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Work on Alzheimer's disease: Studying the brain fibres


Work on Alzheimer's disease: Trying to extract brains
Aaron Klug Scientist
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[Claude] Wischik didn't know very much, he'd never done any real biochemistry or chemistry, he'd been a medical student and what he'd worked on was catecholamines and drug action and things like that. So I said, 'Well, you must get them out' and I said, 'You must describe various recipes and we're doing things on sucrose gradings', the kind of things we did on... chromatin, I gave him papers to read and Jo Butler gave some advice but then... so what happened was that he started, now we couldn't extract brains because there was a belief, spread by Carleton Gajdusek who was a Nobel laureate that this was... that Alzheimer's was caused by a slow virus and therefore you couldn't... you had to work in special quarters so I managed to get a special centrifuge which Jim Gowans gave us from MRC private funds one in the lab and Roth set aside a place in the medical school and Wischik worked there and he would bring the preparations and for several months nothing happened and I was mystified. We couldn't even get any soluble material, and I was mystified because I was doing other things as well so I did watch on a daily basis, then I suddenly twigged. You see I said... the idea was to get patients who had just died, they were on the record so we kept tracks, there was lots of patients on the Addenbrooks Hospital's register so as soon as they died Wischik would conduct a post-mortem examination, he was the only doctor and to take the... extract the hippocampus which you can do by dissection. Of course, we had the patient's permission or else a relatives permission to do all this, as I first mentioned, it's rather tricky but some people don't want it, other people are quite glad to leave their brains if it's going to be of any medical use. And nothing happened. Now this was being done in the medical school so I didn't see what was happening. Then I suddenly twigged, and that goes back to the fact I'd once been a medical student. What you do when you dissect is you put things into formalin. Absolutely true and suddenly I woke up so to speak, of course that's what he would do because there was a brain bank where they were studying samples and they put things into formalin and of course he didn't know any chemistry or biochemistry so I nearly had a fit and I said what's the first thing... I assumed he took the brains out and froze them. And no, he was putting them into formalin and then you couldn't extract anything so sometimes having been a medical student is of some help, because I could suddenly remember the smell of formalin in the dissecting room. So I put a stop to that and then Wischik began to extract the brains and as we cut out the hippocampus and the idea was of course to get brains which were heavily... had heavy deposits of these tangles, you can see that in the... so we gradually began to build up supplies of the neuro-fibrillary tangles, we had amyloid fibres as well but decided not to work on those.

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: Addenbrooks Hospital, Carleton Gajdusek, Jim Gowans, Claude Wischik

Duration: 3 minutes, 30 seconds

Date story recorded: July 2005

Date story went live: 24 January 2008