Interview transcript

Professor Nirenberg, thank you for coming to this interview.

Marshall W. Nirenberg: You’re very welcome, you’re welcome.

We’re very happy to see you here in Lindau.

Marshall W. Nirenberg: I’m glad to be here.

Great. I just want to start off right away with the day or the night or the weeks when you realised you’d made this made this major discovery. Was it a race of time? You knew there were several people doing the same research.

Marshall W. Nirenberg: No, no.

No?

… I literally jumped for joy, because I knew it was exciting …

Marshall W. Nirenberg: We were doing our own research and we asked the right question. We were asking the question: Does messenger RNA exist? and we prepared RNA and were directing cell-free protein synthesis with it and the very first experiment with radioactive amino-acids, very sensitive assay, worked and I came back after supper to look at the quick counts and I knew that it worked because all the controls were there and I literally jumped for joy, because I knew it was exciting and I knew that we had real problem going.

It was wonderful and everything fell into place after that. We got different kinds of RNAs and used them to direct cell-free protein synthesis. In one of the RNAs that we got was a synthetic RNA which consisted of only one of the four kinds of letters in RNA and so we looked for the synthesis of a protein that contained only one of the 20 kinds of amino-acids in protein and we found it and it was incredibly exciting.

Did you understand the implication it would have?

Marshall W. Nirenberg: Of course. I mean it’s wonderful to work on a problem that’s important and it’s wonderful to work on a problem that’s working, that where you can do experiments and get answers and the answers are always publishable answers. You know it’s thrilling to do that work.

In what field do you think that it has had the most immediate impact if you look at the kind of diseases, the problems that humankind are facing?

… my colleagues and I deciphered the genetic code …

Marshall W. Nirenberg: My colleagues and I deciphered the genetic code and the code is the language of all living things. It’s the language that you inherit from your parents that all of the information to synthesise the many kinds of molecular machines that the body is composed of are encoded in DNA and the sequence of letters in DNA determine the sequence of amino-acids in protein. There are about 30,000 genes and each gene maybe contains 300–1000s of amino-acid residues so that it’s a lot of information that you inherit from your parents, and we found that essentially all species, all forms of life on this planet use the same molecular language.

The code consists of, as I said, four kinds of letters in DNA, 20 kinds of letters in protein and so it’s a translation of … You take three DNA letters at a time, corresponds to one letter in the amino-acid code and you know we compared the code in bacteria to the language that’s used in an amphibian to a mammal and found it’s the same language, so that had a profound philosophic influence on me.

Of course, yes.

Marshall W. Nirenberg: You can look at trees, flowers, squirrels, birds and you know that we’re all related basically, we all use the same molecular language.

Did it make you change your outlook on life completely to some extent?

Marshall W. Nirenberg: It had a big philosophical effect on me, yes. You know, I knew all about evolution and all about Darwin of course but the demonstration that the language is used to synthesise the proteins in the molecular machinery of life is the same in all forms of life, means we’re all related, we’re related to all forms of life.

I was thinking with my earlier question a little bit about, we know that we can inherit sicknesses from our parents as they’re genetically translated into our body. What would you like to see, how far can we do and try to prevent, for example, certain sicknesses or make humankind well prevented really. What do you think, how far do you think one can use this knowledge?

Marshall W. Nirenberg: I think that it can go a long ways but I think that it has to be done very slowly because you have to be careful that you don’t do any harm. I think that now, every day, molecular biologists and scientists all over the world use the genetic code to interpret the sequences and DNA that they obtain when DNA is rid to synthesise particular segments of DNA that will encode specific amino-acid sequences. It’s used in many, many ways and it’s used by 1000s of people every day. For genetic diseases, of course the human genome has been sequenced and many other genomes have been sequenced, so we know the structure of the genes and we know what proteins they should encode but they’re mutations and they’re genetic diseases.

… to cure genetic disease you have to rectify the error in DNA that was made. It’s complicated …

Now, when you ask how far can you go, can you cure genetic diseases? That’s a complicated question and a very complicated problem because to cure genetic disease you have to rectify the error in DNA that was made. It’s complicated because if the DNA that you use to correct this defect is inserted into the wrong place in DNA, this will cause a mutation, this is equivalent to a mutation and it can interfere with the function of the gene that it’s inserted into. It can cause even things like cancer for example, so one has to be extremely careful about how it’s used.

