Maclyn McCarty

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Maclyn McCarty bigraphy, stories - American geneticist

Maclyn McCarty : biography

June 9, 1911 – January 2, 2005

Maclyn McCarty (June 9, 1911 – January 2, 2005) was an American geneticist.

Maclyn McCarty, who devoted his life as a physician-scientist to studying infectious disease organisms, was best known for his part in the monumental discovery that DNA, rather than protein, constituted the chemical nature of a gene. Uncovering the molecular secret of the gene in question — that for the capsular polysaccharide of pneumococcal bacteria — led the way to studying heredity not only through genetics but also through chemistry, and initiated the dawn of the age of molecular biology. McCarty was the youngest and longest surviving member of the research team responsible for this feat (known as the Avery-MacLeod-McCarty experiment), which also included Oswald T. Avery and Colin MacLeod; he died on January 2, 2005, from congestive heart failure.

Life

McCarty was born in 1911 in South Bend, Indiana, the second of four sons of a branch manager for the Studebaker Corporation while it was still a firm for horse-drawn carriages. In his teens, McCarty set himself the goal of becoming a physician-scientist, and he pursued a successful strategy to prepare for admission to, and early success in, Johns Hopkins University Medical School. As an undergraduate at Stanford University, he presciently began his studies in the nascent field of biochemistry, working with James Murray Luck on protein turnover in the liver. In 1937, he began his clinical training in pediatrics at the Harriet Lane Service at Johns Hopkins University. There McCarty developed a special interest in infectious diseases — in particular, antibacterial sulfonamide drug treatments that were just entering medicine — which he subsequently pursued by moving to New York University to work with William Tillett. A National Research Council Fellowship in the medical sciences and an opening in Oswald T. Avery’s laboratory spurred his move to Rockefeller University in 1941.

At that time, research in the Avery laboratory was focused on the pneumococcal transformation, the heritable alteration of a pneumococcal strain from a nonvirulent rough form to a virulent smooth encapsulated form. McCarty’s arrival at the Rockefeller Institute in September 1941 marked 13 years since this discovery, also known as the Griffith phenomenon. Prior to this discovery, the 1920s had been marked by a medley of disparate observations on Streptococcus pneumoniae that seemed to involve an exchange of receptors among diverse bacteria either grown together in liquid media or exposed to various kinds of extracts and supernatants. With rare exception, the early researchers in this area were utterly confused about the distinction between genotype and phenotype. No single experiment was carried forward to confirmation by other observers, so the entire field of "para agglutination" was in some disrepute.

However, in 1928, Fred Griffith, a leader in public-health research in Britain, demonstrated that the conversion of one strain to another could happen in vivo in mice. Shortly after the publication of his results, they were confirmed in several quarters, including Avery’s lab. The analysis relied on serotyping: it was known that phenotypic differentiation of pneumoccocal groups could be diagnosed by their reactions with specific antisera, already recognized to reflect chemically distinct capsular polysaccharides. Griffith had neither the resources nor the inclination to purify and identify the responsible agent in pneumococcal extracts that induced the changes of serotype. But the phenomenon of transformation was at least vaguely understood to comprise an alteration of what we would now call genetic factors.

Though interrupted, sometimes for years at a time, these studies were from 1928 onwards the centerpiece of Avery’s lab agenda. Around 1940, they were activated by Colin MacLeod’s efforts to purify the chemical agent responsible for changes of serotype — whether protein, nucleic acid, or some other class of molecule — and demonstrate that it was necessary and sufficient to cause the Griffith phenomenon. Studies on pneumococcal transformation were grossly burdened by a wide variety of variables, which needed to be controlled to allow quantitative estimation of transforming activity in extracts undergoing various stages of purification. MacLeod, over a number of years of research, had resolved several thorny technical issues to render the experimental system somewhat more reliable as an assay for biological activity. By the time McCarty arrived at the Rockefeller University, Avery’s team had just about decided that the active reagent was not a protein. But what was it then? Could it be a soluble saccharide, RNA, or, least likely, DNA? The progress of this research over the next three years is beautifully described in McCarty’s memoir The Transforming Principle, written in the early 1980sMcCarty M (1985) The transforming principle: Discovering that genes are made of DNA. New York: W. W. Norton. 252 p. ISBN 0-393-30450-7.