by Ian Sample
21 December 2011
Scientists warn that
redacting information from new research on H5N1 virus
could hinder the discovery of a vaccine
Bird flu virus
Moves by the US government to restrict
the publication of papers describing potentially dangerous new
strains of bird flu could do more harm than good by hampering
progress towards a vaccine, scientists warn.
The US biosecurity watchdog has asked two leading scientific
journals, Science and Nature, to remove sensitive details from the
papers amid fears the research might fall into the hands of
But scientists involved in the research discussed their experiments
at public conferences earlier this year, leading some experts to
doubt whether redacting the papers will have much effect.
"There is a cause for concern, but
to restrict publication now is shutting the stable doors after
the horse has bolted," said John Wood, the former chief
virologist at the UK's National Institute for Biological
Standards and Control. "It will only impede progress."
The US National Science Advisory
Board for Biosecurity (NSABB)
contacted editors at the journals after reviewing two papers
Ron Fouchier at Erasmus
Medical Centre in Rotterdam
Yoshihiro Kawaoka at the
University of Wisconsin, Madison
The papers described experiments in which natural strains of H5N1
bird flu, which do not spread easily from human to human, were
mutated to make them more transmissible.
Though bird flu outbreaks have killed many of those infected, most
people who contracted the virus caught it directly from birds. Since
the virus became known, scientists have been racing to work out how
it could mutate in the wild into a more transmissible strain that
would spread quickly from person to person.
The mutated strains were created for research into drugs and
vaccines, but if released from their high security containment
facilities at university laboratories, have the potential to trigger
a global pandemic.
In November, Dr Fouchier
told a reporter on the journal, Science,
that the strain of bird flu his team had created was,
"probably one of the most dangerous
viruses you can make."
The journal quoted Paul Keim, the chair
of the NSABB, who worked extensively on anthrax, saying:
"I can't think of another pathogenic
organism that is as scary as this one. I don't think anthrax is
scary at all compared to this."
The NSABB urged the journal editors to
remove paragraphs from the manuscripts that explained how the
experiments were done, along with other details that could help
potential terrorists replicate the work and unleash a dangerous
The Department of Health and Human
Services supported the requests.
The journals are now working with the US authorities to agree on a
procedure whereby edited versions of the papers are published, but
bona fide researchers can gain access to the crucial methods and
other details that have been removed. The papers could be published
Richard Ebright, a professor of molecular biology at Rutgers
University in New Jersey, said the planned redactions would have
"absolutely no practical impact" as the information had already been
presented at conferences, seen by journal staff and sent to
scientists for review.
The full manuscripts had also seen by NSABB staff and shared with a
dozen US government agencies, and key information described in them
had appeared in scientific and mainstream media.
"The proposed redactions are nothing
more than a public relations measure - window dressing -
intended to convey the impression that the issue is being
addressed and thereby to minimise negative public reaction and
deflect calls for effective regulation," Ebright told the
Wendy Barclay, head of influenza
virology at Imperial College London, said the mutations described in
the papers would not be a surprise to anyone with a reasonable
knowledge of the influenza virus, and doubted moves to restrict
access to the full the publications.
"I am not convinced that withholding
scientific know-how will prevent the highly unlikely scenario of
misuse of information, but I am worried that it may stunt our
progress towards the improved control of this infectious
disease," she said.
"The technical details of the experiments are important to share
with other experts in the field so that the robustness of the
findings and implications of the data can be truly assessed, and
so that this new information can be used to move the state of
the art forwards," she added.
Scientists Brace for Media Storm Around...
Controversial Flu Studies
by Martin Enserink
23 November 2011
ROTTERDAM, THE NETHERLANDS
Locked up in the bowels of the medical
faculty building here and accessible to only a handful of scientists
lies a man-made flu virus that could change world history if it were
ever set free.
The virus is an H5N1 avian influenza strain that has been
genetically altered and is now easily transmissible between ferrets,
the animals that most closely mimic the human response to flu.
Scientists believe it's likely that the pathogen, if it emerged in
nature or were released, would trigger an influenza pandemic, quite
possibly with many millions of deaths.
In a 17th floor office in the same building, virologist
of Erasmus Medical Center calmly explains why his team created what
he says is,
"probably one of the most dangerous viruses you can make"
- and why he wants to publish a paper describing how they did it.
Fouchier is also bracing for a media
After he talked to
Science-Insider yesterday, he had an
appointment with an institutional press officer to chart a
Fouchier's paper is one of two studies that have triggered an
intense debate about the limits of scientific freedom and that could
portend changes in the way U.S. researchers handle so-called
dual-use research: studies that have a potential public health
benefit but could also be useful for nefarious purposes like
biowarfare or bioterrorism.
The other study - also on H5N1, and with comparable results - was
done by a team led by virologist Yoshihiro Kawaoka at the University
of Wisconsin, Madison, and the University of Tokyo, several
scientists told Science-Insider. (Kawaoka did not respond to
Both studies have been submitted for
publication, and both are currently under review by the U.S.
National Science Advisory Board for Biosecurity (NSABB), which on a
few previous occasions has been asked by scientists or journals to
review papers that caused worries.
NSABB chair Paul Keim, a microbial geneticist, says he cannot
discuss specific studies but confirms that the board has,
"worked very hard and very intensely
for several weeks on studies about H5N1 transmissibility in
The group plans to issue a public
statement soon, says Keim, and is likely to issue additional
recommendations about this type of research.
"We'll have a lot to say," he says.
"I can't think of another pathogenic organism that is as scary
as this one," adds Keim, who has worked on anthrax for many
years. "I don't think anthrax is scary at all compared to this."
Some scientists say that's reason enough
not to do such research.
