NHGRI’s Oral History Collection: Interview with Mark Guyer and Jane Peterson

NHGRI’s Oral History Collection: Interview with Mark Guyer and Jane Peterson


Can you tell me what your name is and what
your position is at the institute? I’m Jane Peterson, and I’m currently the senior
scientific adviser — no. Is that right? Senior scientific adviser to the office of
the director of NHGRI. I’m Mark Guyer. I’m currently the deputy director of NHGRI. And what have you — start with Mark — what
have you been for most of your run here at the NHGRI? How would you describe what your role has
been? And I’ll turn over to you in a minute. In various ways, leading or helping to lead
the development of the policies and scientific programs for NHGRI. Prior to that, it was NCHGR, and prior to
that, it was OHGR. So I’ve been a program director from the time
I came here, and then, I don’t know, 10 years in, Mark and I worked together in leading
the Extramural Program. And I’ve done a lot of leading and initiating
projects — this is after the Human Genome. During the Human Genome, I was one of the
project directors who worked hard to try to keep us all together and — Making sure — contributing to running the
consortia, you know, making sure that we were getting reports, making sure that everything
behind the scenes — scientifically behind the scenes was working well, as well as management-wise. Can you tell us about the earliest days of
the Human Genome Project at NIGMS? I got involved in 1988, I think, after the
National Academy study had started. NIGMS was asked or assigned to be the liaison
to the discussions into the idea, and the person — the program director or staff member
in NIGMS who was assigned to this was Irene Eckstrand. And Irene worked on it for a while, and then
she went off on maternity leave. So I filled in for her during that, and when
she came back from maternity leave, she took over again. And then, shortly after that, she was detailed
up to DOE to help their genome program get started and get organized administratively,
and so I stepped back in. So — and that was mostly keeping up, writing
documents, and things like that. There was, I guess, the biggest issue at the
time about genomics was — or a human genome — an incipient human genome project was how
much money it would take away from NIH — from NIGMS, rather. Well, and I thought you were going where — when
you said it wasn’t the Human Genome Project, there was a big fight over whether the name
“human” should be in the project name at all, especially coming from GM. And I have to say, I wasn’t totally convinced
because I was so much in GM culture where we really did nothing on human particularly. And the inclusion of “human” in the name was
very much Watson’s — Yeah. — insistence for political reasons. He — He thought — — but — — it would not be politically acceptable,
or politically popular, at least, if it wasn’t directed ultimately at the human. Who opposed this? Who opposed the inclusion of “human?” Ruth Kirschstein, and the entire NIGMS, I’d
say. [affirmative] The basic research community because they
were convinced all this money was going to get taken away from the non-human research
side, and so it was definitely split. It was — I would say there were more people
against adding human than not. Probably. Yeah. What impact did HGP actually end up having
on the R01 style of funding for research? I think you’d have to ask NIGMS that because
we left soon enough that I don’t know how it impacted their R01 loads. I think they’ve gotten generous increases
just like the rest of NIH did up until, you know, five years ago or so. Our model has been not to emphasize R01, so
you could say that all this new money came to NIH and it didn’t get used for R01s, and
there are people who would think that was a bad thing. I don’t think you could’ve done the project
that way but that was again in another controversy. [laughs] Certainly, the money that was spent on human
genome research was not taken from NIGMS, so — Right. — the amount of money they had for their
R01 program didn’t increase, so it was clearly new money into NIH. I guess the most ardent opponent would have
argued that possibly that additional money would’ve come to NIH anyway and could’ve gone
for more R01 research. That’s pretty speculative, and the way politics
works, I think. I would doubt that it would’ve come to NIH. It really was bringing new money into NIH. Before it was called the Human Genome Project,
who was in charge? Ruth was in charge. I mean, Ruth was a good soldier. I mean, she did what NIH asked of her. She just wasn’t out there enthusiastically
pushing it. But in terms of making sure that NIH participation
in the discussions at the time was effective, and whatever administrative actions needed
to be taken, she was a good person to do that. But I would say there was a community saying
NIH should not take a lead in this, and while she — Right. — in, yeah, genomics, and while she didn’t
articulate that, I don’t think, I can’t remember specifically if ever she said that at a meeting. I think she was working pretty hard behind
the scenes with Wyngaarden to say that she thought that this DOE would not — here I
go saying something I don’t want quoted again. Well, I’ll — [laughs] Okay. — I’ll say it, I mean — Okay. — the feeling among, I think, the leaders
in the scientific community, the people like Watson and Botstein and others, was that a
genome project, sequencing human DNA as originally proposed by DOE was going to happen, and those
people didn’t want to cede that to DOE. They thought that if it was going to have
to be done, NIH was the best place to do it because NIH brought the biology to it. Was it — And does a better job. Once the Human Genome Project became established,
who was in charge? I guess that was actually before I moved from
GM because I remember — Jane Peterson:
Yeah. — when I was offered the job. So Jim was the director, Elke Jordan was hired
as the deputy director. The third person to be hired was Carolyn Mohan
