10 September 2002

by Apoorva Mandavilli

While people across the United States pause to reflect on the terrorist attacks one year ago, scores of researchers are looking back at the effect on their daily work. For those in certain fields, 9/11 was the day they moved into the fast lane.

A year ago, bioterrorism, biometrics, and biomarkers for chemical agents were esoteric topics, pursued quietly by a thankless few. But the events of a year ago transformed such once-niche industries "from a slow simmer on the backburner to a medium-high on the front burner," in the words of biometrics expert Michael Yura. The new national concern about security in the US has brought a bloom of recognition to certain fields of science - but only to work that was already underway, according to many scientists who have gained unexpected attention in the last year.

For instance, in light of the events of September 11, and particularly the anthrax incidents in the US, the National Institute of Allergy and Infectious Diseases (NIAID) have fast-tracked existing development of a second-generation vaccine, which is now expected to be ready in two years. The vaccine based on protective antigen (PA), a component of the anthrax toxin, is "more refined" than the existing vaccine made from the attenuated bacterium, according to John Collier, professor of microbiology and genetics at Harvard University.

Collier is co-founder of PharmAthene, Inc., where researchers are developing dominant-negative mutants and polyvalent inhibitors to PA, which binds to host cell surface receptors. At least two other groups, including a team at Merck, are developing therapeutics that inhibit the toxin at later stages. Last month, researchers at Rockefeller University proposed bacteriophages as an effective alternative to antiobiotics against anthrax.

"Obviously anthrax has received a lot of attention from basic scientists," Collier said. But "research is emerging very rapidly" on several other microbes listed by the US Centers for Disease Control and Prevention as possible agents of bioterror, he added.

For example, NIAID has shown that existing stockpiles of the smallpox vaccine could be diluted to provide 300 million doses. But the government still intends to purchase and help develop a newer and better smallpox vaccine.

The US government's Medical Chemical and Biological Defense Research Program has awarded contracts to various institutions and companies to develop human monoclonal antibodies to botulinum neurotoxin, a proprietary B-cell sensing technology for rapid and sensitive medical diagnostics, and DNA microarrays to identify signature transcriptional profiles for host responses to infectious agents. NIAID has also awarded seven new contracts to Vaccine and Treatment Evaluation Units, including a $22 million grant to the University of Maryland.

In the last year, there has been "a heightened level of concern about all avenues that terrorists might take - chemical, biological, nuclear," said Rudy Richardson, Dow professor of toxicology at the University of Michigan.

As a result, most of his colleagues are now engaged in "putting together technologies that already were in development" to detect and treat the effects of chemical and biological agents, Richardson said.

Richardson himself is interested in identifying biomarkers of exposure to chemical agents. For example, the nerve gas Sarin blocks acetylcholinesterase, jamming nerves in the "on" position, and eventually causing muscle paralysis and death. Cataloguing similar biomarkers for other agents can help researchers determine whether individuals, or the terrorists themselves, have been exposed to a substance, Richardson explained.

At the University of Michigan and elsewhere, scientists are also developing miniaturized mass spectrometers to detect chemical agents like organophosphates and nerve compounds. At the University of California in San Diego, researchers are using dust-size "smart" silicon crystals to detect chemical and biological agents from a distance, using a laser light source. Their research, reported in the October 1 issue of Nature Materials, details results of nearly 20-meter distances. The researchers' eventual goal is to increase that distance to at least one kilometre.

But many of the techniques now featured in the press are not new, Richardson told BioMedNet News. Pieces of many devices have been built painstakingly by a small group of niche researchers; under heightened interest, they are now "putting those pieces together," he said.

The same is true of technologies used in biometrics, said Michael Yura, program director for the forensics identification program at West Virginia University. "From a development standpoint, I'm not sure things have changed that radically."

While it may seem like science fiction, scientists now know how to build tanks and airplanes that can be operated only by specific identified personnel, Yura said. "That technology is there now," he said. "It's just putting it together."

While the technology has been around for years, each team of researchers has operated under its own standards and structure, he said. For example, although the neighboring states of California and Nevada had both acquired fingerprinting technology, the two systems could not "talk to each other," Yura explained.

But thanks to the focus on biometrics in the past year, he said, the federal Judiciary Committee has been working toward uniform standards so that various systems and machines, developed by different teams, can cross-connect.

At West Virginia University, home to the only undergraduate biometrics training program in the country, Yura and his colleagues are also working with government agencies to train personnel in biometrics and forensic identification techniques.

If the infrastructure can keep pace with the technology, biometric devices will completely replace signatures in 20 years, Yura predicted. Some banks already have heat-sensitive fingerprint readers to match the bank card to the cardholder. Other technologies make use of hand geometry, iris scans, digitized fingerprints or facial recognition.

Unfortunately, the events of last September also brought some unwelcome attention to the industry, Yura said, turning national security into an "entrepreneurial" issue. Several companies claim to have made the "ultimate biometric device" but "that doesn't exist," he said. "Various problems require various solutions."

In infectious disease research as well, the intense focus on terrorism threatens to have some unfortunate consequences, said anthrax expert Collier. Although most new projects are focused on agents of bioterror, the work will have beneficial spillover effects on existing and emerging infectious agents, he predicted.

But because scientific discovery is often serendipitous, to reap those benefits, "we've got to maintain a strong level of curiosity-based research," Collier said. Recent accouncements that the proposed new Department of Homeland Security may take over the reins of all government-funded research on bioagents jeopardizes scientific endeavor, Collier says.

The US National Institutes of Health is "the best vehicle for overseeing research on these agents," perhaps with some input from the Department of Health and Human Services, Collier said. It's essential that scientific expertise be brought to bear on this research, he noted; it can be "lacking in agencies that are focused on security."

Switching solely to directed research on specific agents "won't work," Collier added. "We will be shooting ourselves in the foot."

In the meantime, Collier said, the most important pathogens for bioterrorism research are still the usual suspects - anthrax, smallpox and plague. Despite the public's fears, "I don't think it's going to be as easy to make a better strain of pathogen as a lot of people think," Collier said.

Making an invincible pathogen would require a major research effort, not a small operation run by a few terrorists, so the first order of business should be to "cover our bases" with existing strains of those agents, Collier said.

"I don't think we have to worry too much about Al Qaeda doing this right now," he added. "But who knows?"

Send us your comments for publication.

Sign up for BioMedNet News weekly email alerts.