The Medical Research Council Laboratory of Molecular Biology
by Max F. Perutz
1962 Nobel Laureate in Chemistry
On a summer day in the late fifties a delegation from the Soviet Union appeared in Cambridge demanding
to see the "Institute of Molecular Biology". When I took them to our shabby prefabricated hut in front of the University Physics
Department, called Cavendish Laboratory after its nineteenth century benefactor, they went into a huddle until finally one
of them asked me: "And where do you work in winter?" They wanted to know how I had planned our successful Research Unit, imagining
that I had recruited an interdisciplinary team as Noah had chosen the animals for his ark: two mathematicians, two physicists,
two chemists, two biochemists and two biologists, and told them to solve the atomic structure of living matter. They were
disappointed that the Unit had grown haphazardly and that I left people to do what happened to interest them.
||John Desmond Bernal, the discoverer of X-ray diffraction from protein crystals.|
Proteins were Black Boxes
In 1936, when I joined J. D. Bernal's Crystallographic Laboratory as a graduate student from Vienna, it
was a small, dingy sub-department of the famous Cavendish Laboratory headed by Ernest Rutherford, the discoverer of the atomic nucleus, who was regarded as the world's greatest experimental physicist. On the other hand,
I was trained as a chemist, and my interests grew in another direction. It had just been discovered that all chemical reactions
in living cells are catalysed by enzymes and that all enzymes are proteins. Genes were also believed to be made of proteins,
but next to nothing was known about the structure of proteins, let alone their mechanism of action. They were black boxes.
Protein structure therefore seemed to be the central problem of biology, and X-ray crystallography was the only method in
principle capable of solving it.
Haemoglobin Enters the Scene
Haemoglobin was easily available and happened to be one of the very few proteins to have been crystallised.
In an early attempt at finding something out about the species specificity of proteins, two scientists at the Carnegie Institute
in Washington had published a comprehensive atlas of haemoglobin crystals of different animals (Reichert & Brown 1909).
In 1937, when I began the X-ray analysis of haemoglobin crystals, so little was known about it that every morsel of structural
information was a gem. The Cambridge respiratory physiologist Joseph Barcroft once remarked that all that was known about
haemoglobin could be written on the back of a postage stamp. My first results showed that it was a spheroid with a well-defined
atomic structure, a new concept when proteins were still widely regarded as woolly colloids, that it consisted of two identical
halves which were not penetrated by diffusible electrolytes, and that its four haems were roughly parallel to each other.
The problem was how to get further.
Two Strokes of Luck
Rutherford died in 1937, and W. L. Bragg, the founder of X-ray analysis, succeeded him as Cavendish Professor. This was a blow to the atomic physicists in the Laboratory,
but extremely lucky for me. Bragg was fascinated by the idea that X-ray analysis, which he had started with the determination
of the sodium and chlorine positions in common salt, might be extended to the immensely complex molecules of the living cell.
When my money ran out after Hitler's annexation of my native Austria, he obtained a grant from the Rockefeller Foundation
for my support which saved my scientific career. It continued until the mid-sixties and was to prove crucial for the success
of our Research Unit.
||Sir Lawrence Bragg, around 1965.|
Towards the end of the war, Bragg recommended me for a University Lectureship, but the mills of Cambridge
University grind slowly, and it took nine years to materialise. On the other hand, the Rockefeller Foundation considered that
the University rather than they, should pay my salary, and I found myself out of a job. John Kendrew had joined me in 1945 and had started a comparative X-ray study of adult and foetal sheep haemoglobin, a grossly premature
project for the state of X-ray analysis in those days. He had a grant for two years, but nothing after that.
bleak outlook we were rescued by another of Cambridge's great scientists, David Keilin, the genial, Russian-born biologist
who had discovered the cytochromes and headed the Molteno Institute of Parasitology. He had given Kendrew and me bench space
in his biochemistry laboratory for the preparation of our crystals and was keenly interested in all haem proteins, including
Foundation of the Medical Research Unit for Molecular Biology
Keilin was friendly with Sir Edward Mellanby, the formidable head of the Medical Research Council (the
British equivalent of the National Institutes of Health), and he suggested that Bragg should apply to Mellanby for support.
