Nurse Sharks: Key to Anthrax Diagnosis, Treatment?

Bijal P. Trivedi
National Geographic Today
July 16, 2003
Nurse sharks may help detect—and treat—anthrax and other infectious diseases.

At the National Aquarium in Baltimore, a team of researchers is working with a pair of 4-foot-long nurse sharks to investigate how the creatures' immune system responds to the anthrax bacterium.

In nature, antibodies are the best defense against disease: these proteins, produced by immune cells, recognize invading bacteria and viruses and grab on, in effect, target them for destruction.

Nurse shark antibodies turn out to be not only sensitive but also hardy enough for quick transport to a battlefield or the site of a bio-terrorist attack.

"Most vaccines and diagnostics need refrigeration, and it just isn't that practical to carry around a fridge in the middle of Iraq," says Les Baillie, a microbiologist and head of bio-defense vaccines for the Navy at the Naval Medical Research Center in Silver Springs, Maryland.

Baillie was formerly the principal scientist for anthrax research at the Defense Science and Technologies Laboratory at Porton Down in Great Britain. He engineered anthrax proteins for a new anthrax vaccine that is now undergoing Phase one trials in the United States.

"There is a critical need for diagnostics for Class A agents, as we call them: things like anthrax, tularemia, plague and smallpox," says Brad Smith, a microbiologist and a fellow at the Center for Civilian Biodefense Strategies in Baltimore, Maryland. "In an attack, resources are limited and people on the front lines need to make quick decisions—who is sick, who isn't."

Shark Antibodies and Bio-defense

No rapid diagnostics for Class A agents have met FDA approval. A measure of the need is that the National Institutes of Health bio-defense research and development budget this year is $1.7 billion.

Baillie came upon the idea of shark antibodies as anthrax detectors when he met researchers nearby at the University of Maryland: immunologist Martin Flajnik, a specialist in shark and amphibian immune systems, and Helen Dooley, an antibody engineer who had developed antibodies to detect environmental pollutants.

Flajnik had discovered a new type of antibody—called IgNAR—in the nurse shark. IgNAR is simpler and tougher than mammalian antibodies, making it an attractive candidate for producing in the lab.

Sharks are the oldest living animals that have what scientists call an adaptive immune system.

"This is the earliest version of the human immune system," says Flajnik. Sharks and humans share immune-system components like B cells—which manufacture antibodies—and T-cells.

Baillie wondered whether sharks exposed to anthrax would produce robust anthrax-fighting antibodies. He provided Flajnik and Dooley with anthrax proteins—which alone cannot cause disease—from his research in Great Britain.

Flajnik and Dooley used the proteins to immunize two nurse sharks—a delicate procedure. Aquarium handlers in wet suits remove the sharks from their home tank and place them in a smaller one laced with anesthetic, which calms them. Then they are loaded onto a trolley for their injection—under their skin near the fin.

Immunizing Sharks

"It's the equivalent to giving a TB shot in the arm," Dooley says. The sharks received booster shots at one-month intervals for the next three months.

Dooley and Flajnik took monthly blood samples from the sharks and found that with each successive booster the quantity of antibodies in the sharks' blood rose.

Back in the lab, the serum collected from shark blood reacts with the anthrax proteins to produce a bright yellow color.

"Ultimately, with this antibody you could see within a minute whether anthrax was present," Flajnik says.

The researchers have isolated the antibody that binds tightest to the anthrax protein and thus has the greatest potential for both diagnosis and treatment. They are currently determining its genetic sequence, which will help reveal how to mass-produce the antibody.

One day the antibody might even serve as a treatment for humans exposed to anthrax.

"The shark does all the hard work," Flajnik says. "It makes all these very specific, sturdy antibodies and all we have to do is analyze and use them."

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