Interview transcript

We are now in Lindau and we are here at the 50th anniversary of the Nobel Prize Laureates meetings with students and we are lucky to have come to Professor Manfred Eigen and he got the Nobel Prize in Chemistry in 1967 and we just welcome you here.

Manfred Eigen: Thank you.

And then we ask if we could please ask you some questions.

Manfred Eigen: Yes, of course.

So why then not start with the sort of traditional question: how did you come into research and what made you chose the field you chose?

Manfred Eigen: That’s a difficult question because I was grown up in a family of musicians and I learnt to play the piano from my 5th year of age and I always thought I would have to study music. And at 12 I played already concerts, but then there was a war, and I was about between my age of 15 and 18 I couldn’t see a piano, and this is the most important time for a musician because he has to print his /- – -/.

So when the war was over, one day later I got 18 years old, and of course before that I have thought I like as much mathematics, physics, chemistry, and funnily enough I always thought if I am going to study natural sciences it has to be in Göttingen. So I went to Göttingen and it was the first university to open after the war, and they told me I am too young and still would have to go back to school, but I asked them whether I could do it with an examination and so I was accepted and started in 1945 and then it was my teachers who convinced me. I had very good teachers.

But you also told me that you made a very impressive and short career to get your thesis. Could you please tell the story about your thesis?

Manfred Eigen: My student time the first semester was physics. I was the student of Heisenberg and of Richard Becker and in experimental physics of Kopfermann and Paul, and in physical chemistry Arnold Eucken, these are all great heroes, and I learnt a lot from them. So I started quite early to do a master thesis in 1947 already, and had to matter the specific heat of heavy water over a large temperature range up to as high as possible – 150, 180 centigrade –  limited by the vapour pressure since that was a big glass vessel in glass which could stand perhaps pressure of 5 or 10 atmospheres, and there was a debate between Arnold Eucken, my teacher, and his assistant. His assistant said “No, it wouldn’t go above 140, 150 centigrade” and Eucken “Oh, you can go at least 200”, because he wanted to have the data. And it was precision management up to 5th decimal because he wanted to test his theory of water and he needed the isotope effect. So I decided in my first experiment to go up to 175 whatever could a poor student do …

And it was at the time when heavy water was very limited and it was very precious.

Manfred Eigen: Oh, it wasn’t even available in Germany then any more. He had still something, 99% purity, and it couldn’t be paid anyway. So I had 450 gram, 450 millilitre of that stuff he gave me, I think his hands were …

Shaking.

… there was a big explosion and the water evaporated and the machine was under the ceiling and it was really a big bang …

Manfred Eigen: … shaking. So it happened at 169 there was a big explosion and the water evaporated and the machine was under the ceiling and it was really a big bang and everybody came to my room and “Oh, poor fellow”, and Eucken came also and said “What did you do with my heavy water”? I said “Yes, but you were the one who told me 200 centigrade”. “But not in the first experiment”, he said.

Well, I wanted to tell him something but he shouted at me and I couldn’t say anything, so I finally went home and next morning came to clean up the room and he came right at first and say “What am I going to do with you now the whole thesis is gone?” I said “Well, I will have built a new calorimeter in 3 or 4 weeks. I know now how it works and “Oh” he said “don’t talk nonsense it’s not the calorimeter, it’s the heavy water”. I said “No wait, don’t start again”, went to the board and said “Here you have your heavy water”. He wouldn’t believe that I did my first experiment with heavy water.

You were clever.  

Manfred Eigen: So then I got quite some freedom in doing my work. So it happened that I finished that work very soon with heavy water and accuracy and not as he suggested to put it on large graph paper – I worked out some /- – -/ functions by which you can approximate it in a suitable way, but then he said “Well, I want to have some data on electrolytes also” I say “Yes, but let me first do my examination”. “Oh” he said, “then we lose time. Why do you need that examine and go on as a doctor please”. “Yes, but what will the faculty say?” He said “That’s my business”, so I finished very early.

So then in something like three years you passed your thesis and you were 21 when you had your PhD?

Manfred Eigen: I finished my thesis was 21 and got my examination was 22 years.

Excellent.

Manfred Eigen: And yes, at 27 I got my first offer for a professorship.

Yes, good.

Manfred Eigen: And so I started very early then having all the students were older than me.

Yes. And then also you have become sort of the father of physical calculations on the evolution of life and origin of …

Manfred Eigen: Oh, that was much later. The Nobel Prize was for fast reactions.

I know that.