This was duly granted in October 1947 and was the turning point in our fortunes. The Council established a "Research Unit
for the Study of the Molecular Structure of Biological Systems", a mouthful which we changed later to "Molecular Biology Unit",
with Kendrew and me as its founding members. The subject became a magnet for the attraction of talent. Francis Crick, Hugh Huxley and Jim Watson were among the first to join us. Vernon Ingram came from London, Sydney Brenner from Johannesburg, Paul Doty, Alex Rich, Seymour Benzer and many others from the United States. By 1956, the Unit had grown
so large I spent my time scrounging for a little bench space in a butterfly museum here or the abandoned cyclotron room there,
and toyed with the idea of asking the Medical Research Council to build us our own laboratory. On the other hand, though my
introduction of the method of isomorphous replacement with heavy atoms had made the solution of protein structures possible
in principle, none had yet been solved. Watson & Crick's mechanism of replication of DNA, though highly plausible, was
still unproved; and we were too weak in biochemistry to qualify as an interdisciplinary laboratory, a concept yet to be invented.
|Perutz and other members of the Medical Research Council Unit for Molecular Biology outside the hub next
to the Cavendish Laboratory in Cambridge where the Unit was housed from 1956 to 1962.|
|Bror Strandberg and Richard Dickerson outside the hub with the output from the electronic digital computer
Edsac II. The pictured tapes specified the phases of the X-ray reflections used to calculate the first atomic model of a protein;
sperm whale myoglobin.|
The Laboratory of Molecular Biology Comes into Being
That situation was transformed in 1957 when Kendrew's first low resolution structure of myoglobin emerged,
when Matthew Meselson proved that each of two DNA daughter double helixes was made up of one parent strand and one newly synthesised
strand, and Arthur Kornberg showed that the base sequence of the newly synthesised strand was complementary to that of the parent strand, exactly as
Watson & Crick had predicted. Most important, Fred Sanger in the University Department of Biochemistry had just completed the amino acid sequence of insulin, the first sequence of
a protein to be determined, and he agreed to join us.
I submitted a report on Recent Advances in Molecular Biology
together with plans for the new laboratory to the Medical Research Council. When I was invited to present this to a meeting
of the Council, I spent a sleepless night worrying how it would be received, but as soon as I entered the Council room, one
of the members told me that it was the most interesting report he had ever read and, to my relief and delight, the Council
approved our plans that same day.
John Kendrew demonstrating his model of myoglobin to the Queen at the opening of the Laboratory of Molecular
Biology in May 1962.
In the back from left to right Mavis Bhow, Gisela Perutz, Lady Himsworth, Sir Harold Himsworth and
Sir William Shawcross.
The Laboratory of Molecular Biology was built next to, and simultaneously with, a new hospital south of Cambridge,
initially with a floor area of 22,000 sq. ft. We moved in in February 1962, and in May the Queen came to open it. Crick and
Brenner stayed away because they disapproved of royalty, but Watson came specially from Harvard in order to be presented.
When we proudly showed the Queen and her party the atomic models of DNA and myoglobin, one of her Ladies-in-Waiting exclaimed:
"Oh, I had no idea we have all those little coloured balls inside us!"
