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The Nobel Prize Internet Archive's Exclusive: Interview with Prof. Lederberg, Winner of the 1958 Nobel Prize in Physiology and Medicine conducted by Lev Pevzner March 20, 1996

Lev Pevzner - You were born in New Jersey. Where were your parents born?

Prof. Joshua Lederberg - In Israel. They came to the US in 1924.

LP - Did they settle down and find jobs here right away?

JL - Well, I don't really know the details. My father was an orthodox rabbi, and I think he had a very temporary position in Montclair after I was born, and then six months later he got a more permanent position in a synagogue in Washington Heights, which is when we moved to New York City.

LP - Did your parents have a large formative influence on you?

JL - Certainly so. My father was quite an idealistic person. He was committed to a religious vocation, and I reacted quite strongly to that: I was as early as I could remember interested in scientific and secular affairs. We still shared a great deal. He eventually gave in, and said "Joshua, I guess there are many ways to follow the Torah, and if you want to seek truth through science, that's alright too."

LP - What about your mother?

JL - Well, she was a heroic soul in many ways. My father was ill during most of my upbringing, and she had to work very very hard to help keep the family together. She had very little education: it is not generally expected that the girls would get such advanced education in orthodox families. Did you see the movie "Yentl" with Barbra Streisand? It's a very poignant picture. This is a girl who rebels against that, and in fact pretends to be a boy in order to be able to go to the Yeshiva. It leads to comic circumstances.

LP - Do you have any siblings?

JL - I have two brothers, they are both younger. One is close to my age. He's a professor of biology at Brown University. And I have a much younger brother, almost another generation, 16 years younger. And, he's become very devout, and ended up with the Lubaviche rabbi's group of the Hassidem, and he is living in Jerusalem. So, he is much closer to my father than I was in that regard.

LP - What influence did Stuyvesant have on you?

JL - It enabled me to pursue the ambitions that were already very clearly fixed.

LP - When did they become fixed?

JL - Oh, by the time I was 6 or 7.

LP - Oh really? You were already interested in science?

JL - Yes.

LP - Biology in particular, or...?

JL - No, it was everything. It became more differentiated into biology by the time I was 12 or 13. I was studying biochemistry textbooks by then.

LP - Do you still have contact with some friends from Stuyvesant?

JL - No, not at this time. Three of us were quite close together. Two of them have died in the interval, and one I saw a few years ago: a retired chemist in New Jersey.

LP - Do you know why it is that you became interested in science so early in life?

JL - Not really, I think it was kind of a -- I'll use the word in its technical sense -- sublimation of my father's and family traditions, religious impulses, but within a secular framework of what a second-generation American in the melting pot tradition would be looking for. So I certainly saw science as a kind of calling, and one with as much legitimacy as a religious calling.

LP - Do you know about Stuyvesant's new building?

JL - Oh, yes.

LP - How do you think it has changed since when you went there?

JL - I haven't been in the building since it was completed, I was there during its construction. I had a little bit to do with some of the planning for it. Well, obvious pluses or minuses: I think the school has had to have new facilities and it certainly accomplishes that. It's remarkable that anything is possible in the current budgetary limitations. There had previously been some discussion of a site out at 28th Street and Hudson River, which I thought was a disaster from the point of view of difficulty of transportation to it: since Stuyvesant serves all of New York City, to have a central location is pretty important. You tell me, I'm hoping that works out pretty well.

LP - Yes, it does. Well, the escalators don't work once in a while. We all make fun of it sometimes, because other schools don't have escalators. What kind of an atmosphere was it in the school during your time?

JL - I don't think it's changed much, at least judging from the visits that I've made. A peer group which is very self-confident, who is actually almost as talented as they thought it was, and an interesting mix of competition, and conviviality, and fraternity. A very big difference is that it was pure fraternity: we didn't have girls, when I was there. A very drastic change, one I would have been eager to have seen happen sooner.

LP - I gather that Mr. [Francis] Ryan was a very large influence on you.

