By Tom Randall
A half-hour later, Alexander was sitting at a table in the dean’s office with researchers, lawyers, administrators and campus security officers, he recalled in an interview. The stricken colleague, Malcolm Casadaban, a 60-year-old genetics and cell biology professor, had checked into a hospital five days earlier and died within hours. Lab results were positive for the plague, and the university’s “biosafety fire alarm” had been triggered, Alexander said.
“The first question was: Do we think this is real,” Alexander, chief of infectious diseases at the university’s pediatrics department, said yesterday in a telephone interview. “The answer was yes. So the onus was upon us to do two things; to notify the health infrastructure and act as if this were a worst-case scenario.”
That meeting on Sept. 18, 2009, began an investigation into the medical mystery of Casadaban’s illness that concluded with a report detailing the events, published yesterday by the U.S. Centers for Disease Control and Prevention in Atlanta.
Considered Harmless
Casadaban was conducting laboratory research on the bacterium that causes the plague when he became sick. The germ was genetically weakened and considered harmless to humans. It was considered so safe, Casadaban’s work with the live plague bacteria wasn’t noted when he fell ill, according to the CDC. A professor at the university for 30 years, by all accounts he had followed the proper safety protocols, the report said.
Casadaban’s research focused on describing the chain of cellular events that occurs as a person is sickened by the plague bacterium, called Yersinia pestis. Scientists suspect that Casadaban may have harbored a previously unknown vulnerability to the laboratory plague strain that was revealed only in his death.
An autopsy found the researcher had a medical condition called hemochromatosis, which causes an excessive buildup of iron in the body, according to the CDC report. The disorder affects about 1 in 400 people and goes unnoticed in about half of patients.
Casadaban’s illness is important because of the way the plague bacterium had been weakened. Yersinia pestis needs iron to survive. Normally it gets this iron by stealing it from a host’s body with proteins that bind to it and help break it down. To make the bacterium harmless, scientists genetically stripped it of the proteins needed to consume iron.
‘So Much Iron’
“It’s like having a lion, where we took out all its teeth and all its claws,” Alexander said. “But in the case of Dr. Casadaban, the lion didn’t even need to have teeth. There was so much iron that it was freely available and easy to get.”
Plague infects more than 2,000 people worldwide each year, according to the World Health Organization in Geneva. Early detection and treatment with antibiotics are important, and about 90 percent of reported cases survive. About 5 to 10 cases occur in the U.S. each year, passed through rodents and the fleas that feed on them, the CDC said. The last time a scientist was sickened by the plague was in 1959, the CDC reported.
The hemochromatosis that contributed to Casadaban’s fate has been credited with protecting people from strains of plague that circulate in the wild. Sharon Moalem, an evolutionary biologist and author of “Survival of the Sickest,” posited that the disorder shifts iron from certain white blood cells, where it is typically sought by the plague bacterium.
Genetic Disposition
People of European descent are twice as likely as the rest of the population to have hemochromatosis, according to previous studies. That’s because people with the condition were more likely to survive epidemics of the bubonic plague that killed millions of people in medieval Europe and pass the hereditary condition to their descendants, according to Moalem.
The day plague was diagnosed in Chicago, researchers tested the strain to make sure it hadn’t mutated. By a second emergency meeting that afternoon, high amounts of iron had already been discovered in Casadaban’s liver, adding credibility to the early hypothesis of hemochromatosis formed by his colleagues.
The CDC later confirmed the tests with mouse experiments that proved the strain that killed Casadaban was the same that has been safely used by hundreds of scientists doing similar research. The agency is now studying animals to learn how hemochromatosis may increase susceptibility to infection by bacteria with weakened iron-acquiring abilities.
Casadaban’s death shows that no matter how a germ has been hobbled, some people may always be vulnerable, Alexander said. While research with viruses, bacteria and vaccines that employ weakened strains should continue, scientists must take precautions and be aware of hidden vulnerabilities, he said.
“I’m sure that if Dr. Casadaban had had one comment for us as we sat around that table it was: ‘Listen guys, I’m trying to teach you something, and you better damn well learn it,’” Alexander said. “And I think we did.”
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