It was a Merger
In business jargon the laboratory would have been called a merger, because four groups joined to bring
it into being: Fred Sanger's from the Cambridge University Biochemistry Department; Kendrew's, Crick's and my groups from
the Cavendish Laboratory; Aaron Klug's from Birkbeck College and Hugh Huxley (on his own) from University College, London. Cesar Milstein arrived from the Argentine to join Fred Sanger soon afterwards. The laboratory started with about thirty scientists employed
by the Medical Research Council and a roughly equal number of graduate and postdoctoral students and visitors. By now it houses
about a hundred scientists paid by the Medical Research Council, fifty paid from other sources and a hundred students and
visitors. Initially, the Laboratory comprised three divisions: Protein and Nucleic Acid Chemistry under Sanger, Molecular
Genetics under Crick and Brenner, and Structural Studies under Kendrew and me. By now, Molecular Genetics has become Cell
Biology, Protein and Nucleic Acid Chemistry includes Immunology and a new Division of Neurobiology has been added. We are
also closely linked to Alan Fersht's and Greg Winter's Protein Engineering Laboratory.
|Perutz, Bernal and Crick at the opening of the Laboratory of Molecular Biology in May 1962. In the center
the double helical model of DNA.|
How the Laboratory was Governed
Since there was no difference in age or distinction between us, I persuaded the Medical Research Council
to appoint me Chairman of a Governing Board rather than Director, the Board to be made up of Crick, Kendrew, Sanger and myself.
This arrangement reserved major decisions of scientific policy to the Board and left their execution and financial responsibility
vis-à-vis the Medical Research Council to me. The Board met only rarely when such decisions needed to be taken. This worked
smoothly and left me free to pursue my own research. Seeing the Chairman standing at the laboratory bench or the X-ray tube,
rather than sitting at his desk, set a good example and raised morale. The Board never directed the laboratory's research,
but tried to attract, or to keep, talented young people and gave them a free hand. My job was to take an interest in their
research and to make sure that they had the means to carry it out.
Importance of Good Technical Facilities
I was able to do this thanks to our excellent technical facilities. Shortly after the foundation of our
Research Unit, Kendrew and I asked the Medical Research Council for funds to appoint an engineer, D.A.G. Broad, to design
an X-ray tube with a rotating anode. His design provided us with a beam ten times stronger than the commercial tubes then
available. Together with the precision cameras bought for us in America by the Rockefeller Foundation, it equipped us better
than anyone else in the field and made possible the solution of the first protein structures. This early experience and also
the technical facilities we enjoyed at the Cavendish Laboratory made us decide to equip our new Laboratory of Molecular Biology
with large mechanical and electronic workshops for the development of new instruments, as if it were a physics lab. We also
included a photographic workshop and stores to provide all routine chemicals and supplies, thus avoiding delays in delivery.
Finally, we appointed a service engineer to keep instruments in running order, rather than having to rely on firms to send
us their own service men. These facilities were, and they still are unique, and they allow people to get on with their work
faster than anywhere else I know.
|Left: Max Perutz with his model of haemoglobin and John Kendrew with his model of myoglobin
Making People Talk and Listen to Each Other
Experience had taught me that laboratories often fail because their scientists never talk to each other.
To stimulate the exchange of ideas, we built a canteen where people can chat at morning coffee, lunch and tea. It was managed
for over twenty years by my wife, Gisela, who saw to it that the food was good and that it was a place where people would
make friends. Scientific instruments were to be shared, rather than being jealously guarded as people's private property;
this saved money and also forced people to talk to each other. When funds ran short during the building of the lab, I suggested
that money could be saved by leaving all doors without locks to symbolise the absence of secrets.
Left to right: Maurice Wilkins, John Steinbeck, John Kendrew, Max Perutz, Francis Crick and Jim Watson
after the Nobel Ceremony in Stockholm in December 1962.
For most mortals, the Cavendish Professor of Physics used to be approachable only through his secretary's
office. To do away with this barrier I ensured that the door of my office opened directly into the passage, so that anybody
could just walk in. Once a foreign visitor did so unannounced and asked: "Can I give you a lecture?" When I replied: "No,
thank you, not just now", he proceeded to give it, proudly demonstrating his diagrams on cards, instead of slides, to his
Most laboratories hold seminars where its scientists report their work, but they are often attended
only by those scientists' own group. To ensure that everyone is aware of all the work in the lab, Crick instigated an annual
week of seminars which used to be known as Crick Week, to be attended by all members of the laboratory. He used to dominate
it by his searching questions and sharp comments, and it was a sad day when he left us for the Salk Institute in La Jolla.