JL - Yes, he was my mentor at Columbia College, a very important one. It was the first time I had a chance to work very closely with an active scientist, and really understood the actual operations and workings of a scientific career.

LP - What were your scientific goals back then?

JL - Well, when I was in high school, I became interested in cytochemistry: chemical analysis under the microscope, and trying to understand the composition of cells. I've had some not very insightful research projects, looking at effects of different fixatives, and the staining protocols themselves, to see if we could learn more about the chemical composition of the material being studied under the microscope, like different behavior with different fixatives. Even to this day there's not much discussion about these so-called fixatives.

So, we used acetic acid, and formaldehyde, and uranyl acetate, and all kinds of poisonous materials, and we hoped they somehow or other preserved the details of cell structure, but how they can be expected to do that and exactly what the chemical basis is for the fixatives being effective or not effective is still not very well studied. It's a very empirical kind of art that has developed there, and people don't question it very much. So, I'd say the experiments I was doing have really not been advanced since then. It's not a very interesting subject, because there is no chemical specificity to it. So, things that have become interesting in cytochemistry have to do with development of very highly sophisticated reagents, through the use of antibodies, the use of enzymes, and that's a very positive way in which cytochemistry in fact has advanced since my encounter with it. But I learned from Ryan that if you wanted to dissect the structure of living cells, that genetic analysis was an extremely powerful method, so my interest turned to that.

LP - Was there anybody else around that time that had a very large influence on you?

JL - Well, not to match Francis, but there were professors...I took their courses, and learned a great deal from, but with none of them did I have very personal relationships, as I did with Francis. I ended up working in his lab, and spending more than half of my time not doing my studies, and working on Neurospora (a mold) in his lab.

LP - And what made you choose Columbia in the first place?

JL - I knew that [Thomas Hunt] Morgan had been there, and had founded modern cell biology and genetics. I may even have thought incorrectly that he was still there, I have to say based on very vague premises. I knew that E.B. Wilson had been there, and there was a magnificent textbook: "The Cell in Differentiation and Heredity", which is one of the great classics. Let's hope nobody reads it any more. It came out in 1925. But I had read it cover to cover. It was mostly about cytology, about chromosome behavior. Very insightful. The initiating monograph of cell biology, I would think it fair to say that. About 1600 pages. Considering that was in 1925, it encompassed all existing knowledge. And that had come from Columbia, so I knew they had a great biology department. I can't say that I actually knew who was there at the time, when I applied. We didn't get that level of advice, and it wasn't that easy for a high school student then to contact people in colleges, and that's something I've been trying to promote since then, on the other side of the table, and I think the teachers and advisors are a little more sophisticated about those relationships too.

LP - We do get a lot of information about colleges now.

JL - Well, you know, many undergraduates shouldn't be looking at what the graduate programs are at a university: they are not going to graduate school, but...since I had very firmly differentiated interests, I guess I was lucky not to be disappointed, because they were based on very limited facts, but Columbia had a great reputation. It was in New York, which meant it was economically much more feasible than if I had to support myself or have a way to live, so this way I was able to start going there while I was living at home. And I did get a scholarship there. Otherwise I'd probably have had not choice but to go to City College, which many fine people have done. So, I did get a very fine education, and not just in science. It took some pressure on the part of my elders to convince me that I really should take an interest in humanities, and history and contemporary civilization. I value those just as highly as my scientific training. And, I keep my connections with Columbia. I'm glad to be on the adjunct faculty there, and I have a little bit of a debt, and I have students from Columbia working at my laboratory. I like to think that's a commemoration to Francis Ryan.

LP - Were you one of the better student in high school and college?

JL - To put it in simple terms, yes.

LP - You say you were very inquisitive of your teachers.

JL - Well...They actually had standardized IQ tests, and I found this out later on: I knew I had a high score, but I had scored the highest in the Northeastern region, so...make your own conclusions. Well, that's just one test. I was reading 5 or 6 years ahead of my grade, as a simple matter... During public school I was pretty bored. I made a contract with some of my teachers that if I didn't ask too many disruptive questions, I could sit and do my own work in the back of the room. Sometimes they would ask me to help out, and be sort of an assistant teacher. But, I was reading medical textbooks when I was 11-12 years old, to give you some idea of that... That's probably not so unusual for Stuyvesant students, but...

