Albert Lasker
Basic Medical Research Award

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An Interview with Pierre Chambon
Interview by Richard Axel

Chambon: I think our role, as scientists, is to inform the lay people of what we have found and about what could be done with what we have found, and to refrain from giving our own opinion on what should be done. Because I am convinced that my own view of what should be done with science is not better than the view of anyone in the street.

Axel: Do you really believe that?

Chambon: Yes, I do believe it.

Axel: Do you wish to leave the issue in the hands of politicians and theologians?

Chambon: You know, there is no alternative. Either you take the power or you leave the power to others. But what we absolutely have to do is to inform. This is important, and to inform honestly.

The problem is that scientists are human beings! And therefore, when they present their discoveries they often make predictions on what could be done with them. Cloning is a typical example. Whether it will be possible in the future to clone a human being, I don't know. I think it's not for tomorrow. But we have lived during the last 10 to 15 years with the idea that human cloning could be done at any moment. It is not. So I think we have to be more careful — I mean scientists have to be careful before saying something like "tomorrow we'll have new drugs for this and this," or making a lot of optimistic predictions, forgetting the complexity of problems which have to be solved before these predictions will turn into reality. This explains also to some extent why the public has been disappointed by what was actually brought about by recent discoveries. In some way, it is the fault of scientists.

This being said, the public at the same time forgets what has been actually achieved. For instance, without all of these advances in biology, we would probably not know the viral origin of AIDS, and would be guessing that it could have an auto-immune origin or any other fashionable origin, and therefore would invoke words and not facts. It is true that we are still waiting for a vaccine against AIDS, but the problem is complex, and whether there will be a vaccine or not in the future, I don't know. But what is clear, is that with today's molecular understanding of the biology of the virus, great progress in AIDS therapy has been made, and it can be safely predicted that ultimately we will win the fight against this devastating disease.

The problem is that we live now in a society where not all diseases have been defeated, but many of them have been. And the younger generation ignores all of what has been learned during the last century. We don't die, at least in our countries, from tuberculosis any longer. We don't die from high blood pressure — we don't die from diphtheria. And so on. Saying that science and especially biology has not brought progress is totally wrong. We should teach better the history of science at school. It's important for future generations.

Most of the problems concerning human cloning were not raised by scientists. There will always be a scientist to say "human cloning is possible and will be useful." A famous name amongst the biological community said 50 years ago that if one would mate Nobel Prize winners together it would speed up the progress of science — which is, of course, crazy. But it's not because some scientists make statements which are crazy that one should automatically conclude that all of the scientists are crazy and that they will necessarily generate monsters. Even if human cloning one day turned into reality, would it be a real problem for a society? In any event, there are presently problems in our society which are much more important for the future of our world than a putative human cloning. But these problems are rarely evoked on the front page of newspapers.

Take another example. Thanks to what has been learned in endocrinology, it is now possible for a menopausal woman to have babies. There has been heavy discussions whether this should be authorized or not. But who cares? Is it really a problem for our society? No. It's a problem for individuals — if they want to have a child at the age of 65, it is their problem. It will never be a problem for society, because the number of women who are ready to be pregnant at the age of 65 is very limited.

So let's look at the real problems: you evoked the problem of the cloning of plants, and of modern man doing things which will be generating catastrophes. Remember that humans have manipulated the genome of plants for the last 10,000 years at least, mixing genomes which had nothing to do with each other without any catastrophe. What is actually catastrophic is to erase forests in Amazonia — systematically, with nobody being really concerned.

I do not know whether it is done consciously or not, but we pay too much attention to problems which, in my opinion, are not endangering nature and our societies. It could be our fault because, as I said earlier, we scientists often selectively point out what is singular — which looks exciting — pushed, in fact, by the mass media. It is well known that what is emphasized by journalists is always the exceptional, which is often frightening in some way. Progress in science is similarly reported with an emphasis on the sensational at the expense of what is really significant for our future.

Axel: To continue this argument — there has been a concern that the power of genetics has allowed scientists to begin to address questions that have social and ethical implications. This has led to the disturbing notion that the government has both the responsibility and the power to determine what knowledge a scientist is allowed to obtain. This concern is particularly relevant in this country now with the cessation of federal funding for much of stem cell research.

Do you believe that there are limits to knowledge that a scientist should obtain?

