Interview  transcript

Alfred G. Gilman, co-recipient of the 1994 Nobel Prize in Physiology or Medicine, together with Martin Rodbell, welcome to this archival interview for Nobelprize.org.

Alfred G. Gilman: Thank you and thanks for coming and visiting us here in Dallas.

I’m happy to be here. Your part in the work was the identification of the nature of the transducer, hypothesised by Martin Rodbell, as the protein complex which we now know as the ubiquitous G-proteins, and I’d like to come back to the time of the discovery a little later, but to start off with, I’d like to discuss your scientific beginnings a little. You had quite early exposure to science, and biomedical science in particular, through your father.

Alfred G. Gilman: I’m reminded that, there’s an expression of, I guess, particularly wealthy people that were both with a silver spoon in their mouth. A former governor of Texas, Anne Richards once, in commenting on her opponent George Bush, said he was born with a silver foot in his mouth, I think. I was born with a scientific silver spoon in my mouth.

A silver spatula.

Alfred G. Gilman: Yes, and my father was a Ph.D. in biochemistry, he turned to pharmacology, he was on various medical school faculties and he was a terrific father and showed me the pleasures and joys of science as a kid. I’d go down to his lab and watch things and had a wonderful time.

You were even named after the textbook?

Alfred G. Gilman: That is interesting, yes. They had no idea what they were doing at the time, but I was born the same year as my father and Lou Goodman first wrote this textbook, The Pharmacological Basis of Therapeutics, so I was given my father’s friend’s name Goodman as a middle name and that has enormously confused generations of medical students for quite some time now as to how that came to be. They imagined all sorts of strange relationships.

And you took over the editing of the textbook.

Alfred G. Gilman: Yes I did, in the mid 1970s.

Did you know when you were a child that you wanted to be a scientist then?

I remember with great excitement, signing up for a trip to the moon …

Alfred G. Gilman: Yes, I wanted to be an astronomer and some of my favourite memories of being a kid, we lived in suburbs of New York city, going into the city and visiting museums but especially the hidden planetarium in New York. I remember with great excitement, signing up for a trip to the moon. I can’t remember how, I was probably well maybe 10 years old, so this was maybe in the early 50s and they had a book you could register for a reservation and it seemed quite fanciful at the time.

Biology then came to supplant astronomy at some point.

Alfred G. Gilman: The thing is, a friend of mine had similar thoughts as a child and she once mentioned, but I figured out that astronomers don’t spend all their time looking at stars and interest turned, yes. I became much more interested in biology in high school and college.

Then Yale and then you made what on reflection was the fairly momentous decision to go and do the MD Ph.D. programme at Case Western with Earl Sutherland, but you refused the first time.

Alfred G. Gilman: That’s correct. You know, that was another good example, really, of an advantage I had, I think. Earl Sutherland, who won the Nobel Prize in, and you can probably tell me better than I, maybe the mid-60s, no, probably the mid-70s. He discovered cyclic AMP along with Ted Rall and maybe in 1956-57 he had gone to Cleveland and started this new programme, MD Ph.D. programme. It was quite unique; he knew my father well. He recruited every student into that programme individually, you know, there was no advertising, no marketing, he just got to know people one way or another and it was a small programme and he recruited it.

I think he knew he would see my father in meetings and my father liked to talk about his family, so Earl knew that I existed. He sent me a note and asked me if I’d be interested in looking at the programme and I got the letter when I was a junior in college and I looked at it and said Seven years in Cleveland, no thank you, and I responded back, politely I hope, that I wasn’t interested, but he tried me again in the fall of my senior year and I thought, oh, what the hell, I’ll go check this out, and I did and was very excited about it, so I did it.

So what ‘the hell’ led to your first exposure to second messengers and a career.

Alfred G. Gilman: That’s about right, yes. My big concern was that he was Chairman of a pharmacology department, I was majoring in biochemistry at Yale and I didn’t want to just, you know, follow along in my father’s footsteps too precisely and my father was much more of a physiology and I was more interested in biochemistry. I said to Earl, My only real concern here is that this is pharmacology and he patted me on the back, said don’t worry, he said, pharmacology to us is just biochemistry with a purpose so I think that was the clinching line for him.

And what was the question that they were asking at Case Western that really got you going? Were you even at that stage interested in the big questions such as how do hormones work?

