Interview with Professor Erwin Neher by freelance journalist Marika Griehsel at the 53rd meeting of Nobel Laureates in Lindau, Germany, 30 June-4 July 2003.
Professor Neher talks about science as a lifestyle; the story of the discovery and the collaboration with Bert Sakmann (4:32); the way the discovery has developed (13:29); and the moral responsibility of scientists (17:14).
Professor Erwin Neher, welcome. My first question would be about the lifestyle as a scientist. Is there a particular lifestyle?
Erwin Neher: During these days here in Lindau, I was asked several times by students: What do you do outside science and what other interests do you have? Of course I have other interests, but on the other hand, science is a lifestyle in the sense that it’s a combination of profession and hobby. What you like to do, I mean as a scientist you have the chance to combine these two things, you know, and I think in that way it’s a lifestyle. I mean you do what you like because you just follow your curiosity and you are happy when you find new things about nature, about how things work around us and inside us.
How old were you when you decided that this is the way you wanted to go?
Erwin Neher: It was pretty clear even when I was a little child that I was very interested in nature, in all these things that I observed and later in school I would think I was pretty much determined to say at the age of 15, 16, 17, first of all that I would try to study basic sciences, physics, chemistry and then also by the time I graduated from high school it was pretty clear that I wanted to do what at this time just was a kind of wake discipline which was not really established yet, biophysics, you know an interdisciplinary field between physics and biology.
What was the question you wanted to have answered?
Erwin Neher: Quite, quite specifically, I mean during my high school years I had a chance to read about the findings which were quite new at this time, the late 1950s, on the nerve conduction, on the generation of the nerve and pulses, electrical phenomenon which happens inside our bodies, in our nerve cells and I was fascinated by this fact because, I mean, I had this interest in biology on the one hand, on the other hand I knew from what I learnt at school that physics and chemistry about things which I understood well which was easy for me at school to cope with, you know, so to combine these two things in the form of biophysics was easy for me to do.
You need to find like-minded people, I believe, as well you found friends and even I believe your wife in the field of science?
Erwin Neher: Yes, that was of course much later. I did meet my wife in the laboratory which is part of her lifestyle you know, and of course over the years I had many friendships which developed in the lab which were connected to our work of course and so part of this lifestyle of a scientist is that you do a lot of travelling that you have friends all over the world which you first learn to know by means of your work, but then they become friends and wherever you go you have friends and you don’t go as a tourist to some place but you have friends and these friends tell you much better than a tourist guide can do what the specialties of a given location are.
Professor Sakmann of course is still a friend and a colleague that you eventually made this fantastic discovery with, how did it come about?
Erwin Neher: This is a story which comes in two steps: While I was doing my PhD in Munich at the Max-Planck-Institut for Psychiatrie, he also was doing his PhD in a different department on a different floor of the same building, but we met each other and we realised that we had joint interests. I came from the physics field, he came from medicine, he was a medical student at this time. He was very interested in this more physically oriented things which were going on in the laboratory where I was, which was run by Dr Lux, who also was a medical person but very deep into the quantitative description of things and quantitative methods. So when we met three years later at Göttingen again it was immediately clear that we would try to collaborate because he in between had been in London working with Bernhard Katz.
I changed from Munich to Göttingen, doing a kind of detour for two years or so into more physical chemistry. Our Institute in Göttingen is called the Max-Planck Institute for Biophysical chemistry, which means a combination of all three of them, and so I went to Göttingen to learn about the currents of recordings of channel currents in artificial systems, more physicochemical approach to these things. We had already developed ideas in Munich about recordings in the channels in biological cells, you know, but this more or less were put back for some time so that I would have the chance to more or less practice with these less complicated physical or artificial systems.
Then when Bert Sakmann came from London joining the same institute where I was again in a different department, we got together again. He meanwhile had obtained tremendously valuable experience for that purpose of recordings in channels. Bernhard Katz lab where he learned how to isolate the cells of the neuromuscular junction, the muscle cells and the nerve cells which make this connection where he learned to enzyme treat these preparations so that they would have clean surfaces. With his expertise on the cells and my expertise on the recording currents and dealing with pipettes also, this combined was clear to the two of us that it should be a good start point for a collaboration and that should give us a good chance to tackle this problem which was one of the problems which was in the minds of quite a few researches at this time can one record discreet steps in current when single channels open and close.
And you developed this little glass pipette
Erwin Neher: Yes. I had been dealing with little glass pipettes in my PhD project, I mean the little glass object is not very special in physiology. Microelectrodes, pipettes drawn out to very fine tips you know, were standard in electrophysiology since the late ’40s I think. The problem was that this and the techniques of this time which recorded currents or electric little signals in biologic tissue use these very fine microelectrodes to penetrate the cells. What we did differently was that we in fact made these pipettes a little bit larger, the openings were larger, not designed to penetrate but just designed to place them on top of the cells to isolate a small patch of membrane for the purpose of electric measurement without destroying it, you see.
And when you did this and when you got the results, how did you react, the two of you, what did you do when you realised?
