Today NIH celebrates the 4th annual Rare Disease Day, which makes it the perfect time to remember the sudden and totally unexpected death, on 13 September 2009, of Malcolm Casadaban, a 60-year-old associate professor of molecular genetics and cell biology and microbiology at the University of Chicago. On Friday, a report by the Centers for Disease Control and Prevention (CDC) revealed that the researcher died from the bizarre intersection of not one but two rare diseases.
A specialist on researching Yersinia pestis,
the bacterium that causes plague
, Casadaban fell ill on 10 September with symptoms a doctor diagnosed as the flu. Casabadan sought no further medical care at that point. Three days later, however, he was rushed to a hospital by ambulance with symptoms that included severe shortness of breath. Doctors first treated him for heart failure and then, after tests, for infection. Twelve hours after arriving at the emergency room, he received a breathing tube. An hour later, he died.
To the shock and horror of Casabadan’s colleagues, tests soon revealed that he had perished from the bacterium he had devoted years to studying. But this did not appear to be a death caused by careless or sloppy technique, such as those on which Science Careers has repeatedly reported
in the past. The bacterium Casabadan worked with had been carefully altered to make it harmless to humans. Standards of safety in the lab were high, according to the Occupational Safety and Health Administration, and records revealed no other cases of work-related illness or accident among workers there. Although the route of infection was a mystery, over 90 of Casabadan’s co-workers, relatives, and other associates received prophylactic treatment in the week following his death, and no one else has shown any sign of the disease. Tests showed that the bacterium had not mutated to become virulent.
But, the CDC report shows, Casabadan turned out to be suffering from not one but two rare diseases. The other one was primary hemochromatosis
, a hereditary condition that affects 5 American Caucasians in a thousand, half of whom do not know they have it. It causes an overload of iron to build up in the body.
The fatal interaction between the two diseases occurred for two reasons. First, neither Casabadan nor anyone else mentioned to the doctor treating him that he worked with plague, which is so rare that doctors do not think to look for it, but highly curable when treated early with antibiotics. This may have happened because Casabadan was so confident that the attenuated bacterium was safe.
Second, CDC notes, “animal studies have shown that the virulence of [the bacterium] can be enhanced by the simultaneous injection of iron” into the animals. The bacterium Casabadan worked with had been attenuated by removing the proteins it ordinarily uses in the process of consuming iron. This works so well for most people that no other known cases of illness or death from plague have ever occurred among the many hundreds researchers who have worked with it. But, “conceivably, hematochromoisis-induced iron overload might have a similar effect” as the iron injection into the lab animals, the CDC report continues. Or, in the simpler words of Casabadan’s University of Chicago colleague Ken Alexander, as quoted by Bloomberg
, “It’s like having a lion, where we took out all the teeth and all the claws. But in the case of Dr. Casabadan, the lion didn’t even need to have teeth. There was so much iron that it was freely available and easy to get.”
Ironically, then, Casabadan’s unsuspected genetic condition appears to have made him especially suscpetible to infection by the disease he was working to understand. Had the first doctor who treated him known of the particular nature of his research, he could have prescribed treatment that had a good chance of saving his life. But, tragically, this fact of his work does not appear in the medical records of either the clinic he initially consulted or the hospital where he died.
“Existing laboratory policy called for laboratory workers with illness consistent with plague to report to the university’s occupational health clinic,” CDC observes. Even though researchers are using what appear to be safe, attenuated strains of infectious agents, unknown susceptibilities may exist, as this case so hideously illustrates. CDC therefore recommends that labs handling infectious agents should scrupulously maintain the highest safety standards even if the agents appear safe, institutions should “implement and maintain effective surveillance programs to identify and monitor acute illness among laboratory workers,and health care providers should routinely inquire about occupational exposures when evaluating patients.”