THE “GRANDFATHER OF MOLECULAR GENETICS”
DNA pioneer. Typewritten carbon copy excerpt: “Part of a letter from Dr. O. T. Avery to his brother Roy C. Avery, dated May 13, 1945, just after his retirement from the Rockefeller Institute, when he was considering moving to Nashville, Tennessee. Original in the possession of R. C. Avery, Vanderbilt University Medical School, Nashville, Tenn.”
Oswald Avery writes about his work on pneumococci and its amazing implications-his determination that the substance in cells containing the hereditary material was DNA and not proteins, as most biochemists had assumed in the past. “If we are right, & of course that’s not yet proven, then it means that nucleic acids are not merely structurally important but functionally active substances in determining the biochemical activities and specific characteristics of cells-& that by means of a known chemical substance it is possible to induce predictable and hereditary changes in cells. This is something that has long been the dream of geneticists. Sounds like a virus-maybe a gene. But with mechanisms I am not now concerned-one step at a time. Of course the problem bristles with implications. It touches genetics, enzyme chemistry, cell metabolism & carbohydrate synthesis-etc. But today it takes a lot of well documented evidence to convince anyone that the sodium salt of deoxyribose nucleic acid, protein free, could possibly be endowed with such biologically active & specific properties & that evidence we are now trying to get. Its lots of fun to blow bubbles,-but it’s wiser to prick them yourself before someone else tries to.”
Oswald T. Avery (1877-1955) was a physician who became tired of working in the clinic and went to the Rockefeller Institute in New York, where he dedicated his life to the study of pneumococci, a type of bacteria that can cause pneumonia. In 1932 he began work on a phenomenon first reported by Fred Griffith in 1928. Griffith had observed that heat-killed virulent pneumococci could convert a nonvirulent strain to a disease producer in vivo. Later investigations showed that this change in immunological specificity could be brought about in vitro, and that the alteration was permanent. Avery decided to isolate and analyze the active factor in the transformation. After years of studies, Oswald Avery determined that the transforming substance in the organisms was, in fact, DNA. This was a great surprise to biochemists at the time, who had assumed that the genetic material was in proteins, because proteins were such complicated molecules, and DNA, with its monotonous repetition of nucleotide components-A, C, G, and T-seemed boring by comparison. In fact, Avery’s experiments showed that the preparations most active in bringing about transformation were those purest and most protein-free. Avery’s work culminated in a 1944 paper, written with Colin Macleod and Maclyn McCarty, that is now a classic.
Before the 1944 paper was published, portions of Oswald Avery’s letter to his brother were distributed among biochemists, with the intention of getting reactions to Avery’s findings before the major announcement was made. The present letter is one of this handful of copies. It comes directly from Nobel Prize winner Max Perutz. This paper was well known to the members of Perutz’s section of the Cavendish Lab, including James Watson and Francis Crick. It was a major influence on their decision to study the structure of DNA.
The importance of Oswald Avery’s work in the DNA story is expressed perhaps most succinctly by Ulf Lagerkvist in DNA Pioneers and Their Legacy (Yale University Press, 1998): “ this gentle, quiet little man, always very neat and as discretely well dressed as an old-fashioned family doctor, is one of the towering figures of biomedical research. Even if both James Watson and Francis Crick can claim with equal justification to be the father of molecular genetics, there can be no doubt that the grandfather was Oswald T. Avery” (p. 117).