Black Lives Matter

Beam Me

2018

TWO YEARS AGO

 US MILITARY CONTRACT

FOR

UNIVERSITY OF WISCONSIN

IN MADISON

TO DESIGN AND MAKE

VIRUS MORE DEADLY

FOR WARFARE

In December 2017, a scientific journal published a short News Brief that the University of Wisconsin in Madison was given a grant by the US government to make a naturally occurring virus into a more deadly form of virus for warfare.

Year: 2018

  This was followed up by an article in January 2018.

  During that time, I made a copy and gave it to healthcare workers in Hawaii where I resided at the time, because I believed that it was morally wrong, and, thus, healthcare workers needed to be prepared to care for citizens in advance of the military use of designer viruses for warfare that was approaching in the horizon.

The following is the January 2018 article in the scientific journal, Nature, that I copied and gave to healthcare workers in Hawaii in 2018 so that they could be prepared for a highly certain occurrence of a pandemic.

*    *    *    *

Ban on Pathogen Studies Lifted

United States allows work to make viruses more dangerous.

BY SARA REARDON

The US government has lifted its controversial ban on funding experiments that make certain pathogens more deadly or transmissible. On 19 December, the National Institutes of Health (NIH) announced that scientists can once again use federal money to conduct ‘gain-of-function’ research on pathogens such as influenza viruses. But the agency also said that researchers’ grant applications will undergo greater scrutiny than in the past.

The goal is to standardize “a rigorous process that we really want to be sure we’re doing right,” says NIH director Francis Collins.

The NIH announcement ends a moratorium on gain-of-function research that began in October 2014. Back then, some researchers argued that the agency’s ban — which singled out research on the viruses that cause flu, severe acute respiratory syndrome and Middle East respiratory syndrome (MERS) — was too broad. The 21 projects halted by the policy included studies of seasonal flu and efforts to develop vaccines. The NIH eventually allowed ten of these studies to proceed, but three projects using the MERS virus and eight dealing with flu remained ineligible for US government grants — until now.

While the ban was in effect, the NIH and other government agencies examined the costs and benefits of allowing such research. In 2016, the National Science Advisory Board for Biosecurity — an independent panel that advises the NIH’s parent agency, the US Department of Health and Human Services (HHS) — concluded that very few government-funded gain-of-function experiments posed a significant threat to public health.

The new policy outlines a framework that the HHS will use to assess proposed research that would create pathogens with pandemic potential. Such work might involve modifying a virus to infect more species, or recreating a pathogen that has been eradicated in the wild, such as smallpox. There are some exceptions, however: vaccine development and epidemiological surveillance do not automatically trigger the HHS review.

The plan includes a list of suggested factors for the HHS to consider, including an assessment of a project’s risks and benefits, and a determination of whether the investigator and institution are capable of conducting the work safely. It also says that an experiment should proceed only if there is no safer alternative method of achieving the same results.

At the end of the assessment process, the HHS can recommend that the work go ahead, ask the researchers to modify their plan or suggest that the NIH refuse funding. The NIH will also judge the proposal’s scientific merit before deciding whether to award grant funding.

Scientists have long debated the merits of gain-of-function research and the new decision could reopen that discussion.

Yoshihiro Kawaoka, a virologist at the University of Wisconsin–Madison, whose work was affected by the moratorium, says the new framework is “an important accomplishment.” Kawaoka, who studies how molecular changes in the avian flu virus could make it easier for birds to pass the infection to humans, now plans to apply for federal funding to experiment with live versions of the virus.

But Marc Lipsitch, an epidemiologist at the Harvard T.H. Chan School of Public Health in Boston, Massachusetts, says that gain-of-function studies “have done almost nothing to improve our preparedness for pandemics — yet they risked creating an accidental pandemic.”

Lipsitch argues that such experiments should not happen at all. But if the government is going to fund them, he says, it is good that there will be an extra level of review.

EYE OF SCIENCE/SPL

Influenza viruses can be modified in the lab.

Gain-of-function studies “risked creating an accidental pandemic”

.4 J A N UA RY 2 0 1 8 | VO L 5 5 3 | N AT U R E | 1 1

© 2018 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.

Seeing Terror Risk, U.S. Asks Journals to Cut Flu Study Facts

By Denise Grady and William J. Broad

Dec. 20, 2011

For the first time ever, a government advisory board is asking scientific journals not to publish details of certain biomedical experiments, for fear that the information could be used by terrorists to create deadly viruses and touch off epidemics.

In the experiments, conducted in the United States and the Netherlands, scientists created a highly transmissible form of a deadly flu virus that does not normally spread from person to person. It was an ominous step, because easy transmission can lead the virus to spread all over the world. The work was done in ferrets, which are considered a good model for predicting what flu viruses will do in people.

The virus, A(H5N1), causes bird flu, which rarely infects people but has an extraordinarily high death rate when it does. Since the virus was first detected in 1997, about 600 people have contracted it, and more than half have died. Nearly all have caught it from birds, and most cases have been in Asia. Scientists have watched the virus, worrying that if it developed the ability to spread easily from person to person, it could create one of the deadliest pandemics ever.

