Sidney Altman


Interview, June 2000

Interview with Sidney Altman by Sture Forsén at the meeting of Nobel Laureates in Lindau, Germany, on 26 June 2000.

Sidney Altman talks about how he became interested in science (2:12); the difficulties of being a pioneer (9:54); his thoughts on the Human Genome Project (13:15); the number of genes in the human genome (20:11); and his careers advice for young students (21:29).

Interview transcript

I’m very happy and pleased to be sitting here with Sidney Altman. We are sitting here on 26th June 2000 which is a special day. And we are here in Lindau at the Nobel Prize meeting. Meeting of some 16 Nobel Prize Laureates. We have taken the opportunity to catch a few of the Laureates to have the chance to interview them for a short while. Let me ask you first of all, you are the son of an immigrant. Did your family encourage you to go into education?

Sidney Altman: Yes, my family felt that the pass to advancement in the new society that my parents had come to was through education. That education was the means to understand new things, to understand the new world they were in and to enable their children to do better than they had done. And some of the older relatives in my family were teachers of one kind or another so it was not so out of the question to think so highly of education and the value of education.

And they didn’t push you in any special direction?

Sidney Altman: No, I feel very fortunate about that. That they didn’t impose what their views of what might be the best things to do. For example many kids who were in the same situation I was in were encouraged to go into medicine or law because they were very secure professions. And I never had that kind of constraint put on me by my parents and I felt free to choose whatever I enjoyed and whatever I was interested in.

How did you become interested in science by the way?

… I somehow knew about Einstein when I was growing up as a kid …

Sidney Altman: I have of course been asked that question frequently and I try to remember it correctly but it’s always hard to know if you remember the past correctly, let’s put it that way. I recall a few incidents. And one of them may not be so exciting in terms of the rest of what the world may perceive as something that interested me, but I somehow knew about Einstein when I was growing up as a kid. I think I had been given a book, short biographies of great men for children, and I was six years old when the atomic bomb was dropped to end the Second World War in Japan. Naturally the whole world was full of the news. The newspapers were full of pictures. The story of the bomb and how it was built was written up everywhere. And the role of scientists and pure research in generating the ideas and then the success of the bomb were clearly laid out at that time and a direct connection to Einstein, although he might not have wanted it to be so direct, was there.

So as a kid I was impressionable, being young, and this made me feel that science was very important. At the same time I was interested in natural phenomena. Obviously if I didn’t have both sides of these things going I might not have pursued it. But I would say in terms of the specifics of science, when I was about 12 years old somebody gave me a book to read, and I can’t remember who it was. It was written for I would say kids or the layman and it was called Explaining the Atom. But the significant thing I remember in it was the periodic table. A very lucid explanation of the periodic table and how Mendeleyev formulated his ideas and even more important the notion that Mendeleyev was able to predict the properties of elements that had not yet been found. And to me that was absolutely amazing when I was 12 years old. It was so elegant. So beautiful, that I think it was at that time I decided really to try and study physics which I went on to do. And so that was the beginning, I think, of my real interest in science.

I switched to molecular biology later on, from physics. And I do remember actually reading one paper when I already had my Bachelors degree in physics. I just came across it one day in the journal Nature. I wasn’t looking for it because I wasn’t knowledgeable in the field of molecular biology. It was a paper on the nature of the genetic code. It said that the genetic code is read in groups of three letters from DNA essentially. And it was a paper from Cambridge England and Francis Crick and Sydney Brenner were the senior authors. And I remember thinking to myself, not merely this is again very elegant, beautiful, but thinking to myself how could they possibly have understood this. How did they find this out? It seems magical that you would be able to say something about the way we are encoded in a sense in nature. And that stimulated greatly my interest in molecular biology as a discipline also. I thought it was something I’d never heard of before. Something I wasn’t really in touch with. I’d heard about DNA. I knew a little bit about it but to be able to do that kind of experiment I thought was amazing.

You mentioned to me that you were a little disappointed with your studies in physics. That you were not allowed to go into the lab from the very start.

… I was able to do some research as an undergraduate and I enjoyed it enormously …

Sidney Altman: No at my undergraduate degree I was able to do some research as an undergraduate and I enjoyed it enormously. And when I went to graduate school first in physics it just so happened that where I was it was very hard to be able to, at least I found it difficult. I couldn’t find the right way somehow to get into somebody’s lab to continue my work. I had to take couple of years more study of coursework. And I found that extremely discouraging. So it wasn’t physics per say. It was just the personal situation and I was very unhappy about it and I left that place.

It’s striking when you read the autobiographies of the Nobel Laureates that many of them started out in a field very different from where they ended up. I sometimes sense that youngsters of the day are a little worried that they start out in the wrong field and they will get trapped there. Would you like to say something about that?