The laboratory owes much of its success to the enlightened policies of the Medical Research Council, especially
to Harold Himsworth, its secretary from 1949 to 1968, whose foresight and courage led him to support our early work for many
lean years when we had little to show for it yet, and when there was only the faintest hope of it ever benefiting medicine.
staff did not burden us with bureaucratic rules and futile floods of paper, but saw it as their prime responsibility to help
us carry out our research. I reported directly to Himsworth, rather than a Committee; he negotiated the annual grant to the
Medical Research Council with the Treasury directly, rather than being allotted the Council's slice of the overall science
budget by a ministerial committee, and he had the authority to take decisions within the broad lines of policy laid down by
the Council. This system ensured smooth and efficient running, but Thatcherism has now destroyed much of it. Under her all-pervasive
rule and in the name of "accountability", bureaucracy has multiplied and directors are burdened with mountains of paperwork
that leaves them less time to devote themselves to scientific work, the talent for which (and not for filling in forms) earned
them their positions in the first place.
Fortunately, none of this has so far affected the amazing productivity of the Laboratory of Molecular
Biology. Under Aaron Klug, its director since 1986, the laboratory has remained a magnet for talent from all corners of the
world, and young as well as not so young scientists continue to solve problems that would have been considered beyond the
reach of science only a short time ago. Some of these, such as Nigel Unwin's structure of the acetylcholine receptor, or Richard
Henderson's atomic model of bacteriorhodopsin, or John Walker's mitochondrial ATPase structure, have required sustained efforts
lasting many years and could never have been solved if we had had to depend on short-term grants. Best of all, some of our
work is now finding applications in practical medicine, thus justifying Himsworth's early faith in molecular biology's future.
The Medical Research Council Laboratory of Molecular Biology when it was opened in 1962.
Photos: Courtesy of Prof. Max Perutz, The Medical Research Council Laboratory of Molecular Biology.
History of Caltech
by Judith Goodstein
California Institute of Technology
The California Institute of Technology is a small, independent university of research and teaching in science and engineering, with 900 Ph.D.-level researchers,
including almost 300 regular faculty, 900 undergraduates, and 1,000 graduate students. In spite of its small size, it has
become one of the world's leading institutions of scientific research and education.
Caltech's beginnings are rooted in a modest little college founded in Pasadena in 1891 by wealthy former
abolitionist and Chicago politician Amos Throop. Initially named Throop University, the school changed its name to Throop
Polytechnic Institute in 1893. In its first fifteen years, Throop served the local community, teaching a great variety of
subjects, from arts and crafts to zoology, with considerable emphasis on vocational training. By 1906, Throop needed a fresh
sense of purpose. The American astronomer George Ellery Hale, the first director of the nearby Mount Wilson Observatory and a newcomer to Pasadena, would provide it.
Courtesy of the Archives, California Institute of Technology
A scientist bubbling over with educational, architectural, and civic ideas, Hale was elected to the school's
board of trustees in 1907 and promptly set about to transform it. He persuaded school officials to abandon Throop's high school
and other programs and concentrate on expanding and developing the college along engineering lines; recruited James A. B.
Scherer, who served as Throop's president between 1908 and 1920; and enticed Arthur A. Noyes, former president of MIT and
the nation's leading physical chemist, to join him in Pasadena. In Noyes, Hale saw not only an opportunity to bring chemistry
at Throop College (Throop officially changed its name to Throop College of Technology in 1913) up to a level with that at
MIT but also to put Throop itself in the national limelight. The third member of Hale's scientific troika was the physicist
Robert A. Millikan who began, in 1917, to spend several months a year at Throop as director of physical research.
|Portrait of Noyes, Millikan and Hale hangs in the main dining room at the Athenaeum, Caltech.|
of the Archives, California Institute of Technology
The three of them spent the World War I years in Washington, organizing and recruiting scientists to work
on military problems, but also building a superb network of contacts that would later serve the school well. Collectively
ambitious for American science, eager to see their country play a larger role on the world's scientific stage, and determined
to put Throop on the map, Hale, Millikan, and Noyes had become a formidable scientific triumvirate by 1918. By Armistice Day,
they had set the stage to transform the engineering school into an institution that put pure science first.