Alfred G. Gilman: That was Earl’s question, how does a hormone work and the system he was studying, he had grown up under the tutorage of Carl and Gerty Cori, so a train of Nobel’s. He was in St Louis at Washington University which was in many ways the birthplace of so much in biochemistry in the United States. Earl was particularly interested in epinethrine and glucagons and how did the action of those two hormones result in hypoglycaemia, that was the increase in blood sugar. It was a biochemical parameter that could be measured.

We gave a hormone to an animal, blood sugar went up, what was in between and Earl ultimately took that problem to understanding that the hormone worked at the outer surface of the cell, stimulated somehow the generation of this so called second messenger, cyclic AMP, which was his key discovery and that cyclic AMP went on inside the cell to stimulate the enzymatic reactions that cause the breakdown of stored sugar or glycagon, broke down into sugar and released into the body. So that was the problem and Earl brought it to a very substantial level and others included us picked up from there.

So you picked up on the question of what lay between the outer surface and cyclic AMP?

Alfred G. Gilman: Really, yes.

And that fascinated you from the beginning?

Alfred G. Gilman: That was the black box. The inside part was pretty well worked out, the details of what went on inside the cell, but what happened at the cell surface, how that information got from outside to inside was a mystery.

Were you aware when you sort of pondered taking on this question that there was a great lineage of august figures behind you or was it just …?

Alfred G. Gilman: I guess intellectually I was, but I’m not sure emotionally whether that was, probably not a big factor.

Because there’s so many questions to ask, it’s lovely to find your questions so early and then stick with it, it shows great foresight but also great luck.

Alfred G. Gilman: I’m not sure, you know, how well the question was framed at that point. When I took my first job, the first grant I wrote, the title was The Role of Cyclic AMP in Neurons and Glia.

Hedging your bets.

Alfred G. Gilman There was more of focus on deciphering specificity in the nervous system and just who was doing what to what cells types and what those interactions looked like. This was in the very early 1970s and there was certainly a piece of it interested in the receptors and how that all worked but questions were phrased more broadly and less specifically. I think I probably became a lot more specific as data and experimental success led you on one path or another.

Because I suppose there are a lot of people, young scientists, who are fishing around for the right question to ask and are very worried about the finding of that right question, which will lead them on the correct path.

I don’t think that the questions need to get too specific too soon …

Alfred G. Gilman: I think one shouldn’t be concerned about being too specific about that question too early. You need to find an area of importance and something where there are big questions, hopefully more than one and to begin to hone in on an area first. I don’t think that the questions need to get too specific too soon.

There’s a balance between not getting too specific and being too broad and therefore being a bit dissipated, I imagine.

Alfred G. Gilman: Yes, yes.

Another great influence on you at an early stage was Marshall Nirenberg at NIH. I was interested to wonder what attributes this people Ted Rall, Earl Sutherland, Marshall had that you particularly picked up on that made them good mentors?

Alfred G. Gilman: Marshall is a very creative and free thinking man. The reason I ended up in his lab was because he made a huge switch in his field of interest and just that alone takes a great deal of courage. He won his Nobel Prize for deciphering the genetic code and was particularly interested in how information got from genes to proteins and mechanisms as protein synthesis but in the late 1960s, the field of molecular biology was looking mature to some, which is sort of funny, but many molecular biologists had that point in time said that we’ve figured it all out now and neuroscience, neurobiology is the big frontier and so let’s go there and that’s an important lesson to be learned there.

First of all, they were of course wrong, molecular biology wasn’t quite done but it was a great move for many of these guys to move onto the next big challenge and Marshall was one of those and it was his move into studying the nervous system, particularly the use of cultured cells to do that, that attracted me to his lab so I went there with that notion. His imagination was always very inspirational, he was quite different from other mentors I had, he would imagine that you could discern things and learn things in ways that were not obvious to me and it was mind opening.

So how did he do that?

Alfred G. Gilman: He saw paths that were, I think tenuous, that would take courage to pursue. He had it, he had the courage.

And was he able to instil some of that courage in the people working for him?

Alfred G. Gilman: I think so, I hope so. That was a time of great talent at NIH, National Institutes of Health. The Vietnam war was on and that is unfortunate, the set of circumstances that it was, provided a lot of motivation for a lot of young physicians to go into research careers, rather than to go into military service and so there was huge talent at NIH, it was sort of the heyday of NIH in many ways, so there were a lot of bright young people there, working in those laboratories and they profited hugely from mentors like Marshall and many others that were there.

How interesting, so there was a generation of doctors who wanted to look at basic science for a while?

