It can wreak havoc on a baby’s growing nervous system, and it can kill an adult or lead to months of paralysis. For years, government agencies have worried that it might be used as a weapon.
 Markus Kalkum and Karine Bagramyan (Photo by Darrin S. Joy)
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Now, Markus Kalkum, Ph.D., and Karine Bagramyan, Ph.D., of City of Hope’s Division of Immunology, have devised a new method for detecting botulinum toxin, the substance responsible for botulism. The test is useful in an array of substances, including food products, and it may benefit immune-compromised patients, such as cancer patients receiving stem cell transplants.
Botulinum toxin is produced by the bacterium Clostridium botulinum. When ingested, the toxin disables nerve function, resulting in paralysis and even death.
Botulism normally results when a person eats food tainted with C. botulinum bacteria or if bacteria infect a wound. Infants, whose digestive systems are not yet fully developed, also are susceptible to the disease if the bacterium gains a foothold in their intestinal tract. That’s why experts warn against giving infants honey, which harbors C. botulinum spores.
And though experts agree the technology is beyond most terrorists, government agencies indicate that botulinum toxin could be used in a terrorist attack. The poison is so potent, just one gram could kill more than a million people, according to a 2001 study in the Journal of the American Medical Association.
The new assay developed by Kalkum and Bagramyan is less expensive, faster and easier to perform than the current standard and doesn’t require the use of mice. It’s also far more sensitive.
“We can detect about 300 molecules [of toxin] in a one milliliter sample volume,” making the test 12,000 times more sensitive than the standard, said Kalkum.
Added Bagramyan: “There are other assays that are similarly sensitive, but those use deionized water or buffers. In contrast, our assay can use virtually any solution,” including milk and juices, making the test more effective and flexible.
The scientists also successfully tested the assay using blood serum. That’s encouraging because they want to adapt the technology to test immunocompromised people, including patients who underwent organ or bone marrow transplants, for potentially deadly fungal infections. Sampling their blood could make testing fairly easy and routine.
“I see no reason why we can’t adapt this technology to benefit transplant patients,” said Kalkum. The mechanism would be very similar, “and we’ve already been able to detect other biomolecules associated with fungal infection,” he said. Kalkum currently is conducting a clinical trial aimed at improving early detection of such infections.
Jason R. Barash, C.L.S., M.T., and Stephen S. Arnon, M.D., of the California Department of Public Health’s Infant Botulism Treatment and Prevention Program, collaborated on the research.