Between 1919 and 1921, the school obtained a handsome endowment, drafted a new educational philosophy,
took its present name, and selected a new man to guide its destiny for the next twenty-five years. Hale and Noyes wanted to
use Caltech to reshape the education of scientists. Millikan wanted to make Caltech one of the physics capitals of the world.
To do that, he needed research funds.The three men came to an agreement. Hale and Noyes promised Millikan the lion's share
of the school's financial resources and minimal administrative duties as head of the Institute. In return, Millikan agreed
to come, as director of the Norman Bridge Laboratory of Physics, and administrative head of the Institute. By then, Noyes
had resigned from MIT and accepted a full-time appointment as director of chemical research in Pasadena.
In the early 1920s, Caltech was essentially an undergraduate and graduate school in the physical sciences.
Indeed, until 1925, the institution offered graduate work leading to the doctorate only in physics, chemistry, and engineering.
Geology joined the list of graduate studies in 1925, aeronautics in 1926; biology and mathematics in 1928. Physics was king
from the very beginning. It had more students, more faculty, and more money than other departments had. Millikan initiated
a visiting-scholars program shortly after his arrival in Pasadena. The list of scientists who accepted Millikan's invitation
represented the cream of European physics, including Paul Dirac, Erwin Schrödinger, Werner Heisenberg, Hendrik Lorentz, and Niels Bohr. Albert Einstein's visits to the campus in 1931, 1932, and 1933 capped Millikan's plans to put physics on the map in southern California.
If nothing else, Einstein's visits showed dramatically that the Caltech that Hale, Millikan, and Noyes had set out to build
in the twenties had come of age in the thirties.
Millikan, who functioned as the school's president between the wars, was fiercely opposed to government
funding of research. He relied on the major private foundations, especially the Rockefeller and the Carnegie, and a growing number of southern California philanthropists to provide the funds he needed. He believed that the modern
world was basically a scientific invention, that science was the mainspring of the twentieth century, and that America's future
rested on the promoting of basic science and its applications. Caltech, in Millikan's view, existed to provide America's scientific
|Photo taken at March Field during JATO experiments with the Ercoupe airplane by USAF. Rockets developed
by CIT/JPL. From left: C.B. Millikan, M. Summerfield, T. von Kármán, F.Malina and Capt. H.A. Boushey|
Date: August 1941
Courtesy of the Archives, California Institute of Technology
The focus of scientific research at the Institute under Millikan during the 1930s ranged from Drosophila genetics and the biochemistry of vitamins in biology, to the theory of turbulence and airplane wing design in aeronautics;
from cancer therapy with radiation and the radioactivity of the light elements in nuclear physics, to soil erosion and the
transmission of water from the Colorado River to Los Angeles in engineering; from the application of quantum mechanics to
molecular structure in chemistry, to the introduction of the magnitude scale in seismology.
An educational institution in name only during the war, Caltech had a war arsenal that included rockets,
proximity fuses, the Jet Propulsion Laboratory, and $80 million in federal funds for war-related research and development.
Caltech's history is divided into two distinct eras. The first Caltech era was created by Hale, Millikan,
and Noyes. Thirty years later, after World War II, the physicists Lee Alvin DuBridge and Robert Bacher did the job all over
again. DuBridge, the head of MIT's wartime radar project, became Caltech's new president in 1946. Bacher, the leader of the
Los Alamos atomic bomb project's "G" Division (the "G" stood for gadgets), arrived in 1949 to head up the division of physics,
mathematics, and astronomy and later became the Institute's first provost.