I did attend a party one time, it was given in the Senate office building in Washington for the people at NIH, the National Institutes of Health in Bethesda who had used genetic engineering as therapy to cure children that were suffering from adenosine deaminase deficiencies, mutations in the gene for adenosine deaminase. There was no treatment for this disease beforehand and one by one the parents of the children got up and said how thankful they were for the help that the physicians and basic scientists had been to their children and the children were there, so that you could talk to the children also. That was very moving but on the other hand, some people were killed by DNA that was inserted into the wrong gene and that’s terribly disturbing, so you have to be very careful in using this. I think in the long run, it’s going to have tremendous effect and helpful effect as therapy for some genetic diseases, but it’s going to take a long time.

You mentioned the responsibility. Is it both scientists and politicians and the public in general who have to be aware of the kind of responsibility they have, I suppose?

Marshall W. Nirenberg: Absolutely, yes.

How would you as a Laureate feel. Do you have a certain kind of responsibility to make people aware of this?

Marshall W. Nirenberg: Yes, yes. I think it’s important that people be aware of the details of what’s possible and the pros and cons of using it. These therapies are experimental at the present time and there’s no really tried and true method that has been found that works in all cases so I think every case is as special and as different and is experimental right now but in future years, I’m sure that many of the problems that people face now will be worked out. The problems of getting DNA in at the proper place, without causing any harm, those problems will be solved and so the potential for doing good is enormous.

When you meet young students here in Lindau as we are in Lindau now, what kind of questions do they pose to you and is it something that you learn from them?

… it’s fun to discover things and it’s important to discover things …

Marshall W. Nirenberg: I love to talk to students here, I enjoy it. They’re very bright and very good and they have wonderful opportunities to do things in science that they’re basically a lot of fun. I enjoy talking to them, I envy them in many respects because they have this opportunity to solve problems, to work on problems right now and I think that they’ll have and I hope that they’ll have enjoyable lives. I think that the best kind of science is basically a lot of fun to do, it’s fun to discover things and it’s important to discover things so I think there’s a wonderful interaction between students and so called faculty here and I think it’s a wonderful meeting.

Is there any specific area that you, if you were to start afresh now, that you would go into?

Marshall W. Nirenberg: Oh, I would continue doing what I’m doing right now, no question about it but I definitely would continue to work in neurobiology because I think that the potential for neurobiology is enormous and because there are so many unsolved problems that can be worked on. I mean, nobody understands right now what the molecular basis of memory is and nobody understands how this highly complicated nervous system, the brain and the peripheral nervous system, how it’s assembled from different cells. How do you select appropriate synaptic partners to communicate with in the nervous system and nobody really truly understands these questions and these solvable problems, they’re problems you can work on and you can make headway on, so they’re very important problems and it’s fun to work on them.

It’s amazing.

Marshall W. Nirenberg: They’re difficult problems.

Yes, I’m sure. I mean, do you think one day, as you said, it will be solvable. How long a time will it take, do you think?

Marshall W. Nirenberg: Well, I can give you a guess. You know I’ve only guessed once in public before and that was a long time ago in the ’60s actually when I realised that we could synthesise nucleic acids, add them to cells, the cells had machinery that could read these instructions. You could programme cells and they would follow the programme and they would synthesise whatever protein you programmed in to synthesise. When I realised that I wrote a little piece which ultimately was published as an editorial in Science, saying that we have this ability, we can do this, although there are problems that exist. We don’t know how to get the message of the programmes inside the cells and I thought that maybe it would take 25 years before we could do this with human cells and exactly 25 years later somebody did it with human cells, but that was an accident that I was accurate. It was an absolutely accident.

… what seems to be science fiction right now I think will eventually prove to be a reality …

If you ask me how long it would take for example to understand how the molecules that are needed to form a synapse, to form different kinds of synapses, I would say that research is coming along pretty well now, that within 25 years that we’ll know an awful lot about how you assemble a nervous system and the molecular basis for assembling a nervous system. Once you know that it is theoretically possible to repair a damaged spinal cord for example and defects in the nervous system. It’s also theoretically possible to connect computer chips to the nervous system because, you know, I think that once you know the molecules that are needed to form synapses, you can form artificial synapses with computer chips. I think that technology is possible and so, what seems to be science fiction right now I think will eventually prove to be a reality and who knows where that will lead. You know, in 25 years from now, the technology of making computer chips will have advanced tremendously so that the complexity of a circuit on a computer chip may almost approach that of the human nervous system and if you can devise ways of linking those computer chips to the nervous system, I think initially it will be done to repair defects, broken spinal cords for example, things like that or damaged retinas or even hearing maybe, but who knows where that will lead.

