Albert Lasker Award Laureate: Maclyn McCarty
Augustinian priest Gregor Mendel began his studies of inheritance in the 1860s; by the turn of the 20th century, variations of the word “gene” were in use by scientists and by 1910, the cellular location of so-called “genes” had even been pinpointed to the chromosome. Though decades of investigation around the world continually turned up new knowledge about genetic inheritance, the central discovery of what, exactly, a gene is blew the doors open on modern genetic research. For his role in the 1944 identification of deoxyribonucleic acid — DNA — as the carrier of genetic information, Maclyn McCarty received the 1994 Albert Lasker Award for Special Achievement in Medical Science.
In 1900 German bacteriologist Frederick Neufeld had discovered that pneumococci bacteria exist in different types, each of which elicits a different immunological response. At that time, science held that bacteria reproduce by cloning and thus that Neufeld’s types must be fixed and unchanging through generations. Following World War I, British medical officer Frederick Griffith, while working on a vaccine for the Spanish flu pandemic, found evidence challenging that belief. Griffith compared the virulent type III strain of Streptococcus pneumoniae, called “S strain” for the smooth polysaccharide capsule that surrounds it, with avirulent type II strain, called “R strain” for its rough appearance due to the lack of a capsule, and made a crucial discovery. Although heat treatment kills S strain bacteria, there exists a “transforming principle” by which even heat-killed S strain can turn avirulent R strain bacteria into an infectious agent by somehow providing it with the protective capsule. He furthermore found that the “transformed” R strain retained its acquired virulence through several generations.
A team of scientists at The Rockefeller Institute for Medical Research, including Oswald T. Avery, Colin M. MacLeod and Dr. McCarty, immediately took up the study of the transforming principle, first developing a method to transform bacteria in vitro (as opposed to the Griffith experiments in mice), and next extracting cell-free aqueous solutions containing the transformative property, proving that it was a chemical substance. By the 1930s, the scientific community was widely convinced that cellular protein was the substance in question.
Since Dr. Griffith had already demonstrated that heat-killed S strain bacteria retain a viable transforming principle, Drs. Avery, MacLeod and McCarty heat-killed several different types of pneumoccoci and extracted saline-soluble components from them. They then separated out and broke down the bacteria into their individual chemical constituents, testing each for the transforming property. They eventually hit upon a molecule whose chemical composition was consistent with DNA, and went on to prove that it wasn’t a smaller part of the molecule — an unseen, attached RNA or protein contaminant, for example – that carried the transforming principle. Applications of trypsin and chymotrypsin — enzymes known to lyse protein — failed to affect the extract, as did ribonuclease — known to break down RNA. Desoxyribonucleodepolymerase, however, destroyed the transforming principle — revealing its identity to be DNA. Drs. Avery, MacLeod and McCarty published their discovery in the February 1944 issue of The Journal of Experimental Medicine.
The results were soon verified, and even bolstered with other experiments that showed the protective capsule to be only one of several “transformable” traits. But the reigning scientific dogma that bacterial reproduction involved nothing more than cloning proved the basis for a persistent skepticism of the DNA conclusion. The elucidation, three years later, of how bacteria reproduce — by Joshua Lederberg — and the discovery of DNA in the chromosomes of higher eukaryotic organisms dissolved most remaining doubt. The Avery-MacLeod-McCarty experiments thus set the stage for James Watson and Francis Crick’s discovery in 1953 of the double-helical structure of DNA, and the revolution in genetic research that followed.
Born in South Bend, Indiana, in 1911, Dr. McCarty received his medical degree from The Johns Hopkins University, where he then spent three years as a pediatric house officer before joining Dr. Avery’s laboratory at The Rockefeller Institute. In 1946, he established his own laboratory at Rockefeller, at which point his research turned to focus entirely on group A Streptococcus. Dr. McCarty served as The Rockefeller Institute Hospital’s physician in chief from 1960 to 1974 and as the university’s vice president from 1965 to 1978. He was also an editor of The Rockefeller University Press’s Journal of Experimental Medicine from 1963 nearly until well past his retirement in 1981. Dr. McCarty also served as chairman of the Public Health Research Institute in New York from 1985 to 1992. He was a member of the National Academy of Sciences and a charter member of its Institute of Medicine. In addition to the Lasker Award, he received the Wolf Prize in Medicine and an Eli Lilly Award in Microbiology and Immunology. Dr. McCarty died in 2005.