LP - Well, I guess...for some. So, what led up to your first discovery: conjugation (the process by which two lower organisms, such as bacteria and protozoans, mate)?

JL - click here for in-depth answer

LP - And how did you feel about that?

JL - A little scared. The first positive results, I was "Take it easy Josh, don't commit yourself to it, it's all gonna blow up, be prepared for the possibility it's all a fluke." And, repeat them, do them over and over again, to be sure, but after 5 or 6 times, it was unmistakable, and that didn't take very long, so...so I said ok, well, it really happened, so what's next, what's the next thing to investigate. I began a rather detailed experimental program, which ended up with mapping starting from the fact of crossing to generating linkage maps, and showing a lot of other markers, laid the foundations of doing genetics in E.coli.

LP - How long have you worked in this field? You discovered transduction (the process in which a bacterial virus carries genetic material from one host bacterium to another) also?

JL - click here for in-depth answer

LP - My brother pointed out that what makes you very interesting is that you are a person of more than one discovery in that most scientists just basically discover one thing, and that is all that they are famous for, but you did a number. What motivated you to go on?

JL - Well, I wish I had a talent for dropping things as well as taking on new ones. It gets to be quite a clutter after a while, but I've just been excited about, doing, I get curious about new things, and I think I have a particular penchant, my real strength is going into a field that has not been investigated before, and finding new approaches to it, so I've applied that notion to a few of the fields that you know about. And, I guess I'm not easily inhibited by the fact that I don't know something about a subject. It doesn't stop me from dabbling in it, everybody has to learn it for the first time, so why not. And being successful at a very young age gave me the confidence and the capability to try out other things. If it takes you 20 or 25 years to establish yourself in one field, you really ought to be pretty careful not to stray too far, you really need a lot of focus of attention, and you have to be able to make your original entree, but I was very lucky, and I had the capacity to try out a lot of other stuff.

LP - At the same time that you were discovering molecular genetics, in Russia, which is where I'm from, Lysenko was suppressing it.

JL - Oh, I was condemned, I have a very interesting article in Priroda, talking about this mental Morganist, who's got these crazy ideas about genes and bacteria when genes don't exist at all. I suspect the person who wrote the article was embellishing the story with the appropriate propaganda in order to then tell the message. Levedet was his name. I know someone who knows him, and assures me that was the case. The one most courageous opponent of that doctrine who survived was David Goldfarb. His son Alec is a professor at Columbia....and I rather know him very well. I met David once or twice, he visited Stanford in 1960. He was one of the first DNA people in Russia, and by talking about DNA rather than genes he was able to get away with it. He was also a hero of Leningrad, and that gave him some standing as well, so he kept some spark of continuity of serious science going which was very hard to do when Lysenko wiped out all his competitors, and put a lot of mediocre hacks in charge of institutes. It's a terrible problem. Do you know Valery Soifer's book on Lysenko? It's a wonderful piece of historical writing, and it covers the entire episode from beginning to end. I really recommend it to you very strongly. He wrote it while he was still in Russia, he managed to get it published during the Perestroika, and then had it translated after he emigrated to the US, so it's available in English.

LP - How did you feel when you won the Nobel Prize?

JL - Well, it was something of a shock, a total surprise, and I had no idea what it would all mean, and, you know, very gratified about it -- to have the recognition of your colleagues is great. The public attention is a mixed blessing, but it sort of goes with the territory and it gives you a sense of responsibility, that as a scientist who commands that degree of public attention one ought to be super-careful about the things that he says, and they are gonna be taken very seriously as reflecting scientific validity, and two, there is a message that science has to offer to the public: the style of thinking, the integrity of argument, you honor your adversaries, and you put all the evidence on the table, you have an absolute obligation to feed your critics with all the data, it's very different from the legal adversarial process, and that there are certain commentaries about sticking close to scientific fact that should be articulated as well. I have no doubt at all that my interest in being a public exponent was enhanced by the Prize, but I'd already been doing a fair bit of that anyhow, so it didn't start with that, but I was already a pretty well-known scientist. Winning a portion of the Prize sort of put a cap on that.

