Recorded: 01 May 2000
Amar: I am Amar Klar. As Jeff mentioned about how we got together for the first time around. I had actually met Ira Herskowitz about a year ago before and I started with the mating type simply from the point of view that—there is a gene called HO Gene or a homohalogen. Somehow that gene worked when cells are haploid but it doesn’t work when cells are diploid. So mentally, I was confused by that: How could a gene know if the system was haploid or diploid? You can imagine lots of scenarios, but in this case it involved mating type switching. So that was my interest to this mating type story. When I was doing this, I figured out that Jim Hicks—one of the other colleagues (Hicks, Strathern, and Herskowitz and sometimes Hicks, Strathern, and Klar)—is that he had done work in Ira Herskowitz’s lab on that question already, so apparently the paper which I did under the supervision of Seymour Fogel—my post doc advisor at Berkeley, when I was there—apparently went to Ira Herskowitz for the review along with other things which were in the paper. So my advisor was asking me that Ira wanted to put these papers together because they had similar information that Jim Hicks had collected as part of his thesis. So I didn’t know and said, “Sure, why not.” So the paper got published, so Ira knew me, I think, because of that, because I never met him before.
While we were doing this, we discovered in Berkeley this silencing phenomenon, which was later on called the silencing phenomenon. There is a gene, which keeps the mating type loci silent. Once it’s silent—and that was a specific proposal in the cassette model with Jeff and Jim Hicks and Ira Herskowitz—I was curious whether if you can select mutations in the silent genes—then would they move to the mating type locus. Remember, this was before DNA transformation in the yeast was invented, before cloning was popular, and I was simply a geneticist in a geneticist’s lab. So we had a genetical argument. While doing that we made mutation in the silent genes and once the silent gene—at Berkeley, yes—and once mutations were done and then we made the cells switch a few weeks before, and when the cells switched, it only made mutant MAT. So it genetically showed the DNA must be coming from the silent genes and moving to the MAT locus. You can imagine other scenarios, but that was the simplest one [and] which turned out to be correct.
So with that information in mind, at that time usually mating type used to be very complicated. So they always put, at Cold Spring Harbor yeast meeting they put mating types on the very first day. I remembered talking to and relating this story at the Cold Spring Harbor [meeting]. I hadn’t met [Jeff] before and I wanted him to hear what I was going to say in my talk. I remember still Jeff Strathern had the same weight and same look as he has now, just around his legs gotten a little chubbier. [I remember], and another colleague and friend of mine, David Kabak.
So [I’m] telling the story of the mating type and Jeff was asking questions, and so was everybody, and saying, “Ok, so what happened? What happened?” And so I told them that you switch MATα over to A in the mutant strain, the cells switch only to the mutant MAT. That was formal proof of the cassette model and I remember Jeff got excited at the steps of Blackford Hall. He got up and said, “Right here, they should make a mating type shrine.” And then, right away, Ira told Jeff—I remembered that, because it was my first meeting—and [I was] meeting lots of people, so being young, my memory was better—so he told Jeff, “Go get Jim Hicks and introduce him to Amar.” So I remember very quickly Jeff brought Jim Hicks and on the way he told him everything so quick- fast. Jim Hicks statement was “What the fuck are you doing at Berkeley? Come join us. We have a lab [for you].” So the next day – that was another job offer – and it was the next day when… one of them showed me the lab, where the lab is. They still wanted to grab something out about me. I remember Jim Hicks took me to play tennis. He is a very good tennis player; I am not that good a tennis player.
Amar: No, I am not that good. The first time I ever got stoned, I was playing tennis with him. And that’s not a way to arrange a job. That made a good impression on Jim Hicks that this guy was still playing it [tennis] even though he’s stoned, but he’s not ashamed of it or anything.
Then at Cold Spring Harbor, Jeff was already there. He was talking with Jim Watson, Ray Gesteland, and all of the other people. So the issue was—they wanted to open a yeast lab—but the issue was: What subject on yeast they should have a group on. The group was to open up this lab. The mating type at that time, [it] was very clear to all of us that transposition was going to work. Now it was a question of getting together and grinding it out and cloning it and everything, so a lot more people can understand it. So that’s what we tried to do—tried to get together.
