Washington—With questions regarding national security omnipresent since September 11 and the anthrax attacks last year, it was simply a matter of time before scientists were called on to defend the practice of publishing research that government security watchdogs deem potentially harmful. Now, following a string of recent basic biology articles, two groups who until recently rarely shared a stage—scientists and national security experts—are finding themselves at odds.
In response, the National Academies (which includes the National Academy of Sciences and the Institute of Medicine) and the Center for Strategic and International Studies brought scientists and policymakers together last month for the first in a string of meetings meant to bridge the chasm between scientific openness and concerns about bioterrorism.
OPENNESS VS CAUTION
Predictably, the scientists spoke out—sometimes fervently—in favor of unfettered openness; the security experts pleaded for caution.
Parney Albright, PhD, who works for the Office of Homeland Security and the White House Office of Science and Technology Policy, said that the Bush administration agrees that scientific openness is paramount. In fact, he said that National Security Advisor Condoleeza Rice, PhD, reaffirmed that principle on November 1, 2001, when she signed off on National Security Decision Directive 189, a Reagan-era document for "controlling the flow" of scientific knowledge.
"It is the policy of this Administration that, to the maximum extent possible, the products of fundamental research remain unrestricted," states National Security Decision Directive 189. "No restrictions may be placed upon the conduct or reporting of federally-funded fundamental research that has not received national security classification."
Yet after these statements, which Science Editor Donald Kennedy, PhD, found "enormously reassuring," Albright raised the specter of government wriggling its way deep into scientific publishing.
"The basic message here is that the [scientific] community has got to get its act together or someone will get it together for you," said Albright. He went on to say that Congress abhors a vacuum: in the absence of clear criteria for handling "questionable or unexpected results," lawmakers would surely step in with "what will probably be onerous and ineffective legislation."
Editors from top journals responded that they have, in fact, developed procedures for handling articles with potential security implications (see "How Some Journals Are Vetting Security Concerns"). Invariably, the editors pledged to err on the side of openness.
"It is impossible to gauge if a finding could ever be used for nefarious purposes," said Kennedy. "I'm worried about the papers that I don't get from scientists who have been dissuaded by public officials." Instead of a strict "Napoleonic code" handed down from on high, Kennedy said that the research community needs to build a collection of "case law."
CASES IN POINT
Three such cases were presented in an afternoon session. The first, published by Ariella Rosengard, PhD, and her immunologist colleagues at the University of Pennsylvania School of Medicine, in Philadelphia, detailed how an enzyme produced by the smallpox virus defeats the immune system (Proc Natl Acad Sci U S A. 2002;99:8808-8813). Because smallpox proteins are not available for research, the team engineered the enzyme, called the smallpox inhibitor of complement enzymes (SPICE), from published DNA sequences and an analogous protein found in vaccine-strain vaccinia.
"The main conclusion of the paper was that a few amino acids are necessary for the functioning [of SPICE]," said Rosengard. "It provides insight into the pathogenesis of smallpox." Such insight also could advance research into autoimmune diseases such as arthritis, she added.
While planning the research, Rosengard contacted her university's safety officer, who, although not required by law to do so, alerted the Centers for Disease Control and Prevention and the World Health Organization. The research team complied with recommendations from the two agencies, said Rosengard. Nevertheless, she found herself in the center of a media storm when US News & World Report described her research and then other reporters began questioning if her work would in some way help terrorists.
While Rosengard said that she initially was conflicted about the research, she decided that the "potential for good outweighed the potential for evil."
"Once you know the mechanisms [of pathogenesis] you can find new ways to disable smallpox," she said. "And then you've truly disarmed the terrorists." In a commentary published concurrently with Rosengard's article (Proc Natl Acad Sci U S A. 2002;99:8461-8462), Cambridge University Professor Peter Lachmann, PhD, agreed, arguing that the new knowledge presented little danger. He wrote that "it is very unlikely" terrorists could somehow make a weapon using the newly synthesized SPICE enzyme.