A government advisory panel, the National Science Advisory Board for Biosecurity, overseen by the National Institutes of Health, has asked two journals, Science and Nature, to keep certain details out of reports that they intend to publish on the research. The panel said conclusions should be published, but not experimental details and mutation data that would enable replication of the experiments.

The panel cannot force the journals to censor their articles, but the editor of Science, Bruce Alberts, said the journal was taking the recommendations seriously and would probably withhold some information but only if the government creates a system to provide the missing information to legitimate scientists worldwide who need it.

The journals, the panel, researchers and government officials have been grappling with the findings for several months. The Dutch researchers presented their work at a virology conference in Malta in September.

Scientists and journal editors are generally adamant about protecting the free flow of ideas and information, and ready to fight anything that hints at censorship. I wouldn't call this censorship, Dr. Alberts said. He is trying to avoid inappropriate censorship. It is the scientific community trying to step out front and be responsible. He said there was legitimate cause for the concern about the researchers techniques falling into the wrong hands.

This finding shows it is much easier to evolve this virus to an extremely dangerous state where it can be transmitted in aerosols than anybody had recognized, he said. Transmission by aerosols means the virus can be spread through the air via coughing or sneezing.

Ever since the tightening of security after the terrorist attacks on Sept. 11, 2001, scientists have worried that a scientific development would pit the need for safety against the need to share information. Now, it seems, that day has come.

[Photo] The A(H5N1) virus largely affects birds and rarely infects people, but it is highly deadly when it does. Credit...National Institute for Biological Standards and Control/Photo Researchers

"It is a precedent-setting moment, and we need to be careful about the precedent we set," Dr. Alberts said.

Both studies of the virus, one at the Erasmus Medical Center in Rotterdam, in the Netherlands, and the other at the University of Wisconsin-Madison were paid for by the National Institutes of Health.

The idea behind the research was to try to find out what genetic changes might make the virus easier to transmit. That way, scientists would know how to identify changes in the naturally occurring virus that might be warning signals that it was developing pandemic potential. It was also hoped that the research might lead to better treatments.

Dr. Anthony Fauci, head of the National Institute of Allergy and Infectious Diseases, said the research addressed important public health questions, but added, sure there will be some people who say these experiments never should have been done.

Dr. Fauci said staff members at the institutes followed the results of the research and flagged it as something that the biosecurity panel should evaluate.

The lead researcher at the Erasmus center, Ron Fouchier, did not respond to requests for an interview. The center issued a statement saying that researchers there had reservations about the panel recommendation, but would observe it.

The Wisconsin researcher, Yoshihiro Kawaoka, was out of the country and not responding to queries, according to a spokesman for the university. But the school said its researchers would respect the panel recommendations.

David R. Franz, a biologist who formerly headed the Army defensive biological lab at Fort Detrick, Md., is on the board and said its decision to intervene, made in the fall, was quite reasonable.

My concern is that we don't give amateurs or terrorists information that might let them do something that could really cause a lot a harm, he said in an interview.

It is a wake-up call, Dr. Franz added. We need to make sure that our best and most responsible scientists have the information they need to prepare us for whatever we might face.

Amy Patterson, director of the office of biotechnology activities at the National Institutes of Health, in Bethesda, Md., said the recommendations were a first.

The board in the past has reviewed manuscripts but never before concluded that communications should be restricted in any way, she said in a telephone interview. These two bodies of work stress the importance of public health preparedness to monitor this virus.

Ronald M. Atlas, a microbiologist at the University of Louisville and past president of the American Society for Microbiology, who has advised the federal government on issues of germ terrorism, said the hard part of the recommendations would be creating a way to move forward in the research with a restricted set of responsible scientists.

He said that if researchers had a better understanding of how the virus works, they could develop better ways to treat and prevent illness. That is why the research is done, he said.

The government, Dr. Atlas added, is going to struggle with how to get the information out to the right people and still have a barrier to wide sharing and inadvertently aiding a terrorist. That is going to be hard.

Given that some of the information has already been presented openly at scientific meetings, and that articles about it have been sent out to other researchers for review, experts acknowledged that it may not be possible to keep a lid on the potentially dangerous details.

But I think there will be a culture of responsibility here, Dr. Fauci said. At least I hope there will.

The establishment of the board grew out of widespread fears stemming from the 2001 terrorist attacks on the United States and the ensuing strikes with deadly anthrax germs that killed or sickened 22 Americans.

The Bush administration called for wide controls on biological information that could potentially help terrorists. And the scientific community firmly resisted, arguing that the best defenses came with the open flow of information.

In 2002, Dr. Atlas, then the president-elect of the American Society for Microbiology, objected publicly to anything that smacked of censorship.

The federal board was established in 2004 as a compromise and is strictly advisory. It has 25 voting members appointed by the secretary of health and human services, and has 18 ex-officio members from other federal agencies.

Federal officials said Tuesday that the board has discussed information controls on only three or four occasions. The first centered on the genetic sequencing of the H1N1 virus that caused the 1918 flu pandemic, in which up to 100 million people died, making it one of the deadliest natural disasters in human history.

He chose to recommend publication without any modifications, Dr. Franz, the former head of the Army lab, recalled. The more our good scientists know about problems, the better prepared they are to fix them.

