CONNECTING THE DOTS: WAS THE PRECURSOR TO THE “WUHAN VIRUS” CREATED IN 2012 IN LABS IN MADISON, WI AND THE NETHERLANDS? …AND HOW WAS DR FAUCI INVOLVED?

PART 1

Following controversy, UW researcher's findings on bird flu virus published

DAVID WAHLBERG | Wisconsin State Journal | | 608-252-6125 May 2, 2012

“Four mutations in a bird flu virus enabled the virus to spread among ferrets in a lab, UW-Madison researcher Yoshihiro Kawaoka reported Wednesday in the journal Nature.

The study, which identifies the mutations, was published after months of international controversy that delayed public release of the findings.

Critics said the potentially deadly altered virus could be accidentally released from the lab or replicated by terrorists. Kawaoka and his supporters said the study shows how H5N1 bird flu, frequently fatal in people but rarely spread among them, could cause a human pandemic — or massive outbreak of disease.

Identifying mutations that could make the virus more transmissible in people should help health authorities better monitor bird flu and prepare drugs and vaccines, Kawaoka said. The H5N1 virus has been circulating in Asia and the Middle East since 2003.”

…A research moratorium on altered H5N1 viruses, which Kawaoka, Fouchier and other scientists agreed to in January, remains in effect. Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, told a U.S. Senate panel last week that the moratorium should be extended but didn't say for how long.

Kawaoka carried out his study at UW-Madison's Institute for Influenza Virus Research at University Research Park. 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.

Kawaoka set out to see if the H5N1 virus could adapt to transmit in mammals — and, if so, what changes in the virus were needed to do that.

He used ferrets, whose response to the flu is thought to mimic that of humans. By exposing individually caged ferrets to strains of the virus in a series of experiments, the study revealed the four mutations that caused so much controversy.

First Kawaoka introduced random mutations into the HA gene of the H5N1 virus. A strain with mutations known as N224K and Q226L was able to attach to receptors in the trachea of mammals.

That is significant, Kawaoka said, because flu viruses must replicate in the upper respiratory tract in order to spread through coughing and sneezing. In people, H5N1 strains typically grow only in the lower respiratory tract, he said.

Kawaoka combined the HA gene containing the two mutations with seven genes from the 2009 swine flu virus known as H1N1.

The resulting virus didn't spread among the caged ferrets. But one ferret infected by researchers had especially high levels of virus in its nose. That animal's virus contained a third mutation, N158D.

When scientists exposed other ferrets to that virus, one developed a strain with a fourth mutation, T318I, that spread even more readily through the air to other ferrets.”

Read the rest of the article here: https://madison.com/wsj/news/local/health_med_fit/following-controversy-uw-researcher-s-findings-on-bird-flu-virus/article_c7fbb55c-946c-11e1-a8c8-0019bb2963f4.html

>>8963212

PART 2

Bird Flu Paper Is Published After Debate

By Donald G. McNeil Jr. June 21, 2012

“The more controversial of two papers describing how the lethal H5N1 bird flu could be made easier to spread was published Thursday, six months after a scientific advisory board suggested that the papers’ most potentially dangerous data be censored.

The paper, by scientists at Erasmus Medical Center in the Netherlands, identified five mutations apparently necessary to make the bird flu virus spread easily among ferrets, which catch the same flus that humans do.

The paper’s publication, in the journal Science, ended an acrimonious debate over whether such results should ever be released. Critics said they could help a rogue scientist create a superweapon. Proponents said the world needed to identify dangerous mutations so countermeasures could be designed.

“There is always a risk,” Dr. Anthony S. Fauci, the director of the National Institute for Allergy and Infectious Diseases, said in a telephone news conference held by Science. “But I believe the benefits are greater than the risks.”

…Dr. Fouchier’s work proved that H5N1 need not mix with a more contagious virus to become more contagious.

By contrast, the lead author of the other bird flu paper, Dr. Yoshihiro Kawaoka, of the University of Wisconsin-Madison, took the H5N1 spike gene and grafted it onto the 2009 H1N1 swine flu. One four-mutation strain of the mongrel virus he produced infected ferrets that breathed in droplets, but did not kill any.

The controversy erupted in December when the National Science Advisory Board for Biosecurity asked that details be removed before the papers were published. On March 30, it reversed itself after a similar panel convened by the World Health Organization recommended publication without censorship.

Dr. Kawaoka’s work was published by the journal Nature last month.

Dr. Fouchier had to delay until the Dutch government gave him permission, on April 27.

Some of the early alarm was fed by Dr. Fouchier speaking at conferences and giving interviews last fall in which he boasted that he had “done something really, really stupid” and had “mutated the hell out of H5N1” to create something that was “very, very bad news.” He said his team had created “probably one of the most dangerous viruses you can make.”