During DuBridge's tenure (1946-1969), Caltech's teaching faculty doubled in number, the campus tripled
in size, and new research fields blossomed, including chemical biology, planetary science, nuclear astrophysics, and geochemistry.
1948 saw the dedication of a new 200-inch telescope on Palomar Mountain, the world's most powerful optical telescope for more
than forty years. Unlike Millikan, DuBridge argued that the federal government had a responsibility to support scientific
|Robert Bacher and Lee Alvin DuBridge|
Courtesy of the Archives, California
Institute of Technology
As Caltech's new physics head, Bacher rebuilt the physics department, and he did so with a vengeance,
starting with high-energy particle physics. Then a new field, particle physics hardly existed at Caltech in 1949, except for
the work of Carl Anderson and his students, including Donald Glaser, a later Nobel-Prize winner, who used cosmic rays from space as a natural source of high-energy particles to do particle
physics. While chairman, Bacher initiated construction and use of a new electron accelerator, so that the Caltech group could
make its own high-energy particles. The Institute closed down its electron synchrotron in 1969, shortly after ground was broken
for the national accelerator laboratory--Fermilab, in Batavia, Illinois. Theoretical physics, always a stepchild under Millikan, entered a golden age with the acquisition
of Richard Feynman and Murray Gell-Mann. Feynman, then at Cornell, was Bacher's first acquisition.
|Richard Feynman lecturing.|
Courtesy of the Archives, California Insitute
Historical studies of the development of Caltech as a research university after the war are scarce. There
are no biographies of key figures from George Beadle, Charles Richter, and William Fowler onwards.
Ajzenberg-Selove, Fay. "A Matter of Choices: Memoirs of a Female Physicist." New Brunswick: Rutgers University
Florence, Ronald. "The Perfect Machine: Building the Palomar Telescope." New York: HarperCollins, 1994.
Geiger, Roger L. "Research and Relevant Knowledge: American Research Universities since World War II."
New York: Oxford University Press, 1993.
Goodstein, Judith R. "Millikan's School: A History of the California Institute of Technology." New York:
Gorn, Michael H. "The Universal Man: Theodore von Karman's Life in Aeronautics." Washington, D.C.: Smithsonian
Institution Press, 1992.
Kargon, Robert. "The Rise of Robert Millikan: Portrait of a Life in American Science." Ithaca: Cornell
University Press, 1982.
Kevles, Daniel J. "The Physicists: The History of a Scientific Community in Modern America (1978)." Paperback
reprint, with a new preface, Cambridge, Mass.: Harvard University Press, 1995.
Murray, Bruce C. "Journey into Space: The First Three Decades of Space Exploration." New York: Norton,
Reingold, Nathan. "Science and Government in the United States since 1945." History of Science 32 (1994):361-386.
Servos, John W. "Physical Chemistry from Ostwald to Pauling: The Making of a Science in America." Princeton:
Princeton University Press, 1990.
Sinsheimer, Robert. "The Strands of a Life: The Science of DNA and the Art of Education." Berkeley: University
of Calfornia Press, 1994.
Emil von Behring: The Founder of Serum Therapy
Based on an exhibition at Marburg Castle*
Arranged and documented by Kornelia Grundmann
Upbringing and Education
Emil Behring (1854-1917) was born on March 15, 1854 in Hansdorf, West Prussia, as the first child of the couple August and Auguste Behring.
His father was a village school teacher, who during his first marriage had had four children and after the birth of Emil had
another eight children.
A talented pupil, Emil Behring was above all assisted by the village minister, who made it possible for
him to attend the Gymnasium (High School) in the village Hohenstein. His orientation as a theology student appeared to have
changed after a friend who was a military doctor arranged for him to start his medical studies at the University of Berlin.