This fall, federal officials said, the board wrestled with the content of H5N1 papers to Science and Nature, and in late November contacted the journals about its recommendation to restrict information on the methods that the scientists used to modify the deadly virus.

The ability of this virus to cross species lines in this manner has not previously been appreciated, said Dr. Patterson of the National Institutes of Health.

Everyone involved in this matter wants to do the proper thing. A version of this article appears in print on Dec. 21, 2011, Section A, Page 1 of the New York edition with the headline: Journals Asked To Cut Details Of Flu Studies.

Thu Jan 23 18:38:17 PST 2020

WATCH: UW-Platteville monitoring six students for coronavirus

University of Wisconsin

University of Wisconsin - Platteville is monitoring six of its students for coronavirus after they returned from a trip to Wuhan, China, where the deadly virus seems to have originated from.

UW-Madison Scientist Creates New Flu Virus in Lab

June 11, 2014

Yoshihiro Kawaoka, the UW-Madison scientist whose bird flu research sparked international controversy and a moratorium two years ago, has created another potentially deadly flu virus in his lab at University Research Park.

Kawaoka used genes from several bird flu viruses to construct a virus similar to the 1918 pandemic flu virus that killed up to 50 million people worldwide. He tweaked the new virus so it spread efficiently in ferrets, an animal model for human flu.

Dissension over such work continues. Harvard and Yale researchers criticized such studies last month, saying the viruses could escape from labs and spread disease. Safer approaches could be more effective, they said.

Kawaoka, who reports on his new work Wednesday in the journal Cell Host and Microbe, said his research helps efforts to identify problematic viruses and develop drugs and vaccines against them.

“The work we do provides scientific data so there can be an informed risk assessment of viruses circulating in nature,” he said in an email. “The more we learn, the better prepared we will be for the next pandemic.”

His previous creation of an altered H5N1 bird flu virus, along with similar H5N1 work by Dutch researcher Ron Fouchier, prompted a year-long moratorium on the projects in 2012 and months of delay before the results were allowed to be published.

Some scientists said the viruses might not only be accidentally released from the labs but potentially replicated by terrorists.

The moratorium ended last year. Kawaoka said he resumed his H5N1 research this May, after approval by federal officials.

The research on the 1918-like virus was done during the moratorium, which covered only the altered H5N1 virus work, Kawaoka said. UW-Madison approved the 1918-like virus research, and the National Institutes of Health reviewed the new report on the findings, university officials said.

Both projects were carried out at UW-Madison’s Institute for Influenza Virus Research at University Research Park on Madison’s West Side. The lab is classified as Biosafety Level 3-Agriculture, the highest biosafety level at the university and half a notch below the top level anywhere of BSL4.

In the new research, Kawaoka and his colleagues searched public databases of information on various flu viruses isolated from wild birds from 1990 to 2011. The researchers identified eight genes nearly identical to the genes that made up the 1918 pandemic flu virus.

Using that information, they created a virus that differed from the 1918 virus by only 3 percent of the amino acids that make virus proteins. That virus was more pathogenic in mice and ferrets than regular bird flu viruses, but it wasn’t as harmful as the 1918 virus and didn’t spread among ferrets.

They made various substitutions to the virus and found that just seven mutations enabled it to spread among ferrets as efficiently as the 1918 virus. The new virus didn’t kill the ferrets, however, Kawaoka said.

“These viruses could evolve in nature and pose a risk to humans,” he said. “In a sense, it demonstrates that influenza viruses that don’t normally arouse alarm should be monitored.”

Marc Lipsitch, an epidemiologist at Harvard University, and Alison Galvani, an epidemiologist at Yale University, said in a paper in PLOS Medicine last month that such experiments pose “a significant risk to public health, arguably the highest level of risk posed by any biomedical research.”

If 10 labs did such bird flu experiments for a decade, with similar precautions, there would be a 20 percent chance of a lab-acquired infection, which would have a 10 percent chance of spreading widely to others, they said.

Flu studies using lab dishes, computer analysis, virus components or seasonal flu viruses would be safer and “more scientifically informative and more straightforward to translate into improved public health,” Lipsitch and Galvani wrote.

Kawaoka said potential pandemic viruses replicate quickly and act differently than seasonal flu, so relying on lab dishes and seasonal flu strains “can be highly misleading and, in fact, can be harmful.” The work he and Fouchier did on the altered H5N1 flu virus helped authorities realize they need to keep stockpiling H5N1 vaccines, he said. “Thus, human populations have already benefitted from the H5N1 ferret transmission experiments,” Kawaoka said.

Yoshihiro Kawaoka, professor of pathobiological sciences in the School of Veterinary Medicine, talks with a group of media representatives during a tour of the Influenza Research Institute (IRI) at the University of Wisconsin-Madison on Feb. 2, 2015. The high-security research facility was closed down for annual decontamination, cleaning and maintenance. (Photo by Jeff Miller/ UW-Madison)

Yoshihiro Kawaoka, a UW-Madison flu researcher, has created a new type of flu virus in his lab.

David Wahlberg | Wisconsin State Journal

David Wahlberg is the health and medicine reporter for the Wisconsin State Journal.

