Microbiology and Immunology

WORLD OF MICROBIOLOGY AND IMMUNOLOGY Krebs, Hans Adolf

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extracted by bleeding the animals and separating the anti-

serumin 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 seri-

ous 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 Timesas 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 antibodyagainst each

antigen; and César Milstein once told the New York Timesthat

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 cultureof

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 typeof antibody. Because of this, Köhler

wanted to initiate a cloningexperiment that would fuse plasma

cells able to produce the desired antibodies with the “immor-

tal” myeloma cells. With Milstein’s blessing, Köhler began his

experiment.

“For seven weeks after he had made the hybrid cells,”

the New York Timesreported 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 win-

dowless 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 suc-

cess: Astoundingly, his hybrid cells were making pure anti-

bodies against the test antigen. The result was dubbed mono-

clonal 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 lympho-

cytes, 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 remunera-

tion. 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 alsoAntibody-antigen, biochemical and molecular reac-

tions; 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

KKrebs, Hans AdolfREBS, HANSADOLF(1900-1981)

German biochemist

Few students complete an introductory biology course without

learning about the Krebs cycle, an indispensable step in the

process the body performs to convert food into energy. Also

known as the citric acid cycle or tricarboxylic acid cycle, the

Krebs cycle derives its name from one of the most influential

biochemists of our time. Born in the same year as the twenti-

eth century, Hans Adolf Krebs spent the greater part of his

eighty-one years engaged in research on intermediary metab-

olism. First rising to scientific prominence for his work on the

ornithine cycle of urea synthesis, Krebs shared the Nobel Prize

for physiology and medicine in 1953 for his discovery of the

citric acid cycle. Over the course of his career, the German-

born scientist published, oversaw, or supervised a total of

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