Recorded: 04 Jun 2001
How far back to go. I might as well start at the very beginning. In deciding finally to bail out of the University of Wisconsin, where I was going to school, one of the options was to go to graduate school at Harvard, and it was interesting – the biology and the biochemistry department going on there. In talking to various folks they said, “Yeah that would be a great place to go, but, whatever you do, don’t work for that crazy guy Watson, he’ll drive ya nuts.” So I went there, not knowing anything more than that about Jim.
That was ’61. And only later on, when I came back and after to give a seminar, did I learned (as Jim described it) that the only reason that I had gotten into a program at Harvard was I had a brother who was at MIT, at the time, who was working with Jerry Letvin, the very famous physiologist who knew Jim. And Jerry Letvin had told Jim that my brother was smart and that maybe I was. So this was just one of those curious circumstances. But, after arriving at Harvard and taking a virology class from Jim, I just found him intriguing and intellectually different from most folks. And it was an irresistible opportunity to see about working in his lab.
So, I was quite timid myself and found Jim quite intimidating. But I did get up, finally, the courage to walk into his office and ask about the possibility of working in his lab. And he said, “Are you married?” And I said, “Yes.” And he said, “The answer’s no; you won’t work hard enough.” So with my tail between my legs, I went out of the office and a month or two later I decided I should try once more. And with an enormous effort, I made myself knock on the door once more and finally [he] said, “We’ll give it a try and see if it will work out,” and so it finally did work. But… I guess it was the first summer I was there, Jim decided that he was going to try to work in the lab some more and continue to work in the lab. It was just when the RNA phages had been discovered, so he said, “Why don’t the two of us try to figure out how to grow and purify this RNA phage, R17?” So I grew batches of stuff, as I remember. There was a crucial moment about half way through the summer when, doing major preparation, the flask broke and the stuff fell all over the floor and Jim stomped out and never came back to the lab again. I think that was the very last time he was in the lab and touched any lab equipment, so I was the source of the end of his active scientific career.
There’s one little bit of history with that. When I was at the University of Wisconsin, I was in a graduate program, where you can get a Master’s Degree and I was working on cattle, feeding them fluoride to see how fluoride poisoned the cattle. It’s a problem in the West. You get your feet tramped on and have to carve up the cattle and it was just awful. It was clear I didn’t want to work on anything big, biologically, so when I went to Jim’s lab, [phage] was the very smallest biological thing that people worked on, these very small RNA phages, so there was a great contrast, which I found very comfortable.
With the RNA phages, I was doing a couple of things [and] using light scattering techniques to understand the size and shape of these things. I was working with Helga Doty, Paul Doty’s wife from the biochemistry department, and with Elizabeth Crawford getting pictures, electromicrograph pictures of the RNA phage stuck to pilly (??) on the outside of cells, and then working with the RNA itself, doing translation of the RNA into proteins. The other thing I did was related to ribosomes. One of the difficulties of studying E.coli ribosomes was that they had a ribonuclease absorbed to them. And as you isolated them, well, this nuclease came along. So if you did things to manipulate them, the nuclease would chew up the ribosomes and you have nothing left. And I found a way to be able to assay that nuclease just in a colony of cells. So I realized that you could get rid of that nuclease maybe by getting a mutation that knocked out that enzyme. So I found a way to heavily mutantize cells, pick (??) them out, and select the colonies that have lost the nuclease. And I think that that was the first time anyone had done that kind of enzymatic screening with a mutagenesis scheme like that. So we ended up with bacteria that were free of that nuclease and it was useful in the short run and it turns out that in the long run, it wasn’t an issue anyway. That was one of the other things that I did there.
[Jim] was very hard to predict. There was a time when I was doing some message decay experiments, and I had just finished getting a bunch of samples ready, and he managed to follow me into the room to watch them to go through the scintillation counter to see what the numbers were going to be. And there are times when there would be no particular directions unless you wanted some idea or some results. But the lab was interesting because it was run by the graduate students. Jim had very little day-to-day involvement in running the lab. Most of the discussions, and ideas, and problem solving had been done by graduate students. The post docs were there but didn’t really play as big a role as the students did, so a very interesting learning opportunity. Jim was very much hands off, letting people fend for themselves but really making sure they were really making some progress on occasion.
I think that everybody realizes that in choosing to work in Jim’s lab you have to be pretty independent. Everybody knew that it wasn’t his style to be looking over your shoulder all the time. And he really selected people who were really willing to stick their necks out a bit. It wasn’t a protective lab, the way some labs were. Yet you’d have exciting and fun people around the lab to work with. It was a really magical environment.
I have to tell you one more thing that actually says a lot about my relationship with Jim. That was towards the end of my Ph.D. So for the final exam for the Ph.D., there was no oral presentation, you just went before the commission, [and] so it was Jim, Matt Meselson, and Tale Shayne (??), the ribosome guy who’s now back in Geneva. So I walked, in full of trepidation of course, and waited for the first question to happen and Jim picked up a piece of paper and said tell me about, “Tell me about this D in organic chemistry you got as an undergraduate.” This was the first salvo for my Ph.D. exam. Fortunately I remembered the story about the professor that gave me that grade, and I was actually a chemistry major so this was a serious problem. Shortly before the exam where I was sitting, this professor had walked out into the hallway and a student had walked out into the hallway a little way down and pulled out a gun and shot this guy because he had been so foul in giving grades. He had given D’s to 90% of the people. And the implication was that if Jim wasn’t careful… So we had this rather strange relationship.
Raymond Gesteland, biologist, has made progress in describing essential mechanisms for controlled gene expression. His research on recoding provides insight into replication of RNA viruses such as HIV and the genetic code. Gesteland also concentrates on ribosome function and response to mRNA signals.
He received a master’s degree in biochemistry at the University of Wisconsin and earned his Ph.D. from Harvard University. After working at Alfred Tissières Laboratory in Geneva, in 1967, Gesteland arrived at the Cold Spring Harbor Laboratory to work under Jim Watson as Assistant Director for Research.
Gesteland is currently Vice President for Research, Distinguished Professor of Human Genetics, and Chairman of the Department of Human Genetics at the University of Utah.