Obituary: Georges Khler
Tuesday 04 April 1995
Georges Khler was an immunologist whose research in the mid-1970s resulted in one of the most significant developments in 20th-century biology. His discovery, with Csar Milstein, of "monoclonal antibodies", not only produced a new way for cell and molecular biologists to analyse their specimens, but also revolutionised diagnostic clinical chemistry and created a large part of the biotechnology industry which emerged in the 1980s. For their discovery, Khler and Milstein shared (with another immunologist, Niels Jerne) the 1984 Nobel Prize for Physiology or Medicine.
Khler was born in Munich in 1946. He studied biology at Freiburg University and in 1971 went to the Basle Institute for Immunology, where he obtained his PhD under the supervision of Fritz Melchers. At the Basle Institute he developed an interest in antibodies and how they are produced as part of the normal immune response in the blood and spleen of mice (and other animals including humans). He was fascinated by the enormous diversity of antibodies which a single animal can make and the way in which this process is controlled.
In Basle he learnt experimental techniques for studying normal antibody- producing cells, including one invented by Jerne (who was then the Director of the Institute) for counting the number of cells making a particular antibody amongst the millions of cells making different antibodies. This experience was to prove invaluable when, in 1974, Khler moved to England for a two-year post- doctoral fellowship, to work with Milstein in the Medical Research Council Laboratory of Molecular Biology in Cambridge. Khler developed a very close collaboration with Milstein and, after a few false starts, within a year the work for which they were to share a Nobel Prize had been completed and submitted for publication in the scientific journal Nature.
Before this breakthrough, antibodies for research and medicine were prepared by injecting animals with a "foreign" molecule purified from another species and waiting for several weeks to allow the animal to respond to this immunological challenge. If the immunisation process was successful, then the blood of the animal was removed and the serum ("anti-serum") separated. This process was unreliable and required the use of laboratory animals.
Scale-up for industrial production of antisera for medical use involved the use of larger, farmyard animals, or human volunteers. Khler took cells from an immunised mouse and fused them to mouse tumour- derived cells, which had previously been developed in Cambridge for cell fusion. Khler's first attempt was successful and produced a clonal cell population, which could be propagated indefinitely and which produced a pure, "monoclonal" antibody of known specificity. For the first time, a pure antibody could be manufactured in unlimited qualities. Thus, almost 20 years ago, and before he had reached the age of 29, Khler had made the discovery which was to make him famous.
However the full practical and commercial significance of the discovery was realised at the time by neither the inventors, whose aim in carrying out the work was purely academic, nor by the journal, which agreed to publish the report only on condition the article was condensed to an abbreviated letter format. The government authorities also failed to appreciate the potential of the discovery and no patents were applied for (an omission to which Margaret Thatcher, as Prime Minister, was often to refer).
After a second year in Cambridge, making a series of monoclonal antibodies to prove the generality of the method, Khler returned in 1976 to the Basle Institute and his original interest in normal antibody synthesis. He used the technique of fusing cells as a tool to understand the molecular mechanisms involved and the differentiation of antibody-producing cells. He left to others the commercial exploitation of monoclonal antibody production.
By 1980 the technique of producing the monoclonal antibodies was established in laboratories throughout the world and the importance of the technology both in research and industry had become widely recognised. A Nobel Prize was expected by many and the Nobel Committee - and the scientific press - were keen to dissect out the relative contributions of Khler and Milstein to the original discovery. These deliberations indicated a reluctance to accept that, in the closest scientific research collaborations, it may be impossible to attribute a particular idea to one collaborator or the other. However, public speculation, which must have been distasteful to both scientists, continued until the announcement of the prize.
In 1985 Khler moved to Freiburg, where he had been invited to become Director of the Max Planck Institute of Immune Biology. His scientific distinction and reputation attracted to the institute not only talented scientists, but also funding from the regional government of Baden-Wrttemberg for a programme of building and expansion. He also developed the links with the University of Freiburg (his alma mater) resulting in a joint chair in Molecular Immunology.
In parallel with his administrative duties as Director, he continued to do research and publish scientific papers. He adopted new techniques of mouse genetics to continue his interest in antibody diversity. Most recently he was studying the role of growth factors (cytokines) in antibody synthesis and his laboratory had developed a series of mouse strains, each genetically deficient in a particular cytokine. Recent collaborations with others indicate the breadth of his interests, ranging from genetics to cellular immunology and from parasitology to microscopy. Although none of his subsequent work had the impact of his Nobel Prize work, there was obviously much more to come from this career, cut tragically short.
The imagination and persistence which Khler displayed in the laboratory was also evident at home. When, in Cambridge, he found himself living in a house with a piano, he decided to learn to play. Not for him the conventional route of lessons and scales. He bought the score of a piece by Chopin and began to teach himself to play it. For the remainder of his stay in Cambridge, guests at dinner parties were entertained to successive - and improving - performances of that work.
Khler's family was not one of those neglected by a busy research scientist. The adventurous holidays undertaken in a very old camper van each summer from Cambridge retained their priority, even at the height of the excitement over monoclonal antibodies.
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