He obtained a scholarship and from 1874 through 1878 he studied at the Academy for Military Doctors at the Royal Medical-Surgical
Friedrich-Wilhelm-Institute, where he also earned his medical degree. In the following years he had to perform as a military
doctor and also worked as a troop doctor in various garrisons. After having been assigned as captain of the medical corps
to the Pharmacological Institute at the University of Bonn, he was given a position at the Hygiene Institute of Berlin in
1888 as an assistant to Robert Koch (1843-1910), one of the pioneers of bacteriology. During this time, Behring's first authoritative publication on diphtheria
and tetanus serum therapy appeared.
|Emil von Behring in a military uniform.|
Photo: Courtesy of Aventis Behring
The Behring Family
During his early years as a military doctor, Behring's income was not sufficient for him to think about
starting a family. Only in 1896, when he had a regular salary, did he marry the 20 year old Else Spinola. They went on a three-month
honeymoon to the island of Capri. Else, born August 30, 1876 in Berlin, was the daughter of Werner Spinola, Administrative
Director of Charité, the university medical clinic in Berlin.
In 1898, after having become professor at the University in Marburg (then part of Prussia), Behring moved
with his family into a house in Wilhelm-Roser-Strasse in Marburg, where his six sons were born. Behring was a family man,
though rather patriarchal, which at that time was quite normal. In the circle of his family he felt content, although his
scientific work presumably did not leave him much time for his wife and children.
|Wedding picture of Emil and Else von Behring.|
Photo: Courtesy of Aventis Behring
On March 31, 1917, Behring died and was entombed in a mausoleum at the Marburg Elsenhöhe. After Behring's
death, Else von Behring served as chairwoman of the Women's National Organisation in Marburg, Germany. She died in 1936 of
a heart attack at the age of only 59.
Family and Friends
On the list of his sons' godfathers, it appears obvious who stood closest to Emil von Behring besides
his family. His first son, Fritz, had the bacteriologist Friedrich Loeffler (1852-1915) and Behring's friend and co-worker,
Erich Wernicke as godfathers. The godfather of his third son, Hans, was the Prussian Under-Secretary of Education and Cultural
Affairs, Friedrich Althoff. His fifth son, Emil, had as a godfather the Russian researcher Elias Metschnikoff (1845-1916), founder of the theory of phagocytosis, with whom Behring had continuous scientific exchange of ideas. Emil's
second godfather was the pupil of Louis Pasteur, Émile Roux (1853-1933), who like Behring Sr. dealt with the fight against
diphtheria. In 1913, the godfather of his sixth son, Otto, was the physician Ludolph Brauer (1865-1951), who had taught together
with Behring at the Marburg Medical Faculty as a professor of internal medicine.
The Development of the Diphtheria-Therapeutic-Serum
Behring, who in the early 1890s became an assistant at the Institute for Infectious Diseases, headed by
Robert Koch, started his studies with experiments on the development of a therapeutic serum. In 1890, together with his university
friend Erich Wernicke, he had managed to develop the first effective therapeutic serum against diphtheria. At the same time,
together with Shibasaburo Kitasato he developed an effective therapeutic serum against tetanus.
|Behring together with his colleagues Wernicke (left) and Frosch (center) in Robert Koch's laboratory in
Photo: Courtesy of Aventis Behring
The researchers immunized rats, guinea pigs and rabbits with attenuated forms of the infectious agents
causing diphtheria and alternatively, tetanus. The sera produced by these animals were injected into non-immunized animals
that were previously infected with the fully virulent bacteria. The ill animals could be cured through the administration
of the serum. With the blood serum therapy, Behring and Kitasato firstly used the passive immunization method in the fight
against infectious diseases. The particularly poisonous substances from bacteria – or toxins - could be rendered harmless
by the serum of animals immunized with attenuated forms of the infectious agent through antidotes or antitoxins.
Photo: Courtesy of Aventis Behring
The Introduction of Serum Therapy
The first successful therapeutic serum treatment of a child suffering from diphtheria occurred in 1891.