Alfred G. Gilman: I recall also, I was one of the very early MD Ph.D. graduates. The path for many at that time was to get a medical degree and that’s the path I thought I was going to follow, to get an MD and then get research training afterwards and many, many people did that, that’s the way that academic departments of medicine were populated with researchers, was via that route and there was a lot of motivation for people to go that route at that period of time. Let me go back a little bit though because we’ve neglected someone who was very important.

Earl Sutherland recruited me to that programme in Cleveland, but he left very shortly after I got there and my Ph.D. advisor was his young colleague, Ted Rall who was the one I did all my work with and I owe an enormous amount to him and he was a spectacular mentor. I was married early during that period of time and that programme and a classic line in our household when I get home at 8 or 9 o’clock for dinner was, make my excuses to my young wife saying, I just stopped in Ted’s office to say a couple of things around six and that was 8.30 before we stopped. So he was incredibly generous with his time and advice and we just had a wonderful relationship.

Was he very selective in the people he brought into the lab to work with, I imagine he must have been if he was going to devote such time to their relationships?

Alfred G. Gilman: It was a relatively small lab and most labs were relatively small in the 1960s, it was sort of before big science or bigger science.

It must have been both exciting and overwhelming to have somebody focus on you to that degree, when you’re so young.

Alfred G. Gilman: It seemed natural. It was the way it worked and that was the way it was in that department, it was the Department of Pharmacology at Western Reserve, now Case Western Reserve. I think there were many things that were done on a smaller scale then and there was a lot more time. There was a lot more time to think, a lot more time to interact more closely with people.

What about in the way that you did experiments. Was that very different from now, somewhat?

Alfred G. Gilman: Everything was much less automated, much more manual, much more hands on. It was reasonably primitive by today’s standards.

Primitive, but you understood what you were doing, you understood what the technology was delivering.

Alfred G. Gilman: Yes, there wasn’t that much technology but we certainly understood what it was delivering.

And do you think that makes a difference?

Alfred G. Gilman: I’m not sure exactly what level you’re asking the question. We could not envision then things that can be done in a matter of a day or a week now. The notion of purifying a protein was daunting enough, let alone having the sequence of a protein, there were two or three examples at the time and so on and probably not much else. The notion of understanding how proteins worked and the level of detail, the notion of understanding what a protein looked like, how it interacted with the … These were pretty difficult to fathom at the time.

True, but I suppose at some level, the experiments were also more accessible because you didn’t need such resource to undertake them. More accessible but both in the sense that …

Alfred G. Gilman: More accessible but a lot less definitive and a lot less clarifying, yes.

But maybe more accessible to young students as well, that you could undertake experiments that other people were doing in their labs without having to go out and get a big grant to get the equipment etc.

Alfred G. Gilman: That’s true but the equipment was also expensive and … the grants were much smaller. I’m sure that everything scales. But the question at the time and Earl Sutherland phrased this question … The technical way to ask the question was the beta-adrenergic receptor, the enzyme that made cyclic AMP. To put it in more allayed terms was, was there just a single component in the cell surface membrane that allowed the information to get across.

Or were there a chain of events?

Alfred G. Gilman: Yes, chain of events or was it all one thing and it was very difficult even to think about how to answer that question. Today it’s trivial to think about how to answer that question but it wasn’t at the time.

We might come back to mentorship again in a little while but after NIH, you then moved to Virginia and then down to Dallas and the move to Dallas was of course key. You were, I gather attracted here by Donald Seldin in the end.

Alfred G. Gilman: Many things attracted me here.

Many things, yes, so I was going to ask, what made you come and stay?

There really is strong institutional support for people who succeed …

Alfred G. Gilman: Let me say first, I had a wonderful 10 years at the University of Virginia, it was a terrific place to launch my career. It was, I think, a pretty nurturing environment with a good, excellent Department Chairman Joe Larner, who recruited me there. He had been in Cleveland, I had known him as a student and I got a great start there. Dallas offered opportunities on a grander scale. This is a very ambitious place and it’s ambitious to excel, particularly in terms of research. It’s ambitious, I think, in all the finer senses of the word to have fantastic research programmes of highest quality, answering major questions and I think it’s reasonably entrepreneurial, people who do well are well supported by the institution in ways that I couldn’t imagine ever changing. There really is strong institutional support for people who succeed and I think that was obvious in the way that people’s careers were going here, particularly my good friends Joe Goldstein and Mike Brown who were instrumental in recruiting me here.

