Geneticist Malcolm J. Casadaban, Dead of Plague

related: Plague Incubation Period
September 20, 2009
Chicago Chicago Tribune

City health officials and the University of Chicago Medical Center today began the precautionary measures of offering antibiotics to the family, friends and co-workers of a geneticist who died last week from exposure to a plague-related bacterium.

Infectious disease experts couldn't completely rule out the possibility that the federally approved weakened strain of Yersenia pestis Malcolm J. Casadaban was researching at the University of Chicago had somehow become dangerous.

But largely because nobody else exposed to the bacterium or to Casadaban has developed plague symptoms, it seems more likely there was something about the professor's health or genetic makeup that made him susceptible, officials said today.

Further study is under way after an initial autopsy showed no obvious cause of death other than the presence of the bacterium, officials said.

"While the death of this individual researcher is terrible and tragic, there is currently no indication that his case of illness spread to anyone else," the Chicago Department of Public Health said in a statement. "There is currently no indication of a threat to public health."

Casadaban, 60, was working with a strain of Yersenia pestis that, stripped of its harmful components, has been used as a vaccine against the plague since the late 1960s.

Once the world's worst health scourge, the plague today affects between 1,000 and 3,000 people per year, with most of the 10 or 15 annual cases in the U.S. occurring in rural areas of the Southwest where rodents carrying the bacterium are more common, according to the federal Centers for Disease Control and Prevention.

Casadaban, a renowned molecular geneticist with a passion for new research, had been working to develop an even stronger vaccine for the plague, said his daughter Leigh Casadaban, 21.

"He was a brilliant, brilliant guy," Leigh Casadaban said about her father. "He had such a love for genetics."

On the morning of Sept. 13, Casadaban developed intense flu-like symptoms and arrived at the emergency room of the university's Bernard Mitchell Hospital, hospital officials said. He died 12 hours later.

Initially, doctors did not know they had a plague case on their hands, said Dr. Ken Alexander, chief of pediatric infectious disease at the medical center.

After blood test results came back Friday, the hospital notified city and state public health officials, he said.

Alexander -- who compared the bacterium Casadaban was working with to a "crocodile that doesn't have teeth" -- said the risk for an outbreak is very low.

"The more likely possibility, I'd say 999 to 1, is that there was something unusual about him," said Alexander, explaining that other strains of Yersenia bacteria linked to intestinal disease have been known to prey on people with abnormalities in their iron metabolism.

"As colleagues, we all feel we owe it to this man to find out what was different about him," Alexander said. "Given his field of research, I think that's what he would have wanted."

Casadaban's family said they were not aware of any pre-existing health problems that would have made him more susceptible to the weakened bacterium.

They remembered Casadaban as a fitness enthusiast who rode his bike to work every day and considered a family day at the Six Flags amusement park a great opportunity to log in some walking miles.

A native of New Orleans, Casadaban enjoyed teaching his family about genetics, said Leigh Casadaban, herself a genetics student at her father's alma mater, the Massachussetts Institute of Technology.

"He made it seem like it was all fun," she recalled.

Casadaban's other daughter, Brooke, 28, remembers her father as the quirky family figure who showed up to gatherings with relatives in New Orleans with new microscopes or math problems for his nieces and nephews.

Among the many topics Casadaban loved to expound upon -- the obesity gene, the "basic" nature of cloning -- her father's favorite was the notion that human beings are destined to live longer, Brooke Casadaban said.

"He really believed that life would last longer in the future," she said, noting the random nature of her father's passing. "None of us were prepared for this."
-- Antonio Olivo

http://www.chicagobreakingnews.com/2009/09/yersenia-pestis-malcolm-j-casadaban-university-of-chicago-medical-center-genetics-research-antibioti.html

Background

We are interested in molecular genetic processes and their application to new techniques for biological studies. We are using DNA transposition, non-homologous recombination, and gene fusions with reporter genes. We begin our studies and applications with the well-developed bacterium E. coli and then extend them to other prokaryotic and eukaryotic organisms. We have used the high frequency bacteriophage Mu transposon to fuse reporter genes and regulated promoters to other genes for studies of gene expression and regulation and also to clone genes in vivo without in vitro recombinant DNA. Genetic applications of Mu at least provide futuristic model systems for higher organisms. Other experiments with Mu involve targeting it's transposition to specific DNA regions with gene fusions of the B targeting gene to specific DNA binding proteins. This is part of our quest for a universal, high frequency transposon, which can be used in all organisms. Our work with reporter genes involves the development of new, more sensitive reporter genes and their application to new processes including protein-protein interactions. We have focused on genes for hydrolytic enzymes, which can use a wide spectrum of substrates for chromogenic assays and growth selections. The tbg gene from Thermus aquaticus encodes a thermostable -galactosidase which can not only function at high temperatures, where most proteins from eukaryotes and mesophilic bacteria would denature, but also in adverse conditions such as with detergents on polyacrylamide gels. Potentially these hybrid proteins may have new applications in studies of protein structure and interaction.
http://molbio.bsd.uchicago.edu/Faculty_and_Research/03_Faculty_by_Research_Interest.php?faculty_id=32



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