I think it’s an interesting story at this time—Jim Hicks, several times mentioned, and other people mentioned—I was the only person who was hired without [an] interview. But these guys were working for me (pointing to Jeff). It was very interesting that Watson called after they had decided and said that “Ok, the cassette model and the spore?? of the cassette model is very good— get all these people together. Jim Watson called Berkeley, to my post doc advisor, Seymour Fogel and says “Hi Sy”. When Jim calls, everybody pays attention. He said, “Where is this guy Amar Klar?”
And [Fogel] he said, “He’s not here today. He is giving a talk at Caltech.”
And I think the conversation went like this: “Who is he visiting?”
“He is visiting Norman Davidson.”
And of course Jim Watson knows Norman Davidson. He knows his phone number by heart, so he calls Norm: “There’s a guy named Amar Klar.”
And [Davidson] said, “Yeah, he was here yesterday and gave a good talk on mating type.”
“Where is he?”
“He’s not here today.”
“Where did he go?”
“He’s at Irvine giving a seminar today.”
“Who is his host?”
“His host is…” (not Ron Davidson – the name will come back to me.) It’s amazing! I was giving a seminar on… (??) (13:45:23) or something.
In the seminar, the secretary ran in and stopped the seminar. She said, “Stop!” I am giving the seminar; people are listening. She said, “Stop!” I stop, and she said, “Jim Watson called. He wants you to call him right away.”
I had to play cool and everybody thought, “Oh Wow! This guy must be hot! Jim Watson knows him.” And I finished the seminar (??). And I think those people wanted to offer me a job right there. So I remembered the secretary had saved the phone number, so I called Jim Watson and I said, “This is Amar Klar. I understand you called me.”
He said, “I know you. I know what you do. We are opening up a lab on mating type. Whatever you want, I’ll arrange it.” I should realize—he said—I should realize that my appointment has to go through a committee, “But I’ll get the letter tomorrow and you sign it and send it to my assistant director, Bill Urdy, and bye.”
That was my hiring. So I met everybody at Cold Spring Harbor the day I joined. Within a few days, Ray Gesteland was leaving. All the senior people who hired me essentially said, “That is very unusual. We don’t hire people like that. I’d better be good.”
So we got together and we pooled our resources, and something which I am very proud of is that #1: They were wonderful colleagues. It always helps to get a good job; it’s absolutely better to have wonderful colleagues. And the third thing was that I have an Indian background. I grew up in India and both these people were regular American. I found that their thinking, in the beginning, I was a little bit shook up—but I found that their thinking process was different from mine, even though we could communicate. It was culturally—that was helpful for all of us, because different backgrounds, different definition of what is right and wrong, and what was truthful, how to go about… I personally benefited from that and hoped it rubbed off on other people too. That is how we got together and I stayed there for ten years.
Jeff was the first to leave because he brought lots of pets and broke all of Jim Watson’s rules—not having any pets in the lab. Jeff was a country boy.
Jeff: I didn’t leave because of the pets. I left because my wife wanted to keep the pets and I wanted to keep the wife!
Amar Klar and Jeff Strathern worked together in the Cold Spring Harbor Yeast group from 1977 till 1984 where they made outstanding discoveries about the mechanism of mating type switching in yeast.
Amar Klar, is a leading yeast geneticist, concerned with the molecular biology of gene silencing and mating-type switching. Klar came from India to the University of Wisconsin in 1975 to receive his Ph.D. in bacteriology. From 1977 to 1984, he worked with Jeff Strathern and Jim Hicks in the Cold Spring Harbor Yeast Group studying the mechanism of mating type switching. Klar served as Director of the Delbruck laboratory from 1985 to 1988.
He left Cold Spring Harbor to join the ABL-Basic Research Program as Head of the Developmental Genetics Section. In 1999, Klar joined the National Cancer Institute Center for Cancer Research and is now a Principal Investigator in the Gene Regulation and Chromosome Biology Laboratory at NCI-CCR.
Jeffrey Strathern, a leading yeast geneticist, obtained his Ph.D. from the Molecular Biology Institute at the University of Oregon in 1977 and then moved to Cold Spring Harbor Laboratory, where he became a Senior Staff Member with the yeast genetics laboratory.
In 1984, he joined the ABL-Basic Research Program at the NCI-FCRDC. His research remains centered on aspects of gene regulation and genetic recombination as revealed by studies in yeast. In 1999, Strathern joined the Division of Basic Sciences, NCI. Strathern worked together with Amar Klar and Jim Hicks 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.