The white powder that arrived in envelopes addressed to lawmakers and journalists in 2001 proved to be a deadly delivery for several people. The lethal substance—spores commonly known as Anthrax (from the bacterium Bactillus anthracis)—can cause a toxic reaction in a host's blood stream, killing cells and leading to tissue damage, bleeding and death.
But just how toxic anthrax is to an individual might depend on their genetic makeup, according to a new study, published online Monday in Proceedings of the National Academy of Sciences. Researchers found that some people's lymphocyte cells, when exposed to a laboratory mixture of the bacterium, were less likely to die than cells of others. That difference seemed to be related to the regulation of a gene (capillary morphogenesis gene 2—or CMG2) that creates a protein on the surface of cells. This protein determines how easily the toxin can enter cells to destroy them—and lead to an "unexpectedly broad range in cellular toxin sensitivity among individuals," wrote the researchers, led by geneticist Mikhail Martchenko at Stanford University School of Medicine.
"We already knew that infection by the same organism in different people can have very different outcomes," David Relman, chair of the Institute of Medicine's Forum on Microbial Threats, said in a prepared statement. "But until now it's been very difficult to determine whether this variability was due to genetic or environmental factors."
The researchers used cells from 234 people from African, Asian, European and North American descent whose tissues were taken for the HapMap Project, a freely available genome database. Of those cells, most fell to assaults from the anthrax bacterium. But cells from three people—of European descent—required hundreds or even thousands more times as much anthrax toxin to kill them. Furthermore, people who were closely related seemed to have similar reactions to the bacterium. The new, targeted examination—pinpointing differences in susceptibility against individuals whose genetic information is already catalogued—could make for more efficient investigations of toxins' effects than general, genome-wide association studies.
This discovery "could lead to the development of novel treatment strategies, perhaps by blocking the interaction between the toxin and the receptor or by down-regulating its expression," said Relman, who was not involved in the new research, which was funded by the U.S. Department of Defense. "The findings could also provide a possible means for predicting who is likely to become seriously ill after exposure, which could be extremely useful when faced with a large number of exposed people."