by Dan Vergano,
January 25, 2011
It was a public health nightmare:
A deadly flu bug spread like
wildfire around the world, killing tens of millions of people.
That was nearly a century ago.
Fears that the nightmare could return
today - perhaps with even more terrifying consequences - have set
off a heated debate among scientists and, for the first time,
delayed the publication of scientific flu research in two
The object of those fears:
a threatening new version of the bird flu
virus that didn't emerge from nature but was born out of experiments
in a lab.
Researchers in the Netherlands and at the University of
Wisconsin-Madison, who were trying to determine what genes might
mutate and make bird flu attack humans, created a strain that can
pass easily among ferrets.
Why should we care that ferrets get the bird flu?
Ferrets are the closest lab animal models to humans for flu vaccine
studies. Until now, cases of bird flu passing from infected birds to
humans were limited to people - farmworkers usually - who worked
closely with the birds. And bird flu almost never passes from person
So creation of a strain easily transmissible between mammals poses
What if the strain escaped from the lab and
spread among humans?
David Nabarro, a World Health Organization expert, estimated that
such a pandemic could kill 20 million to 150 million people
What if terrorists intent on doing harm learned enough from the
published scientific work to reproduce the strain on their own?
They could release it to start a pandemic.
The National Science Advisory Board for Biosecurity (NSABB) reviewed
the work, and last month, it requested for the first time ever that
two scientific journals, Science and Nature, withhold from the
public details of the two potentially dangerous bird flu studies.
Journal editors, sensitive to the security issues, have delayed
publication of the studies.
"We have to protect the public by
making sure the critical information doesn't get into the hands
of those who might misuse it," says Science editor-in-chief
On the other hand, he says,
"This knowledge could be essential
for speeding the development of new treatments to combat this
lethal form of influenza."
Last week, leaders of the two labs
involved announced a two-month halt to research on bird flu viruses
engineered to pass among mammals, citing "perceived fears" that the
microbes may escape from the lab.
They called for the World Health
Organization to discuss the risks and benefits of their research.
"I think it is a reasonable first
says University of Michigan virologist Michael Imperiale,
a member of the federal NSABB group.
The strains are securely locked down in
labs in the Netherlands and Wisconsin, but the episode raises
questions about whether such experiments should be done in the first
"I'm not convinced a 'doomsday'
strain is what we have here," says NSABB chief Paul Keim, an
anthrax researcher at Northern Arizona University in Flagstaff,
"but now at this point, we can see the trajectory creating
something of very grave concern."
A high rate of
Why the concern?
Bird flu, or H5N1 avian flu, has killed
342 people in the past decade out of 581 who were infected, a death
rate of almost 60%, according to the World Health Organization.
percentage is much debated by researchers, who argue it's skewed
because many milder cases aren't reported. That rate is about 120
times higher than for the 1918 flu, and roughly 600 times greater
than for the 2010 seasonal flu.
The 1918 flu virus strain that killed perhaps 50 million people,
including 675,000 Americans, according to the federal Centers for
Disease Control and Prevention (CDC), hangs heavy over the debate.
That bug, emerging near the end of World War I, had new genetic
features and wreaked havoc on the unprepared immune systems of
people at the time.
The nightmare for scientists today is that the mutation-prone bird
flu virus - which they say is similarly foreign to the human immune
system - could evolve into a strain that could be transmitted from
person to person and trigger a similar deadly outbreak.
ferret flu studies, biologists may have completed that step in the
laboratory. The researchers reinfected ferrets with bird flu until a
strain evolved that seemed able to move from ferret to ferret by
sneeze, raising fears it could travel the same way among people if
Outside the lab, some question the wisdom of putting the world at
this kind of risk.
Bioterror expert Michael Osterholm of
the University of Minnesota asks what good it is to identify
threatening new flu genes in a lab when no way exists to monitor
Asia's poultry cages for an outbreak.
"We have worried about this for a
long time," says microbiologist Ronald Atlas of the University
Atlas was a member of the 2004 National
Academy of Science panel that described this very scenario - a lab
creation aimed at combating a disease triggering pandemic fears -
and called for the creation of the NSABB.
"My sense is the scientific
community is really divided on this," Atlas says.
At the dawn of the atomic era, weapons scientists tried "tickling
the dragon's tail," in the words of Manhattan Project physicist
Richard Feynman, handling radioactive blocks just close enough
together to gauge where nuclear chain-reactions start, at
considerable risk to themselves and everyone in the vicinity.