Higher education

UW virus researcher Yoshihiro Kawaoka awarded for his work

UW-Madison researcher Yoshihiro Kawaoka has been awarded the 2014 Popular Mechanics Breakthrough Award for his work in understanding and preventing pandemic influenza.

Local News

UW-Madison scientist says flu virus mapping could improve vaccine

May 24, 2016

The development by virologist Yoshihiro Kawaoka follows research he did last year.

Why the Scientific Debate Over a UW Bird Flu Study Isn’t Going Away

by Will Cushman, WisContext. GlobalBioDefense.com

16 Mar 2019

A University of Wisconsin-Madison laboratory is set to resume experiments that could build the foundation of an early warning system for flu pandemics. The research is based on altering a deadly type of the influenza virus in a way that could make it more dangerous, though, and critics say its approval lacked transparency and creates unnecessary risks.

Yoshihiro Kawaoka is a virologist and professor at the UW School of Veterinary Medicine and the University of Tokyo who has figured prominently in Wisconsin’s long-term central role in flu research. Kawaoka’s work has been the focus of fierce debate among epidemiologists ever since he announced in 2011 that his lab had successfully altered the H5N1 subtype of the influenza A virus to be transmittable through the air among ferrets. These small mammals are a common laboratory stand-in for studying human flu transmission.

The H5N1 flu primarily affects birds. On occasion, though, the virus can jump to humans, and can kill more than half of those infected. While deadly, wild H5N1 is confirmed to have infected fewer than 1,000 people around the world. Those who have come down with this virus are thought to have almost always been infected directly from birds with which they were in direct contact. That’s why Kawaoka’s 2011 announcement, made around the same time that a research team in the Netherlands made public similar findings, caused a contentious debate in the scientific community.

That debate has lingered since 2011 and intensified in early 2019 after the federal government approved funding for Kawaoka to continue his research.

Marc Lipsitch is a professor of epidemiology and director of the Center for Communicable Disease Dynamics at Harvard T.H. Chan School of Public Health. He’s a longtime critic of research that modifies flu viruses to be more dangerous in humans.

“What worries me and my colleagues is the effort to modify viruses that are novel to humans and therefore to which there’s no immunity in the population, and where a laboratory accident wouldn’t just threaten the person who got infected … but potentially could be the spark that leads to a whole pandemic of infectious disease,” Lipsitch told WisContext.

“The issue is that when you take a strain of flu where there’s no immunity in the population because it’s only been circulating in birds, and you modify [it] to transmit, that is creating a potential pandemic pathogen,” Lipsitch said. “The question is whether that’s a good idea or not.”

In 2014, Lipsitch organized the Cambridge Working Group, made up of hundreds of scientists, to call for a reassessment of biosafety measures for viruses altered by researchers. The group formed in response to a series of lab accidents involving potentially dangerous pathogens.

“An accidental infection with any pathogen is concerning. But accident risks with newly created ‘potential pandemic pathogens’ raise grave new concerns,” the group declared in a July 2014 statement calling for a reassessment of experiments like Kawaoka’s. “Laboratory creation of highly transmissible, novel strains of dangerous viruses, especially but not limited to influenza, poses substantially increased risks.”

Assessing Risks During a Research Moratorium

In October 2014, partly in response to the Cambridge Working Group’s concerns, the National Institutes of Health announced a funding moratorium on some types of what’s called “gain-of-function” research, including the H5N1 experiments at the UW, to assess the potential risks and benefits of this work, and review of biosafety standards.

Gain-of-function research aims to identify mutations that give rise to a new genetic function in viruses and microbes. Yoshihiro Kawaoka’s 2011 findings — published in the journal Nature in May 2012 — identified four genetic mutations in the H5N1 virus that made it transmissible among ferrets.

Rebecca Moritz chairs UW-Madison’s biosecurity task force and leads the university’s handling of “select agents,” a class of potentially dangerous subjects of research that includes the H5N1 viruses Kawaoka studies. Moritz has worked closely with Kawaoka to develop safety protocols for his lab, which is located in University Research Park on the west side of Madison.

She spoke on behalf of Kawaoka’s lab and its work.

Moritz told WisContext that Kawaoka’s research could lead to more effective treatment and prevention options and help build an “early warning detection system” for pandemics by mapping mutations that might make wild H5N1 contagious among humans.

“We don’t understand the mechanisms involved in [influenza] transmission very well,” Moritz said.

She explained that understanding those mechanisms could result in new drugs and approaches to deter the transmission of influenza viruses by identifying certain genetic characteristics that health officials can watch for while monitoring wild strains.

“The goal of this research is … not to intentionally create influenza viruses that can transmit,” Moritz added. “Nature is already doing that for us.” She pointed out that the 2011 experiments created an H5N1 virus with less severe symptoms than the wild type, and none of the ferrets died from the infection.

Yoshihiro Kawaoka, a professor of pathobiological sciences at the UW School of Veterinary Medicine, gives a presentation during a tour of the Influenza Research Institute on Feb. 13, 2013.

[photo] Credit: Bryce Richter/UW-Madison

While the goal of Kawaoka and his collaborators is to prevent future flu deaths, their critics point to the risk — however miniscule — of this work of setting off the very health crisis it aims to prevent by way of a lab accident. That prospect is at the heart of objections to the research and why the Cambridge Working Group called for a wholesale reassessment of work like it.

