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Oswald T. Avery

By the 1940s, genes were understood as discrete units of heredity, which also generate the enzymes that control metabolic functions. Contemporary wisdom suggested that genes were proteins. But in 1944, experiments by Oswald T. Avery showed that a nucleic acid, deoxyribonucleic acid (DNA), known to be ubiquitous in organisms, was the chemical basis for specific and apparently heritable transformations in bacteria.

Avery, an immunochemist at the Hospital of the Rockefeller Institute for Medical Research, worked for many years with pneumococcus, a bacterium that causes pneumonia. As early as 1928, he and other scientists were baffled by results of an experiment with these microbes. Mice were injected with a live but harmless form of pneumococcus and also with an inert but lethal form. Although expected to live, the mice in fact soon succumbed to infection and died. Bacteria recovered from the mice remained lethal in subsequent generations.

Colin MacLeod

How did the nonlethal form of the bacteria acquire the virulence of the killed strain? The difference between the two forms lay in their protective casings. The immune system could detect and destroy the "rough" outer coat of the innocuous "R" form of the bacteria. But the lethal "S" form had a smooth capsule that evaded detection, enabling the bacteria to reproduce.

Avery soon discovered that "R" bacteria could become deadly simply when combined with inert lethal "S" form in a test tube—the mice were unnecessary to the equation. Such types of bacteria were at the time thought to be as stable as species. What enabled the "transformation?" As Avery posed it, the question became entirely biochemical: "What is the substance responsible?"

Together with Colin MacLeod and Maclyn McCarty, Avery undertook to purify—from some twenty gallons of bacteria—what he called the "transforming factor." As early as 1936, Avery noted that it did not seem to be a protein or carbohydrate, but a nucleic acid. Further analysis showed that it was DNA.

Maclyn McCarty

A cautious scientist, Avery was long reluctant to publically ascribe a genetic role to DNA. (Both he and other scientists suggested as much privately.) But in 1944, Avery and his colleagues published a paper in the Journal of Experimental Medicine in which they set out the nature of the "transforming principle."

• Deoxyribonucleic acid (DNA) plays a central role in determining specific characteristics in the course of reproduction. If experimental results could be confirmed, wrote Avery, "then nucleic acids must be regarded as possessing biological specificity the chemical basis of which is as yet undetermined."

Avery's paper was not initially widely read by geneticists, but it excited commentary and further research into the nature of DNA—including the relative composition of the bases that comprise it and X-ray diffraction studies of its structure. Almost a decade passed before, in 1953 in England, Francis Crick and James Watson discovered that DNA was comprised of paired sequences of complementary bases. DNA, by the order of its bases, encodes the genes.

Avery, meanwhile, had retired from the Rockefeller Institute in 1947. His death, in 1955, came before widespread recognition of his role in discovering the significance of DNA.

Oswald T. Avery winner of the 1947 Albert Lasker Award for Basic Medical Research

Maclyn McCarty winner of the 1994 Albert Lasker Special Achievement Award

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