[spelled phonetically], Elke’s secretary, and then I was the fourth person hired as
— and I can’t even remember what the title was — assistant director or something like
that. When I was offered the job, it was a real
decision because I was not convinced that this was a good thing. What were your doubts? A lot of the same doubts as being expressed
in the community, that could it be done, would it be useful if it were done, and is it going
to be worth the money? The two reasons — I talked to a lot of people. The two reasons I ended up taking the job
was, first of all, I heard who some of the other candidates were, and they were — a
couple of them were really very gung-ho about genomics at that point, and I thought it would
probably be better to have a skeptic in this position rather than somebody who, at that
time, was unthinkingly in support of it. To lead it, yeah, because I thought in terms
of making hard decisions that a lot of thoughtfulness was needed, would be needed, so… There was a great theory that people were
going to go into this mindlessly and just line up all the sequencing machines, not even
— not even — There weren’t even sequencing machines then. Well, once the first — yes, there were. Yes, there was a really bad one. Craig had a couple and there were a couple
on campus. And, you know, they calculated the number
of years and the number of machines and all that kind of stuff, and there was concern
we weren’t even going to map the genome, so that what’s the gung-ho people really were
interested in. The other reason that I took the job was how
could you pass up the chance to work with Jim Watson? That worked out great. Mark worked with him much more closely than
I did. I didn’t have that much experience with him. Jim, I thought, had the one thing that you
want your boss to be when you’re a staff person, and that is — and I’ve said this many times
— he held and expressed opinions more strongly and more ferociously than anybody that I’ve
ever met. But if you as a staff person had a better
argument, he would change his opinion on the spot, turn around on a dime, and argue that
as forcefully as before. So, you know, in terms — what more could
a staff person want than that? What’s his working style like? I don’t know how to answer that question,
I mean, he was — I would say he didn’t have much of a style. He came and went; I mean, he really wasn’t
around that much, and it was less and less as the years went by. I don’t know how many years was it. Was it two years, three? Two or three years. But you guys sat and talked to him much more
— Yeah. — than I did. I mean, he was very focused, and he was very
— I think he saw his role here as using true political means or addressing the political
issues that needed to be addressed in order to get this established on a firm footing. How much of the actual scientific strategy
of how to do the job did he provide? What he provided was the — at least the encouragement. I don’t know if centers were his idea originally,
but the idea of organizing this enormous task, having to be done at the center level, making
it clear that not every center had to be successful; that, in fact, if the majority of them weren’t
successful, that didn’t matter. What mattered was having at least a couple
being really successful. And he also was committed and saw it as necessary
to go for the best and the brightest. Yeah, he definitely recruited the PIs and
got them to apply. I think I told you about recruiting Francis
Collins even though the grant put forward — it was really a P30, which means there’s
a core and, you know, projects that feed into. That was not to be the style of these grants
because they were to be really much more focused. But it didn’t matter because it was Francis. So he picked people more than projects? Yeah. He couldn’t get them through review, but he
picked well enough that — on their — I mean, on the merit of really smart people you get
really good applications. And, you know, whatever the number was that
we initially funded, 10 or something like that, the last two he picked for reasons other
than pure score. He picked for programmatic reasons, because
these were the things that — like including at least one that was working on human disease. Even then, he thought that was important for
the program. But as it went on in years, the applications
started rising to the top — this is beyond the first 10 or so — that weren’t as good
as the other ones, and that — we started having trouble then. I can’t remember if he was gone when we had
to really — I think he was but — — reduce the size of the center that got
to — there was this whole chromosome by chromosome mentality which lasted for a long time, and
there were the chromosome committees and all that and they wanted to keep their identity
and their — you know, what they’re working on, and they would get to the study section
with great scores, and we really had to start watching out for that because it happened
a couple of times. But they really weren’t that good scientifically? Not for the genome project. They might’ve been good if the genome project
hadn’t existed and you wanted to get that chromosome done. But the genome project wasn’t about necessarily
doing it chromosome by chromosome. We didn’t really appreciate that at that time,
but when other centers started taking on five or six chromosomes to make it higher throughput,
and then eventually Craig came along and — Mark Guyer:
When that — Yeah. I mean, there was that about not funding some
initially but there was also a couple, at least one, maybe more, which got shut down
after — Later on. — later on — Yeah. — because they weren’t doing — they were
doing good science but they weren’t doing the genome. And in the earlier days when Watson was here,
how much of his time or your time working with him evolved around strategizing around
the relationship with Congress and how to keep the money flowing? I have two of my favorites. One was when he had to test — well, three
— when he had to testify at some hearing or something, and he came down that morning