During the federal funding moratorium, NIH sponsored multiple public meetings where the risks and benefits of gain-of-function research on “enhanced potential pandemic viruses” were debated and evaluated. The deliberations included two symposiums of the National Academies of Sciences, Engineering and Medicine, held in 2015 and 2016, as well as a 1,000-page risk-benefit analysis and an ethical analysis. Following this process, NIH decided that the benefits outweighed the risks and lifted the funding moratorium in December 2017.

However, the end of the moratorium did not mean that Kawaoka’s research was automatically approved to resume. It took more than a year for NIH’s National Institute of Allergy and Infectious Diseases to reinstate the funding for the UW-based H5N1 research, as Science reported in February 2019. In fact, funding for any “enhanced potential pandemic virus” research must be approved on a case-by-case basis going forward.

We are glad the United States government weighed the risks and benefits … and developed new oversight mechanisms,” Kawaoka told Science. “We know that it does carry risks. We also believe it is important work to protect human health.”

Transparency is Another Subject of Debate

The way in which NIH disclosed a new round of research at Yoshihiro Kawaoka’s lab at UW-Madison — by way of an update on its public reporter database — did not sit well with critics of the research.

Harvard epidemiologist Marc Lipsitch and Johns Hopkins Center for Health Security director Tom Inglesby wrote a Feb. 27 op-ed in the Washington Post with the headline “The U.S. government is funding dangerous experiments it doesn’t want you to know about.”

Lipsitch went further in an interview with WisContext, saying that the federal approval of Kawaoka’s research was “less transparent than the average grant review,” noting that the identities of the reviewers were never revealed. Identifying grant reviewers is standard procedure, Lispitch asserted, and helps guard against conflicts of interest.

“We just don’t know anything about even the identities of the people doing the reviews, although there’s U.S. government policy statements listing the many kinds of expertise that are required to do that work,” Lipsitch said. “We don’t know whether the U.S. government is following its own policy or whether it’s doing something less than that,” he added.

Elleen Kane, a spokesperson for the Department of Health and Human Service’s Assistant Secretary of Preparedness Response, which led the department’s review of the research proposals, declined to identify the reviewers, but shared its framework for guiding funding decisions related to research like Kawaoka’s. “Reviewers are all federal employees which enables us to avoid conflicts of interest,” Kane wrote in an email to WisContext.

Lipsitch said that, in his opinion, the experiments are less like typical grant-funded research and more akin to a large public works project, and should therefore require an extraordinarily transparent review of the risks and benefits.

He said that a publicized event would be appropriate “where the government said proudly ‘We have decided to fund research that is so groundbreaking and so important to the future of our medical preparedness for pandemics that we think it’s worth risking creating such a pandemic … but they’ve done the opposite.”

In response, spokespeople at NIH pointed to its public deliberative process leading up to the funding decision.

NIH spokesperson Emma Wojtowicz told WisContext that it is providing more materials online. “Moving forward, to increase transparency even more, [the Department of Health and Human Services] is posting projects that fall within the scope of review and have been awarded funding on their website.”

One new condition of federal funding means that the Kawaoka lab has to adhere to new communication standards developed through the NIH’s deliberative process. These include immediately informing officials at NIH if Kawaoka identifies mutations allowing bird influenza strains to be contagious in mammals. A 1976 transmission electron microscopic image depicts avian influenza A H5N1 viruses, which are digitally colorized blue.

Cynthia Goldsmith/Centers for Disease Control and Prevention

Rebecca Moritz at UW-Madison emphasized the long, public deliberative process leading up to the reapproval of Kawaoka’s research.

“It involved multiple public hearings, opportunities for public input and input from experts outside the virology field, including Dr. Lipsitch, over the course of four years,” Moritz told WisContext. “What has emerged is what the consensus of experts has agreed is best practice.”

Those best practices include maintaining environmental safety procedures used before the moratorium, Moritz said. Kawaoka’s lab is rated as Biosafety Level 3 Agriculture, or BSL-3Ag, which Moritz described as one half-step below the CDC’s highest possible biosafety rating.

“Our biosafety and biosecurity practices are like an onion — layers and layers build on each other to mitigate risks,” Moritz said. “The [lab] is a stand-alone facility expressly built for work with influenza viruses,” she added. “It has built-in redundancies; is constantly monitored by lab personnel, law enforcement and other first-responders; and has more than 500 alarm points.”

Additionally, lab workers are strictly vetted, including undergoing an FBI background check, and must adhere to stringent security protocols. If a fire were to break out in the lab, Moritz said local fire departments have been instructed to let it burn. And if lab workers were to have a medical emergency while inside the facility, they would have to be decontaminated by qualified lab staff before receiving treatment.

Lipsitch pointed out that even some of the most secure labs in the world have dealt with safety breaches, usually due to human error.

“What these experiments do is ramp up the consequences of an accident to a whole new level,” Lipsitch said. “When you take an error-prone process and ramp up the consequences of an error to global pandemic levels, that’s not me being dramatic, that’s just describing what the consequences are of something we don’t need to be doing.”

