Werner Arber

Interview

Interview, July 2003

Interview with Professor Werner Arber by freelance journalist Marika Griehsel at the 53rd meeting of Nobel Laureates in Lindau, Germany, July 2003.

Professor Arber talks about the positive changes after the award; how it wasn’t obvious what the discovery would lead to (2:51); whether scientists dealing with basic science are different to the more technically orientated (8:42); whether simplifications are always an aid to understanding (13:12); the positive uses of his achievement (17:08); the qualities young students must have (22:50); big problems yet to be solved (23:59); and theological perspectives on evolution (28:38).

Interview transcript

Professor Werner Arber, welcome to be with us here in Lindau.

Werner Arber: Thank you.

Though some years have passed since you were receiving the big honour. At the time, what did you think would come out of being given the prize? Did it change your scientific work in any way, or your general life?

Werner Arber: When I got the prize, 25 years ago now, of course I pretended it shouldn’t change my life, I did try to behave as before. I got, however, quite frequently obvious contacts from persons, from organisations, from groups, to ask me for giving some of my opinions, help in committees and so on and I did realise rather rapidly that that was a good opportunity for me. I had the liberty to choose, to say “no” or to say “yes” and I think I made usually a good choice sometimes. When I discovered that I shouldn’t have said “yes” I tried to get out of the business and … 

Give us an example, what was a good outcome after the prize so to speak …

Werner Arber: I have for example been asked in the 1980s, I was at the University of Basel and I had been asked whether I would be willing to become rector of that university for two years’ time. In fact, I would be a member of directorate during six years because there was a rector designated a period of two years then a rector in full office and a past rector for another two years so that was the group of directorates. After some reflection I accepted and it was really well seen, you know, that having been honoured by the Nobel Prize, I wasn’t thinking that I should do only science and that brought me into science politics and then sometime after I had been asked to become a member of the Swiss Science Council in which I have also been more than ten years and that brought me into really problems of science politics which I think was good for my own country and also for the world altogether.

When you had your discovery back quite a number of years ago …

Werner Arber: Around 1960, yes.

… there are, people said there are many risks, can you see those risks today, why people …

Werner Arber: OK. When I made the specific discoveries in 1960 of course it wasn’t obvious at that moment what that would lead to. It needed to have the enzymes purified, that took another almost ten years and other people in our own lab contributed essentially to that and it is then in the early 1970s that the enzymes which are able to cut the DNA into fragments, which allows to act, to analyse the genetic information more properly than if you have the very long chromosomal filaments. At that moment it became clear that certain fragments could be recombined differently together and also amplified in so called gene vectors which could be viruses or other small DNA molecules, that actually gave rise to genetic engineering, the recombinant DNA techniques and at that moment the question was raised whether there were contractual risks into doing so. Now I felt, because I had contributed to the knowledge that there are these enzymes and then the enzymes were used, I felt also more of an obligation to think about more deeply on these risks and from today’s point of view I think I did contribute a lot for the evaluation of such more long-term risk which would relate to the biological evolution. I have studied for the last about 30 years intensively the molecular processes of molecular revolution, how do genetic variations which is the basis for evolution occur in nature and are these similar or very different from what the genetic engineer can do in the laboratory.

I work with bacteria and this I found out that there is a big opportunity to understand molecular processes by which the genetic information spontaneously undergoes changes. This can be compared with what in genetic engineering is done reflectively, by human beings and perhaps I could just tell you that there are a relatively big number of natural processes on work too which contribute each in its proper way to the formation of genetic variations at very low frequencies of course because for any living being the genetic information must have quite good stability. However, it’s not absolute. If the stability would be absolute there wouldn’t be any evolution and the evolution is a source of biodiversity. I think it’s a wonderful thing.

But if you then go in and if you can control it, the humans can go on.

