A Path to Discovery: The Career of Maclyn McCarty


A Path to Discovery: The Career of Maclyn McCarty

Joshua Lederberg*, Emil C. Gotschlich


PLoS Biol 3(10): e341 doi:10.1371/journal.pbio.0030341. [Open Access]


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 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.


  1. McCarty M (1985) The transforming principle: Discovering that genes are made of DNA. New York: W. W. Norton. 252 p.
  2. Avery OT, MacLeod CM, McCarty M (1944) Studies on the chemical nature of the substance inducing transformation of pneumococcal types. Induction of transformation by a desoxyribonucleic acid fraction isolated from Pneumococcus type III. J Exp Med 79:137–158. 
  3. McCarty M, Avery OT (1946) Studies on the chemical nature of the substance inducing transformation of pneumococcal types. 2. Effect of desoxyribonuclease on the biological activity of the transforming substance. J Exp Med 83:89–96. 
  4. McCarty M, Avery OT (1946) Studies on the chemical nature of the substance inducing transformation of pneumococcal types. 3. An improved method for the isolation of the transforming substance and its application to Pneumococcus types II, III, and VI. J Exp Med 83:97–104. 
  5. Amsterdamska O (1993) From pneumonia to DNA: The research career of Oswald T. Avery. Hist Stud Phys Biol Sci 24:1–40. 
  6. Olby R (1974) The path to the double helix. London: Macmillan. 510 p.