Why The Scientific Debate Over A UW Bird Flu Study Isn’t Going Away was originally published on WisContext which produced the article in a partnership between Wisconsin Public Radio and Wisconsin Public Television.

The NIH Restarts Funding for Work With Deadly Pathogens

The government decides the risk of research into dangerous viruses is worth the reward.

by Robby Berman

21 December, 2017

"I believe nature is the ultimate bioterrorist,” says chair of the National Science Advisory Board for Biosecurity, Samuel Stanley, “and we need to do all we can to stay one step ahead." Certainly deadly pathogens on the loose have been the stuff of horrible narratives, including books like The Hot Zone and movies such as Contagion and Outbreak. And then there’s biological warfare, the deliberate weaponization and dissemination of deadly diseases to achieve military or political objectives. It’s all terrifying stuff. This week, in hopes of getting ahead of such threats, director Francis S. Collins of U.S. the National Institutes of Health (NIH) has lifted the three-year moratorium against the funding of “gain-of-function research,” the study of potentially deadly viruses including influenza, MERS, and SARS. The goal, his announcement says, it to “identify, understand, and develop strategies and effective countermeasures against rapidly evolving pathogens that pose a threat to public health.”

Anthrax cells (U.S. ARMY MEDICAL RESEARCH INSTITUTE OF INFECTIOUS DISEASES)

The moratorium had originally been implemented in response to some unnerving biocontainment errors. In one case, staff at the CDC was inadvertently exposed to anthrax, and in another case, a harmless flu sample was mistakenly replaced by a strain of the dangerous avian flu.

The Obama administration began the moratorium, and many scientists oppose the NIH’s new policy, alarmed that such lapses are inevitable should humans begin interacting with lethal pathogens again. Richard Ebright of Rutgers University, for one, recently told STAT, “I am not persuaded that the work is of greater potential benefit than potential harm.”

Advocates of the NIH’s action are convinced that only through further study of these diseases can we stand a chance of defending ourselves against the deliberate or accidental release into the population. “The only way to get ahead of the risk is to do the research, but in a way that tries to minimize the risk of accidental release,” says L. Syd M Johnson, a bioethicist at Michigan Technological University in an email to Big Think.

The urgency to learn more about dangerous pathogens was reinforced in July, 2011 when a team from Erasmus University led by virologist Ron Fouchier, and another team at the University of Wisconsin led by Yoshihiro Kawaoka “easily” created airborne variants of deadly avian flu. It’s a nasty virus that otherwise only rarely spreads between humans but that has nonetheless killed a minimum of 386 people since 2003.

The new airborne strain is especially dangerous, only 3% different from the 1918 flu that killed about 50 million people.

The outcry was immediate. According to Lord May, former U.K. chief science advisor, “The work they are doing is absolutely crazy. The whole thing is exceedingly dangerous.”

Ebright said simply, “This research should not have been done. It will inevitably escape, and within a decade.” And yet, says Johnson, “There was initially a lot of handwringing about Fouchier’s research, and whether it should be published. It seemed to provide a blueprint for bioterrorists, showing them how to produce a deadly, airborne avian flu virus. But Fouchier’s work was published five years ago, and the worst did not happen.”

Fouchier explained that the purpose of his work was to convince scientists that others could find it relatively simple to weaponize such viruses, or that the mutations could simply arise naturally. Though other scientists found comfort in their present low communicability, Fouchier told New York Times, “I wasn’t convinced. To prove these guys wrong, we needed to make a virus that is transmissible.”

Harvard’s Marc Lipsitch tells STAT, "A human is better at spreading viruses than an aerosol. The engineering is not what I'm worried about. Accident after accident has been the result of human mistakes." Still, he agrees with the NIH that newly strengthened handling guidelines can ensure safety, with researchers seeking to study pathogens having to prove that their labs are secure. “We see this as a rigorous policy,” Collins tells the Times.

Safety training (U.S. FOOD & DRUG ADMINISTRATION)

“The new NIH policy allows the agency to resume funding of research involving ‘Potential Pandemic Pathogens,’” says Johnson. “It’s not like no one has been doing research on these pathogens — the scientists of the world are not beholden to the NIH. And importantly, viruses mutate all by themselves in nature, which is how avian flu occasionally jumps into humans already. It’s just a matter of time before the next deadly pandemic emerges. Does the US want its scientists working on this research? Given the potential threat of these pathogens, and of deadly discoveries falling into the wrong hands, I think we do.”

Excerpts from the book:

"Viruses"' by Arnold J. Levine, published by Scientific American Library, New York: 1992.

Year: 1900

US Army isolates a

Human Virus for study

Year:  1950

US Designs Lethal Virus

to Selectively Kill

a Race of Rabbits

*   *   *   *

BACKGROUND

[p. 171-172]

A good case has been made that the earliest life forms on Earth used RNA polymers both to store information in the nucleotide sequence and to catalyze chemical reactions.

Studies over the past few years have shown that, under the right conditions, RNA polymers can replicate and even cut themselves into pieces of defined sizes.

RNA is a very reactive polymer, but this very property makes it poorly suited to store information.

If your goal were to store information stably, whether on a computer tape or in a polymer, we would not want all sorts of chemical reactions to occur over the length of our tape that might alter the information stored there.