Sidney Altman: Well, I think that I’m not sure that I would include myself in this statement, but a lot of the people who for example are at this meeting are extremely imaginative and curious people. And I think people like that will always be looking for new challenges and new ideas that are not necessarily established ideas in their own field or derivative ideas from things in their own traditional disciplines. They will always be looking at the borders of knowledge. And one can’t predict exactly where that will take you. I think that’s part of it. I don’t really want to get into a sociological analysis of today’s students but in my particular field molecular biology, I will say that it was not really a field per se for example when I went to university. So that everybody who came into it before that time and about the same time as I did had to come from another field. There was no training in molecular biology.

Today, because of the success of modern molecular biology, every university department has a department of molecular biology or called something else maybe. But similar. And you have a lot of people going into what is now an established field. And a lot of these students, as you say, do it because they know there are jobs available at the other end. And that’s what they want. And there’s nothing wrong with that. A lot of people go to university for security and a profession and that’s fine. But one hopes one still gets the occasional student who has that restlessness of intellect and curiosity to want to go on and do research.

Being a pioneer is not always easy and you made a discovery that was met with disbelief by many of your fellow scientists. How did this affect you? At one stage you lost a grant at least temporarily.

Sidney Altman: The first significant observation about the enzyme I worked on occurred when I was still a junior faculty member. That is to say, I did not have tenure in the American system. And it was extremely discouraging, because one felt that one’s further progress was in real jeopardy. And I should be a little more specific and say that by obstacles we were having a lot of difficulty getting our work published for various reasons. First time we sent a short note into one of the more prominent journals we got a reply from the editor without even having the article reviewed, saying you really ought to do more work on this, you don’t really know what you’re talking about.

… I have faced the prospect of having to close down my lab …

And then there were other difficulties. And then we did in fact lose our funding temporarily. That is to say the panel that reviewed our progress felt either we weren’t making any progress or what we were doing was not interesting or both. And so I have faced the prospect of having to close down my lab. And I was just on the borderline and there was enough money left so that after three or four months they managed to give me some more money and I continued. But that period was extremely discouraging. More than half of the little world I was in would not accept the results. But I want to mention a conversation I had with one of my post doctoral mentors, Matthew Meselson, who I happened to encounter at a scientific meeting during that period. We hadn’t seen each other for a while. He asked how things were going and I told him. And he listened and said: Well look, are you sure you did the experiments properly? Are you confident that you carried them out correctly? You did all the right control experiments? The results are real. In your mind what you have observed is what nature is telling you.

And I said yes we’ve done it up and down, backwards and forwards. I’ve done everything I can think of. It always comes out the same way. And he said: Well, then you really don’t have any choice you have to believe and you have to go on regardless of what everybody else is saying because that’s what nature is doing. And sooner or later the rest of the world will come around and realise that, probably because somebody will repeat your results and then they’ll have to be accepted. And that is the way science works in all cases and that is the way it did work ultimately. But for a period of a few years it was emotionally very hard.

Today, the 26th June 2000, is a very special day in a way that a joint group of scientists from many countries have announced that they have completed and also published at least the first version of the human genome. This is of course is a major step in the history of mankind and history of science. Would you like to comment on that?

Sidney Altman: I think there are several important things to say about the actual announcement which I just happened to see when I was taking a little rest before. And it was very interesting for a number of reasons. First of all let’s talk about the science. Of course if you are in molecular biology you knew this was coming. So it’s not striking or surprising that this stage has been reached in our knowledge of the genome. I thought that during the talks given by various people today it was clear that they are trying to be very careful about the practical implications and the timeline for fulfilling some of the practical promise of this knowledge. We have to understand exactly what all this information means. We have a huge amount of information in front of us. We don’t know how much of it is relevant to the everyday function of the human body. We don’t know at the moment. But I am perfectly confident as are the scientists who have been working on this project that within five to ten years, perhaps even sooner, we will know a tremendous amount because of this information. About how the human body works. That is to say in comparison to what we know now. We’ll know much, much more. And it will have a very major bearing on our understanding of human disease and probably give us new insights into treatment of disease.

Now I’ve made some great generalisations just now and I’m probably not the person to become more specific about it, except to say that I think I agree with you it is a milestone event and it is important but it will be a few years before we derive the benefits. But that’s not surprising. It happens with every major scientific advance. I also want to comment on some other thing that were said and how the announcements took place because I think they’re almost equally important. There were two factors in addition to the science that I thought were important. One was the fact that you had the political chiefs of two of the leading countries of the world. Leading in terms of advanced technology, financial comforts, standard of living and things like that. The Prime Minister of Great Britain and the President of the US participated in a joint transatlantic television conference which in itself is interesting. And both these heads of state were clearly knowledgeable about the advance. They seemed to feel at ease talking about what it meant.

