Perspectives in Biology and Medicine

PERSPECTIVES IN BIOLOGY AND MEDICINE Volume 18 · Number 2 · Winter 1975 KNOWLEDGE AND PREMATURITY: THEJOURNEY FROM TRANSFORMATION TO DNA H. V. WYATT* The scientific work which led to the recognition that DNA is the carrier of genetic information continues to fascinate both those who were alive at the time and those who are now students. Griffith is commemorated by the memorial lectures of the Society for General Microbiology, while memories of Avery continue to warm those who knew him. Yet there are still many aspects which are puzzling. Why was it that Griffith's discovery of transformation led eventually to DNA, whereas Avery's demonstration of DNA as the genetic material did not lead immediately to a new paradigm? Stent has claimed that in Avery's case the demonstration was premature [I]. I should like to suggest that in the case of both Griffith and Avery, there were two elements, one technical, the other concerned with the acceptance of a new idea. A parallel case is penicillin, where the idea of an antibiotic was not acceptable until after the discovery of sulphonamides . Fleming did, however, persist but was defeated because it was not technically possible, at least in his circle of associates, to purify the crude samples. It was only after the acceptance of the idea that it was thought worthwhile to solve the technical problems. Thus we may extend Stent's use of"premature" and my use of "knowledge and information " [2] if we include a new concept: discovery can be premature if it is not capable of being extended experimentally because of technical reasons. Griffith's discovery of transformation was extended because this was technically feasible, and in the next 10 years steady progress was *Department of biology, University of Bradford, Bradford BD7 IDP, United Kingdom. I am deeply grateful to the many persons who wrote to me following my paper in Nature, and I am particularly grateful to those who wrote giving personal reminiscences and details, especially Dr. R. D. Hotchkiss and Dr. R. M. Herriott. It is a very striking tribute to Avery that so many of his former associates wrote so warmly about him. Perspectives in Biology and Medicine · Winter 1975 ] 149 made by Avery's associates at the Rockefeller Institute. Each step brought Avery nearer to the identity of transforming principle. It was only when a new paradigm was desirable in 1944 that the story seemed less clear. Transformation and DNA If genetic recombination in bacteria is rare, it is not easy to see with ordinary culture techniques. Demonstration requires conditions which kill or prevent growth of the parents while allowing growth of the recombinant . Such selective systems can be deliberately produced, as by Tatum and Lederberg [3], but do not often occur except by design. Tatum and Lederberg used a selective system to test whether sexual conjugation occurred in bacteria: a reasonable if remote possibility. To test for the possibility that small pieces of genetic material could enter a bacterium and change its genotype would not have been an experiment which would have occurred to a bacteriologist. Yet transformation was discovered accidently before 1928 by Griffith. This was due to a remarkable combination of circumstances. He intended that the mouse should act as a selective-agent medium and should kill the avirulent bacteria. If, however, normally avirulent bacteria could be made to produce a capsule , the bacteria would multiply and the mice would die. He performed the experiment to test whether avirulent (capsuleless) bacteria would produce capsules if provided with sufficient concentration of polysaccharide to restore some kind of autocatalytic process [4]. In some experiments, however, the capsule type produced by the previously avirulent type could be identified as belonging not to that of the avirulent pneumococcus but to the same capsule type as the dead virulent pneumococcus which had been the source of the heat-treated polysaccharide. This Griffith called transformation. The gene or genes responsible for capsule synthesis could be recognised not by one character but by three interrelated characters: (1) in the mouse by virulence; (2) on agar medium by the gross morphologic appearance of the colony: smooth as opposed to rough; (3) by the presence of a capsule under...