— I guess it was an afternoon session — came down, came to the office, we were talking
about whatever it was we were talking about, and then when it was time to leave, he stood
up and said, “Well, I guess it’s now time to go downtown and play the clown.” And, you know, he had to perform like the
wild, crazy scientist that the Congress was expecting him to be. So that was one. He said that many times. Going out and raising money, he does the same
thing. Let me, you know, I don’t absolutely know
that. I think what it was, was that he found that
that persona was effective, and so he used that when he needed to. I mean, that may have been his basic personality
anyway, but he was very much — very clear on how to use it to get what he wants. So that’s one anecdote. The other is he came down, or he was scheduled
at some point to meet with the secretary of HHS, who was Louis Sullivan at the time. So, in preparation, he asked us to prepare
a number of talking points for him, which we did. And shortly after we finished that, we got
a request from the secretary’s office asking us to prepare talking points for the secretary
to talk to Dr. Watson with, so we wrote the talking points on both sides for that one. It was a good meeting. So I imagine it’s clear he didn’t live here. He lived at Cold Springs Harbor. He didn’t change where he lived, and he came
— he never came for a week at a time, did he? I don’t think so. It’s one or two days at a time. Yeah. And he could go — A couple of times a month. — weeks without ever being here. But Elke was — Yeah. — you know, in constant communication with
him. How did that first communication between Venter’s
aspirations to get into this business and the work that was going on in the HGP office
connect, and what did that look like? We had interactions with him before HGP so
— and I think I probably had — Yeah. — some of the first interaction. So tell us about the earlier ones. And this was, I mean, this was — we were
a couple of years into this already by the time you started talking with Craig. Well, it was certainly before — In GM. — certainly a couple of years in GM, and
then — Yeah. — you know, it wasn’t really until we started
talking about incipient sequencing — Yeah. — that — Yeah, well, but you know, I had the Fred Blattner
grant, and we were interested in what these new machines could do. And I can remember actually walking over to
the convent where we had a big sequencing meeting. We also had a big sequencing meeting that
we worked with him out at Wolf Trap. And I would say that the relationship was
pretty collegial. He invited us in to come see them working,
you know, machines going; they didn’t have very many. I know that it was a big deal when he got
it, and I think there was one other on campus somewhere, but you know, it really — then
I met Claire. It really was a very positive relationship,
I think. So — and he was probably part of the reason
that intramural could fly. Is that right? Probably. Yeah. But — so I don’t think at the beginning he
necessarily had big aspirations to become the human sequence guru. I think he wanted to be part of the — He wanted to be part of it. — part of it. But he was one of the people arguing for lining
up the machines. I mean, not that generation necessarily, maybe
the next one. And what was Watson’s reaction to him? I don’t know if they ever met him at that
level. I don’t know. It was not — I don’t remember any particular
reaction, any particular — He wasn’t that — Well-known at that — — negative. — he wasn’t well known. I think it changed when he applied for a grant,
and his first application wasn’t a success. Did he come in with Caskey first? Oh, gosh. I can’t remember. Yeah, I don’t remember that. I don’t remember the specifics but I believe
he applied a couple of times. It wasn’t successful. And was this the intramural? Yes. Well — No, I don’t know. I think he could — No. Well, no, I don’t remember. I think it was — he’d gone to — what was
first? Tiger? Tiger. Yeah, I think it was the tiger. And then the one that he got shut down on,
which we can’t discuss, really caused the big blowup. But maybe he was mad at us by then already. No, I think — I mean, the application that
caused it was his application to sequence mycobacterium, to do the whole genome sequencing
of that organism and — He has the summary statement posted — used
to have it posted in his office. Yeah, I think I kept his copy of the summary
statement also. Can you talk about Elke Jordan and her role? She ran the place. I mean, she was the power behind the throne. Yeah. And he — I think he was involved in selecting
her as deputy director, and I don’t really know about that but I think he was, and it
was — I thought the story was that everybody told
him he had to — you know, Botstein, Lander — everybody told him that he had to hire
Elke because she had, even in GM, she had been really the person who was the most logical
about — The organizer. Yeah. Had she been a long time GM program manager? No. She was head of the — what was it called? Yeah. She was — she started as a program manager
— Yeah. — but by the time I came to GM in ’86, she
was, I don’t know, deputy director for programs or something like that. There was — Well, program was separate — — the extramural activities. — activities. She was head of review and grants management. But she was also involved in doing the sort
of budget analysis and giving to each division — Yeah. — how much they had so she was — But she wasn’t in program — Right. — anymore but she started there. What happened after Jim Watson’s departure? I remember very clearly being in St. Louis
in a hotel and in the bar with Eric Lander, and expressing great concern and maybe almost
despair about Jim’s departure and who was going to become the next director, and Eric
just said, “Don’t worry.” Eric always says that to us. He said, “Don’t worry. You’ll like what you get.”

Leave a Reply

Your email address will not be published. Required fields are marked *