For a variety of chemical reasons, DNA is much less reactive than RNA and therefore is better suited to serve as an inert storage molecule. Most living organisms, accordingly, use RNA to carry the messages for protein production, but not to store their genomic information.

Since RNA has greater reactivity than DNA, RNA viruses evolve more rapidly than do DNA viruses. The source of RNA's higher mutation rate can be seen by comparing the duplication of RNA with that of DNA. As the enzyme RNA replicase copies one strand of RNA into a complementary polymer, it averages one mistake per 10,000 nucleotides copied.

As DNA polymerase copies DNA into its complementary strand, it makes about one mistake in every million to ten million nucleotides. Part of this difference in accuracy is due to the reactivity of RNA and to the variable fidelity of the duplicating enzymes.

Another part reflects the fact that DNA polymerases have evolved the ability to correct mistakes in their synthesizing process.

. . . .

In effect DNA polymerases, but not RNA polymerases, have proofreading abilities. RNA genomes, therefore, retain more mistakes in their copies than do DNA genomes.

There is an additional reason that influenza A viruses evolve rapidly. All viruses, as we have seen, go through a very large number of duplication cycles in a short time. A single viral RNA genome may reproduce ten thousand copies of itself in six hours, while the generation time of the host for an influenza A virus is measures in years -- for humans, perhaps a quarter century.

Not only is the error frequency in the original RNA genome high, but the large number of generations yearly causes the progeny viruses to diverge rapidly. it has been estimated that 0.03 to 2 percent of the nucleotides in the genome of an RNA virus are altered every year.

EVOLVING FASTER THAN ANY OTHER LIVING ORGANISM

Some RNA viruses -- those whose polymerases have high error frequencies - are evolving much faster than any other living organism.

[p. 204]

HOW VIRUSES

CHANGE

Two major mechanisms act upon the genetic information of a virus (or any life form) to produce change: mutation and recombination. Mutation is a change in the sequence of the nucleotides in DNA (A, T, G, and C) or RNA (A, U, G, and C) polymers.

Recombination is the exchange and bringing together or new sequences of nucleotides, in new combinations, from two parental polynucleotide strands of DNA or RNA. Both processes generate diversity in all living organisms, which can then be tested for environmental advantages and replicative fitness in the real world.

Because viruses can encode the enzymes for their own replication and recombination, some viruses have a good deal of control over their mutation rates and frequencies of recombination.

[pp. 207-208]

YEAR 1900

FIRST HUMAN VIRUS

ISOLATED

BY

US ARMY

The yellow fever virus played a central role in the history of virology.

Walter Reed and the US Army Commission, in 1900, identified it as the first human virus to be isolated. Reed's team went on to prove that the virus was transmitted by mosquitoes and that eliminating the breeding grounds for these insects eliminated the disease.

Yellow fever is a zoonotic disease,  which means that it has a major animal reservoir. In central Africa, where it is thought to have originated, wild nonhuman primates such as howler, owl, spider [monkeys], and squirrel monkeys are infected.

The virus replicates in many organs of their bodies and spends time in the bloodstream.

HOW MOSQUITOES TRANSMIT VIRUSES

The aedine mosquitoes, like Aedes africanus, breed and lay their eggs in tree holes; they feed in the forest canopy, taking blood meals from the monkeys to provide nutrients for their developing eggs. The virus is taken up with the monkey blood and replicates in the mosquito, principally in the cells of the gut.

When the mosquito bites again, the virus is in the saliva, which the insect regurgitates into the wound to prevent coagulation.

Thus the virus circulates from a primate host to an insect and replicates in both, even though they are very different types of animals.

[pp. 209-210]

US EXPERIMENT

IN THE YEAR 1950

LETHAL VIRUS

DESIGNED TO

SELECTIVELY KILL

The wild European rabbit was first introduced in Australia in 1859. It very rapidly spread over the southern half of the continent, where it became a major pest in agricultural and grazing areas.

The situation got so bad that, when other methods to keep the rabbit population under control failed, introduction of a lethal myxoma virus from the Americas was tried in 1950.

The virus was shown to be restricted to rabbit populations -- that was critical -- and was spread by a mosquito biting the host.

The original virus strain killed more than 99 percent of the infected animals, and the first few years after its introduction saw an enormous decline in the rabbit population.

The virus spread efficiently during the spring and summer, when mosquitoes were abundant, but the incidence and spread of disease were poor in each cold season because of the paucity of insects.

In some places the virus even died out over the winter because of the lack of infected rabbits and poor transmission; but on a continent-wide basis, the disease and the virus persisted.

During each winter, rabbits that were infected with the most virulent virus died, so this most lethal strain of myxoma virus was not efficiently delivered to mosquitoes the next spring.

By contrast, some mutations in the virus created less virulent strains, permitting its hosts longer life and a better chance to survive the winter: these rabbits were available in the spring for mosquitoes to bite, thereby transmitting the less lethal disease.

The requirement for survival over the winter months imposed a strong selection for a less lethal virus.  

Attenuated strains appeared in the spring of the very first year after the introduction of the myxoma virus into Australia, and three of four years later they were dominant.

