Why the Scientific Debate
Over a UW Bird Flu Study Isn’t Going Away
by Will Cushman,
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
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
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
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
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
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
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
“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
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
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
Transparency is Another Subject of
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
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
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
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.