Werner Arber: If you look at which kind of changes nature does spontaneously there are in fact three strategies, one strategy is within the genetic script, changing one or very few letters, these are local changes. The second strategy is within the genetic information of the organism rearrange longer segments of that DNA and sometimes duplicate one thing and delete it or invert it or put it in another sector within the DNA and the third large strategy is to acquire from another organism by horizontal gene transfer a segment which that receiving organism hadn’t had before. These are the three much natural strategies of genetic variation and their qualities of course with regard to contribution to evolution is different. Now, if one looks at what in genetic engineering has done where also artificially reflected the DNA sequences are changed in order to make mutants on which one want to study what is the effect of such changes on the life, on the phenol type, that can be locally, it can be by deleting a segment, by inserting another segment from another origin and so on and so forth. So, the strategies are just the same and my conclusion for the time being is that we shouldn’t worry too much about the risk of genetic engineering because the risks are very similar to absolutely normal, natural evolution which is actually a natural phenomenon without which we wouldn’t live today and our surrounding world wouldn’t be as it is.

Somebody said to me that the scientists who are dealing with basic science, are different to those who maybe do medical research or develop certain kinds of products and so on with the technique so that the moral high ground is high within the researchers and the scientists so to speak, the basic scientists, but there might be other people who are not as morally, they might have other interests, financial interests.

Werner Arber: OK, you’re right, if a technique has proven to be applicable to something of course the inventor of that technique has no guarantee that someone else will misuse it for another purpose, that’s clear, but this is true in any human doing so that’s a general problem and it can be properly contained I think by bringing this particular issue into the political legislation so that some things are actually favoured and other things should be not allowed, that’s the usual case but of course I do realise that this takes quite a number of years going through all this political debate and so on to have it finally implemented.

So it would be good from your point of view to have some kind of similar legislation all over the world on these issues?

Werner Arber: Harmonisation of the legislation in these fields would be very appropriate and thanks to not at least through the activities of the scientists themselves I have already recalled the Asilomar conference more than 25 years ago, have helped enormously to make all the countries attentive to these developments and in many countries the laws have been adapted to really conduct the appropriate research properly.

To be able to understand this valuable research that scientists are doing and which often takes many, many years, you then have to be able to explain it as well and I read a beautiful story that your daughter came up with. Could you just briefly relate them to us, as a way of describing what you found out.

Werner Arber: Sylvia was ten years old when I got the announcement of the prize in October of 1978 and the next weekend we went to some walks and we talked about what has happened during that week which was really also impressing our two children and then Sylvia said, “If the children in school tomorrow ask me what was that all about, what should I tell them?” And then I tried to explain to Sylvia in relatively simple terms what my contributions were and after some reflection she came up with some comparisons saying “Well, DNA, is that correct, DNA is like the king? And these enzymes which you found, the restriction enzymes, are like some of the servants of that king?” And I said “Well, that’s perfect, good comparison. What is the role of the servants?” And she said “If a foreign king, another DNA molecule tries to penetrate into these cells, the servants kill that invading king by cutting it into fragments” and then I said “It’s perfect, Sylvia” and then I asked Sylvia “Why don’t you write this story up?” and she wrote it and I then included it into my CV for the book which the Nobel Foundation gives out and therefore later on it has spread worldwide, it’s a nice story.

Is it important to be able to, in simple terms, describe science today, natural science to make it more popular and more understood?

Werner Arber: I think it is important, but it also has some throwback. One has to be careful enough so that it’s not being misinterpreted. Simplifications help to understand better, but they also could lead to some misunderstanding, in this particular case of the king and his servants I think it’s no big problem but if one uses simplifications too often, that can at long term be a source of misunderstandings of some principles of nature.

Some people have the feeling that there is now a mistrust between the general public and natural scientists. Have you got that feeling and why is that in that case or is it rather mistrust of what one can do with science so to speak?