Today's biological equivalent comes from "dual-use" microbes, grown
in labs to be strong enough to test vaccines but running the risk
the microbes could accidentally escape or be hijacked for
Case in point: the anthrax attacks in 2001, which killed five
people. The strain of Ames anthrax bacteria used in the attacks was
specifically grown for vaccine testing.
FBI investigators concluded the culprit was a lab insider,
researcher Bruce Ivins, who committed suicide in 2008 while the
investigation was underway.
Over the past decade, a litany of other microbe reports have drawn
In 2002, Stony Brook (N.Y.) University researchers reported the
re-creation of polio virus from stitched-together DNA fragments. The
study raised concerns that bioterrorists could patch together attack
bugs from gene scraps alone, not even needing the bugs themselves in
a Petri dish.
In 2005, federally funded researchers published a reconstructed
gene map of the 1918 flu virus after a review by Keim's panel.
Then-CDC chief Julie Gerberding called the research "critically
important in our efforts to prepare for pandemic influenza."
Last year, the National Research Council reported that the FBI and
the "U.S. intelligence community" had inspected a suspected al-Qaeda bioterror lab during the anthrax murder investigation. Critics of
the FBI case, such as Rep. Rush Holt, D-N.J., worried that
terrorists were growing microbes for bioterror purposes.
Much like the knowledge that atomic bombs were possible spurred
nuclear proliferation during the Cold War, news that bird flu can be
made transmissible to mammals could suggest ideas to a well-trained,
would-be bioterrorist, Keim says.
"The research is out there," he
The pages of one journal in the middle of the debate, Nature, reveal
the wide disagreement among scientists about whether publishing the
lab-made bird flu strain represents a step too far.
"I believe that the risk of future outbreaks in humans is low,"
wrote flu genetics expert Peter Palese of the Mount Sinai School of
Medicine in New York in a Jan. 12 opinion piece.
Bird flu has had millions of chances in tightly packed chicken coops
of evolving the capability of transmitting among people, he argues,
a natural experiment showing there is little chance of the bug
triggering a pandemic.
"Slowing down the scientific enterprise will not 'protect' the
public - it only makes us more vulnerable," Palese said.
Palese and some other researchers question the high mortality rate
ascribed to bird flu, saying it more likely reflects deaths among
the very sickest patients, ones who headed for the hospital.
Mild cases never showed up in records, they suggest. The death rate
from the dreaded 1918 flu was about 0.5% (still very high for the
flu - that's one in 200 patients), according to a U.S. Armed Forces
Health Surveillance Center review.
On the other hand, smallpox researcher D.A. Henderson of the
University of Pittsburgh's Center for Biosecurity in Baltimore
in Nature's Jan. 19 edition,
"We should not publish a blueprint for
constructing such an organism."
The lab creation, in his estimation,
produced "the ultimate biological threat."
"The real question is, where do we find some middle ground, to make
a system that preserves scientific openness but also safety?" Atlas
"The irony is that we do have the bones of a biosafety system
already in place. Everyone seems to forget that."
Under federal law, bird flu must be investigated within a "Biosafety
Level 3" lab, requiring special training, equipment, ventilation and
Related regulations require that labs register "select
agents," including bird flu.
"Obviously, it went through that process," says spokesman Terry
Devitt of the University of Wisconsin-Madison, who notes that the
National Institutes of Health approved the research in the first
However, Atlas points out the 2004 National Academy of Sciences
report that called for the creation of the NSABB also said extra "biosafety"
reviews should be conducted at the university level.
acknowledges this wasn't part of the school's review process.
Some researchers, such as chemical biologist Richard Ebright of
Rutgers University, have called for assigning the ferret study virus
strains to Biosafety Level 4, the highest level of security.
Worldwide, at least 42 labs investigate bird flu, or bugs just as
deadly, according to Lynn Klotz of the Center for Arms Control and
Non-Proliferation in Washington, and Ed Sylvester of Arizona State
Looking at the history of lab infections, such as the SARS death in
2004 of a student in Beijing who caught the disease from two
graduate students infected in a lab, they put the odds of a lab
"escape" at 80% within four years. An escape doesn't mean a
pandemic, but it does offer one an avenue.
Federal officials, according to Keim, have asked the NSABB to review
the safety of communication of similar bird flu infection studies.
"We had a debate a decade ago and decided that this science was too
important to restrict," Atlas says. "The real responsibility for
control has to come from the scientific community."