Blindness as well?

Marshall W. Nirenberg: Blindness, yes, yes. I mean, it’s limitless, basically, what is theoretically possible but I think that, you know, it’s going to take a long time, I would say 25 years before it will be possible to do that, although people are doing experiments trying to do that very thing right now, but it will take time.

It’s amazing. If I just ask you to look back a little bit and we go back to 1968 when you got the award. How was that? You are one of the younger Laureates. What impact has it had on your life?

Marshall W. Nirenberg: The continuity of the work has been the important stability in my life and the important driving force in my life so that has surpassed I think most other changes. I think that being a Nobel Laureate, people think that you know a lot about perhaps many things related to questions of public interest, global warming, things of this sort and so you have a responsibility to try to do whatever you can to inform the public about the scientific issues that are important and that I think I’ve done. But I think that the continuity of the work is the most important thing so, yes, I would say that definitely it changes your life in some ways, but that in other ways it doesn’t affect anything that you do, life goes on.

Because one of the challenges, I would imagine, as a scientist is to be able to get funding, to be able to make politicians and other decision makers who are putting the money into the different research institutes to actually see the importance of the work that you’re doing and how is it today for young students?

Marshall W. Nirenberg: Tough.

Tough.

Marshall W. Nirenberg: It’s very difficult, I mean it’s extraordinarily difficult for people who are just getting started in science because there isn’t enough money to go around to support everybody’s research and in the United States, there’s been an enormous influx of extremely well qualified scientists from all over the world, so there’s great competition for position. There are not enough positions to go around and so that can lead to a lot of personal tragedies because somebody who is a good scientist and a very skilful scientist may not be able to find a position and that’s terrible, I think.

I think that the way it worked when I started out was perhaps a little bit easier because there were enough jobs to go around, there were enough positions to go around for qualified people, so I think there’s a little too much competition these days among people for positions, for money to do research and I think that the research suffers because of it. For example, when you get your first position you’re supposed to hit the deck running and prove that you’re a competent scientist and a productive scientist and so to do that, you have to work on a problem that’s safe, that you know is going to work.

… people should be encouraged to explore and maybe to do risky projects …

The best science may be to work on something where you don’t know if it’s going to work, to work on an idea that may be a really interesting idea and may be a very exciting idea and may lead to a lot of extraordinarily interesting things but whether it’s going to work or not is up in the air, you don’t know if it’s going to work and you risk ruining your life by working on something like that if it doesn’t happen to work, if it doesn’t pan out and that’s not good for science, I think that people should be given the opportunity to fail without it ruining their lives and people should be encouraged to explore and maybe to do risky projects in the hopes that maybe some of these projects are going to work. I think that’s the best science.

Because I believe in many cases, there can be discoveries that were just almost by chance, you know, you do a project and you think it’s going to have that result and there is something else that comes after it which might be even more exciting.

Marshall W. Nirenberg: It’s possible, it’s entirely possible but the competition is so keen now, competition for jobs, for grants, for money that that kind of exploratory science is overlooked. I mean, many people don’t want to take the chance to fail because failure could mean loss of the ability to continue to do this work. That’s wrong.

Do you get that kind of question from some of the students as well, you know, do they ask your advice on these fields?

Marshall W. Nirenberg: Well, I can tell you my experience. With a post-doctoral fellow I suggested a problem one time, a research problem who came to my lab which was a very good question, a very good science but was risky and the post-doctoral fellow refused to do it because he thought it was too risky to do and he was right, it was too risky to do and so he did a different problem that was safer and less exciting, less potential but safer. I mean there was no doubt that he was going to get results on this, so it does influence the way science is done and I don’t know if the students here, they’re mostly graduate students although some are experienced scientists, but the graduate students may not understand this yet, they’ll understand it after a while.

Would you like to see the politicians and those who provide money to be more adventurous? Could you see that that could happen or that it should happen?

Marshall W. Nirenberg: I would hope that it would happen. It requires a greater investment in science, it requires more money for grants for example but that’s a political question that I think things, at least in the United States are quite sort of stable now, there’s no increase. We went through a period where there were large increases in money available for science, so that the budget at the NIH, which gives grants to people in universities and so forth, doubled in about five years, but then now it’s levelled off and even it’s going down somewhat, it’s not keeping pace with inflation.

Well Professor, we’ll call that the end of our interview. Thank you so much.

Marshall W. Nirenberg: Well, thank you, I enjoyed it.

So did I and good luck.

Marshall W. Nirenberg: Thank you very much.

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