The virus could escape from the lab, or
bioterrorists or rogue nations could use the published results to
fashion a bioweapon with the potential for mass destruction, they
"This work should never have been
done," says Richard Ebright, a molecular biologist at Rutgers
University in Piscataway, New Jersey, and the Howard Hughes
Medical Institute who has a strong interest in biosecurity
The research by the Kawaoka and Fouchier
teams set out to answer a question that has long puzzled scientists:
Does H5N1, which rarely causes human
disease, have the potential to trigger a pandemic?
The virus has decimated poultry flocks
on three continents but has caused fewer than 600 known cases of flu
in humans since it emerged in Asia in 1997, although those rare
human cases are often fatal.
Because the virus spreads very
inefficiently between humans it has been unable to set off a chain
reaction and circle the globe.
Some scientists think the virus is probably unable to trigger a
pandemic, because adapting to a human host would likely make it
unable to reproduce. Some also believe the virus would need to
reshuffle its genes with a human strain, a process called
reassortment, that some believe is most likely to occur in pigs,
which host both human and avian strains.
Based on past experience, some
scientists have also argued that flu pandemics can only be caused by
H1, H2, and H3 viruses, which have been replaced by each other in
the human population every so many decades - but not by H5.
Fouchier says his study shows all of
that to be wrong.
Although he declined to discuss details of the research because the
paper is still under review, Fouchier confirmed the details given in
in New Scientist and
Scientific American about a
September meeting in Malta where he first presented the study.
Those stories describe how Fouchier
initially tried to make the virus more transmissible by making
specific changes to its genome, using a process called
genetics; when that failed, he passed the virus from one ferret to
another multiple times, a low-tech and time-honored method of making
a pathogen adapt to a new host.
After 10 generations, the virus had become "airborne": Healthy
ferrets became infected simply by being housed in a cage next to a
sick one. The airborne strain had five mutations in two genes, each
of which have already been found in nature, Fouchier says; just
never all at once in the same strain.
Ferrets aren't humans, but in studies to date, any influenza strain
that has been able to pass among ferrets has also been transmissible
among humans, and vice versa, says Fouchier:
"That could be different this time,
but I wouldn't bet any money on it."
The specter of an H5N1 pandemic keeps
flu scientists up at night because of the virus's power to kill.
Of the known cases so far, more than
half were fatal. The real case-fatality rate is probably lower
because an unknown number of milder cases are never diagnosed and
reported, but scientists agree that the virus is vicious.
Based on Fouchier's talk in Malta, New
Scientist reported that the strain created by the Rotterdam team is
just as lethal to ferrets as the original one.
"These studies are very important,"
says biodefense and flu expert Michael Osterholm, director of
the Center for Infectious Disease Research and Policy at the
University of Minnesota, Twin Cities.
The researchers "have the full support
of the influenza community," Osterholm says, because there are
potential benefits for public health.
For instance, the results show
that those downplaying the risks of an H5N1 pandemic should think
again, he says.
Knowing the exact mutations that make the virus transmissible also
enables scientists to look for them in the field and take more
aggressive control measures when one or more show up, adds Fouchier.
The study also enables researchers to test whether H5N1 vaccines and
antiviral drugs would work against the new strain.
Fouchier says he consulted widely within the Netherlands before
submitting his manuscript for publication. The U.S. National
Institutes of Health (NIH), which funded the work, has agreed to the
publication, says Fouchier, including officials at the National
Institute of Allergy and Infectious Diseases. (NIH declined to
answer questions for this story.)
Now, Fouchier is eagerly waiting for
Osterholm says he can't discuss details of the papers because he's
an NSABB member. But he says it should be possible to omit certain
key details from controversial papers and make them available to
people who really need to know.
"We don't want to give bad guys a
road map on how to make bad bugs really bad," he says.
But some scientists say the board's
debate comes far too late, because the studies have been done and
the papers are written.
"This is a good example of the need
for a robust and independent system of PRIOR review and approval
of potentially dangerous experiments," retired arms control
researcher Mark Wheelis of the University of California, Davis,
wrote to ScienceInsider in an e-mail.
"Blocking publication may provide
some small increment of safety, but it will be very modest
compared to the benefits of not doing the work in the first
Scientists have long discussed whether
to have mandatory reviews of dual-use studies before they begin, and
given the global risks, some have even argued for some
international risk assessment system for
For instance, a
proposal by four researchers from
the Center for International and Security Studies at Maryland would
have classified Fouchier's work as an "activity of extreme concern"
that would have required international pre-approval.
But NSABB advised against such mandatory systems in 2007, and most
countries don't have formal mechanisms in place to review studies
before they start. (In the United States, it's "recommended" that
researchers ask an institutional review board for advice if they
think a study raises concerns.)
Fouchier's study was
greenlighted in advance by the
Dutch Commission on Genetic Modification (COGEM), but that
only means the panel is satisfied with safety procedures at
Fouchier's lab, explains chair Bastiaan Zoeteman; it's not COGEM's
job to decide whether a study is desirable.
NIH didn't give the funding proposal a
special review either, says Fouchier.
"The creation of a pandemic virus
has been the classical example of dual-use research of concern
the past decade," says Ebright. "It's remarkable that the NSABB
is discussing it in 2011."
Keim agrees about the need for reviews
"The process of identifying dual use
of concern is something that should start at the very first
glimmer of an experiment," he says. "You shouldn't wait until
you have submitted a paper before you decide it's dangerous.
Scientists and institutions and funding agencies should be
looking at this. The journals and the journals' reviewers should
be the last resort."
NSABB does not have the power to prevent
the publication of papers, but it could ask journals not to publish.
Even Ebright, however, says he's against
efforts to ban the publication of the studies now that they have
"You cannot post hoc suppress work
that was done and completed in a non-classified context," he
says. "The scientific community would not stand for that."