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MAX LUDWIG HENNING DELBRÃCK 81 one-step growth curve and devised the single-burst experiment, anticipated in essence by Burnet, which permitted a comparison of phage multiplication in individual cells, both key methods for the future progress of phage research. Of this and two other papers by Max on the same topics (1940c,d). T. F. Anderson wrote 16 years later that, of the many scientific papers he must have read at the time, he could remember only these three: "The experiments were beautifully designed and reported in an elegant style that was new to me. The three papers carrying the Delbrück label formed a little green island of logic in the mud-flat of conflicting reports, groundless speculations, and heated but pointless polemics that surrounded the Twort-D'Hérelle phenomenon" (2, p. 63). Max had no difficulty renewing his Fellowship for a future year, and when this extension expired the war had started so that a return to his old job in Berlin, which had been guaranteed by Hahn and Meitner, was virtually impossible even had he wanted it. On the advice of the Rockefeller Foundation he accepted a lowly academic position of Instructor of Physics at Vanderbilt University, Nashville, Tennessee, where he remained from 1940 until 1947, being finally promoted to Associate Professor. However, the Foundation, with generous foresight, agreed with the university to pay half his salary on the condition that half his time was free for biological research. Vanderbilt University and the Phage Group Max had no students of biology at Vanderbilt and his only recruit there was A. H. Doermann who had just obtained his doctorate in Neurospora genetics and later became a prominent phage worker. At the end of 1940, Max met Salvador Luria, a recent Italian refugee from Europe, who was working on phage at the College of Physicians
MAX LUDWIG HENNING DELBRÃCK 82 and Surgeons in New York. As Luria remarked 25 years later, "We were probably the only two people interested in phage from the point of view of molecular biology." They arranged to collaborate in experiments with mixed infections by phages T1 and T2 in the summer of 1941 at Cold Spring Harbor where Max was to read a paper at the annual symposium. In August that year Max married Mary (Manny) Adeline Bruce whom he had met during his fellowship at Caltech. The marriage took place in Pasadena and Manny has related that "Max took a whole week off from his experiments to get married. He couldn't wait to get back to Cold Spring Harbor" (7) where they spent their honeymoon. For the mixed infection experiments Luria had isolated bacterial indicator strains, separately resistant to each of the two phages, and when he visited Max in Nashville a year later they began to discuss the problem of whether resistance arose by the adaptation of a constant small proportion of bacteria, induced by contact with the phage, or by spontaneous mutation. The obstacle to direct experimentation was that the only way to demonstrate resistance was by exposing the culture to the phage. It was Luria who first conceived the idea of comparing the numbers of resistant bacteria arising in otherwise identical independent cultures, initially seeded with only a few sensitive cells, with the numbers from equivalent samples from a single culture. If resistance was induced by contact with the phage, then variation in the numbers of resistant cells would, in either case, be within the limits expected by random sampling. In contrast, the occurrence of resistant mutants, which might arise spontaneously and begin to multiply at any time during the growth of each independent culture, would lead to a much wider variation. By this reasoning, a fluctuation greater than the sampling error, in the numbers of resistant bacteria from independent cultures, means that
MAX LUDWIG HENNING DELBRÃCK 83 these variants arose as clones in the cultures before they were exposed to the phage and, therefore, were mutants. Luria wrote to Max about his idea and two weeks later Max provided the manuscript of a fully worked-out mathematical theory as a basis for experiments. The experiments showed unambiguously that bacteria acquire resistance to phage by mutation, a finding which has subsequently been established by virtually all other bacterial variations. The paper by Luria and Delbrück (1943a) reporting their findings and conclusions is a landmark in the history of molecular biology, for it provided the first real evidence that bacterial inheritance, like that of the cells of higher organisms, is mediated by genes and not by some Lamarckian mechanism of adaptation as was widely held at the time. Thus, it signaled the birth of bacterial genetics which became a basic tool for exploring the molecular basis of life. Indeed publication of this paper has been compared in importance to that of Mendel in 1865, ushering in the science of genetics itself (4, p. 56). At about the same time, in Nashville, Salvador Luria initiated his studies of host-range mutations in phage, but these were not completed until later and were published in 1945. Max and Luria had become interested in some papers on phage by Alfred H. Hershey, a microbiologist at the Medical School of Washington University, in St. Louis, and at the beginning of 1943 Max invited him to Nashville for a few days and wrote to Luria about him. Then, at the end of the year, Luria gave a seminar at St. Louis which "had the good fortune of impressing Hershey with the remarkable possibilities of phage genetics" (2, p. 173). These three formed the nucleus of the Phage Group consisting, as Max quipped, of two enemy aliens "and another misfit in society" because of Hershey's liking for independence and solitude (4, p. 53).