And Joe and you had been post-docs together.

Alfred G. Gilman: Joe and I were both in the Nirenberg lab all though he was still in the protein synthesis section which was being led by Tom Caskey at the time, so Joe and I knew each other and we were on separate floors, sort of in different areas of interest but I knew Joe. Joe had been a medical student here, he went off to clinical training in Boston and in Seattle, research training, pardon me, in clinical training in Boston and then research training at NIH in Seattle and Joe and Mike had gotten together and were doing fantastic things and were having great careers here and were a shining example of success and how successful people were treated in Dallas. Joe Goldstein called me to ask me about the position in maybe 1979, I think, and I was very busy and told Joe I wasn’t interested.

The story gets sort of amusing because then they really successfully recruited Marty Rodbell, of course with whom I shared the Nobel, and Marty accepted the job here but then for personal reasons had to back out at the last moment. Seldin came back to me and called me one day on the phone and Don remains an extraordinarily forceful personality with incredible vision and great gift of gab and he called me up, said would you do me the courtesy of just giving me 15 minutes on the phone and I got the next word in I think about 1½ hours later and I was pretty well hooked, perhaps, at that point. Made a visit and it all went very quickly. But this was and still is a young school, they had a great vision of growth and great plans for success and it was very attractive and a terrific decision I made to come here. Schools continued to grow enormously and have been very successful.

Certainly so and they seem to have an unerring accuracy for recruiting future Nobel Laureates to their faculty.

Alfred G. Gilman: You know I’d put a lot of that good decision making in the hands of relatively few people who are gifted. Don Seldin had the gift from the very beginning and he is the man, I think, if you wanted to pick a single individual who really got the school going in the proper directions and fostered its growth, he’s the man and the stories are famous. He had really nothing to work with, it was a pretty primitive place and he would go into the medical school class and identify bright young talent and take that talent under its wing and with his strong persuasive powers, sculpt its career and there are many famous examples of that, Joe Goldstein being the best. Joe came here. He was born in South Carolina, went to William and Mary, I think, as an undergraduate, came here to medical school thinking that he might be a neurosurgeon and Don Seldin turned him into a molecular geneticist so that’s it, that’s persuasion and there are many other examples but the ability to identify talent like that is something quite unusual and Don had it and Joe has it and Joe and Mike especially have played a huge role in sculpting the school further and others of us have joined along the way.

I guess the standalone medical school faces certain challenges of not having the surrounding media for research, but that’s also a problem that has been addressed.

Alfred G. Gilman: I think, in terms of the history of this school in Dallas, I think it being a standalone medical school has at times been an advantage and at times it’s a disadvantage. We have profited in this city enormously from generosity of the Dallas community and philanthropy has played a very important role in the growth of the school.

Did that increase greatly once Nobel Laureates were there?

Alfred G. Gilman: It certainly helped. I think that made a big impact and there are certainly some major donors who were perhaps sceptical of the school’s future and the Nobel Prize puts a seal of approval, quite like no other on an enterprise and so yes, I think that was hugely important and the first one which involved two individuals, Joe Goldstein and Mike Brown, the first one, was incredibly important, the second one was wow and then there was a little bit of frosting on the cake, so I think it has had a huge impact. Dr Wildenthal, our president, loves to show a slide of the four of us together and proudly proclaims that no other president of a medical school in the world perhaps can show that he’s got four still active Nobel Laureates on the faculty. So, that’s been a great help and so philanthropy in Dallas has been hugely important to us.

Modern communication makes it a lot easier, you can move electrons a lot faster than people …

At the same time, I think particularly now in this century, the need for interactions of medicine that interfaces with virtually all the other sciences are critical. 20th century medicine was young and unsophisticated and perhaps couldn’t benefit as much as one might hope from strong interactions with chemistry, chemistry perhaps, yes, but physical sciences, computational sciences, engineering sciences not as much, but that’s changing dramatically now and we need all those interactions and being a freestanding medical school is a disadvantage in that regard, but we’re working hard to fix those things. Modern communication makes it a lot easier, you can move electrons a lot faster than people and so communication helps a great deal. In addition, we have two components to general academic campuses at the University of Texas system in this area, you know, University of Texas at Dallas and University of Texas at Arlington, they both have strong science programmes, particularly in engineering and computer science and we’re establishing strong ties with them and will all go very well for the continued growth of this place.

What do you think the school misses most at the moment?  What does it need?

