A Path to Discovery: The Career of Maclyn McCarty

October 2005 | Volume 3 | Issue 10 | e341 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, which also included Oswald T. Avery and Colin MacLeod; he died on January 2, 2005, from congestive heart failure. 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 fi rm 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 fi eld 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 Griffi th 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 confi rmation by other observers, so the entire fi eld of “para agglutination” was in some disrepute. However, in 1928, Fred Griffi th, 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 confi rmed in several quarters, including Avery’s lab. The A Path to Discovery: The Career of Maclyn McCarty