Sandia tests disease-tracking approach for detecting rogue bioweapon research

ER staff nurse Dianne Vandiver and medical technologist Brent Butler take a blood sample from an emergency room patient at a Los Alamos public hospital, one of three New Mexico hospitals participating in the hepatitis C project. A fourth hospital, in Chelyabinsk, Russia, also is participating. (Photo by Randy Montoya) Download 150dpi JPEG image, 'HEP_C.jpg', 1.1MB

The Centers for Disease Control estimates that 3.9 million Americans are chronically infected with hepatitis C. New Mexico health officials believe up to 2 percent of the state's population has the disease.

Yet very little is known about hepatitis C risk factors -- behaviors that increase the probability that a person will contract the disease. The hope is that by sharing information about who gets the virus and how it is transmitted, physicians can better understand how to prevent its spread.

The primary goal of the international project, though, is to show how monitoring unusual outbreaks of disease can serve as a worldwide early-warning system for covert biological weapons development.

Sandia scientists have proposed setting up an online health information exchange that would rely on thousands of doctors worldwide sharing disease information about their patients. By keeping an eye on unusual outbreaks, and by asking nations that censor the sharing of health information to explain themselves, the scientists believe an effective "transparency regime" can be created for international treaties such as the Biological Weapons Convention (BWC), which forbids experimentation or acquisition of biological agents or toxins for military purposes.

"We think investigating unusual outbreaks of disease may be the best way to catch a cheater," says Al Zelicoff of Sandia's Nonproliferation Initiatives Department.

The hepatitis C project is the first step in demonstrating how such a system might work.

Called the Cooperative Disease Monitoring Project, the effort is being coordinated by Sandia with funding from the Department of Energy's Chemical and Biological Weapons Nonproliferation Program. Also participating are the New Mexico Department of Public Health, the University of New Mexico School of Medicine, Los Alamos National Laboratory, and the former Soviet nuclear weapons lab Chelyabinsk-70.

Outbreaks can be reason for suspicion
When an outbreak of a rodent-borne disease now known as the hantavirus killed more than a dozen people in the southwestern United States in spring 1993, the U.S. had some explaining to do, says Zelicoff. The outbreak was sudden, it was often fatal, and it was confined to a region where military research takes place. To some, it looked like the U.S. might have been experimenting with biological agents forbidden under current treaties, and that the bug somehow had gotten out among the populace.

A similar outbreak in 1979 in the Russian province of Sverdlovsk, near Chelyabinsk-70, turned out not to be so innocent. Foreign physicians attending a conference there became disturbed by local doctors' accounts of a pulmonary illness that caused 64 deaths in a two-week period. On further study, pathologists found the victims had been infected with several strains of anthrax. The Soviet government first blamed the outbreak on contaminated meat, but a 1994 study published in Science suggested that a release of windborne anthrax from a Sverdlovsk biological weapons factory probably caused the infections.

More than 150 nations have agreed to an outright ban on biological weapons research as part of the BWC, ratified by most participants by the mid 1970s. But after more than 20 years, the world community still hasn't agreed on the best ways to verify that all party nations are complying with the treaty.

Epidemiology may strengthen the BWC
Developing a practical compliance regime for the BWC has been difficult, partly because all biological agents have peaceful uses. Even botulism, which was discovered in the early 1980s to be effective in treating an eye-muscle disorder called blepharospasm, now has more than 50 FDA-approved uses.

"There isn't one bioagent you can name that doesn't have a legitimate use," says Zelicoff.

In the early 1990s a multinational BWC Verification Experts Group (VEREX for short) considered a set of 21 confidence-building "transparency" measures for the BWC, including on-site inspections, remote sensing, and voluntary data exchanges between participating countries.

Now the BWC nations are considering including the disease-tracking approach as a way to strengthen the final verification regime, says Zelicoff, who was a member of the U.S. VEREX delegation.

"The primary goal of any treaty is to build trust among participating nations," he says. "Finger pointing detracts from that, so you want to avoid false accusations but still catch the occasional cheater."