Manfred Eigen: So it was in Eucken’s textbook where it said unmeasurably fast reactions and he thought that you mixed two substances it takes a millisecond about because you get tubular and flow and if you do it under pressure you know, so that’s no way. The mixing process takes that much time and if the reaction is faster than you can’t follow it. And I didn’t know how to do it but as a young man you don’t believe what they tell you. I say “There’s nothing which is immeasurably fast” and so I thought of it but couldn’t find a solution. But I learnt by studying electrolytes about the salvation and the interactions and there was a problem in physics which was brought to me that is the high sound absorption of sea water which is, one didn’t have an explanation. I knew it is not the sodium chloride, not the salt in seawater it is …

Well, we soon found out it must be the magnesium sulphur that is the next, because pure water has very little sound absorption and it has two maxima so there must be two processes going on. And there was a suggestion that one was the magnesium and the other the sulphate iron so I said “Well, that’s easy to decide, take magnesium chloride, the chloride iron doesn’t do anything, sodium chloride, and take sodium sulphate and if it’s the sulphate iron the sodium doesn’t do anything”.

And that worked?

Manfred Eigen: No.

It didn’t.

Manfred Eigen: No absorption at all. So my conclusion was it is the interaction and since there were two maxima I thought it must be a coupled reaction. I worked out all the theory like in coupled oscillators with normal modes and so on and it was a quantitative explanation. So at that time I remembered Eucken’s words of “There’s no way to study these fast reactions”. I said “Well, the frequencies we use are one maximum, one  megacycle it’s a millionth of the second, the other is 100 megacycles almost a billionth of a second. I said “Here you see the reaction going on” so the trick is you don’t mix your substances. You start from equilibrium as you do it in a sound wave by the pressure wave and that’s how we started.

… it turned out to be the fastest reaction we know …

And I went to Bonhoeffer – Eucken had died – and proposed to study fast reaction this way and he was enthusiastic about getting me a laboratory and so that was the start of the work for the Nobel Prize and in 1955 we did a very famous experiment, we measured the rate of neutralisation. That means the proton hydroxaline forming water molecule and nobody could measure that before. And it turned out to be the fastest reaction we know. Even faster than an electron with the hydrogen atom or so on. It turns out not only to be controlled by the diffusion of the two partners to each, then when they reach a certain distance where the salvations freeze up they tunnel through it and so it is really the fastest reaction we know. And so you see at the time it was almost Olympic discipline to get the fastest possible reaction.

And then all the inorganic chemists came to us: you can now study the rates of complex formation, then the organic chemists came to measure acid-base catalysis of all types of organic reaction and the bio-chemists came and we did the first studies on allosteric enzymes to measure the control of enzymes, all the elementary steps because this relaxation spectrum is a linearized spectrum gives you like in optics – a spectrum of time content you can resolve mechanisms and then we started to think how can this come about those finely tuned reactions with controlled, and so who did it? When our biologists said of course Darwin explained it but we said but Darwin talked about living beings these are molecules and molecules didn’t know about Darwin as much as Darwin knew about molecules. So that’s when we started to think of evolution and we worked out a theory of molecular evolution which you can formulate in mathematical terms. So we are at your subject now.

That’s very good. How were you told about the Nobel Prize? Can you remember, of course you do, how the initial message came?

Manfred Eigen: About my Nobel Prize?

Yes.

… call them damn fast reactions and if you still have fast ones, call them damn fast indeed …

Manfred Eigen: I will tell you. It was 1967, so the essential work on which it was raised was already in -55, -56, -57, in 1960’s turned out that it’s a generally applicable method and we went down to even nanoseconds. Nowadays they go to femtoseconds, as late as … but they were not yet invented at the time. I remember going in -54 to a meeting of Faraday Society where they talked about fast reactions and Hartridge and Roughton talked about this mixing millisecond, he called that very fast because /- – -/ before that said something about a second that’s a fast and then Norrish and George Porter came with the flash photolysis get to the microsecond range and called it extremely fast reactions. I said “My English is not good enough, can anybody tell me how to call … I was going to call these reactions slow reactions … I’m going to …”. “Oh”, they said “No difficulty, call them damn fast reactions and if you still have fast ones, call them damn fast indeed”.

So people told me that there was a Nobel Prize coming up and our cleaning woman the year before had baked cakes because they thought I would get it and there was nothing. So I told them “Relax, that takes many years so there’s no hope”, and then the next year I got it. And I got a phone call from a camera team, that was the first I got: Can we have an interview with you?”, was it 12 o’clock, mid-noon, I said “Yes”. “We’re from Stockholm.” I said “Yes, which day tomorrow?” “No”, they said, “right now”. I said “But you have to come from Stockholm here, as I said we are already at Göttingen”. And then an hour later there was a phone call.

And that was the same day as it was announced?

Manfred Eigen: Yes.

So they knew in advance too?

Manfred Eigen: Somehow they must have, or they have guessed and perhaps they sent several teams to several cities.

Okay.

Manfred Eigen: But anyway, so was it. And then the next weeks I couldn’t do any work because there were always interviews and such things.

They sometimes say that the Nobel Prize changes their lives? Did it do that? Do you felt it changed your life?