Alfred G. Gilman: I don’t think there are any really glaring weaknesses. There are areas where we are stronger than others. The laboratory based sciences are our traditional strength and we’re very good at it. Things that we’re really trying to build now include greater strength in clinical research and translational research on the one hand and on the other these interfaces, particularly with engineering, computationals, computer science, chemistry and physics.

So on the former, have you got drug discovery efforts, for instance, going on here on campus?

Alfred G. Gilman: Yes and that’s a very nice outgrowth of one of our first moves to establishing interfaces, so Steve McKnight who’s chairman of biochemistry here has built a very strong, basic chemistry programme within biochemistry. Some are very pleased to look at this department and say Steve has put the chemistry back in lab chemistry, and there are half a dozen really superb young chemists in that department. And these are young people who I think have had the courage and vision to say, no I don’t want to be part of a traditional chemistry department, being here is like being a kid in a candy store because you’re in the midst of all this biology, so you’re sort of swimming in a possibility of interactions and collaborations.

One by one, these young folks have come here and taken advantage of it and really done very well with it so, you know, companies have been spun off, drugs are in clinical trials and it’s easy to see how this has come about from interactions of strong biochemists and molecular biologists on the one hand and the chemists on the other. Targets have been identified, screens have been run and targets of, you know, drug candidates have been discovered and optimised and the process is moving on, so it’s going very nicely and now we’re building the capabilities to move those things further down the stream and really do much more in terms of clinical trials ourselves.

Right and is it a disadvantage? I suppose it is a little bit of a disadvantage that there isn’t very much major pharma based around here.

Alfred G. Gilman: I think that is a disadvantage and we have tried to and are trying to catalyse the growth of biotechnology in Dallas, it’s been slow, it’s been slow almost everywhere except the coast and just really in a few major cities on the coast and there’s a huge focus. I think it’ll happen, it’ll come.

I suppose there’s an effort in biotech and drug discovery to put the clinical back into their efforts so you stand in a good position there.

Alfred G. Gilman Drug discovery is a whole huge and interesting and difficult subject these days but obviously many alliances of biotechnology companies with big pharma to accomplish those things and also with academia.

In terms of forming alliances, I know that you have put your heart and soul, for a while, in the Alliance for Cellular Signaling. A massive collaboration to work out the entire repertoire of signalling molecules within two cell types. What did that experience teach you about the necessary prerequisites for forming such collaborative networks?

Alfred G. Gilman: They taught me a lot about management for one thing but the Alliance has been very successful in some ways and not as successful in others, as I might have hoped and it’s still ongoing and on a slightly smaller scale, which has probably served it reasonably well to scale down some of its ambitions and efforts. Collaboration in biology is a very interesting subject at the moment, I think. Other sciences have gone further in that direction, I think physics being the best example, where it’s been driven by various specific needs for instrumentation and equipment that costs millions and millions, if not 100s of millions or billions of dollars and then collaboration is an absolute necessity and if it’s a necessity, people do it. In biology and biomedical science, successful grand collaborations have been driven by very specific … and the most obvious is the sequencing of the human genome and that was a very specific project and a business-like plan that you could put together and do it.

… it’s more problematic to get people working together at a discovery level than at a more technological level …

At the more fundamental and more discovery oriented biology, it’s still a little harder, I think, to get people together. A lot of that I think is still very much driven by individual genius, individual creativity, individual motivation and egos and egos are certainly a part of this and it’s more problematic to get people working together at a discovery level than at a more technological level. It’s going to come and it will happen more as people begin to get more into the really big problems of biology, how do really complex systems work? The magnitude of the problems is extraordinary and the difficulty is extraordinary and concerted efforts are going to be necessary and they’re happening but I think they’re just more difficult from really sort of a fundamental management point of view.

It is the trend for people to form these networks increasingly …

Alfred G. Gilman: It is a trend.

.And yet a lot of those networks don’t quite fulfil the goals they set out with.

Alfred G. Gilman: I think it’s very early to tell, in terms of the success of many of them, but I think obviously there’s growing success for sure in terms of putting unconventional or not unconventional but interdisciplinary people together and really letting things happen based on interactions that haven’t happened before. We are working now on a concept, I hope it may happen, it’s too early to tell but a concept of an Institute within the University of Texas system for example that would need not be confined to the University of Texas but that would be one possible mechanism, but to create a really interdisciplinary institute that would get into big problems of systems biology and cross fertilisation between biology and engineering sciences, for example. We think the way to do that now would be really to bring really interdisciplinary people together, rather than creating an interdisciplinary Institute composed of a specialist here and a specialist there. The communication barriers remain huge and it’s still very tough for a physician to talk to an engineer.

