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The story of a revolution: César Milstein and monoclonal antibodies

César with a flask containing monoclonal antibodies growing in a fluid (Credit: MRC Laboratory of Molecular Biology)

César with a flask containing monoclonal antibodies growing in a fluid (Image copyright: MRC Laboratory of Molecular Biology)

A new online exhibition about the life and work of luminary MRC researcher César Milstein is unveiled today. Here Dr Lara Marks of the Department of Social Science, Health and Medicine, King’s College London, who put the exhibition together, discusses the inspiration behind it and the stories you can find within a scientist’s notebook.

Today, monoclonal antibodies are intrinsic to healthcare. They’re used every day as probes to unravel the pathways of disease, to diagnose a patient’s condition or as powerful drugs. Everyone who has ever used a home pregnancy test will have, perhaps unwittingly, used monoclonal antibody technology. But they started life as a laboratory research tool, and their journey into clinical use was one fraught with complexity.

Antibodies are proteins that recognise and fight foreign invaders, such as bacteria or viruses. Since the early twentieth century scientists had been keen to produce large amounts of antibodies specific to a particular target for research or clinical purpose, but with no success.

In 1975 César Milstein and his colleague Georges Köhler at the MRC Laboratory of Molecular Biology in Cambridge developed a way to produce monoclonal antibodies by fusing myeloma cells — a type of cancerous immune cell — with mouse spleen cells that had been exposed to a target. As well as creating a research tool for investigating the immune system and the pathways of disease, this also laid the foundations for the production of antibody-based drugs against specific diseases.

Despite their prevalence, few outside the scientific and medical community are aware of the existence of monoclonal antibodies, let alone their importance for diagnosing and treating disease. The exhibition, Healthcare Revolution in the Making, is an effort to let the outside world know about monoclonal antibodies and the life and work of César Milstein, who was not only instrumental in the development of the technology, but was also pivotal to showing its clinical application. Included in the exhibition are some of Milstein’s notebooks and writings, shown to the public for the first time.

I was first inspired to create the exhibition while combing through Milstein’s collection of papers kept at the Churchill College Archives at the University of Cambridge for a book I am writing about the history of monoclonal antibodies and how they have transformed healthcare.

Record of dispatch of myeloma cells to Hilary Koprowski (Source:  Milstein's notebook, Churchill Archives Centre, Milstein Papers, file MSTN/C.282)

Record of dispatch of myeloma cells to Hilary Koprowski (Source: Milstein’s notebook, Churchill Archives Centre, Milstein Papers, file MSTN/C.282)

I was excited that the notebooks and letters provided a unique window into the many challenges Milstein and his colleagues faced in transforming a laboratory research tool into a product for patients, and the difficulties scientists go through in transferring their knowledge and materials to others for wider use. I could see the process of technology transfer in the making.

One notebook that particularly caught my attention was the one in which Milstein recorded the samples he sent to other scientists — capturing the moment that Milstein and Köhler’s antibody-producing cells first ventured into the outside world. One entry of particular interest was the dispatch of myeloma cells, listed as X63Ag8, to the Polish-American virologist Hilary Koprowski at the Wistar Institute in Philadelphia.

Dated 7 September 1976, this record is of major historical significance, as Koprowski and his Wistar colleagues then went on to be granted a patent for monoclonal antibodies. This patent, and another granted soon after, made broad claims on the technique behind the antibodies and prompted a major outcry in both British political circles and the international scientific community, with many believing Koprowski and his colleagues had patented what was effectively Milstein and Köhler’s technique.

Together with other papers in Milstein’s collection, this notebook captures first-hand the messy business of patenting research, and the implications this holds for those working in both the laboratory and the commercial world.

Lara Marks

Lara.Marks@kcl.ac.uk

A Healthcare Revolution in the Making was sponsored by the MRC as part of our Centenary programme and sponsored by the Department of Social Science, Health & Medicine, King’s College London.

3 Comments Post a comment
  1. Very interesting blog piece. Both César Milstein and Georges Köhler were enthusiastic participants in the first ever Wellcome Witnesses to Twentieth Century Medicine seminar on ‘Technology Transfer in Britain: The Case of Monoclonal Antibodies’. Those with a historical interest in this topic may wish to download a copy of the transcript, available free of charge from the
    History of Modern Biomedicine Research Group website, here:

    http://www.history.qmul.ac.uk/research/modbiomed/wellcome_witnesses/volume01

    February 19, 2013
  2. Jefferson Foote #

    An interesting find. I also loved your main piece, which had loads of stuff I didn’t know — and I worked with César for 7 years! Your science writing was very accessible, César’s early struggles had a nice human touch, and you got the politics of the patent screw-up and Koprowski rip-off just right.

    February 28, 2013

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