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Does Forewarned = Forearmed With Lab-Made Avian Influenza Strains?

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Science  17 Feb 2012:
Vol. 335, Issue 6070, pp. 785-787
DOI: 10.1126/science.335.6070.785
Hog-tied research.

Pork producers in many locales resist active surveillance for flu.

CREDIT: GREGORY GRAY/DEPARTMENT OF ENVIRONMENTAL AND GLOBAL HEALTH, COLLEGE OF PUBLIC HEALTH AND HEALTH PROFESSIONS

Behind the increasingly contentious debate over whether journals should publish the full details of how two labs engineered the deadly avian influenza strain H5N1 so that it spreads more easily among ferrets, and presumably humans, lies a conundrum: Knowledge cuts both ways.

No one at the front of this protracted battle wants to stifle free scientific exchange. But two camps have formed that view risks and benefits through different lenses. Proponents of full disclosure, including the researchers who conducted the work, contend that knowing the genetic signatures of these potentially devastating viruses might prove pivotal to shoring up surveillance measures and controlling an emerging threat.

Maybe, say opponents in the other camp, but they stress that in the predominantly poor countries where H5N1 circulates, surveillance and control systems are too rudimentary, or nonexistent, to take advantage of the new knowledge. They worry that if published, that data could provide a recipe for bioterrorists to unleash a doomsday scenario.

Ideally, a robust surveillance system will detect novel flu viruses in animals when they arise, which in turn will aid control efforts with vaccines and culling, preventing economic loss to farmers and the introduction of dangerous strains to humans. Early detection of new strains in humans can similarly give public health officials a jump on fashioning an effective response. Ideally.

The reality is far messier—a point that both camps agree is troubling.

When avian influenza viruses infect and adapt to humans, they have the potential to cause devastating pandemics because we have little, if any, immunity to them. Although public health officials have documented fewer than 600 cases of H5N1 infections since it surfaced in humans in 1997, H5N1 has received intense attention because more than half of the people who had symptomatic disease died (see sidebar, p. 786). The saving grace is that it has not spread easily among people. But two labs have made the virus transmit readily among ferrets by introducing mutations or creating a “reassortant” of H5N1 and the H1N1 virus that caused the 2009 flu pandemic. Papers about the studies, stuck in limbo at Science and Nature, remain unpublished while scientists, journal editors, and public health officials weigh the benefits and risks of full disclosure.

Influenza specialists often stress that surveillance has improved since H5N1's emergence in Hong Kong 15 years ago. They particularly praise virologist Malik Peiris at the University of Hong Kong and colleagues, who worked on the 1997 outbreak and then began to hunt for flu viruses in birds at markets and pigs at slaughterhouses. (Peiris makes the case online in Science that the new experiments will help surveillance, http://scim.ag/_h5n1.) “The folks in Hong Kong are a model of what should happen in the world,” says Robert Webster, who studies influenza at St. Jude Children's Research Hospital in Memphis, Tennessee, and helped Peiris launch the program.

But Hong Kong remains the exception. At a debate held 2 February by the New York Academy of Sciences about the mutant H5N1s, the state of the world's surveillance efforts received a drubbing from a member of the U.S. National Science Advisory Board for Biosecurity, which made the controversial recommendation to remove from the papers details of the genetic changes that made the virus transmissible as well as the methods the scientists used to produce those mutations. “Surveillance out there right now is like a whole lot of broken smoke alarms,” said flu expert Michael Osterholm of the University of Minnesota, Twin Cities.

Veterinary microbiologist Jürgen Richt of Kansas State University, Manhattan, agrees that surveillance is wanting but says the details could indeed be put to good use. Although H5N1 primarily circulates in poor countries that have limited access to sophisticated laboratories, they widely use inexpensive and relatively simple PCR tests that could hunt for the mutations linked to transmission. “We can design surveillance screens for transmissible versus nontransmissible H5N1,” Richt says. Countries that find transmissible H5N1 in animals could ramp up programs to “immediately stamp it out,” he says. “We would be weeks ahead.”

But having the tools only helps if countries use them properly. “We don't have the surveillance or reaction system, so how is this really going to help?” asks veterinarian Ilaria Capua, who runs an influenza reference lab for Italy at the Istituto Zooprofilattico Sperimentale delle Venezie in Padua. Capua notes that influenza programs in developing countries depend heavily on funding from the wealthy world. “There's less surveillance going on than 3 or 4 years ago, because donors have changed their priorities,” she says. (Despite her surveillance concerns, Capua, who in 2006 persuaded reluctant colleagues to share H5N1 sequences in the name of spurring scientific progress, supports full publication of the new data.)

Capua works closely with Egypt, which has had more cases of human H5N1 than any country other than Indonesia. When it comes to culling H5N1-infected flocks, the primary control strategy, she notes that's easier said than done, too. “Egypt is a very poor country, they have social unrest, and they don't have the infrastructure and just cannot afford to cull the birds,” she says.

Animal vaccination campaigns in poor countries, which complement surveillance and culling, similarly face huge obstacles. To combat H5N1, several countries launched massive vaccination campaigns in poultry, using more than 100 billion doses between 2002 and 2010, according to a recent review in a journal published by the World Organization for Animal Health. But birds have short life spans, and campaign success often waxes and wanes, largely dependent on how widely the vaccines are used.

Delays in moving animal samples from field to lab can also undermine the benefit of detecting dangerous strains. Several months often pass before samples from Egypt reach her lab, Capua says. Sample delays have compromised efforts in wealthy countries, too. In the United States, researchers have pushed for monitoring slaughtered pigs—the type of “active” surveillance Hong Kong does—but have met resistance from the pork industry, which took a financial beating during the 2009 pandemic and fears another backlash if the public learns that novel influenza strains infected their pigs. Hog producers wait until 3 months after slaughter to give samples to Webster's colleagues at St. Jude's, a compromise he says is actually a step forward. The U.S. Department of Agriculture has no mandatory active surveillance of commercial swine or poultry, but many producers have joined voluntary programs that offer financial incentives or agree to not specify the location of infected farms.

Cull of duty.

If surveillance detects H5N1 early, killing flocks can contain it, as the United Kingdom did in 2007.

CREDIT: JAMIE MCDONALD/GETTY IMAGES

Virologist Yi Guan, who works with Peiris in Hong Kong, agrees that knowing the signatures of transmission might help but says there's often a disconnect between the influenza surveillance and control efforts in animals and humans. Vaccination makes it difficult to track the virus in poultry, so mainland China is “using humans as sentinels,” he says. “First they have a human case, then they start looking for bird flu.”

As for surveillance in humans, the benefits of the new experiments are murkier. “Once a new influenza virus begins to be transmitted between humans, whether as a result of a Mother Nature–made pandemic virus or an intentional or unintentional release of a manmade virus, it's like having a screen door on your submarine; you'll never contain it,” Osterholm says.

Whether the new experimental data will help protect humans, the debate has already spotlighted the inadequacies of surveillance and control, Richt says. “This whole discussion stimulates organizations and governments to review their emergency plans if an H5N1 epidemic arises, and that's a critical point,” Richt says. “These people have to rethink.”

  • * With reporting by Dennis Normile.

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