Werner Arber: It is, there is a certain mistrust, I think it has to do with human conservative opinions, humans, many humans are conservative for whatever and if they don’t see a much benefit for their own life, they are often very hesitant to accept technological progress, I think that’s a normal human behaviour and some of these mistrusts can under certain circumstances be misused by political movements, you know, taking this on their flack. I think good examples have been the use of, peaceful use of atomic energy and genetic engineering is another example which has sometimes been misused in that sense.

For example, do you mean the debate around, could we say genetically modified food or genetically modified species like for example Dolly …

Werner Arber: It goes in this direction, yes, without precisely what is behind, but I might add to this question, going further you know, after understanding how the molecular process of genetic variation works. Me as well as quite a number of other colleagues have realised that these are in fact in most of the cases done in nature by the help of particular enzymes. Enzymes are products of genes and these enzymes often do nothing else than helping genetic variation to occur and also, that’s quite important, to not occur too frequently. So I’d say there are gene products which are generated of genetic variation and some do it themselves and some other gene products are modulators of the frequency of genetic variation, to keep it low enough so that the species guarantees a certain genetic stability.

The positive uses though of your achievements are many, the way research, medical research, have gone further. There have been a number of examples, for example in the cancer research. Would you just give us an example that you are really feeling particularly proud of, where you know that your work has really benefited medicine?

Werner Arber: If you go into the field of medicine, I think any, very active protein like, let’s say interferons have been isolated, thanks to these techniques and then the question was, how should one apply them? In which kind of medical problems? Some, there were some deceptions but there were also discoveries that in certain other fields these products were very useful. Another example which has been widely successful is the product of human insulin which made medicine largely independent of insulins harvested from living animals and I think if one looks at these things these are really very good examples. They are also in human populations in the society relatively well accepted while in other fields on which either people themselves or people in their families or in the neighbourhood were not profiting from a treatment, people hesitate much more to accept genetic engineering and their products.

Were there times when you really despaired, said No, I think I’m going to give this up, it’s too much work, or too much people might not believe in what I’m doing?

Werner Arber: I had periods in which for long periods of time my expectations were not fulfilled. I can remember that I had searched for recombinants, giving a new type of research in enzymes by either mutation or recombination. I worked on that for more than one year quite intensively, without success, and I was very pleased only two or three years later that some other scientists working with a related system, but not with the one of ours, just found that spontaneously. We had been working on the rock system, the principle can be found, I also know why in my system with which I worked, it would be much, much more difficult to find this kind of thing which I looked for, but that stimulates you, that indeed you’re convinced that sometimes even if your ideas might be wrong, you don’t find the result but that’s how scientific life is. One shouldn’t be disappointed.

So you need to be flexible, you need …

Werner Arber: Yes, I think it is important, yes.

And you need to share information with other scientists as well.

Werner Arber: Yes. The bad thing is, let’s say if that happens to a very young scientist in his first experimental investigation, that’s relatively bad for her or him. What I told you occurred to me what was it, about 15 years of experience and I was immune against reacting to that, I think, at that moment.

So sometimes it can just be luck as well, hard work and luck?

Werner Arber: Yes, and you have to your eyes open, you know I was finding, identifying the molecular basis of these research in enzymes by working on a completely different project, that was is in 1960, a time when the governments gave extra money to study the peaceful use of atomic energy, power plants, but some of the money had to be given for by safety. We did some experiments in such a project which was trying to find out the effect of different types of radiation on bacteria and in doing that they ran into the phenomenon of restriction and they within just a few months of additional experiments I could show that the phenomenon has to do really properly with DNA, the modification is a mutilation. Once I’d seen that I felt Oh, this is an important discovery. I have, you have to have your eyes open and take your liberty to do a few experiments to clarify what it is and later on I also had of course to tell those people who guided the project that I had done something different than what I was supposed to do but they understood that actually after all it wasn’t so bad and it was alright.

How do you relate that to young students of today, your story and the way you worked and what qualities do they have to have to go on?

