Defense research agency leads push for drugs to counter bioweapons

As the threat of biological terrorism has become more immediate and concern about new strains of pathogens has increased, the Defense Advanced Research Projects Agency has responded by accelerating efforts to find new medicines that will reduce-and perhaps eliminate-the threat of anthrax and many other dangerous agents, scientists and U.S. officials said recently.

An array of five DARPA-supported initiatives have the potential "to take anthrax off the table as a weapon because we can treat it and prevent it," said John Carney, program manager for DARPA Unconventional Pathogen Countermeasures, which oversees the initiatives.

Although the program is intended to develop medicines that would primarily protect soldiers, the general U.S. population could face the same pathogens and benefit from the same initiatives, officials said.

"Somebody who is serious about an attack using biowarfare drugs could, and probably will, engineer resistance to our major antibiotics," said David Perry, chief executive officer of Anacor-one of the five companies involved in the DARPA program. "It's not that hard, frankly. The bacteria they use will be resistant to the antibiotics we have on hand. The government's emergency policy is to have a basket of antibiotics stockpiled."

Agency officials have told Congress that they hope to submit several investigational new drugs for Food and Drug Administration approval within two years, Carney said. The agency is also closely considering the possibility of developing a single antibiotic to defeat several pathogens.

"One drug for all bugs," Carney said.

For example, one antibiotic Anacor is developing might be a "triple-header," said Lucy Shapiro, director of Stanford University's Beckman Center for biomedical research and an Anacor cofounder. The drug has shown promise for use against the plague, tularemia and anthrax, she said.

Initiatives and Goals

While the pathogen countermeasures project began before the Sept. 11 terrorist attacks on New York and Washington, officials are now trying to speed the process.

"Timelines are difficult to predict in pharmaceutical work," Carney said. He noted, however, that "the urgency is greater now" and that the agency is "being aggressive."

Another participant echoed Carney's assessment.

"I think certainly DARPA feels a sense of urgency that is reflected down to the scientific level," said Stephen Benkovic, the other Anacor cofounder and a Pennsylvania State University professor.

Anacor is building on the work of Shapiro and Benkovic, whose research has led to a new class of drugs that inhibit certain pathogenic enzymes, including those found in anthrax and tularemia. The two scientists, who also sit on the company's scientific advisory board, believe that the recently founded company is making good progress toward developing a single drug that could defeat several dangerous agents.

"We began to accelerate as the situation darkened," Benkovic said, referring to the terrorist attacks and the U.S. war on terrorism. "We would like to take it as far as we can, as quickly as possible," he added.

Anacor announced a $21.6 million contract Oct. 29-from DARPA and the Army Medical Research and Materiel Command-to develop antibiotics for use against anthrax, tularemia and other infectious diseases. After initial success with test-tube experiments, the company's researchers are currently taking their enzymes into animal testing.

Vince Fischetti, a professor who specializes in bacterial pathogenesis and immunology at New York's Rockefeller University, is in the second year of another leg of the DARPA-sponsored effort to develop an enzyme that will target anthrax without causing side effects in other systems in the human body. He has worked with the agency before and has sat on its scientific advisory board for four years.

DARPA is funding a clinical trial to test the new enzyme in animals, Fischetti said. Researchers plan to finish animal testing within a year, and if it is successful, human testing could be complete in two years, he said.

If all goes well, the government could have this medicine stockpiled in under five years, and Fischetti said he imagines that it could happen "in three to four."

DARPA is also working with Genesoft in the San Francisco Bay area and PharmAthene and Critical Therapeutics in the Boston area.

Though the five initiatives work toward similar goals, they are not in a competition, Carney said. Each has sufficient funding and its own milestones to reach, he added.

"At the end of the day, they will either succeed or fail on their own characteristics," Carney said.

Academia Meets the Military

The pathogen countermeasures contracts represent a significant infusion of top scientific minds into the world of national security, according to Shapiro.

"DARPA was very instrumental in taking this out of academia and into a real corporate setting … neither Steve [Benkovic] or I had the ability or desire to run a company," she said.

Shapiro applauded the risks that the program has taken to support fledgling scientific efforts. Anacor, which grew from the research of Shapiro and Benkovic, is now well poised to produce important new medicines, Carney said. The antibiotics being developed in Anacor's Palo Alto facility in California might become the first new class of antibiotics since 1978, according to Perry.

While Anacor officials said they anticipate that a commercial application will emerge from their work-the compound has also proven effective against common bugs such as streptococcus and staphylococcus-Shapiro said they hope to develop a drug that is "much more effective" than Cipro in treating anthrax.

"If you want to break barriers and develop the new penicillin, you have to take chances," Shapiro said. "I'm not telling you we have penicillin-we don't-but we might," she added.

Keeping in Touch

Mixing scientists and national security experts is not always a completely smooth process, Carney said. It is important to not merely fund the projects and walk away, he said.

Each week, agency officials conduct either a phone conference call or a face-to-face meeting with representatives from each project. The agency also hosts annual meetings to bring efforts together and share ideas and research.

The annual meetings "bring all of the projects together as a forum-it creates a community," Carney said. The meeting of the different scientists creates a useful "social network" and offers participants "different vantage points on how to attack a problem," he added. Representatives from the Pentagon and the FDA as well as alumni from former DARPA projects have attended the meetings in the past. The most recent meeting was held in February, and the next is scheduled for April 2003.

During the meetings, academics are given a slot of time to present their work, and Carney asks them to pay attention to practical applications as well as general scientific progress. Because some scientists are unaccustomed to displaying the practical facets of their work, Carney has mandated that the first five slides of every presentation focus on real-world application and business matters.

Although DARPA's efforts are not conventional, they are needed to provide new solutions to urgent concerns, Carney said. The agency's mandate is to "disruptively" change the way technology is used and to look "far forward into the future," he added.

The scientists involved in the project agreed that novel treatments must be found for chemical and biological agents.

"If the next attack is a resistant organism, we would have no way to kill that organism," Fischetti said. "It's a capability we don't have right now," he added.