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Lack of interest in therapeutic antibodies


Setting up Cambridge Antibody Technology
Aaron Klug Scientist
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When I inherited the Lab, there was technology transfer going on, that is things developed here which had a potential application, but also potential exploitation. Application means what they say, exploitation means to make money out of... by commercialising it. And the traditional course was to... to get a company to fund... Sydney had done quite a lot of this, Sydney Brenner, he got a company to fund, say, a post doc or a few posts... for a piece of research which we would be doing anyway. We didn't know it, at least I didn't ever start anything with the idea of making money eventually, but my attitude was that if you saw an opportunity to exploit something, you don't be shy about it, you do it. And I think I referred to this yesterday, did I not? About the person who thought I'd be turning the Lab into a Department of Applied Molecular Biology. Well... so in taking transfer, there were several things that I did. In the course... I was there for ten years, the one was... which... basically led to the, in 1990, the setting up of Cambridge Antibody Technology which is a big biotechnology company which really would be making tens of millions a year for the MRC if it hadn't been embroiled... by mounting a court case by a very large pharmaceutical firm that won't pay the royalties to Cambridge Antibody Technology. And I was involved the setting up of Cambridge Antibody Technology in my capacity as a Director. I did other things as well, but I'll just go on to this one.

Now, the Government had realised, and Sydney was very active in all this, there'd been a Spinks Committee in Biotechnology, and Sydney was a very... spent a lot of time in Whitehall, and so on, and resulted in the Government setting up Celltech, a company which was partly funded by the company and which had access to MRC inventions, and the inventions they had at the time were mononclonal antibodies which César Milstein had not commercialised for reasons... well, not through any doing of his own, because the NRDC, National Research Development Corporation, which had been set up by the Government to make sure that there wasn't another debacle as happened with insulin. Insulin was a totally British invention and at the time, Britain was paying royalties to Americans because during the war, the production of penicillin was shipped to America and what the Americans invented, or rather patented, was the improved production of penicillin which they did do. They then imported a man called Healey who is really the unknown hero of the case. Everybody knows about... about Florey and what's the man at St Mary's? You know... the man that everybody thinks is the greatest British scientist? Fleming, Fleming! The discoverer was Fleming. They did ten years without doing anything about his discovery, but it was Florey and Chain who extracted the active principle and made the antibiotic, the first antibiotic penicillin. Anyway it was very grating that this should happen, and I was determined this shouldn't happen again. Now Celltech was a private company, but was backed by the MRC, and it seemed to me that we in the Lab working away had absolutely no... had absolutely no... we got nothing back from it. There was at that time no system of rewards to inventors. By mixing this up with the story of CAT, because they were all intermingled, and it was all part of changing, if I could call it that, the culture of the time, the culture from being a pure research Laboratory to one who still continues to be but exploits its inventions or discoveries, and if I can say right now, for I may forget to say so later, this Lab earns in royalties and licences more than it costs to run the whole place, which is fairly unique I think in any... certainly in any MRC or any average Research Council Laboratory. And you see it's paid for by the public, where we get our money from the public, that's who... eventually the taxpayers of the country pay us, and this ought to be a return to them. But the rewards to inventors came about during the course of these... of this work. They said things would move in parallel.

Let's return to Celltech, and setting up Cambridge Antibody Technology. Greg Winter, who was in one of the other divisions, basically invented a way of making purely monoclonal antibodies, not in the system that César Millstein developed, but making them in human... making effectively human antibodies that had nothing mouse about them inside bacteria. Before that he'd invented a method of what he called humanising antibodies where the antibody was made in the mouse, and he... but by working on antibody structure, he grafted on the determining regions, the regions of the antibody which determine the specificity of the antibody, so this had CDRs which were found from the mice, but were grafted on to a human framework, and these much less immunogenic. You see, the early promise of antibodies when you inject mouse antibodies to humans is anaphylaxis, that people sometimes practically die because you get a reaction against a foreign body. So it went through various stages. Michael Neuberger invented what's called chimeric antibodies and that... that there are still a few being made, but Greg's great achievement was to make fully human antibodies, using phage display selection technique in bacteria, and he did this by cloning the whole the human repertoire, all the V and the... all the V genes and the J and the D, so we had a complete repertoire of all the genes. You could put them together, make combinations as combinatorial chemistry really, put them together and put them into a bacterial cell and make an antibody, which didn't involve animals. That was very much welcomed and on the basis of that, I went. I was Head of the Lab and I thought, well this is something really big.

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: Cambridge Antibody Technology, Spinks Committee in Biotechnology, Celltech, NRDC, National Research Development Corporation, César Milstein, Alexander Fleming, Greg Winter, Michael Neuberger

Duration: 7 minutes, 43 seconds

Date story recorded: July 2005

Date story went live: 24 January 2008