You know the engineer says what’s that squiggly stuff and the doctor says that’s DNA.

Alfred G. Gilman: Yes, so it’s a challenge, but there’s a growing number of rare breeds of people who can transcend themselves and putting those people together in a proper environment, I think there’s potential great gain to be had there and we’re talking about trying to approach problems. All of these problems in biology span huge scales and this is part of the issue so, one way to think about it is that biology build machines or organisms or people whose dimensions are in metres. We build these out of pieces whose dimensions are nanometres, so you know there’s a scale of 9, 10, 11 orders of magnitude and there’s a temporal scale too and motions of molecules that happen in nanoseconds and drive events that are measured all the way to lifetimes of organisms or even evolutionary timescales.

So, there are even more orders of magnitude there and finding people who are driven by the notion of finding out whether things that they can measure that happen in nanoseconds of milliseconds, how relevant are they to events that play out over minutes, days, weeks, years or lifetimes. That’s an interesting way of thinking and I think people who are driven to thinking those sorts of ways will make each contribution.

It’s a very appealing concept to work with, the idea of existing on such a scale that …

Alfred G. Gilman: It’s a daunting concept to work with and the technical challenges are enormous, I mean the ways that you measure things that happen in milliseconds and the ways that you measure things that happen in years.

In your mind that’s one key to the systems biology problem that people have to get away from only thinking about the system that they all study, which may be for instance a very small scale.

Alfred G. Gilman: Another way of thinking about it is the value of understanding how something came to be, not just what it looks like but why does it look that way and what was the process that created it, so really thinking in evolutionary terms. If you can understand why a system was built the way it was and what constraints evolution put on the way that the thing was built, I think, and this isn’t all completely intuitive and obvious but I think that you will acquire deep insight into how something really works if you understand how it came to be, rather than just what it looks like when it was finished.

I heard an analogy once which may be irrelevant but somebody described trying to understand baseball by taking photographs of a baseball game and you can take as many photographs as you like and show them to somebody who doesn’t know what baseball is and they still really won’t understand how baseball works or how it came to be.

Alfred G. Gilman: Well yes, cricket’s even worse of course.

Cricket’s unfavourable to everybody, isn’t it?

Alfred G. Gilman: But yes and I think, let’s see if we can extend that. If you had movies of course it would help rather than the snapshots, but if you had movies of baseball at the beginning of the last century and along the way and you could see how the game changed, that would probably help a good deal too.

So it’s getting that scale.

Alfred G. Gilman: Yes, how did it evolve? What forces led to what changes?

Given that question, you then as you say, need to get people together in the same institute, they need to work in close proximity.

Alfred G. Gilman: I think people working at different ends of that spectrum, of different ends of the spacial scale spectrum and the temporal scale spectrum.

Sounds a very attractive prospective.

Alfred G. Gilman: I hope so and many of these ideas are not mine, they’re circulating around widely but we’ve been talking about the idea of creating this institute and particularly talking with some of my young colleagues here who’s minds are still very flexible and who think very well in these directions and I’ve been trying to learn from them.

Is that the major thrust of your current efforts as Dean of the medical school?

Alfred G. Gilman: It’s one and I think really trying to work on two major things simultaneously, one the translational and clinical side, say in the laboratory research particularly here is in strong shape, we need to push translational medicine and clinical research much further in that way and also the more fundamental interfaces in the other, so we want to span that scale too.

I also wanted to ask you about the effect of the Nobel Prize on your career, in a sort of general sense. It’s a difficult question but I imagine that obviously, it had a very positive effect, it may also have had some detrimental effects on your research I imagine?

If you want a bully pulpit, you sure have one …

Alfred G. Gilman: It can be a distraction. It’s a ticket to travel the world, if you want one, and it’s an opportunity to do many things. It’s an opportunity to be heard, whether you have anything to say or not, some people do and some people don’t and I think people handle it very differently and if you want to stay focussed in your laboratory as many do, you need to acquire a very fine sense of how to say no and because you’re going to be turning down hundreds of invitations. If you want a bully pulpit, you sure have one and many people are doing terrific things with that. Just yesterday evening I was at a dinner with Peter Agre, who won the Prize in Chemistry a few years ago now.

