engineered a form of “aerosolized” bird flu that can easily be passed from humans to humans through the air. The genetically-altered flu is thought to be so virulent that if the vials containing it were to get out, the virus would have the potential to spread around the globe and kill hundreds of millions.

Bird flu, also known as H5N1, first surfaced 15 years ago. It has not caused mass panic because it is only transmitted to humans who have direct contact with infected birds. But when humans do contract bird flu, they are likely to die.

According to the World Health Organization of 573 confirmed bird flu cases in humans since 2003, 336 people have died. That’s a staggering 60 percent mortality rate. Nothing in history comes close to that.

ABC News was given an exclusive inside look at some of the testing facilities the Rotterdam researchers used. With Fouchier as our guide, we donned protective clothing and face masks and passed through three levels of security to see the ferrets he uses for testing.

Watch Jeffrey Kofman’s exclusive report from inside the testing facilities tonight on “World News with Diane Sawyer,” at 6:30 p.m. ET

Fouchier explained how his lab assistants exposed the ferrets to the altered virus and placed unexposed ferrets in cages nearby. All 40 ferrets died. Scientists use ferrets because they have a respiratory system much like humans, which is why the researchers believe the consequences of an airborne bird flu would be just as deadly for humans.

No visitors, however, allowed in the high secret lab at Erasmus Medical Centre where the actual experiment took place. He told us that with U.S. and Dutch expertise Erasmus spent eight years and millions of dollars building one of the most secure lab facilities in the world just for studying H5N1. They call it a BSL3 Enhanced lab – that’s Bio-Safety Level 3. The vials of enhanced bird flu are kept in a bank vault inside the lab. The lab is designed to keep the deadly virus in and intruders out.

The researchers who engineered this super-virus insist they are far from being “mad scientists” as some have suggested. They are public health specialists.

The man in charge, Fouchier is a tall, lanky molecular biologist who began his career studying HIV in Philadelphia, but switched to bird flu when the mysterious virus first surfaced in 1997.

“What scares me is that this can happen so easily,” he says, “it’s scary that it might actually happen in the field.”

And that’s the point behind research that on the surface seems insane to some. Fouchier says what he did in the lab was mutate a few genes. That happens regularly in nature.

Fouchier insists the dangerous part of this virus isn’t what he has created in the lab, it is what can happen if nature creates something similar. He says this should be a wakeup call for public health authorities around the world.

In the history of epidemics and pandemics nothing has been as lethal as the bird flu Fouchier has created. The most deadly epidemic of the last century was the Spanish Flu outbreak of 1918. Virtually everyone in the world was infected. It is estimated that between 50 and 100 million people died — conservatively that means it killed 3 percent of those infected. In a globalized world of air travel and mass transit, the prospect of an airborne bird flu with a 60 percent death rate is terrifying.

At its peak in 2006 bird flu was found in 63 countries, most of them in Asia. The Bush Administration was so concerned about the potential threat to humans from an airborne mutation that it contracted labs in the U.S. and overseas to see if such a human-to-human form really could evolve. The Dutch scientists were the first to prove it is possible. A lab at the University of Wisconsin-Madison has independently created a similar form of the lethal virus.

Since it peaked six years ago, H5N1 bird flu has been eradicated in many countries, but it remains endemic in Bangladesh, China, Egypt, Indian, Indonesia and Vietnam. Fouchier says one of the main reasons the U.S. and other Western government were eager to see if the super-virus could be created was to push the countries where bird flu still exists to take the threat seriously.

“The urgency to eradicate bird flu in poultry markets [in those countries] was not very high,” says Fouchier, “With these experiments we tell these countries please eradicate this virus very aggressively to prevent a pandemic.”

“My first reaction was ‘Oh, my God, why did they do this?'” says Laurie Garrett, Senior Fellow for Global Health at the Council on Foreign Relations. “Second reaction was ‘Oh dear, it works!’ Meaning that nature could do the same thing – that they had proven how dangerous the virus could be. And then my final reaction was ‘we have no capacity to control this kind of work. Our treaty systems our policy systems, will not do the job.'”

Garrett wonders whether the science can be justified. “We have a whole legacy now of labs doing experiments that in the wrong hands could be very, very dangerous. I’m not real comfortable with having this virus exist – anywhere.”

But when ABC News surveyed virologists in the United State for their opinions on the value of such seemingly toxic science the overwhelming response was that Fouchier’s work is a valuable contribution to public health around the world.

“I think it’s a very good idea,” says Dr. William Schaffner, Chairman of the Department of Preventive Medicine at Vanderbilt University in Nashville. “We need to know more about how it is that influenza viruses that start out often in birds can transfer their capacity to make illness in humans and that essential research is going on in Rotterdam.”

Schaffner says if affected countries do not move to eradicate bird flu and public health officials are not prepared for the appearance of a highly lethal airborne strain of the bird flu virus, the consequences could be horrifying. “If we were to have a pandemic caused by this virus in nature, then we are talking about millions of people being ill around the world, hospitals overflowing with sick people, funeral homes not being able to keep up with the deaths. So we need as much scientific information as possible to avert that.”

Fouchier is scheduled to publish his findings in the journal “Science.” He has agreed to omit key details from the paper so that anyone thinking of replicating the virus will not have access to his blueprint. But he notes, the flu virus is hardly an effective form of bioterrorism. What he did is highly technical, requiring skills and equipment that are not widely available. He says nature produces much more accessible biological menaces on its own, although he is quick say he will not name them.

His bigger concern is that the outcry over his research will shut down an important branch of public health research — not just for 60 days, but for good.

“If politics were to shut down this type of research then what we should do is lie in the sun until the next pandemic hits and kills us,” he says. “That, I think, is not the attitude we should follow. Unless that is what we want we have to do this type of research. Otherwise we will be overwhelmed by Mother Nature terrorizing us in the future.”

[https://abcnews.go.com/Health/inside-lab-scientists-created-deadly-bird-flu-virus/story?id=15371697]