Chambon: No. I think that there should not be any limit. Every time there was a limit, we were in Dark Ages. Nobody can stop the progress of knowledge. It's built in humanity and history tells us that it is useful. At least in biology, it has always been useful. As biology is dependent on previous progress in physics, one can safely say that science has been an instrument of progress for humanity. Not only materially, but also sociologically. We have today a different idea of what we human beings are, an idea which is much more objective and which should allow us to behave among us in a more human way, because we know better what we are, and from where we come, which is very important.

The role of a politician is not to limit the progress of knowledge — in fact, there's a lot of hypocrisy in what you mentioned earlier. It's not meant to be a criticism against your country, because I could make the same criticism against the French attitude. Deciding that one can use private, but not public funds to work on human embryonic stem cells is total nonsense, because either it is dangerous or it is not. I don't see why it could not be dangerous with private funds, while dangerous with public funds. People should tell the truth. And the truth is that this interdiction is political, not scientific.

Axel: I agree. So I've known you for over 30 years and you have this intensity which drives you and generates excitement in the laboratory. And I can tacitly assume that for as long as you persist, you will remain in the laboratory. So what are the next 20 years of your laboratory's life going to tell us? Where is the excitement? Where is the conceptual innovation? And finally, what might be the clinical implications of the next 20 years of your research?

Chambon: This is an impossible question to answer: whether I will play any role in conceptual advances.

Axel: Let's tacitly assume you will. What will they be?

Chambon: First, I'm a builder. That's clear. My scientific life has been a challenge, and the challenge was a personal challenge because I wanted to prove myself that I can do something. The challenge was also to build something in France.

I had the chance to spend a year at the Biochemistry Department of Stanford University which was, at that time, the best biochemistry department in the world. I learned there how one should organize research in order to be what we call successful, which means to make discoveries.

I decided to go back to France and to stay in France...and to try to build a laboratory — it would not be the Stanford Department of Biochemistry, but it should be efficient — a place where one could work and discover, and where young scientists could express themselves, and this became the IGBMC.

Fifteen years ago, we started moving away from straight molecular biology studies, which were mainly in vitro work, not only in test tubes but also in cells in culture under situations which sometimes mimic the physiological ones, but are never really actual physiological conditions. I took this decision as I felt that we had learned enough from in vitro studies to start tackling and solving problems in whole animals. Either we are biochemists and so are satisfied by knowing how an enzyme works and how an enzyme catalyzes a reaction, or we are rather physiologists.

With an MD background — I know it is your case, and it is my case — you wish to understand life at the integrated level, in the animal. We want to know whether all of these molecules that, from our in vitro work, appear to be involved, play a similar role in vivo — and at the very end what is relevant to the animal physiology and pathology, and their clinical implications.

To achieve that, we had to move to genetic studies in mammals. I said earlier that sometimes in our research we are facing walls and feel that we cannot move further. This was precisely the case at the end of the '80s for the field of mammalian genetics. Fortunately, a mini-revolution — but for us it was a remarkable advance — occurred, making possible to create mutations in the mouse, to mutate at will a given gene, and therefore, to study the function of that gene in the environment of a mouse.

The new frontier in biology is what people call systems biology — it is to understand how everything is integrated in the animal. There are people who say, "We'll never understand it because it's too complex." True, it is complex. It's extremely complex because of what we said before — because during the conception and the development of an animal and throughout adulthood, there are thousands of factors, of proteins which are interacting in various ways and which finally are responsible for what we see of the animal — for what exists, for what is materialized, for what we call the phenotype.

What we want to understand is not only which genes are important for the formation of a finger, but how all of the products of these genes are making a finger, a question which is quite different. So I decided to switch to the mouse, and to build up a new smaller Institute — what I named the Mouse Clinical Institute, where we can examine the mouse from all aspects.

There, there are cardiologists who are working on the mouse heart, others working on the behavior of the mouse, and so on.

Thus, we may in the future contribute to systems biology by providing explanatory models which could be tested to guess what is the in vivo reality. However, these will remain models, as the complexity is such that it will never be possible to reconstruct it in a test tube. But the pathological and clinical implications are obvious, because whatever will be discovered concerning the normal function of genes in integrated animal systems will be useful to understand the molecular basis of diseases and generate new therapeutic agents.

Axel: Unfortunately, we've come to the end of our time. I just want to say that it's been a pleasure to watch the way in which you have done science over the past 40 years, and it has been a great pleasure to have listened to you recount those 40 years. Thank you very much, Pierre.

Chambon: Thank you, Richard.