MAKING A POLIOVIRUS
The second article in question concerned the construction of synthetic poliovirus by a group at the State University of New York, Stony Brook. Eckard Wimmer, PhD, wanted to show that a virus could be synthesized in the laboratory de novo (Science. 2002;297:769-770). With the published genetic sequence of poliovirus freely available, Wimmer ordered the appropriate chemicals—the point that media outlets latched onto—and synthesized the virus. "On paper, it is quite simple," he said, "but it just hadn't been done before."
To gauge whether his team successfully transfected cell cultures with the new virus, Wimmer introduced 28 genetic mutations. These were supposed to be "silent changes," and not affect how the virus functioned. So Wimmer was surprised when he discovered that the new strain was 10 000 times less pathogenic than the natural version. "This is a point that got lost," Wimmer sighed. "We found a way to effectively disable poliovirus."
Instead, for three weeks reporters bombarded him with terrorism-related questions. Some asked why he was aiding terrorists. He began to worry that his article would lead to restrictions on research and fretted over how media and the public missed the boat.
"Synthesis of a virus is not the way to prepare a bioterrorism agent," he said, detailing the tedious nature of the work. The result may have shocked the public, but it evoked yawns from other scientists, who regarded the research as nothing more than a workmanlike application of commonplace DNA synthesis techniques.
UNEXPECTED OUTCOMES
The third article provides an example of the type of research that will be most difficult to control: the unexpected outcome. While trying to sterilize mice using genetically modified mousepox virus (which contained genes for mouse egg proteins and a gene for an immune regulatory protein, interleukin 4 [IL-4], as part of a contraceptive vaccine), a team from the Pest Animal Control Cooperative Research Centre, Canberra, Australia, discovered instead that their virus defeated the rodents' immune systems (J Virol. 2001;75:1205-1210).
The result was nothing shocking to scientists in the know, said Thomas Shenk, PhD, president-elect of the American Society for Microbiology and editor of the Journal of Virology. Drawing on previous research, a "smart person" could have guessed that engineering the virus to produce more IL-4 would make it more virulent.
"If I want to limit access to information, then, where do I draw the line?" Shenk asked. At the discovery of IL-4? At the elucidation of IL-4's effects in a vaccinia model? At the demonstration that mousepox virus engineered with IL-4 could kill a mouse?
"As a case study, it illustrates that science is incremental," said Shenk, chair of Princeton University's department of molecular biology. "If you want to restrict information before anyone could guess [how to use it destructively], you will disrupt the foundation of biomedical science."
The other editors agreed, stressing that scientific knowledge alone is neither dangerous nor benevolent. The real danger lies, they said, in the gap between the public perception and scientific reality. If every article regarding modified pathogens sparks a roiling cauldron of vague fears, scientific progress will suffer, they warned.
"I'm not patting myself on the back about the reaction to the Wimmer paper," said Kennedy. "We didn't do a good job. We need to do better at learning what the public reaction will be."
| How Some Journals Are Vetting Security Concerns
Following the meeting, a group of editors met to discuss their processes for reviewing papers that pose potential security threats. Many of the editors agreed that a form of targeted peer review and heightened awareness of potential risks were important considerations. Several editors commented on their specific procedures and experiences:
- American Society for Microbiology (ASM). In December 2001, the 11 ASM journals adopted a policy whereby editors screen all papers for security concerns. Those dealing with "select agents," the Centers for Disease Control and Prevention's list of dangerous pathogens, receive additional review. Under the new policy, the ASM publications board has vetted two papers. One is to be published in March and the other is being revised, said Sam Kaplan, PhD, chair of the board.
- Science. Editor Donald Kennedy, PhD, has assembled an outside group of terrorism experts to review articles with potential security implications. Science has not rejected any articles based on security concerns, said Kennedy.
- Proceedings of the National Academy of Sciences. Editor Nick Cozzarelli, PhD, has asked the editorial board to be more aware of security issues. Since implementing this policy last year, 20 papers—about 1% of total submissions during that time—have been flagged for extra review. In two cases Cozzarelli consulted with outside bioterrorism experts. Both articles were published.
- Journal of the American Medical Association (JAMA). According to Editor Catherine D. DeAngelis, MD, MPH, "JAMA, as I believe do most biomedical journals, has a process of peer review by appropriate experts and careful editorial evaluation to handle any paper that might provide information that could be misused by bioterrorists."
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