Speed read: Creating supply on demand
The 1984 Nobel Prize in Physiology or Medicine celebrated the important contribution of theory and practice in shaping our understanding of the body’s immune system. The hypotheses formulated by Nils Jerne presented a clearer image of the way in which a diverse range of antibodies can be engaged to fight an invader. Georges Köhler and César Milstein constructed perpetual antibody-production lines that have become an essential laboratory tool for researchers worldwide.
Jerne’s first major theory, published in 1955, refuted the general opinion that the immune system custom designs new antibodies when it encounters unfamiliar molecules, or antigens, on an intruder. The body has already created its full repertoire of antibodies, proposed Jerne, and it selects the correct one for the task – a hypothesis later refined by MacFarlane Burnet, which stated that each individual white blood cell produces only one specific antibody. Jerne’s network theory in 1975 described how the immune response is exquisitely controlled, and was built on his premise that antibodies can themselves act as antigens. With the various sets of antibodies stimulating or suppressing the production of each other, he visualized the immune system as a self-regulating network that can switch itself on and off in response to a foreign invasion.
Köhler and Milstein were independently trying to test theories about antibody production in the laboratory, and to do so they both sought ways of creating long-living cell lines that could generate large amounts of a particular antibody. Milstein had developed cancerous forms of antibody-producing cells that grew and multiplied forever, but which churned out antibodies of unknown specificity; while Köhler had tweaked normal antibody-producing cells to produce specific antibodies, but they survived for a few days only in culture. Combining forces, the neat trick they came up with was to fuse a normal antibody-producing cell with a tumour cell, forming a hybrid that was both immortal and could create a specific antibody. Köhler and Milstein’s technique for creating any single predetermined type of so-called monoclonal antibody on demand has led to many medicine and biomedical applications, from creating more reliable probes for blood and tissue typing tests, to designing completely new therapeutic strategies for diseases such as cancer.
This Speed read is an element of the multimedia production “Immune Responses”. “Immune Responses” is a part of the AstraZeneca Nobel Medicine Initiative.
Niels K. Jerne – Other resources
Links to other sites
Interview with Niels Jerne from BBC Archive: Discovering how our immune systems protect us
Georges J.F. Köhler – Biographical
Name: Georges Jean Franz Köhler
Born: 17.4.1946 in München. German Nationality
Education and research experience
| April 1965 | Abitur in Kehl, beginning of studies in Biology at the University of Freiburg. |
| January 1971 | Diploma in Biology, work on repair-deficient strains of Escherichia coli and computer assisted instruction. |
| April 1974 | Ph.D., University of Freiburg. Thesis work on immunological studies of the enzyme ß-galactosidase, carried out at the Institute for Immunology, Basel, Switzerland, under the supervision of Professor Fritz Melchers. |
| April 1974 to March 1976 | Postdoctoral work in cell biology (lymphocyte fusion) in Dr. C. Milstein’s laboratorium at the Medical Research Council, Laboratory of Molecular Biology. Work supported by an EMBO long-term fellowship. Publication: G. Köhler and C. Milstein (1975) “Continuous cultures of fused cells secreting antibody of predefined specificity”. Nature 256:495-497. |
| April 1976 to present | Member of the Basel Institute for Immunology; Molecular and cellular work on lymphocyte hybrids. |
Member of the European Organization of Molecular Biology (EMBO), Honory Lecturer at the University of Basel, Switzerland, Doctor honoris causa of the University of Centre Limburg, Belgium, numerous awards, becoming director of the Max-Planck-Institut für Immunbiologie in Freiburg,
Georges J.F. Köhler died on 1 March 1995.
Niels K. Jerne – Nobel Lecture
Niels K. Jerne held his Nobel Lecture on 8 December 1984, at Karolinska Institutet, Stockholm. He was presented by Professor Hans Wigzell of the Karolinska Institutet.
Read the Nobel Lecture
Pdf 220 kB
Georges J.F. Köhler – Nobel Lecture
Georges J.F. Köhler held his Nobel Lecture on 8 December 1984, at Karolinska Institutet, Stockholm. He was presented by Professor Hans Wigzell of the Karolinska Institutet.
Georges J.F. Köhler held his Nobel Lecture on 8 December 1984, at Karolinska Institutet, Stockholm. He was presented by Professor Hans Wigzell of the Karolinska Institutet.
Editor’s note: The first seconds of the Nobel Lecture is missing. Our apologies.
Read the Nobel Lecture
Pdf 253 kB
César Milstein – Nobel Lecture
César Milstein held his Nobel Lecture on 8 December 1984, at Karolinska Institutet, Stockholm. He was presented by Professor Hans Wigzell of the Karolinska Institutet.
César Milstein held his Nobel Lecture on 8 December 1984, at Karolinska Institutet, Stockholm. He was presented by Professor Hans Wigzell of the Karolinska Institutet.
Editor’s note: The first seconds of the Nobel Lecture is missing. Our apologies.
Read the Nobel Lecture
Pdf 293 kB
César Milstein – Other resources
Links to other sites
Obituary from University of Cambridge
Niels K. Jerne – Banquet speech
Niels K. Jerne’s speech at the Nobel Banquet, December 10, 1984
Your Majesties, Your Royal Highnesses, Excellencies, Ladies and Gentlemen,
The Nobel Prize is a precious gift, and it is wonderful to receive this gift rather late in life: one does not then have to carry for a very long time the burden that this distinction imposes. This does not apply to my friends César Milstein and Georges Köhler with whom I have the pleasure to share the prize in Physiology or Medicine. We represent three scientific generations. In fact, I was already working in an immunological laboratory before Georges Köhler was born. That this year’s prize is given for work in immunology follows a long tradition. The first Nobel Prize in our field was given, in 1901, to Emil von Behring who, together with Shibasaburo Kitasato, discovered the presence of specific antibody molecules in the cell-free scrum of immunized animals. This demonstration had a tremendous impact on the direction into which immunology developed. It turned the attention of two following generations of scientists towards antibodies and away from the cells which produce them. These antibodies were polyclonal because many different cells participate. My two fellow-laureates have introduced a marvellous technique which permits the production of antibodies by a single cell and its clonal descendants. I have had no part in this monoclonal invention. Of course, biologists are not just laboratory people that mix liquids in test tubes. Most of their time is devoted to the discussion of ideas and to the replacement of these ideas with better ones. My concern has always been synthetic ideas, trying to read road-signs leading into the future. Thinking back over my own years, my thoughts now often return to a happy childhood. My parents died thirty years ago, and I wish to dedicate my part of this Nobel Prize to them, with a poem from Jutland in Denmark. As we are here in Scandinavia, I hope you will permit me to do this in the language of the poet Jeppe Aakjær:
Her vendte far sin plov, å så mangen, mangen gang,
Nar grålærken højt over sandmarken sang.
Her gik min stille mor i sin grove grå kjol,
Og så med tynget blik mod den synkende sol.
Thi satte eders søn denne liden grå sten,
Til minde om en færd der som duggen var ren.(English translation:
Here did my father turn his plough, oh, so many, many times,
While the grey lark sang over the sandy fields.
Here walked my silent mother in her coarse grey dress,
And turned a heavy look towards the sinking sun.
Thus placed your son this little grey stone,
In remembrance of your journey that was pure as the dew.)
César Milstein – Documentary
César Milstein describes how, while sitting in a meeting at his work at the MRC Laboratory of Molecular Biology, they were suddenly interrupted and he was informed that he had been awarded the Nobel Prize in Physiology or Medicine 1984.
Credit: ITN Archive/Reuters