KÖhler, Georges (1946-1995)

German immunologist

For decades, antibodies, substances manufactured by the plasma cells to help fight disease, were produced artificially by injecting animals with foreign macromolecules, then extracted by bleeding the animals and separating the antiserum in their blood. The technique was arduous and far from foolproof. But the discovery of the hybridoma technique by German immunologist Georges Köhler changed revolutionize the procedure. Köhler's work made antibodies relatively easy to produce and dramatically facilitated research on many serious medical disorders such as acquired immunodeficiency syndrome (AIDS ) and cancer. For his work on what would come to be known as monoclonal antibodies, Köhler shared the 1984 Nobel Prize in medicine.

Born in Munich, in what was then occupied Germany, Georges Jean Franz Köhler attended the University of Freiburg, where he obtained his Ph.D. in biology in 1974. From there he set off to Cambridge University in England, to work as a postdoctoral fellow for two years at the British Medical Research Council's laboratories. At Cambridge, Köhler worked under Dr. César Milstein , an Argentinean-born researcher with whom Köhler would eventually share the Nobel Prize. At the time, Milstein, who was Köhler's senior by nineteen years, was a distinguished immunologist, and he actively encouraged Köhler in his research interests. Eventually, it was while working in the Cambridge laboratory that Köhler discovered the hybridoma technique.

Dubbed by the New York Times as the "guided missiles of biology," antibodies are produced by human plasma cells in response to any threatening and harmful bacterium, virus, or tumor cell. The body forms a specific antibody against each antigen ; and César Milstein once told the New York Times that the potential number of different antigens may reach "well over a million." Therefore, for researchers working to combat diseases like cancer, an understanding of how antibodies could be harnessed for a possible cure is of great interest. And although scientists knew the benefits of producing antibodies, until Köhler and Milstein published their findings, there was no known technique for maintaining the long-term culture of antibody-forming plasma cells.

Köhler's interest in the subject had been aroused years earlier, when he had become intrigued by the work of Dr. Michael Potterof the National Cancer Institute in Bethesda, Maryland. In 1962 Potter had induced myelomas, or plasma-cell tumors in mice, and others had discovered how to keep those tumors growing indefinitely in culture. Potter showed that plasma tumor cells were both seemingly immortal and able to create an unlimited number of identical antibodies. The only drawback was that there seemed no way to make the cells produce a certain type of antibody. Because of this, Köhler wanted to initiate a cloning experiment that would fuse plasma cells able to produce the desired antibodies with the "immortal" myeloma cells. With Milstein's blessing, Köhler began his experiment.

"For seven weeks after he had made the hybrid cells," the New York Times reported in October, 1984, "Dr. Köhler refrained from testing the outcome of the experiment for fear of likely disappointment. At last, around Christmas 1974, he persuaded his wife," Claudia Köhler, "to come to the windowless basement where he worked to share his anticipated disappointment after the critical test." But disappointment turned to joy when Köhler discovered his test had been a success: Astoundingly, his hybrid cells were making pure antibodies against the test antigen. The result was dubbed monoclonal antibodies. For his contribution to medical science, Köhler—who in 1977 had relocated to Switzerland to do research at the Basel Institute for Immunology—was awarded the Nobel in 1984.

The implications of Köhler's discovery were immense, and opened new avenues of basic research. In the early 1980s Köhler's discovery led scientists to identify various lymphocytes, or white blood cells. Among the kinds discovered were the T-4 lymphocytes, the cells destroyed by AIDS. Monoclonal antibodies have also improved tests for hepatitis B and streptococcal infections by providing guidance in selecting appropriate antibiotics , and they have aided in the research on thyroid disorders, lupus, rheumatoid arthritis, and inherited brain disorders. More significantly, Köhler's work has led to advances in research that can harness monoclonal antibodies into certain drugs and toxins that fight cancer, but would cause damage in their own right. Researchers are also using monoclonal antibodies to identify antigens specific to the surface of cancer cells so as to develop tests to detect the spread of cancerous cells in the body.

Despite the significance of the discovery, which has also resulted in vast amounts of research funds for many research laboratories, for Köhler and Milstein—who never patented their discovery—there was little financial remuneration. Following the award, however, he and Milstein, together with Michael Potter, were named winners of the Lasker Medical Research Award.

In 1985, Köhler moved back to his hometown of Freiburg, Germany, to assume the directorship of the Max Planck Institute for Immune Biology. He died in Freiburg in 1995.

See also Antibody-antigen, biochemical and molecular reactions; Antibody and antigen; Antibody formation and kinetics; Antibody, monoclonal; Immunity, active, passive and delayed; Immunity, cell mediated; Immunity, humoral regulation; Immunodeficiency; Immunodeficiency disease syndromes; Immunodeficiency diseases