LP - Did you know any of the winners in other areas?

JL - I knew Beadle and Tatum very well, they were my...but no, I didn't. Pasternak was forbidden, I've not met...Cherenkov, Tamm, Frank, I've heard of their names, but I didn't know much about their work, I have never met them. I took quite a liking to Tamm, he was a very independent minded person at a time when that was hard to do. The other two were much more browbeaten by the system. I don't doubt they were good scientists. I don't have a clear picture of Frank, I certainly do about Cherenkov, he very carefully avoided anything that came even close to political discussion. Tamm was quite outspoken.

LP - How was the whole awards process done?

JL - click here for in-depth answer

LP - In 1960, you were Time Magazine's man of the year, one of them.

JL - Well, they had offered to do a cover story, but I declined. I didn't want that kind of public attention. That was a little earlier, actually, it was '57 or so, but I remember I sort of offended, there was a man named Aaron Bolard, who was the artist in residence at the university of Wisconsin, and he did commission to do the portrait that would then be on the cover. I just didn't want that kind of press attention. Believe it or not, although I am a public figure, I'm still a little shy about that. I'm very interested in putting the consequences of science, I don't think my own personality it important for that purpose. I prefer to keep some small dosage of privacy.

During all this time I was making a lot of momentous personal decisions. I was still very very young: when the prize was awarded, I was 33, the work I had done when I was 21. I had kids. Both of them are past 21, and I sort of marvelled that I didn't get into more trouble than I did. At a very young age.

LP - What was your wife's name?

JL - Well, my first wife was Esther. That was, again, something in retrospect, maybe I was too young to go into: I married in '46, when I was 21, so...We stayed together for a little over 20 years, but we separated in 1966, and I remarried in '68 to Margarite. She is an MD, and attending psychiatrist at a hospital. She's French, she was born in Paris, was a hidden child through World War II in Southern France, came to the US after the war, and had a brilliant career since.

LP - What kind of priorities do you have in life, what goals?

JL - Well, I think we have to believe we are here for some purpose, and I know there are many cynics who will deny it, but they don't live as if they deny it. They have to have some framework of expectation about that meaning, and I think the search for that is what science can help to offer. Now it may all be fabricated, you know, true it's externally given, but almost everything else about it is also fabricated, so I think it has validity.

...I believe I am a person with unusual talents. I think I'd be a liar or stupid if I were to deny that, but I think it poses a very great obligation that I have to use those talents in the best possible way, and that includes looking for whatever deeper meanings you find for yourself, and it also includes whatever benefits you can to make life easier for the rest of the human population. I think the two are in concert. I haven't faced any great dilemmas in choosing one versus the other. That's one of the reasons I decided to go into medical research, to have both of those objectives in parallel.

LP - In terms of that, what do you think is your greatest accomplishment?

JL - Well, I think objectively there's no doubt that opening up genetics of bacteria had an impact. It was part of a movement. This is not the chemical side of it, but it's the cell biological aspect of it. It was not only the experimental results, it was also a style of experimentation... If you look at how did we go about discovering conjugation, discovering transduction, the experimental designs; those are very familiar today, but I think we more or less invented them, and the process of that kind of work, and they've been used over and over and over again by many others. And there's a deeper methodology of how you go about doing genetic analysis, which we exemplified, we didn't invent it, but carried it through one more step, and again that's just so deeply embedded in the tradition of contemporary research that people don't even ask where it came from.

LP - I guess, also, while we are on greatest accomplishments, do you have anything you consider to be a great failure?

JL - Click here for in-depth answer

LP - How did you get involved in space exploration?

JL - Click here for in-depth answer

LP - In Russia, the propaganda was that basically there was no point to putting people on the moon.

JL - Well, Russians made a good try. Now we know that Gagarin was in much more trouble than they let out.

