Now researchers are beginning to reveal a surprising genetic history of the plague. A rash of discoveries show how just a small handful of genetic changes — an altered protein here, a mutated gene there — can transform a relatively innocuous stomach bug into a pandemic capable of killing off a large fraction of a continent.
The most recent of these studies, published in June, found that the acquisition of a single gene named pla gave Y. pestis the ability to cause pneumonia, causing a form of plague so lethal that it kills essentially all of those infected who don't receive antibiotics. In addition, it is also among the most infectious bacteria known. "Yersinia pestis is a pretty kick-ass pathogen," said Paul Keim, a microbiologist at Northern Arizona University in Flagstaff. "A single bacterium can cause disease in mice. It's hard to get much more virulent than that."
Tomas Lindahl first published work in this field back in 1974, when he found a bacterial enzyme that culled damaged remains of cytosines from DNA. He methodically worked out how base excision repair works, and even managed to recreate the process in vitro in 1996. Aziz Sancar's contribution has to do with how DNA repairs damage from ultraviolet light. After struggling to find a lab interested in his work, he went on to show how a group of enzymes identify and excise UV damage. Paul Modrich's focus was on how natural processes corrected base pair mismatches in DNA. He spent a decade laboriously mapping out how each enzyme interacted with this process — an important thing to know, since defects in the repair system can cause cells to turn cancerous.