Manfred Eigen: No, I was happy to be very sick. I had very serious stomach trouble.

So you didn’t notice a change over here?

Manfred Eigen: Oh yes, I noticed a change and at the Nobel dinner they gave special meals to me and that took place and soon later it happened that I got a bleeding and I had to be taken to an emergency operation and so they took me out for several months and every single … for the interruption were finished, my secretary said no he’s not available he’s sick and so when I came back from the hospital, I could go on with my daily life.

And you didn’t come in to all committees and didn’t have to answer all questions?

Manfred Eigen No, I didn’t, I had good excuses.

So should we then switch to the self-replication of the RNA and the further work on evolution?

Manfred Eigen: Yes, there was much discussion what came first, you know, the egg … if the egg is the DNA and the hen is the protein that means the function or the information. Then of course this was back to our present system it’s the wrong question, they had to come in both, but it seems to be if you ask what is the first prerequisite, is it metabolism or is it self-organisation, it’s coping, it’s selection natural selection, and I would say metabolism can be realised in a very primitive way if you have energy rich substances. They will be used up very soon and then you have to incorporate mechanisms which make the sun energy available but you cannot do without self-reproduction.

You cannot do without selection and self-reproduction is the prerequisite of selection. You get really the competing behaviour by the growth laws and so self-reproduction is necessary by two reasons. It yields a mechanism of selection and it keeps information conserved. Without reproduction you lose the information. Everything has a final lifetime, if you don’t reproduce given the huge number of possibilities, you lose it. And so our first interest was directed towards self-reproducing system like an RNA is the simplest one. DNA is already more complicated and evolution probably came much later than RNA.

So when did you do the first RNA experiments?

Manfred Eigen: Beginning of the 1980’s. But we again did also much theoretical work. In other words, we worked out methods to study the evolution of, and we found that the usual way of constructing trees presupposes that there is a tree, the programme, and we wanted to have a method which decides whether it is a tree or some other kind of diverence. And so we worked out something which is called statistical geometry, Ruthild Winkler-Oswatitsch worked on this and Andreas Dress, he’s a mathematician, and we came out with a new method which we called statistical geometry which tells you what kind of divergences it is and also allows you then to reconstruct nodes in the tree or centres of evolution.

One of the works we studied is all the available sequences of tRNA which we realised must be one of the very early molecules, because it adapts the amino acid to the codon. At that time about 1000 sequences were available so then you could study phylogeny of a given tRNA or you can start the diversions of a family of all the 40 tRNA organisms through all the steps of co-organisms and by combining this we found out that the age of the first divergence, that’s say the divergence between eukaryotes and archaebacteria, was at the time and if you also they could find the first divergence of the families, that means the origin of the code with only 25% longer than that.

So if the first divergence of cell was 3 billion years ago, the code couldn’t be older than 4 billion years and everything now points in the direction that this correct. This was the first time we could get measured without assuming anything. Just numbers from experimental data which taught us. So we went on on the RNA /- – -/ and Peter Schuster is going on now to studying the secondary structure formation and third structures in RNA’s and that’s a wonderful evolutionary problem.

The data from all the genetic relationships is quite impressive now.

Manfred Eigen: Yes. Now we have many, and there are not many experimental sciences for the RNA world you know. There was first Tom Cech and Sidney Altman and they have shown these ribosymes, but not only that recently they have found that in the ribosyme’s a machine which makes protein synthesis that round the active sight you have only nucleic acid there is no protein. So probably there was first an RNA machine which incorporated the proteins that finally produced and there are more experiments which make this very strong processes. But eventually all the life could only come about with all the capacity which the proteins could provide and evolution of metabolism certainly is one of the important steps in this.

Do you know several people like you who study evolution sometimes meet religious groups and they have other opinion.

Manfred Eigen: Oh sure, sure. Every week I get letters. I have no problems with them because I tell them “Look, I’m looking how it was created by the Lord, but you want to tell the Lord how he has to do it”.

Yes okay yes.

Manfred Eigen: And that’s even is contradictory to the first commandment.

What’s your view on the discussion we had today whether research in general should be funded by all this that we sell ourselves to companies or contra the old system…?

Manfred Eigen: That’s entirely wrong. I mean everything which is new has to come out of fundamental research otherwise it’s not new.

Yes.

… if you really want to find something new, it can only come out of fundamental research …

Manfred Eigen: If you know before that you can develop a certain thing then okay you go ahead. It’s important. It’s important for industry that they do purposeful research and so, but if you really want to find something new, it can only come out of fundamental research and it often comes out at much later time it turns out to be.

Do you see any risk in the support from the industry to academy and to universities?

Manfred Eigen: I don’t see a risk if it is done in the proper way if it is too much goal directed and if you only get money from industry and even from government if you can prove that it has a useful purpose, that would be better. It would be the end of fundamental research.

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