“An important result of the controversy, Dr. Fauci said, is that the United States is now drafting new guidelines for dangerous research.

For the moment, most researchers are honoring a voluntary moratorium on this line of flu research.

Asked if a rogue researcher could now try to duplicate Dr. Fouchier’s work, Dr. Fauci said it was possible. But he argued that open discussion was still better than restriction to a few government-cleared flu researchers, because experts in unrelated fields, like X-ray crystallography or viral epidemiology, might take interest and eventually make important contributions, he said.

“Being in the free and open literature makes it easier to get a lot of the good guys involved than the risk of getting the rare bad guy involved,” he said.”

Read the rest of the article here: https://www.nytimes.com/2012/06/22/health/h5n1-bird-flu-research-that-stoked-fears-is-published.html

>>8963218

PART 3

EXCLUSIVE: Controversial experiments that could make bird flu more risky poised to resume

By Jocelyn KaiserFeb. 8, 2019 , 8:45 PM

“Controversial lab studies that modify bird flu viruses in ways that could make them more risky to humans will soon resume after being on hold for more than 4 years. ScienceInsider has learned that last year, a U.S. government review panel quietly approved experiments proposed by two labs that were previously considered so dangerous that federal officials had imposed an unusual top-down moratorium on such research.

One of the projects has already received funding from the National Institutes of Health’s (NIH’s) National Institute of Allergy and Infectious Diseases (NIAID) in Bethesda, Maryland, and will start in a few weeks; the other is awaiting funding.

The outcome may not satisfy scientists who believe certain studies that aim to make pathogens more potent or more likely to spread in mammals are so risky they should be limited or even banned. Some are upset because the government’s review will not be made public. “After a deliberative process that cost $1 million for [a consultant’s] external study and consumed countless weeks and months of time for many scientists, we are now being asked to trust a completely opaque process where the outcome is to permit the continuation of dangerous experiments,“ says Harvard University epidemiologist Marc Lipsitch. 

One of the investigators leading the studies, however, says he’s happy he can resume his experiments. “We are glad the United States government weighed the risks and benefits … and developed new oversight mechanisms. We know that it does carry risks. We also believe it is important work to protect human health,” says Yoshihiro Kawaoka of the University of Wisconsin in Madison and the University of Tokyo. The other group that got the green light is led by Ron Fouchier at Erasmus University Medical Center in Rotterdam, the Netherlands.

In 2011, Fouchier and Kawaoka alarmed the world by revealing they had separately modified the deadly avian H5N1 influenza virus so that it spread between ferrets. Advocates of such gain of function (GOF) studies say they can help public health experts better understand how viruses might spread and plan for pandemics. But by enabling the bird virus to more easily spread among mammals, the experiments also raised fears that the pathogen could jump to humans. And critics of the work worried that such a souped-up virus could spark a pandemic if it escaped from a lab or was intentionally released by a bioterrorist. After extensive discussion about whether the two studies should even be published (they ultimately were) and a voluntary moratorium by the two labs, the experiments resumed in 2013 under new U.S. oversight rules.



But concerns reignited after more papers and a series of accidents at federal biocontainment labs. In October 2014, U.S. officials announced an unprecedented “pause” on funding for 18 GOF studies involving influenza or the Middle East respiratory syndrome or severe acute respiratory syndrome viruses. (About half were later allowed to continue because the work didn’t fit the definition or was deemed essential to public health.)

Kawaoka’s grant is the same one on H5N1 that was paused in 2014. It includes identifying mutations in H5N1 that allow it to be transmitted by respiratory droplets in ferrets. He shared a list of reporting requirements that appear to reflect the new HHS review criteria. For example, he must immediately notify NIAID if he identifies an H5N1 strain that is both able to spread via respiratory droplets in ferrets and is highly pathogenic, or if he develops an EPPP that is resistant to antiviral drugs. Under the HHS framework, his grant now specifies reporting timelines and who he must notify at the NIAID and his university.

Fouchier’s proposed projects are part of a contract led by virologists at the Icahn School of Medicine at Mount Sinai in New York City (most of Project 5, Aim 3.1, and Project 6 in this letter). They include identifying molecular changes that make flu viruses more virulent and mutations that emerge when H5N1 is passaged through ferrets. The HHS panel did not ask that any proposed experiments be removed or modified. Suggestions included clarifying how his team will monitor workers for possible exposures and justifying the strains they plan to work with, which include H7N9 viruses, Fouchier says.”

Read the rest of the article here: https://www.sciencemag.org/news/2019/02/exclusive-controversial-experiments-make-bird-flu-more-risky-poised-resume