A combination of vigilant disease monitoring and follow-up pathological studies would help accomplish that, Zelicoff says. Once a mysterious outbreak is identified, the tools of modern epidemiology would be sufficient to determine its origin, he says. In the hantavirus case, it took pathologists only a few weeks to isolate the virus and determine it was transmitted through the excrement of field mice.

"If epidemiologists isolate four strains of anthrax, then you might start pointing fingers," he says.

What about rogue nations that might interfere with doctors' abilities to share epidemiological information over the Internet? Nations that agree to terms of a treaty are entering into a cooperative agreement. If a participant nation begins censoring doctors, you know something's amiss, he says.

Sandia initially is cooperating with Chelyabinsk-70 partly because hepatitis C is a potentially serious worldwide problem, and partly because the virus is clearly not related to military applications -- "it's an apolitical disease," Zelicoff says. Also, both New Mexico and the region surrounding Chelyabinsk-70 have unusually high incidences of hepatitis C.

Info gathering began Monday in New Mexico, Russia
On June 1, hospitals in Snezhinsk, Russia, began taking 1cc blood samples from randomly selected emergency room visitors who agree to the tests. Meanwhile the main hospitals in three small New Mexico cities -- Los Alamos, Silver City, and Alamogordo, selected for their demographic similarities with Snezhinsk -- are collecting samples from randomly selected volunteers. Each volunteer is asked to fill out a 150-item questionnaire intended to isolate behaviors that could be risk factors for contracting the disease.

In all 2,000 patients in Snezhinsk and 2,000 in New Mexico will be tested for hepatitis C over the next four or five months. Statistically about 2 percent, or 40 to 50 people at each site, are expected to be infected. Genotyping, it is hoped, may isolate new variants of the virus as well.

Sandia provided additional emergency room equipment as well as the video conference and computer hardware necessary for the hospitals involved to coordinate their work over the Internet. Sandia also helped design the patient questionnaire and postulate its questions along with hepatitis C experts at the New Mexico Department of Public Health and the UNM School of Medicine.

In the end, Zelicoff hopes, doctors will know a lot more about hepatitis C than before and will be more equipped to stem its spread. Hepatitis C is four to eight times more prevalent than HIV and AIDS in the U.S., and at least half of hepatitis C sufferers develop cirrhosis or liver cancer, he says.

Some 30 percent of those who contract hepatitis C have no identifiable history of exposure to the virus, according to the Hepatitis Foundation International. One in five people infected develops acute liver failure. Currently there is no hepatitis C vaccine.

Results of the study will be submitted for publication in an internationally recognized journal.

Disease monitoring benefits world health community
In the long term, Zelicoff hopes, BWC signatories will set up and maintain an Internet-based information-sharing network based on the hepatitis C model and provide investigative support when new disease outbreaks are identified. A worldwide community of physicians would report the outbreaks, obtain information about new viruses, and make the information available to all BWC parties.

Many disease outbreaks have occurred during the last 30 years, Zelicoff points out. Since January 1998, in fact, the World Health Organization has monitored some 20 separate outbreaks worldwide.

"Setting up a system not only would contribute to BWC verification but would help the world health community continually watch for new outbreaks," he says.

Zelicoff first proposed the hepatitis C project to DOE in 1996. Sen. Pete Domenici, R-N.M., initially supported the project in Congress and announced its creation during a May 6, 1997, news conference at Sandia's Cooperative Monitoring Center, which assists political and technical experts from around the world in evaluating and acquiring technology that can help ease tensions among combatants in regional conflicts and keep weapons and weapons materials secure.

"The surveillance of infectious diseases, because of their destructive potential, is an important national security concern," Domenici said. "I believe projects like this help to reaffirm the spirit of openness and trust that is so important between the United States and Russia in this post-Cold War era."

Sandia is a multiprogram Department of Energy laboratory operated by Lockheed Martin Corporation. With main facilities in Albuquerque, N.M., and Livermore, Calif., Sandia has R&D programs contributing to national defense, energy and environmental technologies, and economic competitiveness.

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