The scenario sounds like it belongs in a summer blockbuster: A terrorist infected with smallpox is trying to expose as many people as possible. The person may take a flight, hop on a crowded subway car, jump in a bus, or head into a bustling shopping mall. Within two weeks, people exposed to the disease start getting sick: High fevers, headaches and rashes that turn into bumps covering their bodies.

Then the people they interact with get sick, and the virus spreads. About 30 percent of the people who develop symptoms die.

That hypothetical describes a real threat that Shane Crotty is working to guard against. Crotty, an infectious disease scientist at the La Jolla Institute for Allergy & Immunology, has designed an antibody that will treat people exposed to smallpox during a bioterrorism attack.

Crotty’s research points in an unusual direction for a scientist: curing a disease that no longer exists. Although smallpox was eradicated in 1979 through a global vaccination campaign, the threat of a bioterrorism attack using smallpox is potent enough that Crotty thinks his work to build defenses against it is vital.

“It wouldn’t take very much to release it and then have it start spreading again in the population,” he said, “and that would be really, really, really, really bad.”

Crotty is just one of many researchers across San Diego working on the forefront of an effort to defend the country against bioterrorism. Last year, the National Institutes of Health gave out $1.5 billion in funding for research on biological agents like smallpox, anthrax, Ebola virus and the plague, and $96.6 million of it went to research institutes and biotech companies in San Diego.

About a quarter of the local awards went to the allergy and immunology institute to fund Crotty’s work and other projects, including a database of infectious diseases created to speed up the development of vaccines during outbreaks. The Scripps Research Institute received $25 million to study a range of biological threats, including anthrax and nerve gas-induced seizures. And the University of California, San Diego received $21.5 million for research on everything from giardia, a water-borne parasite, to salmonella and drug-resistant tuberculosis.

Many of the viruses and bacteria being studied rarely infect people, so this research’s focus is purely for the sake of fighting bioterrorism. And while a terrorist could use any of these diseases to kill or hurt people, smallpox is one of the biggest threats because it is easily transmitted and very destructive, said Michael Kurilla, the director of the NIH’s Office of Biodefense Research Affairs.

“Smallpox is one of the biggest scourges in the history of world — it killed more people on the planet than any infectious agent,” he said.

The virus is easily transferable, and it kills three in 10 people that it infects, making it 10 times deadlier than the flu pandemic that killed 50 million people in 1918. And because no one under the age of 37 has been vaccinated against smallpox, the virus could spread quickly. To make matters worse, the former Soviet Union’s biological weapons program grew large amounts of the disease, and many scientists worry some virus samples could have gotten loose when the Soviet Union dissolved.

“No one really knows what happened to that material,” Crotty said. “Lots of those scientists basically disappeared, so it’s a very real worry that some people could have taken some of the virus with them, and could have given it to bad people.”

Although Kurilla said this is a “plausible hypothesis,” he said there is no evidence the Russians lost control over their smallpox samples.

Since 2001, the government has stockpiled more than 300 million doses of smallpox vaccines, or about one for every person in the U.S. But if an outbreak occurred, many people could become infected with the virus before receiving the vaccine, which is where Crotty comes in.

While studying whether people vaccinated for smallpox retained their immunity over long periods of time — fortunately, he found they did — Crotty realized that the natural antibody created when the body is exposed to the smallpox virus could also be artificially manufactured and used as a treatment.

Over the past seven years, Crotty has developed that antibody treatment and pitted it against strains of smallpox viruses in Petri dishes and lab mice. So far, his antibodies are coming out on top; he said with the right test conditions he saved 100 percent of infected mice.

The next step, which he will begin this fall, is to test the treatment on 15 monkeys infected with monkeypox, a virus similar to smallpox. He will then send his antibodies to a special lab in Atlanta operated by the federal Centers for Disease Control, where it will be tested on the real human smallpox virus — because of safety concerns, Crotty does not use the smallpox virus in his lab. Instead, he mostly tests his antibodies on the virus used in the smallpox vaccine, which is very similar to the real virus.

Although the federal drug approval process for Crotty’s treatment is complicated by the fact that no human cases of smallpox exist to be tested on, he is hopeful the government can begin to manufacture it in the next few years. If an outbreak occurred before his treatment is ready, he said the licensing process could be accelerated but would still likely take a year to complete.

The better outcome to hope for, Crotty said, is that his treatment will be licensed, manufactured and sold to the government, where it will be “put in a freezer somewhere, and hopefully no one will ever see it again.”

Crotty’s colleagues are working on similar efforts with diseases like Dengue virus and tuberculosis. To help prepare for a range of possible biological weapons, including anthrax, botulism, and the plague, Alex Sette, the head of the Center for Infectious Disease at the allergy and immunology institute, has a different type of response. Sette has compiled a database that he calls a “Yellow Pages” of the portions of diseases that the immune system recognizes. This collection is publicly available and easily searchable, so that scientists can speed up vaccine development when a new outbreak occurs — bioterrorism or otherwise.

Although the database was not together when the anthrax outbreak occurred in 2001, it was used last year during the outbreak of H1N1, or swine flu.

“We looked at the data existing in the database, and stood back and said, ‘Wait a minute, before everyone goes crazy about this, let’s look at whether swine flu is more different from last year’s flu,’” Sette said.

Because the database showed that the swine flu was similar, Sette predicted no mass outbreak would occur.

“And that’s exactly what happened,” he said. “We were glad that that was the case, and not just because we were right.”

In this way, Sette’s work is similar to Crotty’s and to many of the other scientists who work on biodefense projects: They devote their research to treating diseases, but also don’t want to see an outbreak that would require their treatments.

“My work is a very unusual project for a scientist,” Crotty said. “I’m making a cure, but I hope it never gets used.”

Claire Trageser is a San Diego-based freelance writer. Please contact her directly at

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