SCIENTISTS FIGHT BIOTERRORISM IN THE LAB
By Eve Jacobs
Bioterrorism: The word has entered our vocabulary with a vengeance. From a nether world we would choose not to visit, if we still had that choice, the reality of using germs to wage war has hit home. And for most of us its been a very rude awakening indeed.
Not so for Nancy Connell. A basic researcher in tuberculosis, her interest in the battle of the bugs has reached beyond the lab for more than 20 years. "I always teach my students that science cant be practiced in a vacuum," she states. "Everything we do impacts society in some way."
Maybe we would not have been caught so off guard had we all taken a class or two with her. A TB researcher at UMDNJ-New Jersey Medical School (NJMS), she dates her interest in the field of biological weapons control to the early 80s. "Looking at the political issues surrounding science was a big part of my training at Harvard University Medical School," explains the associate professor of microbiology and molecular genetics, who earned her doctorate in microbial genetics from that school in 1989.
Connell "joined-up" with the Federation of American Scientists (FAS) Chemical and Biological Arms Control Program while in graduate school. Their mission seems to grow in importance daily. As a member of their Working Group on Biological Weapons Verification, she has joined forces with experts in a variety of fields to put teeth into the Biological Weapons Convention of 1972. "This is an international ban on the development and use of biological weapons," explains the researcher, "but it has no provisions for verification."
According to Connell, 144 countries participate in the convention, which meets in Geneva every few years and is "trying to grind out the protocols to root out cheaters." An agreement spelling out the terms for inspectors to make spot checks of facilities suspected of producing such weapons has yet to be ratified.
Connell points to former President George Bushs campaign to eradicate chemical weapons following the Gulf War. "The President realized how close the Iraqis were to using these weapons on the allied forces," she observes. Ratified in 1997, the Chemical Weapons Convention prohibits the development, stockpiling and use of chemical weapons worldwide. But Connell points out that the strength of the chemical weapons agreement lies in giving a group of 500 inspectors the authority to make spot checks to ensure that no country is breaking the terms of the convention. It is this same level of oversight, she says, that is key to preventing further development and use of deadly germs as weapons.
Although her interest in biodefense and her basic science research on the TB bacillus began as parallel themes in her professional life, the two are now closely intertwined. Connell joined the faculty of NJMS in 1992 at a time of the resurgence of tuberculosis in Newark and other urban areas. The focus of her NIH-funded research: an understanding of the alteration in metabolic processes that occurs in the host cell when it is infected with the TB bacillus. The spread of multi-drug resistant strains now a major problem in Eastern Europe underscores the urgent need to develop new preventive as well as treatment approaches. "We cant really count on antibiotics anymore," she says.
While two billion people worldwide are infected with the TB bacillus, 10 percent of those will develop the actual disease in their lifetimes. The researcher also proposes to look at how the bacillus can remain inactive for years, or sometimes a lifetime; and what triggers it to become active in some cases and produce disease.
In 1999, Connells interests in bacterial infections and the politics of bioterrorism were truly coupled. Following testimony given by UMDNJ Vice President Lawrence Feldman to the House Defense subcommittee, a congressional recommendation to fund a three-year University project on biological weapons set many wheels in motion. According to the researcher, UMDNJ has great expertise in this field, including detection of the release of weaponized germs, the epidemiology of diseases caused by these agents, emergency response, drug resistance, toxicology, training for responders to such situations, "right up to arms control whats in place on a global level."
The Universitys Center for BioDefense was established with grants totaling more than $3 million. The research team will first determine the feasibility of producing a single test able to pinpoint from a blood sample which disease-causing agent a person has been infected with at the very earliest stage possible. Among the infectious agents to be studied are bacillus anthrasis (anthrax), Yersinia pestis (plague), Francisella tubrensis (tularemia), Burkholderia mallei (glanders, a horse and donkey infection that can also affect humans), MDR-TB (multi-drug resistant tuberculosis), monkey pox (a close cousin of smallpox), hanta virus, dengue fever and influenza (flu).
"Most of these agents have been weaponized," says Connell. The bacteria and viruses will be studied in a biosafety level three laboratory, where top-of-the-line safety measures, as well as topnotch security protocols and equipment, have been put in place, tested, examined, re-tested and re-examined. The lab has been given the go-ahead by the CDC and U.S. Army.
First, blood samples will be infected with a viral or bacterial agent and then placed in a petri dish. Next, microarray (computer chip) technology is used to analyze samples of the infected blood, "looking" at thousands of genes at a time to determine which are turned on and which are turned off when a particular infectious agent strikes. From this study, a characteristic gene expression pattern (how the cell responds to the particular infection) will be determined. These patterns can then be used to produce a test that can distinguish between infecting agents.
Quick response to serious infection is key: If a lab can take a blood sample and promptly hone in on which microorganism is involved, then antibiotic or antiviral therapy specific to the disease can be started right away, when chances of successful treatment are high. This work is funded by the U.S. Army/Department of Defense.
"People are taking this research seriously," says Connell. "The work will move a lot faster from now on. Well also see a shoring up of the public health infrastructure, which has been allowed to slide since antibiotics came along."
For Connell, a work day could mean traveling to Washington, DC or Trenton to share her knowledge with lawmakers, teaching a class of medical students, speaking to one or more media people hungry for solid scientific information, or slipping on her "cover-up" suit, booties, HEPA filtered mouthpiece and safety glasses, to work with microbes in the lab. The way things have been going, her work day is often long and includes all of the above.
But like most ultra-achievers, she rarely says no to a request for her time and expertise. And like most idealists, she is ready to take on more. "I have a dream," she quotes another peace-loving activist, but her dream is very twenty-first century. She is determined to get the Biological Weapons Convention of 1972 up and running. She also thinks UMDNJ has the right stuff to become a training site for international inspectors, and she is ready to help train them.
Perhaps this biodefense researcher will have the time and opportunity to take on one more big role that of international biological weapons inspector. We can think of this as risk management. Biological weapons will likely never disappear, but effective controls would save countless lives.
"These kinds of inspections work," Connell says with conviction. "Weve done it before with nuclear and chemical weapons. Well do it again with biological ones."