War on Nerve Gas

An antidote against nerve gases--one of the most publicized weapons in the unused arsenal of chemical warfare--was an nounced this week by Columbia University researchers. A cheap chemical nicknamed PAM, it has proved 100% effective against gases that had always been 100% fatal in test animals. The compound's significance: it may nullify the hazards of nerve gas directed in war against either troops or civilian populations.

Like many another medical victory, the development of PAM (2-pyridine al-doxime methiodide) was the unplanned result of basic research. First, Columbia's Dr. David Nachmansohn showed that the enzyme cholinesterase (one of the body's catalysts) is essential for the transmission of nerve impulses. Trying to learn more about cholinesterase, Biochemist Irwin B. Wilson discovered that nerve gases (and certain insecticides) cause death by adding to the nerve cell's cholinesterase something that damages it. The something is a phosphoryl that destroys the nerves' ability to transmit impulses to muscles.

Armed with this knowledge, Dr. Wilson tried several known compounds as antidotes. They did not work fast or well enough, so he and a research team set out to design a completely new compound that would reactivate cholinesterase by getting close to the phosphoryl group and removing it from the cell's protein. PAM got its test when hundreds of mice were exposed to one of the most deadly nerve gases, then given shots of the compound. The results, reported the researchers, were "dramatic and certain." Not a mouse died. Since protein structure is the same in humans and mice, scientists see no reason why the compound will not work as well on people. Nonpoisonous, it can be made easily in carload lots.

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