HERD IMMUNITY

Rabbit populations infected with this less virulent virus began to show herd immunity -- a phenomenon in which infection of a rabbit already immunized by previous exposure to a virus neutralizes that virus and lowers its probability of transmission to other animals, even if they are not immune. This accelerated the loss of the virulent strain, and the rabbit population resurged.

The rabbits that now bred were veterans of the initial exposure to the highly virulent myxoma virus. Among this group were rabbits that had survived because they were genetically resistant to the virus. The reasons for genetic resistance are complex (an unknown number of genes in specific combinations are thought to be involved), but such rabbits appeared quite rapidly.

Within seven years after the introduction of the most virulent myxoma strain, which killed 90 to 99 percent of rabbits in the field, the same virus reintroduced into a population of rabbits that was not immune -- a group with no previous exposure -- killed only 25 percent. The difference was due to genetic factors in the host rabbit that had been selected for and were present in most individuals seven years after selection began.

 This experiment demonstrates that the most successful virus is one that can replicate many times in its host but is not recognized and causes little or no damage.

These requirements are difficult to achieve, however, and most viruses do not fall into this category.

[pp. 211-212]

VIRUSES GROWN

IN LABORATORIES

WORLDWIDE

Over the past thirty years [since 1992], vaccine production and testing have been carried out in cell culture, using tissue obtained from an organ -- say, a kidney -- placed in culture dishes to grow.

The African green monkey from Uganda is commonly used as a source of such cells, which are prepared at various laboratories around the world.

In 1967, twenty-five laboratory workers from three different locations . . . each processing monkey-kidney cell cultures, all contracted a similar disease: hemorrhagic fever.

The patient typically has a very high fever, rash, and swelling followed by an uncontrollable bleeding in the organs, skin, and mucous membranes. As these patients were admitted to hospitals, six attending medical personnel contracted the disease, indicating human-to-human spread of an infectious agent. Among these thirty-one cases, there were seven deaths.

A virus was isolated from the blood and tissues of these patients, and extensive tests showed that it was unrelated to any known virus.

The isolate caused a hemorrhagic-fever-like disease when inoculated into African green monkeys, and it was noted that several of the monkeys in a single shipment form Uganda had this hemorrhagic disease.

MARBURG VIRUS

CROSSED SPECIES

It seemed likely that a monkey virus had crossed species, becoming more virulent, and attacked these human hosts . . . now called Marburg virus.

The monkeys did not even have antibody against it, proving that these primates were not an animal reservoir for this virus.

. . . .

During this time, a closely related virus that also produced a hemorrhagic fever was detected. In 1976 in the Sudan and Zaire, an epidemic of about 550 cases occurred, with more than 430 deaths.

*   *

MARBURG VIRUS

DEFEATED

HOST ANTIBODIES

BY

TRANSFORMING

INTO A NEW VIRUS

*   *

MARBURG VIRUS

TRANSFORMED

INTO

EBOLA VIRUS

This new virus was isolated and named Ebola virus, after a small river in Zaire.

Electron micrographs showed it to be morphologically identical to Marburg virus, but antibodies made against it did not protect against Marburg virus: these isolates were related but distinct.

STEALTH VIRUSES

REPLICATE AND HIDE

BETWEEN

EPIDEMICS

Extensive tests of possible animal reservoirs have, to date, failed to find where the Ebola and Marburg viruses replicate and hide between epidemics.

[pp. 212-213]

CONCLUSIONS

What have we learned from these stories and observations? First, we have surely been taught that there are rules that govern life processes; try as we may, we cannot violate them.

All life forms are continually changing. Each generation brings new nucleotide sequences, information, and functions, and these are continuously tried out in various combinations in an ever-changing environment.

Some of these changes have been brought about by humanity within a remarkably short time frame, compared to the rates of biological change.

We have learned that all life processes follow the laws of chemistry and physics.

There is a difference, however, between events occurring in living organisms and those in the nonliving world. So long as an organism is capable of reproducing itself, rare events can be selected for and become the dominant form of life.

When a rare event that cannot be replicated happens in the nonliving universe, it often remains minor in the field of observation.

In contrast, a rare mutation that occurs in a virus only once in a million trials will, if it provides a replicative advantage, be selected for, and become, the virus of tomorrow.

If we change the environment, we change the field against which new viruses are selected -- in effect, we change the rules for selection, and new agents will certainly appear.

It has become clear that virus infections select the host that survives, just as we -- by altering the field -- select the virus that survives.

VIRUSES ARE PARASITES

We are what we are in part because we have survived the onslaught of our parasites. But the viruses we have studied have done more.

They have contributed some of their nucleotide sequences to our own genetic endowment. We carry and pass to each generation the vestiges of retroviruses, integrated in our chromosomes and possibly exercising a sustained impact upon our selection and survival.

Viruses can be the conduit to move genetic information from one host to another. Sometimes this results in diseases as dramatic as cancer, as with Rous sarcoma virus and its oncogene; and sometimes this may contribute to an organism's ability to survive, as seen in the T4 bacteriophage and its eukaryotic-like genes.

That special relationship between host and parasite will continue to make human beings -- and all forms of life on Earth -- what we are and what we will be.

 It is important for us to know the rules.