But what it meant to me was that the political establishment in both countries and all the other participating countries in which there are several, therefore the people the societies themselves, were behind this whole enterprise. This is one of the few times I think in history where so much has been devoted by so many countries in a truly international effort with the political heads of all the countries behind them to participate in this project which will benefit mankind in a great way. And I have to also say that both heads of state and the other scientists who spoke did speak about minimising the potential harmful effects that might arise from this new knowledge. The use of the information for example. As an aside I will say that Mr Blair used that word minimise. He didn’t say you could make zero the potential negative effects. He said minimise which I think is the correct way to put it.

… governments alone cannot do everything. They cannot support all research …

The other aspect of this announcement which I thought was very interesting and very significant in many ways, in the States you had accompanying the President the head of a large commercial enterprise which was involved in producing this information as well as the head of a government lab. Actually the head of the international human genome project. And they clearly had reached before this announcement an agreement about how the information was going to be used. How the commercial enterprise would be able to benefit from it but still work together with the public enterprise to make the information available to everybody.  Now we don’t know the details of that agreement yet but I think it is significant that after a few years of rather bitter wrangling supposedly this conflict between funding of private research and public research has either come together or been ironed out with some kind of compromise which will allow everybody to benefit from it. I think that’s also very important because governments alone cannot do everything. They cannot support all research. And this is one case where the private sector has been very energetic and ambitious, and so it’s significant that, in the end, it’s worked out its differences and terms of intellectual property sharing with the government. So that’s my rough reaction to today’s announcements.

On a more lighter side, I noticed that in science there has now been a kind of betting scheme on how many genes there are in the human genome, and I’ve seen numbers from 28,000, which is I think the lowest, up to 153,000, which is the highest I have seen. Would you like to make a bet on how many genes there are in the human genome?

Sidney Altman: Well, the low numbers are very interesting, because the other genomes that have been sequenced recently, for example the fruit fly, Drosophila, and some other bacteria, the nematode C. elegans, have all turned out to have fewer genes than we thought that they would have. However, a mammal is different to some extent, and so I’m not willing to make a wager, but I would say fewer than 100,000, and I also repeat a comment that we heard earlier today, made by one of our colleagues saying that predictions are very hard to make, especially those about the future. I would hedge my bets there.

Maybe we should end up by asking what kind of messages you send to your students, when you talk to them and when they ask you for advice about their careers.

… if students come to us and want to be taught, then we ought to teach them …

Sidney Altman: When dealing with students I think we have to talk about what stage they are at – high school, undergraduate students or graduate students. Let me start at the top and work my way down. With my graduate students I take the following approach: I am supposed to be their teacher. That is my main role – to teach them. What am I supposed to teach them? I am supposed that my view what I am supposed to teach them is how to be independent functioning scientists, so that when they leave my lab and want to go elsewhere, whatever they want to do – postdoctoral fellow, academic jobs, industry, go to a completely different field – I want them to feel sufficiently self-confident intellectually, that they can be scholars, whatever they do, and make real contributions. That’s graduate students. And in terms of their job prospects, they are very much in tune with what is out there. I don’t feel we should limit the number of PhD students if there is a trenching dip in the number of jobs available. I fell that as university teachers, if students come to us and want to be taught, then we ought to teach them, it is a question of passing on our knowledge.

At the undergraduate level, students have still a number of decisions to make about what they want to do and how they want to do it in terms of leading professional life. And I think that my advice generally is do something that you are really interested in and that you like. By the time they are in graduate school supposedly they know that and they’ve made a decision, but at the undergraduate level, especially the way the American education system is set up, they still have a great deal of latitude in determining what to do, and so the best advice I think is simply to tell them that they should find something they like and if possible something that they’re reasonably good at because it’s much more enjoyable to do something every day that you’re good at than something that you’re not especially good at. So, that decision.

At the high school level, I think there are two kinds of advice, perhaps three, that should be given. First of all, because I’m prejudiced in this regard, I’d say to them get as much education as possible. And as a corollary, no matter what your background is, or your financial or other situation is, don’t feel that these are obstacles. If you want to get more education, you’ll find a way to do it. There is nothing special about the people you will see in these series of interviews or in any other way. We come from all lots of life, from all different kind of families, we are simply a group who are especially interested in learning more things and education, but that’s it. Never feel intimidated about pursuing your own desires and beliefs and if education is not for you, then choose something else that you really want to do and work very hard at it. The hard work part is something that I forgot to mention. I don’t know anybody who has done well at what they are doing, no matter what the discipline is. It could be a letter carrier, it could be a sales manager in a store or a university professor. All the people who do well work very hard. Nobody who has a record of achievement has been lazy about it. I think that’s part of the message but students hear that so often sometimes they just tune that out, but it’s certainly very important.

Thank you very much, Sidney.

Sidney Altman: You’re welcome.

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