The University Record, June 11, 1997

Research may unlock ways to protect soldiers from biological warfare agents

From Medical Center Public Relations

Imagine a milky white, peppermint-flavored liquid that, when added to a pool of water teeming with cholera, within minutes makes the water safe to drink.

Imagine a cream that could be used like a sunscreen to protect a soldier from anthrax, botulinum, ricin and other toxins in the biological warfare arsenal.

It may sound like science fiction, but these products may soon be used in humans, says Medical Center researcher James R. Baker Jr., who recently received an $11 million grant to study pathogenic neutralizing agents that could be used by the military in defense of biological attack. "We hope to deliver a first-generation decontamination product within a year for direct testing in humans," says Baker, professor of internal medicine and chief of the Allergy Division.

Baker's four-year project is supported by the Defense Advanced Research Projects Agency (DARPA), an offshoot of the Pentagon that is best known for backing the development of the Internet. His is among 10 biodefense research projects to receive a total of $50 million in DARPA funding this year.

The decontaminating agents he's studying also may have widespread application among the civilian population. In addition to purifying decontaminated water in developing nations, another likely development is an ecologically friendly, odorless spray that could be used to "de-bug" airplanes and hospital rooms, thus preventing the importation of foreign viruses and hospital-acquired infections. Such a spray also could be used to purify some types of foods tainted with bacteria.

Baker's work involves two neutralizing agents---one made from a synthetic lipid, or fat, the other from a polymer. While the lipids and polymers can be used individually to disarm and prevent the absorption of deadly viruses, bacteria and toxins, Baker suspects they will be most effective when used together, as a sort of pathogenic one-two punch.

"Both of the technologies we're working with are brand new," Baker says, "and the two technologies are complementary."

Both materials have been tested in humans and found safe. The agents are very stable; they need no refrigeration and are environmentally and biologically harmless. They can be used topically, via creams and sprays, and possibly internally, via inhalers, nasal sprays and flavored "milkshakes."

The lipids work much like an ultra-powerful antibacterial detergent by disrupting the protective viral and bacterial cellular membranes and rendering them inactive. However, unlike the strongest detergents such as lye, these lipids are not caustic. The lipid Baker is using in his lab is manufactured by Novavax of Columbia, Md. The manufacturer is conducting clinical trials with a small group of ulcer patients to see whether a lipid-based agent, once ingested, will disable heliobacter pylori, the bacteria implicated in ulcer formation.

"This lipid is totally different from anything else that's ever been developed," Baker says. Initially it was designed for cosmetic use in products such as moisturizers.

The polymer Baker is using is called a dendrimer---a revolutionary new three-dimensional, man-made molecule that resembles a hollow ball. The surface of the sphere can be punctuated with "sticky" tentacle-like points that can attract toxins or viruses like a magnet, thus acting as a cellular decoy.

"The reason dendrimers work so well is they can be covered with more receptors than a human cell. The dendrimers will attract the toxin or virus so the cell is virtually bypassed," says Baker, who is a pioneer in adapting polymers for biologic use.

The potential use of dendrimer-based technology extends far beyond military applications. These molecular spheres are also handy for transporting DNA. "They have been shown in some applications to transfer genes into animal cells with a 90 percent success rate," Baker says. In addition to gene therapy, dendrimers also are being explored for use in such areas as drug delivery and cosmetic development. This synthetic material, developed by a former Dow Chemical scientist, is manufactured by Dendritech Inc. of Midland.

"These new agents represent engineering on the molecular level," Baker says. "In addition to biodefense, I strongly suspect we'll be using this technology to address the treatment of cancer, degenerative diseases and genetic disord ers, as well as a whole range of environmental issues."