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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.”
Lipsitch
firmly believes it is not a good idea, and he’s not the only
infectious disease researcher who holds this opinion.
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.
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