2003 I think.

Alfred G. Gilman: I think 2003 is right and Peter has very well thought out and well expressed feelings about the role of science and public policy and the fact that science is not being heard adequately, I think by politicians and public policymakers and he is outspoken on that subject and I think very well spoken on that subject and the Nobel Prize gives him a lot of bully pulpit, gives him a lot of credibility. He’s even thinking of running for public office and I guess I hope he does but if he does, I sincerely hope he succeeds at it, but I’m not sure whether the American public is ready for a Nobel Laureate as Senator from the state of wherever, but it would be interesting. Some states are more ready than others.

The Nobel sort of imprint tends to allow one to comment on things way outside one’s subject area.

Alfred G. Gilman: Yes and some people, you know, occasionally one goes too far but good judgement and all things unless it’s useful.

But you took the other course, you decided not to use it for that but to use it rather for …?

Alfred G. Gilman: Well, I’d say for the first half dozen years ago after my good fortune, really stayed very well focussed on my own laboratory. Other opportunities then came along and I decided to pursue some of them. The most drastic obviously being becoming Dean of the medical school and now Provost here and in some ways there’s a little bit of guilt perhaps for leaving the lab but I’ve enjoyed what I’m doing now a lot. I focussed on the laboratory for the better part of 40 years. I’m a pretty competitive individual really, and I like to think that whatever I’m doing I’m doing my best at it and I don’t necessarily think that I’m as creative a scientist at the age of 65 as I was at the age of 45.

Frankly I don’t think anybody is, brains get a little fossilised. Opportunity to do something really different came along and I decided to take a little try at it and then decided I very much enjoyed it and it’s a very different sort of life. I’ve learned more about how this school and how medical schools and universities work in general in the last two or three beta-adrenergic receptor years than I learned in the prior 30. Interact with a much broader sphere of people, cross a much bigger range of interests and disciplines and I’m enjoying that. I think there’s a little lingering guilt but there’s also some real pleasure in the new activities.

Is there any lingering sense of a career that you might have done other than the one you’ve chosen?

Alfred G. Gilman: Oh sure. We can go back to astronomy and astrophysics and I don’t think I didn’t have a talent for it but, unravelling the mysteries of the universe is a reasonably noble goal. I was a not very talented clarinet and saxophone player as a youth, a career as a musician would have been quite wonderful. Huge numbers of things left undone for sure that everybody would like to do. I also am a pretty focussed individual and maybe excessively so, get very caught up in what I’m doing and I’d like to go back through it all again and spend a little more time with my family and my children than I did. I wasn’t as good a father as my father was to me.

Are they, do you think an understanding family?

Alfred G. Gilman: They’re a very understanding family.

Yeah, they must be very proud?

Alfred G. Gilman: I hope so. I have a wonderful wife and three superb children, who are all doing very, very well.

Did any of them go into science?

Alfred G. Gilman: No. Perhaps they saw someone who was a little too focussed. My kids like to say that when they came to me with a science question based on their schoolwork or other, they wanted the five minute answer and they got the 45 minute answers. Maybe I just didn’t know when to shut up.

They sound like many medical students in the making.

Alfred G. Gilman: Yes, could be. None of them is in science.

But, although of course there are other things you could have done, do you find yourself thinking about them though or are you really basically content?

Alfred G. Gilman: Oh no, not really, no, I made the right choice. It worked out reasonably well.

When you have students coming through or when you had students coming through the lab and now you have whole faculties to look after and you see people making their choices and you want to help them go the right path, is it possible to reflect on what sort of mentor you are to people?

Alfred G. Gilman: That’s really hard I think. Mentoring has become a very, very popular subject. I hear the word constantly and I will admit to sometimes having mixed feelings about it because I think there’s a lot of discussion of mentoring programmes and formal programmes and teaching people to be mentors and of course then evaluating the quality of people’s mentoring activities, etc, etc, etc and I sometimes think it’s getting maybe a bit too programmed and looks a bit too much like a business plan and I think a great deal of it is still very spontaneous and one on one activity.

When I hear we must find someone, a mentor, frequently my first reaction is people need to find their own mentors. Yes, they should be helped and I don’t mean to sound like a bad guy about it but I think there’s still a good deal of spontaneity that’s required here and that it needs to be comfortable from both sides and it’s just not something that necessarily can be assigned. At the sort of level that you get mentored as a Ph.D. student, it requires a reasonably decent personal interaction and close relationship and that’s the most effective sort of mentoring.

