Originally created 12/13/01

Body's immune system a recruit for biodefense



In the quest to protect people against biological weapons, some scientists believe that the best defense is lurking within each of us.

Every healthy body has an immune system that knows, long before our minds do, when we've been invaded by a nasty bug. Special cells spring into motion to intercept the interloper. The trouble comes when some particularly vicious pathogens overwhelm the speed and vigor with which the sentinel cells respond.

Researchers are trying to boost the body's frontline defenses by provoking more cells to respond, and faster. In contrast to the conventional approach of using vaccines to teach the body to resist specific pathogens, this method attempts to manipulate an aspect of the body's defenses known as non-specific immunity.

The aim is to prevent the body from falling victim before doctors can diagnose the illness and prescribe treatment.

"It is a long shot, but everything I know about biological weapons tells me that this is far more promising than attempts to rig office buildings and public monuments with detection devices or to stockpile vaccines," wrote Dr. Ken Alibek, a champion of the strategy.

Alibek is president of a biotech company in Virginia, Hadron Advanced Biosystems Inc., where he is using his knowledge on the other side: to defend against biological attack.

Biodefense has become a popular field since the Sept. 11 terrorist attacks and subsequent mailings of anthrax-laced letters.

Before anthrax became a household word, a few scientists were in the field, many funded by the Defense Advanced Research Projects Agency, an arm of the U.S. Defense Department that supports speculative research.

This fiscal year, DARPA is devoting $140 million to biodefense, of which $60 million is for medical approaches that include exploring general immunity, an agency spokeswoman said.

The concept of boosting non-specific immunity has been accepted only recently, Alibek said. People are more familiar with using vaccines to protect against diseases, and vaccines are based on specific, or acquired, immunity.

When people say it takes a while for the immune system to kick in, they're referring to the acquired immune system, which builds antibodies that tag invaders for destruction. In acquired immunity, the body remembers old invaders and becomes resistant to them.

Less known about the body's defenses is innate immunity, a primitive physiological response that is active from birth. It unleashes cells whose job is to destroy anything that is not "self."

A California biotech company is sifting through genetic material of bacteria, seeking elements critical to bacterial survival. A team in Texas is exploring the use of harmless viruses to push immune cells into overdrive.

At Hadron, Alibek and colleagues are working on an inhaled drug that would bolster normal defenses in the mucous linings of the nose and airways.

Hadron is testing as immune boosters the use of cytokines - proteins found in the body that act as messengers in the immune system - as well as a protein produced in bacterial membranes.

Tests suggest that the approach works, Alibek said.

Making the immune system more vigilant is not without risk. A hyper-reactive system may attack the body itself, as happens in autoimmune diseases such as lupus and multiple sclerosis.

Assuming no hazardous side effects, invoking a non-specific immune reaction seems ideally suited to bioterrorism, because victims could die before doctors diagnosed their specific disease.

The traditional way of finding the source of an infectious disease is by trying to grow the microbe in culture. This takes days. Quicker identification may be possible in the future by interpreting the body's cellular reactions.

Although interest in biodefense is driving much of the work in non-specific immunity, what scientists learn is useful for everyday medicine, said Stephen Albert Johnston, director of the Center for Biomedical Inventions at the University of Texas Southwestern Medical Center.

In one project, Johnston uses parapox, a benign virus related to smallpox, to stimulate the immune system. For reasons unknown, exposure to parapox causes immune cells to rush to the site of invasion - usually the skin - engulf the virus, form a scab and fall off.

Johnston's goal is to identify what in parapox makes the dendritic cells come running. His far-off hope is to exploit the effect to make a "get-well pill" against cold and flu bugs, as well as the nastier viruses of bioweaponry.