US public health experts are mobilizing efforts to monitor, detect and respond to biological threats. Credit: © Tek Image/Photoresearchers, Inc.

With war in Iraq heightening anxieties over the intertwined threats of biological warfare bioterrorism, and naturally transmitted infectious diseases, US researchers and public health officials are intensifying their efforts to develop new or more effective countermeasures. Even as they do so, a fractious advisory chorus is calling for more focused efforts but also for a broader, more encyclopedic approach to combating infectious disease agents, including those that might be deliberately disseminated.

Late in March, a panel of infectious disease and public health experts issued an urgent, albeit familiar plea, for the US government “to fortify its public health system to tackle microbes that trigger infectious diseases” and, in the face of “the potential use of biological agents in terrorist attacks or warfare,” to seek “better strategies and tools to grapple with infectious diseases.” These recommendations are part of a new report, “Microbial Threats to Health: Emergence, Detection, and Response,” compiled by a panel convened by the Institute of Medicine (IOM) of the US National Academy of Sciences (Washington, DC).

“On the whole, aggressively responding to microbial threats is in America's economic, humanitarian, and security interests, and should be a national priority,” says IOM panel co-chair Margaret Hamburg, who is a vice president with the Nuclear Threat Initiative (Washington, DC). Although she and other panel members welcome recent federal efforts to increase investments in infectious disease research and related public health programs, they say that those investments need to be “sustained” and also warn against complacency. The panel “did not make specific recommendations on funding...but called for greater investments across a range of components,” she says.

The recently proposed BioShield Initiative (Nat. Biotechnol. 21, 216, 2003) reflects a “strong commitment by the administration and Congress to remove some of the barriers” to progress in developing bioterrorism countermeasures, according to IOM panel member Gail Cassell, who is a vice president at Eli Lilly (Indianapolis, IN). However, she says, this pending proposal does not go far enough in terms of addressing industry worries over several issues, particularly antitrust constraints. Developing bioterrorism countermeasures “will require the best talent at small and big companies working together,” she explains. “I'm not sure the right measures [are in place] to encourage those collaborations.”

Nevertheless, many such collaborative efforts appear to be up and running, judging from the full agenda and variety of countermeasures research strategies discussed or on display during the first American Society for Microbiology (ASM; Washington, DC) Biodefense Research Meeting, which was held in Baltimore, MD., in March, shortly before the IOM report was released. That agenda features researchers who are proponents of highly focused approaches to developing bioterrorism countermeasures as well as those who favor a broader, more comprehensive assault on infectious disease agents, including those that are not considered candidates for being weaponized.

“Gaps are opportunities,” says meeting participant Anthony Fauci, Director of the National Institute of Allergy and Infectious Diseases (NIAID) at the National Institutes of Health (NIH; Bethesda, MD), referring to expanding NIAID research programs that focus on bioterrorism countermeasures. The institute is fostering “fundamental research, but with the goal of [identifying] definable countermeasures,” he says. “It's tricky...to call for investigator-initiated research [that] is balanced with programmatic directions and can't be completely free-floating.”

Already several actual or candidate products aimed at disarming specific 'A' level agents, including the viruses and bacteria responsible for smallpox, anthrax, several viral hemorrhagic fevers, plague, and tularemia, are in the pipeline, according to Fauci. However, for second- and third-tier threat agents, it is “not appropriate” to seek specific vaccines or antitoxins for each of them, meaning investigators will be encouraged to seek “broader” countermeasures, he says.

Many of these NIAID programs—in part, anticipating the impact of the proposed BioShield initiative—invite and will benefit from greater industry involvement, Fauci suggests. As specific projects move forward, NIAID expects to produce small lots of new vaccines at its on-campus pilot plant, while considerable bioterrorism countermeasures research will be done at other facilities being built on the NIH campus, at Fort Detrick (Frederick, MD), or in still-coalescing 'centers of excellence' that will also serve as 'regional hubs' to respond to 'bioterrorism events,' he says.

Amid these primarily federal and academic research-oriented activities, the BioShield plan is intended to give NIAID flexible authority to expedite reviews and contract arrangements with the private sector. Moreover, Fauci says, “It establishes a secure funding resource for purchase of critical biomedical countermeasures...[including those] that no one may ever use.”

Some researchers are calling for even broader, longer-term efforts to thwart bioterrorism. “Bioterrorism is not a short-term problem,” says Stanley Falkow of Stanford University (Stanford, CA), who recommends studying microbial pathogenesis very broadly “rather than taking a limited look at microorganisms that might be used in a bioterrorist attack. We can't just study a small 'table' of organisms.”

New broad-spectrum antimicrobial agents of any sort represent one of the principal gaps—and opportunities—to which Fauci alluded. Falkow calls the situation for conventional antibiotics “dismal” and “almost a state of emergency.” Cassell from Eli Lilly, who chaired the ASM meeting in Baltimore, agrees, saying that the challenges for those seeking new antimicrobial agents “remain formidable.” There are “lots of new promising technologies, a significant investment in research over the past decade, and a plethora of targets,” she says. “Yet we've come up empty-handed...and this lack of success has dampened enthusiasm and investments.”

For now, government and academic researchers are “driving this sector, but industry will come back eventually,” says Martin Rosenberg of Promega (Madison, WI), a biotechnology company. “Not only large pharma, but some of the small and mid-sized companies are getting out of antimicrobial research. I think industry gave up too soon on new technologies to develop new products.”