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Social life at The Royal Society


BSE and the prion hypothesis
Aaron Klug Scientist
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Scientifically, I did come to believe the prion hypothesis because I myself knew of an example. I wrote a paper with Robert May, who was then a population biologist, on the subject, and it turned out to an old interest in bacterial flagella. Now bacterial flagella I didn't work on myself, but bacterial flagella were a helical array of protein sub-units just like TMV, and a Japanese school had worked on them and they found that the... well, I won't go into the whole story, but the bacterial flagellum is a hollow cylinder and bacteria use them for propelling through the liquid, and I had studied them because... in fact I studied their structure. How do the waves get created, and I introduced Chris Calladine to this. It is quite an interesting subject in itself. And because... they are a quasi-equivalent, because if the axis of the helix is not straight, it has a helical form and the sub-units can't all be in the same orientation. Therefore, they have to be somewhat different. I'd used that as an argument, in fact, when we did our paper with Caspar that proteins can change their conformation, have more than one conformation. It's something which Max never accepted. He thought, Max Perutz... did I say that he thought that what I told him was a very unlikely story? That would emerge later.

So I knew about bacterial flagella, and I knew something about them. Now, the point about bacterial flagella is that in order for them to grow, and this is highly relevant to, believe it or not, to prion diseases, is that they... above a certain concentration, the protein will begin to condense, it nucleates, you get a little aggregate of nucleates, and it grows. However, what the Japanese school had done was if you start off with a little fragment of a bacterium, a small, short piece... bacterial flagella have very, very long wave forms, you find that the... it starts growing as soon as you add any amount of protein, because the existing short length acts as a seed or a nucleus for... as I've told you, I knew about nucleation and growth, and what the [Sho] Asakura in Japan has shown that if you consider different strains of, say, salmonella, different strains have different helical shapes, different wavelengths and they're characteristic of the strain, because the protein of which the flagellum, of which the flagella are made, has a slightly different protein composition, slightly different. And what he showed was that the... that if you have a seed of one strain and you added the protein, the purified protein of another strain, then... and you seeded the growth, the conformation that the added protein took up was not characteristic of its own characteristic wave form, but characteristic of the seed. So this meant, this meant that a protein that the protein structure could induce a change in the structure of another protein. And I wrote a paper with Bob May, because Eigen, Manfred Eigen had written several papers which were... he hadn't got the right idea. It was published in some new journal, whose name I've forgotten, but I pointed out that this phenomenon, so you had the case where... because the argument was that Prusiner had asked that these different strains of scrapie, and different strains of BSE, all produced by different shapes of the same protein, and so this was the... and so, well the different shapes, but I should say that the susceptibility where we turn to humans does depend upon the polymorphisms in the protein composition. And it turns out that almost all the people who are susceptible to new variant disease have a certain methionine to valine change and the... but the ones which... those are the only ones who are susceptible, so there is something that would harm you, but it is protein conformation that... so in the end, all this was part of convincing me that Prusiner was basically right. Because it was argued at the Royal Society we should make him a Foreign Member, you see, and so later the Nobel Committee obviously accepted this, and gave him a Nobel Prize. So it was an interesting scientific, sort of scientifico-politico-economico... episode which I found myself in.

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: John Finch Ken Holmes

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.

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.

Tags: Robert May, Chris Calladine, Max Perutz, Sho Asakura, Manfred Eigen

Duration: 5 minutes, 19 seconds

Date story recorded: July 2005

Date story went live: 24 January 2008