Recorded: 08 Aug 2001
One of those graduate students he didn’t like very well who’s now a professor at Mount Sinai, Jim Roberts. When we were together and drinking beer he would always call him “Herko-vitz” as a semi-slang term for him and now when I hear somebody pronounce it that way I have to laugh. Of course, Ira was was great about his cultural heritage in terms of humor. One of his favorite drop-off lines would be about the cruise to the Caribbean where “A-owitz said to B-owitz that C-owitz was being a problem.” He had a very good sense of humor about the whole Jewish scientist mentality, that stereotype and so forth, especially around the rest of us from California who had no idea about the Northeast mentality about all that.
Ira was brought up to me. I was going to be a third year graduate student and I was working in a physical chemistry lab and not liking it very much. And Carol Gross (who the last time I heard from was in Wisconsin) taught a course in the spring when I was a second year grad student in molecular biology. She was a postdoc. She actually signed up to teach a course by herself even though she wasn’t a faculty member. And it was a very fun course, and it was really at the beginnings of molecular biology. It was about 1972. And at the end of the course she suggested [that] because of my interest and the essays (everything was done in essay format), she suggested that there was this real hotshot coming from MIT and that was Ira. And she said he was working on some new stuff and I’d said that I didn’t want to work on E. Coli, and the reason I was doing the physical chemistry of DNA was that I thought there were a lot of people working on E. coli and the lac operon and so forth and it didn’t seem very interesting. She suggested I wait and talk to Ira when he came to the institute in Oregon that fall. So when I talked to him the first thing he did was suggest looking at a couple of papers and that was the papers by Takano and Oshima in Japan.
I meant to meet him and said that other people recommended that I talk to him about working for him. He didn’t explain very much but he gave me a couple of papers to go read. And that at the time I didn’t realize that he and his boss, David Botstein, had been talking about these papers since they had taken the yeast course the year before. I think he had taken the yeast course just before he came to Oregon. And I set about reading them in the library. They were in the journal Genetics. [The papers were written] by two Japanese geneticists who had been working on yeast for a long time, in saccromyces. In light of what I said before about not wanting to work on E. coli because it was all lac operon, I figured there were enough people doing that. Probably the most profound decision or realization I ever had in science was in looking at these papers and studying them in enough detail to realize that you couldn’t explain the results they’d gotten with a model using the lac operon. So by definition it had to be interesting. And that’s when I went back and told Ira that it was not lac operon, it required something else. And so he just said, “Well, go for it. Try and figure out what it is.”
The exact titles I don’t remember right now. But I could find the papers in a minute in the journal. Takano and Oshima are still active as geneticists in Japan. Looking forward, the interesting tie was at the end of the paper the yeast community was pretty small and as I found out later, their papers ended with suggesting that the mating type genes were like McClintock’s—the so-called controlling elements that Barbara named. Their discussion was very mild considering the results that they had. I found out many years later that Gerry Fink, who was going to be my postdoc advisor in a few years, and several others had reviewed that paper and they couldn’t make heads or tails [of it.] The results in the paper were so against the conventional wisdom for how genes were controlled that they threw up their hands and told them to call them controlling elements because these very obscure things that Barbara had described were the only things close to it. And they actually wanted to say something stronger but the reviewers wouldn’t let them. So to be honest with them they actually did know more about movable genes than they let on in the paper, but when all I could do is read the paper—I realized that they had results that made something very different—that made it necessary to invoke something different than the lac operon, which was a repressor on top of a control sequence turn taking an otherwise express gene and turning it off occasionally with a diffusible protein. It had to be something different because the two chromosomes could behave differently. So I started to work on that problem.
Ira was a very popular new professor at Oregon but he was basically known as a phage geneticist. Jeff Strathern was basically interested in bacteriophage genetics and had done a turn in Frank Stahl’s lab, and he too was waiting for Ira to come. But he was waiting for him to do phage genetics with him. Ira had already an extensive publication list. Ira is the first one in the lab to be doing yeast. But Jeff was fortuitously in the lab doing phage genetics at the same time. And we isolated ourselves in a separate lab, very luxurious space for the two of us which was now—at Cold Spring Harbor the space we had would have been occupied by at least six people! And it was just the two of us on opposite sides of a bench.
Ira was the principal investigator but I was the only one doing yeast so I basically set up the yeast lab within Ira’s lab. Ira had taken the yeast course so he knew a few things about it but he’d only been working on yeast for about three weeks in the yeast course at that time. So it was perfect for me because there weren’t a lot of people doing the same thing, however there were interested people around, like Jeff, who cared about any intellectual question that you could propose. So if you asked how something might happen—Jeff was a real disciple of Frank Stahl’s mode of thinking which was to build a model first and then test it. Try and devise an experiment that would test it and blow it up and then go back and make a new model that took in the new results. Our roles turned into posing questions and often having Jeff propose models for how it might happen. Then you could attack those models either on an intuitive basis or on an existing data basis or the third thing—which was the most fun—which was that you would design an experiment to test it. And the fun thing about yeast and phage, but yeast was fairly close behind in time was that you could design an experiment within a few days to test any model that anybody produced so that before it became stale you could find out that it was either true or not true or consistent or inconsistent. The fun part would be that you’d have to build a new model. And so we talked back and forth, I’m sure that he helped me in dissecting the yeast part of the problem much more than I did help him in his particular problem that he had defined in phage genetics. We talked back and forth but I must admit I was not terribly interested in phage genetics.
I hesitate to say in the active sense that I got him involved [with yeast]. He became involved with yeast by definition because we were face to face every day. I wouldn’t let him not hear my questions; he couldn’t avoid hearing me ask the questions. He was a very responsive partner to ask questions and to say how could this happen or how could that happen. Our roles became as in a marriage almost. You assume roles and then the roles soon became that I would get curious results in an experiment. And then, I think if I had a talent it was in describing the situation very clearly without coloring it with my intuition about it but state the results—and then Jeff would interpret those results as stated and make the simplest model out of it.
Actually, my thesis was supposed to be on yeast, Jeff’s thesis was supposed to be on bacteriophage, but after about two years—actually he started working on yeast about the time that I left.
He was doing phage lambda all the time that most of my work was done. And then he took over, he jumped onto the yeast work as did Jasper Rine eventually. Just about the time I left he was just starting to do the experiments but he was instrumental in the work that I did just as being a member of the group—it was clear that we were partners in thought before I left though he was just barely starting to do yeast work at that time.
James Hicks is a pioneer in the field of yeast genetics. He earned his Ph.D. degree in molecular biology and genetics from the University of Oregon, working with Ira Herskowitz.
Hicks researched with Jeff Strathern and Amar Klar in the Cold Spring Harbor Yeast group from 1977 to 1984 where they made outstanding discoveries about the mechanism of mating type switching in yeast.
Hicks is the co-founder and Chief Technology Officer of ViroGenomics, a Portland biotech company that is searching for new treatments for chronic and acute viral disease.