Matthew Meselson on Graduate Work with Linus Pauling: Density Gradient Centrifugation
  Matthew Meselson     Biography    
Recorded: 17 Jul 2002

And it’s a long story of why I got interested in density gradient centrifugation. It has to do with Jacques Monod and Frank Stahl. He [Monod] came to give a lecture there at Caltech and he was talking about beta-galactosidase. In those days the question was: when you induce bacterial cells and they produce—by giving them lactose or an analog like beta-thiogalactosidase, they now produce a lot of the enzymatic activity of beta-galactosidase, the enzyme involved in digesting that sugar.

But the question was; is this the induction of new synthesis of this enzyme or was the enzyme lying around already in the cells just waiting somehow to be activated? Which is induction: activation or new synthesis? And Jacques Monod gave a lecture at Caltech saying that there was the possibility of attacking this problem by studying the osmotic pressure inside of bacterial cells. Because with Adonin equilibrium if you made a lot of new protean then the osmotic pressure might go detectably up.

I thought it was a terrible idea, too messy. And so sitting there it came to me that maybe—now here I have to digress slightly. I was taking the course, The Nature of the Chemical Bond from Linus. And in it one of the problems was to calculate the zero point energy of the hydrogen bond quantum mechanically, but not with hydrogen but rather with Deuterium or rather the ratio of the zero of the energy of that bond. Zero point, by the way, is the method you use to get the answer to the question.

But, so I was thinking about Deuterium and being interested in biology, I went to the library to read about Deuterium and biology. And I ran across papers by a man named Sam Trelease at Columbia who had grown bacteria, and algae and even tried to grow a mouse on Deuterium compounds in stead of hydrogen. So I was thinking about Deuterium.

And what I thought about during this seminar was: if you grew the bacteria in ordinary water—and Trelease had shown that you could also grow it in Deuterium—so then you induce the enzyme and then very quickly change the water to heavy water and keep on letting the bacteria grow. If you make new beta-galactosidase, de novo, it will have Deuteriums built into its non-ionic, non-acidic hydrogen atoms and so it will be heavier, denser. So now you grind up the bacteria and put that into a sugar solution whose density is adjusted exactly in between what the density would be for beta-galactosidase if it was built only of hydrogen or only Deuterium. And then it would either go up or down. It would go down if it was new synthesis and up if it was old stuff being activated. So that was the idea.

And I went to see Linus about it and he chuckled and said, “Stick to your X-ray crystallography!” But he was always very encouraging cause—the thing about Linus which was really remarkable; he loved to sit and talk science with his graduate students. He was a real educator. I’ve written a paper about Linus as an educator that’s a side of his life that not much was written about, but he wrote textbooks, he wrote many articles in The Journal of Chemical Education, he loved teaching! He really did.

So Linus, although he didn’t think this was something that I should try right away. Anyway I tried it out on Jim. And Jim just said, “Wait and do it in Sweden.” And I thought he meant because that’s where the centrifuges—ultra-centrifuge had been developed by Svenberg. But I think I’ve run across a different explanation that Jim meant that Caltech there were no girls, but in Sweden there were. Cause Jim always—I don’t know if he was just pretending, but half of his talk was about girls. I don’t know why. But anyway, he was not encouraging. Neither was Jim the sort who liked to sit and talk science, at least I didn’t see him as on who did. He would leave a problem, he would tell you about a problem, but unless it was something that he was intensely thinking about himself, I don’t remember him as being the kind of one-on-one teacher.

Matthew Meselson earned his Ph.D. degrees from the University of Chicago in 1951 and from the California Institute of Technology in 1957 under the tutelage of Linus Pauling.

In 1958 with Frank Stahl, Meselson experimentally showed the semi-conservative mechanism of DNA replication as predicted by Watson and Crick.

He is currently the Thomas Dudley Cabot Professor of the Natural Sciences in Harvard University's Department of Molecular and Cellular Biology. His laboratory studies sexual reproduction and genetic recombination, and how and why they are maintained in evolution.

Since 1963 Meselson has been interested in chemical and biological defense and arms control, has served as a consultant on this subject to various government agencies and is a member of the Committee on International Security and Arms Control of the U.S. National Academy of Sciences.

Meselson has received the Award in Molecular Biology from the National Academy of Sciences, the Public Service Award of the Federation of American Scientists, the Presidential Award of the New York Academy of Sciences, the Scientific Freedom and Responsibility Award of the American Association of the Advancement of Science, and the 1995 Thomas Hunt Morgan Medal of the Genetics Society of America. Dr. Meselson is presently a member of the Committee on International Security and Arms Control of the U.S. National Academy of Sciences.