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Influences and heroes


Talking about the future of molecular biology
Aaron Klug Scientist
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Well, I'm not a stargazer and I can only think about three to five years ahead. There are people who claim to see into the future. Max wrote a very lovely article in which he talked about people measuring the amount of information in cricks and mega cricks and things like that. So things like that may happen, but I find my experience tells me there are so many unexpected things coming up. Just at a time when we knew a great deal about the human genome, about the DNA, about transcription, in the last three or four years, there's suddenly a whole new class of information contained in RNA, small RNAs of various kinds of which there are three or four classes. There's short interfering RNAs, there's micro RNAs, there's also modulatory RNAs, and it was known for some time that a lot of the DNA was transcribed but didn't seem to be producing proteins, and so now this has been found out. And it came out in fairly indirect ways, so nobody predicted these things, although Francis years ago used to say... you know there are small circles of RNA found in nuclei, and people had reported them, and nobody knew what they were. They thought... they dismissed them as structural, probably involved, and now it turns out.

So you see, nobody... and the information for this came from various sources. One of them was post-transcription gene sciencing in plants where you find that after post-translation, in other words you have already started making the RNA in the protein and it turns out there's a small species of RNA, and a similar thing was found in the worm by Andrew Fire. The plant work was by David Baulcombe. Andy Fire showed that, that if you used double stranded RNA rather than single stranded RNA, you could switch off some gene action. It's a bit surprising that people have been using antisense RNA and there are double strands that work better. And he showed that they were processed in the factor, that's with the short... there was a short interfering RNA produced from the double stranded to produce this. And this was a totally new thing. So it's completely changed the way that we understand development, because many of these things are used in development, so that the... and I don't think this is the last of the surprises in... in molecular biology or biology.

The other thing... it's well known that Rutherford said that atomic energy is bunk... he didn't use the word. Henry Ford said history is bunk... so he said that atomic energy is... getting energy from the atom is impossible, so one learns never to say these things. And I can tell a very simple story from the Lab. In the Lab Hugh Huxley and I were Heads of Structural Studies, and Sydney Brenner and Francis were Head of Cell Biology, and Sydney Brenner of course is a very interesting and inspiring sort of fellow, and likes to plunge into all sorts of things, and Francis of course is a great man and he sometimes acted as a censor of Sydney in the wilder ideas. So between the two of them, they were a pretty powerful combination. So they used to have meetings, once a month, where they discussed large things to do in the future. One of the issues discussed was the long-term future. Hugh said to me, 'We ought to have the same in Structural Studies.' I said, 'Look I can't think long term, I'm only interested in the things I can see three or four years ahead, and by then, things will have changed again. Probably they will have, but I'm not sure.'

Anyway, what was being discussed... we were invited to these meetings. Other divisions began to have them as well, though Fred Sanger wasn't keen on it. You can image Fred was rather a dour type in that sense. He just got on with things, got on with the present. But so Sydney and Francis were discussing whether we should in the Lab... they were going to shut down work on protein synthesis, because that was regarded as classical molecular biology. One of the things they might do in the future was to study animal viruses. Sydney said, 'Oh, I think we should work on animal viruses. Look, we've done bacterial viruses, we've done bacteria, and we've done quite a lot about cells. The animal viruses will be just like bacterial viruses, but only larger writ, just various degrees of complexity, more complex, basically the same principles.' Well, so they decided not to work on animal viruses. There were people starting to do it here, and there were questions, would they recruit people?

But some years later, four years later, split genes were discovered, that the gene... that the precursor mRNA was spliced into a different protein propellant, into a different mRNA, messenger RNA, producing different proteins, so one gene produced multiple proteins. That was a major discovery... for which Philip Sharp and Richard Roberts got the Nobel Prize, representing the two laboratories who did it. There was really a very large number of people who did it. Well, from that, you see that nobody predicted that genes came in pieces, all eukaryotic genes, and you see, you can find things by looking at individual systems. So I encourage, when I'm asked for advice, I encourage people to look at all sorts of things, plants, fungi, fungi is where Tom Cech discovered the catalytic RNA. Altman discovered it in a more classical situation, but the world is full of wonders and we don't know where they are going to turn up, so I don't believe in talking about the future. I think we've got enough things on in the present, and things will emerge, new puzzles will emerge, for example, as in the puzzle that Andy Fire found that double stranded RNA work better than single stranded RNA which was against all the expectations or post-transcriptional gene silencing. And there are other examples which you can look back on in the history of molecular biology.

Born in Lithuania, Aaron Klug (1926-2018) was a British chemist and biophysicist. He was awarded the Nobel Prize in Chemistry in 1982 for developments in electron microscopy and his work on complexes of nucleic acids and proteins. He studied crystallography at the University of Cape Town before moving to England, completing his doctorate in 1953 at Trinity College, Cambridge. In 1981, he was awarded the Louisa Gross Horwitz Prize from Columbia University. His long and influential career led to a knighthood in 1988. He was also elected President of the Royal Society, and served there from 1995-2000.

Listeners: Ken Holmes John Finch

Kenneth Holmes was born in London in 1934 and attended schools in Chiswick. He obtained his BA at St Johns College, Cambridge. He obtained his PhD at Birkbeck College, London working on the structure of tobacco mosaic virus with Rosalind Franklin and Aaron Klug. After a post-doc at Childrens' Hospital, Boston, where he started to work on muscle structure, he joined to the newly opened Laboratory of Molecular Biology in Cambridge where he stayed for six years. He worked with Aaron Klug on virus structure and with Hugh Huxley on muscle. He then moved to Heidelberg to open the Department of Biophysics at the Max Planck Institute for Medical Research where he remained as director until his retirement. During this time he completed the structure of tobacco mosaic virus and solved the structures of a number of protein molecules including the structure of the muscle protein actin and the actin filament. Recently he has worked on the molecular mechanism of muscle contraction. He also initiated the use of synchrotron radiation as a source for X-ray diffraction and founded the EMBL outstation at DESY Hamburg. He was elected to the Royal Society in 1981 and is a member of a number of scientific academies.

John Finch is a retired member of staff of the Medical Research Council Laboratory of Molecular Biology in Cambridge, UK. He began research as a PhD student of Rosalind Franklin's at Birkbeck College, London in 1955 studying the structure of small viruses by x-ray diffraction. He came to Cambridge as part of Aaron Klug's team in 1962 and has continued with the structural study of viruses and other nucleoproteins such as chromatin, using both x-rays and electron microscopy.

Tags: Max Perutz, Andrew Fire, David Baulcombe, Sydney Brenner, Fred Sanger

Duration: 6 minutes, 53 seconds

Date story recorded: July 2005

Date story went live: 24 January 2008