Werner Arber: It needs of course interest, some degree of curiosity for how nature works. You have to overcome short periods of mis-success and as I said before you have to have your eyes open to the unexpected, sometimes, you know, each experiments that you do, you do it in order to show something which is in your mind but the experiments may be not giving that answer which you expected but another answer and if you just say the experiment failed and you discard it, you make never a new discovery so, but it’s not an old favour that a new discovery of course is inborn so …

What are the big issues yet to be found out?

Werner Arber: Oh, there are many. There are so many. Of course we go more and more into trying to understand complexity, complex systems and there’s a lot of questions which even haven’t been formulated yet I think, there are more. How proteins, which are gene products, mutually influence each other in their activities and so on and also what I found in my own research, the co-existence within the genome of genes which are actually not working for your own personal life, your individual life, but for the biological evolution of the population. These, I call these evolution genes, variation generators and modulators of the frequency of variation which I mentioned already and of course the majority of the genes are other genes which are making your life possible. I mean bacteria, plants, animals and humans and this is a very high philosophical content here, identifying that within the genome there are not only genes whose product work for me but contribute for further evolution, not only for human beings but this is a general phenomenon, bacteria, all the living world and gives the guarantee that nature itself takes care of the biological evolution, rather than that as you still read in many textbooks that evolution only benefits from errors and mistakes occurring to the DNA. Many, practically all of these changes in variations are actively introduced at very low frequencies into the genetic information and of course natural selection, that’s Darwinism, will eventually decide whether such normal mutation is maintained or discarded.

But that is amazing, so those evolutionary genes, the way I could relate to, is that somehow, we are connected, all of us.

Werner Arber: That’s correct, yes, particularly since there is this third strategy of horizontal gene transfer, whatever somewhere in nature normal genetic gadget has been developed, has some chance at some later time by chance at low frequency to be horizontally transferred to other organisms so you can benefit from that perhaps in some future time so we are interconnected of course by common origins in the past but we are also interconnected into the future by possibilities that profit from other developments made by others.

That just makes this absolutely amazing.

Werner Arber: Yes, it is, yes, so that is a kind, for me, you know, if you come to that kind of insight, if it touches you. The first time you think, well it must be wrong, then you reflect it, then what is the consequence of it? There are a lot of philosophical, even theological consequences of that, creation and evolution were often in conflict, but what is going on in nature is in fact the permanent slow process of creation and that gives us a guarantee that also in future times, even if some living conditions are going to change, there is an internal natural potential that by diversity will be amplified again. Of course I have to add to that without your question you may ask this not necessary is developing from humans to superhumans but somewhere else in that evolutionary tree there will be the branches growing.

You mention theology, as you said there has often been a conflict but theology has, a lot of people who are believers of any different disciplines of religion, always have this sort of saying the connection between all human and actually all living beings in some of the …

Werner Arber: Yes, that’s right, yes, actually I think my understanding of molecular evolution is something which can give from the side of molecular biology, a confirmation of these opinions of continuous creation, also I have talked to theologians and it’s an interesting aspect, the question is if you are believers on some religion like Christianism, the question comes up sooner or later why does God, who actually likes creation, his work, and likes the organisms of creation including the human beings, why does he allow that sometimes a genetic variation is against the positive life, genetic inheritance, inheritable diseases and this has been my latest quest. But the duality of the genome having genes working for your own on the one hand and working for evolution on the other hand and we do know that not all genetic variations are beneficial. The majority in fact is detrimental so genetic diseases are among those detrimental ones so God, I believe, according to Genesis, found evolution as good and that implies that mechanism, that once in a while there’s a sacrifice of an individual getting by chance a bad mutation so that’s how I think one could think about, I’m not sure whether that interpretation is correct, but it leads me into really considerations of this kind.

It’s then of course I have to believe, is it possible to be a believer and a scientist at the same time?

Werner Arber: I think many of us can have both in parallel, we do not pretend that natural sciences can explain everything, there is other things behind …

Thank you so much for your time professor, I really enjoyed speaking to you.

Werner Arber: You’re welcome.

Thank you.

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