Publish and Perish? 

Biologists are finally talking about the implications of their work. They'll need to do better than that.

In January 2001, after a team of Australian researchers working on rodent birth control inadvertently engineered a highly deadly, vaccine-resistant strain of mousepox virus, the rodent equivalent of smallpox, they did something almost unheard of. They came clean.

In a press release, the scientists warned of the implications of their work for biological warfare and called for increased vigilance and strengthening of bioweapons treaties. In the same breath, they defended their decision to publish the experiments in the Journal of Virology, which is freely accessible online.

Though publication of potentially dangerous findings has been par for the course among scientists, alerting the public to their studies' implications has not. In fact, before September 11, debate over the wisdom of rushing potentially dangerous results into the public domain was all but nonexistent.

Five days before the Trade Center imploded, Science ran an article describing how a research team tweaked genes on an Asian flu strain to produce a virus that killed infected mice more efficiently than the original. Four weeks later, as the first anthrax cases were incubating in Florida, the British journal Nature published the complete DNA sequence of plague bacterium Yersinia pestis.

The unfettered flow of information and materials has always been at the heart of modern scientific discourse. Journals judge submissions exclusively on scientific relevance and experimental soundness; many require authors to share materials and methods. "Science thrives on the exchange of ideas rather than on the censoring of ideas," says Dr. John Ward, editor of the Morbidity and Mortality Weekly Report at the federal Centers for Disease Control.

While the open exchange of data indeed has enormous benefits, accelerating development of new disease treatments and vaccines, it has also created a literature replete with information that could benefit a lab-savvy terrorist. In readily available articles, there are detailed descriptions of microbial growth conditions and methods for the manufacture of deadly viruses and dangerous flu strains from a DNA sequence. Anyone with Internet access can peruse the genetic blueprint for Ebola, a virus that causes massive bleeding and death and for which there is currently no vaccine or treatment. DNA sequences for smallpox, tuberculosis, plague, cholera, leprosy, and other pathogens are also available -- no subscription or password required.

CDC virologist Brian Mahy was part of the team that sequenced smallpox and several other highly dangerous organisms in the early 1990s. Toward the end of the smallpox project, Mahy says, the team did debate internally whether to go public. "My view is it was scientific evidence that needed to be in the public domain, and we're a public institution, so we published it," he says. "There were suggestions it be burned onto a CD-ROM and chained to [then-CDC chief] Bernadine Healy's desk."

But these debates almost never involve the public. Until recently, only a handful of experts were talking publicly about bioterrorism at all. For years the usual suspects -- including Matt Meselson of Harvard University, Stanford's Steven Block, Nobel Prize-winning Rockefeller emeritus Josh Lederberg, and Pulitzer-winning journalist Laurie Garrett -- called for stronger bioweapons protocols and revamping of the neglected public health system. They also called on scientists to stop ignoring the dangers.

Few listened, at least until last fall's anthrax scare shoved the issue into the science community's face like so much smallpox-cream pie. "Most mainstream biologists have had little engagement with the issues," opined Nature magazine in a May 2001 editorial. "If biologists stick their heads in the sand and pretend that their work has nothing to do with warfare, they will be doing the world a disservice."

Even after the attacks, the science community responded with a sort of bureaucratic arrogance. Addressing colleagues at an infectious diseases conference last fall, Dr. Thomas Inglesby of the Johns Hopkins Center for Civilian Biodefense Studies warned that researchers needed to start talking about ethics. "If we don't," he told his peers, "people who aren't scientists will impose rules on scientists."

The big fear, in other words, was not that well-intentioned science could arm a genocidal killer, but that some researchers would be inconvenienced. It is indeed a valid concern that government would take a heavy-handed approach. Federal officials have already suggested that foreign students be denied involvement in projects involving certain organisms -- a boneheaded strategy that could actually weaken our ability to respond to future biological attacks. On the other hand, many scientists have been living in denial. One virologist, whose lab published methods for reconstituting deadly viruses from their DNA templates, argued that a terrorist would first need the virus to obtain the DNA. When this reporter noted that the viral DNA could be synthesized based on the published sequence, the researcher changed his tune. "You can do it," he admitted, "but it would take forever." A determined terrorist might just have "forever."

This researcher, who didn't want his name used, bristled at the suggestion that perhaps some things shouldn't be published. "That has to be published," he said. "That's science. If you say you shouldn't publish this or that, we should say you shouldn't make knives, or guns, or airplanes, because that was used as a weapon in September."

The problem is, he's dead wrong. In July, Eckard Wimmer, a researcher at the State University of New York at Stony Brook, made a frightening announcement. His team had synthesized infectious polio virus from scratch, using only the published DNA sequence, basic lab machinery, and chemicals available to any laboratory. "The point here, of course, is that the DNA can be synthesized from the sequence, and this could be done by any third-rate terrorist," Columbia University virologist Vincent Racaniello told Science News after Wimmer's announcement.

Even though some biologists are coming to admit that maybe, just maybe, their intellectual freedoms have ramifications, the prevailing attitude is still to publish first and debate it later.

It's a "risk-benefit calculation," said Donald Kennedy, editor-in-chief of Science, in response to e-mailed questions six weeks after the attacks. Science, he says, has never rejected an article out of concern the information could be misused, although, he says, "I suppose one could conceive of a scenario in which one would decline to publish."

Noting failed attempts by some nuclear physicists in the 1930s to prevent publication of fission experiments, Harvard's Matt Meselson expresses skepticism that sensitive, scientifically important results can be kept under wraps. In any case, he says, the impetus should come from scientists, not politicians. "If I were a journal editor and I received an article that said how to make a bioweapon, I'd never publish it, but that would be based on self-regulation, not any government restriction," says the professor. "I've never heard of a case where the government has restricted publication. I don't think it would work."

Some scientists argue that the destructive cat is already out of the bag. "There's a protocol out there to make an atomic bomb," says the virologist who didn't want to be named. "What's the difference? Getting those materials is not that difficult. It's a free-trading world, and people can get almost any raw material. Creating viruses is more sophisticated and much more difficult."

Weapons experts, in fact, are far more worried about biological attacks than nukes or chemical warfare precisely because the materials are far easier to obtain and smuggle. Secretary of State Colin Powell, for one, is of this mind. As for difficulty, Wimmer has demonstrated that it's not that hard to build a pathogenic virus.

There are, at least, indications that scientists have finally started thinking about the potential for misuse of their work. The American Association for the Advancement of Science rushed out a book this spring based on recent talks by prominent researchers, who touched on these subjects and called for further debate. But they'll have to do better than lip service, or the government, which funds the majority of basic research in the United States, may not hesitate to muck about in their business -- which really isn't just their business; it's everyone's.

Going forward, it may well turn out that restricting publication isn't the best way to go. Consider human cloning, a case in which the government has preempted certain ethically troubling lines of research. Nuclear materials and chemicals that could be used to make drugs or weapons have been regulated for years. And while the pursuit of knowledge is an honorable, if egotistical, drive, there are areas of research -- such as swapping pathogenic factors between infectious viral strains -- that perhaps shouldn't have been pursued in the first place; they certainly shouldn't be available on the Internet for just anyone to see. Unless scientists learn to make these distinctions themselves, like Inglesby said, someone's going to do it for them.


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