I suppose it’s a question of time. It’s the spontaneous coming out like for dinner?

Alfred G. Gilman: Yes and you know this is the biggest problem. I mean I sound like an old curmudgeon at this point but the pace of life is much, much faster, everything is faster and if access to information is instantaneous, that’s all great and wonderful but it consumes us and there is not as much time available for and there’s certainly not as much time spent on personal interactions and thought and reflection and everything is just much more fast paced and the biggest complaint I hear from everyone, especially faculties is there’s too many demands, you’re asking us to do too many things and that’s probably true, we are.

Where did the extra demand come from though, because basically what medical schools do now is what they did 40 years ago?

Alfred G. Gilman: Frankly, a lot of it’s economic. On the clinical side, can our clinical faculty teach, can they do clinical research, can they do laboratory research and can they also be clinicians? A lot of that pressure is how they earn their salaries and we go from there to the entire economics of the healthcare industry and if you have a few weeks we could bring in a whole bunch of people and talk about that but it’s enormously complex and there’s a lot of conflicts there and just how people can exist and survive in an academic setting and have clinical activities and research activities and earn their salary for it.

It comes again to that word you use, focus. It’s finding people who can maintain their focus despite all this stuff going on around them and presumably those individuals shine out, it’s easy to spot?

In the United States we’re very well blessed with public funding for science …

Alfred G. Gilman: Yes and an example is they have to make choices. If I want to have an active research career and be a clinician, I’m going to earn less than the person who’s just going to be a clinician, in order to focus exclusively on being a clinician. On the basic science side, there’s a lot of pressure to generate funding for your laboratory research, the money’s got to come from some place. In the United States we’re very well blessed with public funding for science, more so than in any other country in the world but that funding is tight at the moment.

The competition for it is ferocious, only 10 or 15% of new grant applications are successful and that means you write more of them and worry more over each one of them and spend a lot more time competing for the money, than doing the actual research. There are also many issues of accountability for what we’re all doing, rules, regulations, compliance, more forms to be filled out, more regulations to be satisfied and these are distractions too, they’re important ones but they’re distractions and people are increasingly frustrated by them.

Do you think that the situation in future years, funding in this country, is going to be similar? What do the auguries look like?

Alfred G. Gilman: It’s cyclical and things get better or they get worse. The concerns of the moment are the level of funding for sure. Another major concern is the number of young people who are going into scientific careers. There’s a paucity of US educated students who are going into basic science careers and many probable causes for it. A public education system that is I think weak as far as science education is concerned, there are many reflections of that in terms of scientific awareness in this society, so that is a big issue and I think the perceived level of competition and compensation in careers in science is probably a bit of a turnoff as well. So the United States is relying more and more on foreign born scientists, who are coming to be trained here and happily, many are staying here and that’s a clear trend and so those are big issues too.

In terms of the outreach to children and getting children interested in science, it is strange, isn’t it, because the US has a very high level of competence at reading at very young ages and then suddenly it seems to fall behind on scientific education?

Alfred G. Gilman: I’m not aware of the reading statistics, I’m glad to hear that something seems to be going well but, you know, most of the data I see shows US school children well behind many, many other countries in the world in terms of educational competence and there’s growing concern about the problem and various programmes that will hopefully be effective in correcting it.

But I still fail to see a real public commitment to public education in this country and I think there’s sad reflections of that in terms of things that just jar badly with … sensitivities and beliefs. The percentage of people in this country who believe in evolution is horrifying. The number of people who think that human beings and dinosaurs co-habitated the earth – they didn’t. The number of people who think that the earth is 10,000 years old – it isn’t. The scientific evidence there is irrefutable. Other issues of global warming may be more debatable but not that much more, I don’t think and the level of scientific ignorance in this country or even suspicion of science is way too high.

That requires real leadership to push a programme of change through.

Alfred G. Gilman: Leadership and patience and that’s a long-term project.

Let’s hope Peter gets into public office.

Alfred G. Gilman: Oh, that would help.

Well, I think we’ve covered some very nice ground in the interview. Thank you very much indeed for sparing the time.

Alfred G. Gilman: I’ve enjoyed it very much. I think you’re good at your job, you ask good questions and we thank you for coming. You’re going to have some opportunities to talk to other UT Southwestern faculty members and I expect you’ll enjoy those too.

Yes, it’s a real honey pot for us, so thank you very much indeed. Bye bye.

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