Hamilton Smith on From Medicine to Molecular Biology
  Hamilton Smith     Biography    
Recorded: 03 Mar 2006

After graduating from medical school I went on to an internship at Barnes Hospital in St. Louis. I guess the big event of that year was that I met my wife there. We got married at the end of the year. And then I got a letter from the draft board telling me that I was being drafted. They still had a doctors’ draft at that point, but most college graduates were not being drafted. The Korean War was over by that time. And, so, I decided to go ahead and—I could have probably gotten some sort of a deferment, or taken a military or Navy internship, but I figured what the heck, go ahead and, I mean… So my wife and I headed off to San Diego and it was a wonderful two years. You know, the officers’ club, and I was head of the dispensary at the Naval District Headquarters, took care of the captains and the colonels and of the admirals—not the colonels but the, uh, primarily the responsible for the upper echelons of the headquarters there. And it was a pretty nice experience. I had free time – a lot of free time – so I started going to the Naval Hospital at Balboa Park and working one afternoon a week in the endocrinology clinic, where I saw a variety of patients. It was pretty interesting, treating people with radioactive iodine and so on. But I around that time began to read up a course on some of the various endocrine illnesses, things like Klinefelter’s and Turner’s, and so on, and just about that time in the paper I read an article that by using the new squash technique you could disperse all of the chromosomes in a cell and actually count them accurately. Whereas before that all the textbooks said 48 chromosomes and it was only 46. And I was extremely impressed by the fact that such a simple thing would—and then not only could you look and see all the individual chromosomes, but you could correlate those chromosomes with particular illnesses. For example, Turner’s syndrome, you had only one X chromosome and no Y; Klinefelter’s you had two X’s and one Y. So, with such a very simple diagnostic test, you suddenly had gained a lot of insight into these really mysterious illnesses. So I went to the library and got out a college textbook on genetics, and I think in the third or fourth chapter there was something in there about Watson and Crick. In medical school it was never mentioned. Now I went to medical school from ’52 to ’56, but nobody was aware of the work in molecular biology or Watson and Crick’s work on DNA. So this was in fifty—probably around ’58, that for the first time, I learned about Watson and Crick. And, needless to say, that was the end of my medical career. It still hadn’t clicked at that point that I wanted to do medical research in any particular field. I dabbled around with some immunology and things like that in medical school but I hadn’t been turned on yet. There was just not a fit. But once I learned about DNA, all of a sudden, a lot of things became simple. I started reading—I got Mark Adams’s book on bacteriophage, read everything in there, and realized that, you know, I could think of things to do that they hadn’t done. I went back to some collections of papers, there wasn’t a whole lot available but—JMB was not available yet, but there was a couple collections of papers, Adelberg I think, and—who’s the other guy, physicist? Anyway, there were two—two paperback books, one was on sort of phage genetics, and the other was bacterial genetics. Stent. Yeah right, exactly. So I read all of those, and you were basically ready to go with that. But I still didn’t quite see how to make the break out of medicine. Of course my wife was a nurse and she expected me to have a respectable clinical career. So I went on to a residency in medicine in Detroit, at the Henry Ford Hospital. But I have to admit that there I would go up to the library and spend a lot of time reading all these books and things. Then, it was about the middle of my second year of residency – this was around 1960 or early ’61 – I was talking to a friend and he said that he was applying for an NIH fellowship to do research after he finished his residency. And I said, “That sounds like a good idea.” So he told me, you know, where to go to get the applications. I wrote up a single page description of what I wanted to do, and I think there was another page or two of educational background and so on; and they wanted me to get a transcript of my record, which Hopkins would not provide. They don’t give out any grades or anything, they just put you in whatever your ranking in the class was. But I was able to get my undergraduate record, which was pretty good. Anyway, to make a long story short, they approved my fellowship. I guess they were probably approving most of them at that time. I had applied to work with Mike Levine at University of Michigan, Ann Arbor, and had corresponded with him. He accepted me, and I don’t know what he thought of my application, but—none of which I ever did of course. I wrote it up myself. I mean, I guess nowadays normally you would confer with the person you were going to work with as to what you might write in your application. I didn’t have a clue that that’s the way you went about it. I just wrote it up the way I wanted it and sent it in. I proposed sort of a semi—I wanted to work on recombination, but I had some sort of a theoretical end in addition that I put in in there. In fact I worked for a year on some theoretical recombination work and read some of the articles from people that were doing mathematical modeling of genetics and so on.

Hamilton Smith is a U.S. microbiologist born Aug. 23, 1931, New York, N.Y. Smith received an A.B. degree in mathematics at the University of California, Berkeley in 1952 and the M.D. degree from Johns Hopkins University in 1956. After six years of clinical work in medicine (1956-1962), he carried out research on Salmonella phage P22 lysogeny at the University of Michigan, Ann Arbor (1962-1967). In 1967, he joined the Microbiology Department at Johns Hopkins.

In 1968, he discovered the first TypeII restriction enzyme (HindII) and determined the sequence of its cleavage site. In, 1978 he was a co-recipient (with D. Nathans and W. Arber) of the Nobel in Medicine for this discovery.

He is currently the Scientific Director Synthetic Biology and Bioenergy Distinguished Professor at the J. Craig Venture Institute in Rockville, Maryland.

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