LP - When did you first get interested in computer science?

JL - Click here for Lederberg on the past, present and future of computers

LP - You mentioned about the future of genetics before. Is that what you mean when you say that all genes will be classified in the future?

JL - Oh, well, that's the easy part to predict, everyone knows what needs to be done in that area. As soon as you go into any biological process in any real detail, you discover it's open-ended in terms of what needs to be found out about it. Evolution's been going on for 4 billion years, and it's like that neural net, but over a very very long period of time, and it's built wheels within wheels within wheels and we get very exciting glimmers of it every now and then, but a long way from a comprehensive picture. Pictures are getting complicated enough, they are going to go beyond human scale of comprehension, so we are going to have to more and more embody these models in surrogates and have the computers do the models of the things we are trying to understand. And understanding will be second order to saying, well, I've got a rough idea what this model is trying to do, but I put it into the machine, and the machine executes it and comes out with predictions that are roughly in accordance with experimental data, and what you mean by understanding will be a little more remote than today, just because of the complexity of it. I think we are there today in immunology, if you look at a monograph in immunology, and Hall's book, about 2000 pages, still doesn't encompass everything that's going on in the field. I don't believe that anybody can really grasp everything that's even in that one textbook. It may get a little simpler as we understand more of it, but you can see that organisms are, in fact, pretty complex machines.

LP - You are also involved in scientific policy. When did that start?

JL - Click here for in-depth answer

LP - Do you think that's a primary concern in today's society?

JL - Yes, it will, because all of civility depends on being able to contain the rage of individuals, and if we have isolated individuals able to inflict enormous harm, and I think that's technically possible: imagine what a single lunatic can do with a nuclear weapon. I think the whole base of civil society is at risk.

LP - You received the National Medal of Science in 1990...

JL - Yes, I'm proud of that award, because it was very much in recognition of my consulting service. I got my Nobel Prize for my lab work some years ago, and this was a new thing, and if you want to see it, it's right over there.

LP - Oh, alright... [Checking out the medal...] What are some of your interests or hobbies?

JL - Well, I have so much to keep me busy, that call...Life's a hobby.

I don't want to say very much about family life, but I treasure it very much as well, but that is a more private arena, but I have 2 children, and a wife that I'm very deeply attached to.

LP - How old are your children?

JL - David is 31 and Annie is 21. She is a senior at Harvard, he is doing graduate work in Stanford in science policy.

LP - I see. What are your goals right now?

JL - Well, to enjoy the kind of life I've been privileged to up to this point as long as nature will allow, and I have an immediate lab program, which I'd like to see come to some further fruition. We are trying to understand how mutagenesis varies with the conformational changes that DNA undergoes during the cell cycle or under conditions of transcription. So, transcribing genes might be expected to be more open to mutagenesis than dormant ones. That's the general arena of our investigation.

LP - What kind of legacy would you like to leave behind?

JL - Well, I think I have left it behind. I think the scientific work I've done is of the greatest importance, and long after all the policy stuff has been forgotten and chewed up in new ones, I think there are steps of improving of our knowledge, and I hope I've lived a life of science whose style will encourage younger people. And that there is so much intrinsic excitement to it, that it's much more important than the competition for wealth and glory and so on that we hear too much about, and we hardly ever hear about the other, so I'd like to put in a vote for the intrinsic fascination of science.

LP - So, are you generally content with the life you have lived?

JL - Of course not, I have many shortcomings, I've made mistakes, so content is too strong a word. I feel very lucky to have been able to have what I've had.

LP - Do you have any advice for young people today?

JL - I guess, try to come down to something as practical as possible. Try hard to find out what you're good at, and what your passions are, and where the two converge, and build your life around that. And we are all very individual, it's gonna be a different answer for different people. And you really have to find out what you can do best, and what you want the most to do best, and be self-conscious about that, try to think of what the alternatives might be, and make deliberate choices, don't just wait for things to happen.

LP - Well, I guess that's about it. Thank you very much.

For additional information, see also an article in 21stC, Columbia University's on-line magazine.

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