Erwin Neher: Of course we were quite happy but, this didn’t come as in all or nothing things suddenly a … it did take about two years or so you know, during which we step by step improved things. There are certain ways to record signals and to analyse them which doesn’t actually require the single individual steps to be seen, but also when you just do not have the resolution to do that, but have a situation where many such steps superimpose the responses from many channels are recorded together. You have a kind of characteristic fluctuations you see in the current and for years we just analysed these fluctuations which allowed us to infer from these how big these steps actually are supposed to be which we want to measure.
So having this done and made the pipettes smaller and smaller, we finally approached the situation where there was this noise, but now and then you could see some step-like thing which very much looked like the steps that we wanted to see. Then of course one day or other it was a little bit better, a little bit worse and there were certainties, some days where we thought that’s it, you know, and now we are convinced that we see these tiny signals and this was maybe ’74 or so. Then we gradually improved until we came to the point where we not only believed that the steps were there, but where we also dared to publish them.
And then to me, not being a scientist at all, I understand that there must have been times when it was very difficult and maybe one of you wanted to give up and the other said no come on let’s go ahead …
Erwin Neher: Yes, yes, of course there were times when it seemed that we had done everything we could and we couldn’t do it better and still we wouldn’t see this dent, little things. And there were frustrations and as I said at one point we got a little bit frustrated and we took this other project with measuring these fluctuations just to assure ourselves that actually there is something which signified the presence of /- – -/ of these channels and this was it. But apart from that, it was pretty a step by step thing you know, without major frustrations.
How important was it to be two then to sort of encourage each other
Erwin Neher: Oh I think it was important yes, I mean, first of all because we could put together our experiences which were in very different fields you know, and then also because maybe one might have been more easily distracted you know to … maybe the distraction might have lead to a fast response but maybe also it would have prevented the success, you never know.
You have to be very open minded and very hard working I believe.
Erwin Neher: Hard working, yes, definitely and open minded in a sense that we dared to just try new approaches which nobody else does you know.
When you now look at what you have achieved, are you happy in the way it has been used?
Erwin Neher: Very happy. In fact we think the way it has been used, the way it developed without our active participation actually was what won us a Nobel Prize you know. I mean on the one hand there is just the finding, well one can resolve these step-like changes which more or less prove the concept of ion channels, that there are ion channels, this by itself of course would have been a nice finding which would have been hailed by many of the colleagues. But what turned all this that given this new technique the improvement of ways how to look at channels that many colleagues took up this method you know, and so it was a powerful tool in the hands of hundreds and thousands of colleagues.
And through this work, all over the world, it turned out that channels are not only in these cells that we started, I mean when we started, started channels we thought they were a special thing which happened to nerve cells, which happens in muscle and maybe some gland cells.People tended to divide living cells into excitable cells and non-excitable cells and excitable cells are of course a minority in the body, and we definitely thought that channels were only important for excitable cells. But what turned out that you find these channels, I mean different types of channels in all kinds of cells, liver cells and the blood cells, and the white blood cells and the kidney cells, even in plants, you know. And they do the most diverse jobs, they could fill the most diverse functions in these different cell types and that’s a real impact that our discovery and this new method had in the science, and I think this is what won us the prize.
Another aspect which again is a quite unanticipated aspect is that it turned out that these channels are very important targets for drugs. This lies a little bit in the nature of channels I mean, channels have not so many in a given cell, there are maybe thousand molecules of this kind of this channels but their function is to control the cell you know, to regulate the function. And if you think about it, such a molecule then is a good target for a drug because you need only a few drug molecules to block these channels, and though you just influence the workings of the whole cell end. And due to this intrinsic property it turned out that channels are the targets of some of the drugs which have been used over the years to treat hypertension you know, diuretics, psycho-active drugs, all kinds of drugs turned out to be drugs which act on these channels.
Which one didn’t know at the time, when one created. Having made this discovery, do you think scientists like you have some kind of moral responsibility in which way your discovery is used?
Erwin Neher: That’s a difficult question of course, I mean if we see potential harm, potential dangers, of course we have the responsibility to point this out you know, to warn against that. On the other hand one of course thinks that any new knowledge, any better understanding of the matter around us, in us, will give means to handle things and normally of course one would think that people use these things to handle things better of course a scientist can never safeguard against new knowledge to be used against other people you know. It used to be harmful I mean, this started with the invention of the hammer, now you can use the hammer to do useful things, to build a house and you can use a hammer to kill somebody else.
Is that a debate that goes on though, among the scientists?
Erwin Neher: Yes, yes, this debates, and I mean that more or less this issue rests at the basis of the whole problem on whether what we are doing is good or wrong you know, if you, it’s morally a question on what do you think about mankind. Do you trust in your fellow citizens in a sense that whatever they will have in additional tools they will use in balance more to the good or more to the bad. If you think they will use it more to the bad, you shouldn’t do science you know.
My last question Professor. We started off talking about lifestyle and you said it is really a lifestyle, but you also said you have other interests. What are you doing to relax and to just wind down probably from the lab work?
Erwin Neher: What I’m doing to relax, some reading, some music, just being at home with my family, many things but unfortunately time is always very limited because science not only is both a job and a hobby but it also consumes the time which usually spent on both of these issues.
Creative work, basically.
Erwin Neher: Hopefully.
Thank you very much, Professor, and I wish you a good trip home.
Erwin Neher: Thank you.
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