Until then more than 50,000 children in Germany died yearly of diphtheria. During the first few years, there was no successful
breakthrough for this form of therapy, as the antitoxins were not sufficiently concentrated. Not until the development of
enrichment by the bacteriologist Paul Ehrlich (1854-1915) along with a precise quantification and standardization protocol, was an exact determination of quality of the
antitoxins presented and successfully developed. Behring subsequently decided to draw up a contract with Ehrlich as the foundation
of their future collaboration. They organized a laboratory under a railroad circle (Stadtbahnbogen) in Berlin, where they
could then obtain the serum in large amounts by using large animals – first sheep and later horses.
In 1892, Behring and the Hoechst chemical and pharmaceutical company at Frankfurt/Main, started working
together, as they recognized the therapeutic potential of the diphtheria antitoxin. From 1894, the production and marketing
of the therapeutic serum began at Hoechst. Besides many positive reactions, there was also noticeable criticism. Resistance,
however, was soon put aside, due to the success of the therapy.
The Marburg Years
Behring was given the opportunity to start a university career through one of the leading officers (Ministerialrat)
of the Prussian Ministry of Education and Cultural Affairs, Friedrich Althoff (1839-1908), who wanted to improve the control
of epidemics in Prussia by supporting bacteriological research. After a short period as professor at the University of Halle-Wittenberg,
Behring was recruited by Althoff to take over the vacant chair in hygiene at Philipps Marburg University on April 1, 1895.
His appointment as full professor followed shortly thereafter against the will of the faculty, who besides all of Behring's
outstanding discoveries, wanted a university lecturer who would broadly represent the field. However, Althoff rejected all
counterproposals and Behring took over as Director of the Institute of Hygiene at Marburg. His position included giving lectures
for hygiene and concurrently held a teaching contract in the history of medicine. In 1896, the Marburg Institute of Hygiene
moved to a building on a road nearby Pilgrimstein Road, previously the Surgery Clinic. Behring divided the Institute into
two departments, a Research Department for Experimental Therapy and a Teaching Department for Hygiene and Bacteriology. He
remained Director of the Institute until his retirement as professor in May 1916.
Behring belonged to a scientific discussion group called "The Marburg Circle" (das Marburger Kränzchen),
whose other members were the zoologist Eugen Korschelt (1858-1946), the surgeon Paul Friedrich (1864-1916), the botanist Arthur
Meyer (1850-1922), the physiologist Friedrich Schenk (1862-1916), the pathologist Carl August Beneke (1861-1945) and the pharmacologist
August Gürber (1864-1937). They often met at Behring's home where they had rounds of vivid and prolific scientific discussions.
Active Protective Vaccination against Diphtheria
|Old vials (1897 and 1906) with hand-written labels.|
Photo: Courtesy of Aventis Behring
The therapeutic serum developed by Behring prevented diphtheria for only a short period of time. In 1901,
Behring, therefore, for the first time, used a diphtheria innoculation of bacteria with reduced virulence. With this active
immunization he hoped to help the body also produce antitoxins. As a supporter of the humoral theory of immune response, Behring
believed in the long-term protective action of these antitoxins found in serum. It is well-established knowledge today that
active vaccination stimulates the antitoxin (antibody) producing cells to full function.
The development of an active vaccine took a few years. In 1913, Behring went public with his diphtheria
protective agent, T.A. (Toxin-Antitoxin). It contained a mixture of diphtheria toxin and therapeutic serum antitoxin. The
toxin was meant to cause a light general response of the body, but not to harm the person who is vaccinated. In addition,
it was designed to provide long-term protection. The new drug was tested at various clinics and was proven to be non-harmful
Tetanus Therapeutic Serum during World War I
In 1891, tetanus serum was introduced considerably more quickly in clinical practices than the diphtheria
serum. The Agricultural Ministry supported research efforts to develop a therapeutic agent against tetanus to protect agriculturally
valuable animals. The large amounts of serum required were obtained through the immunization of horses. However, there was
no substantial clinical testing on humans; this led the Military Administration to accept it only on a small scale at the
beginning of World War I.
During the first months of the war, this restraint led to massive losses of human lives. Also, after the
distribution of the tetanus antitoxins in the military hospitals, many futile attempts at therapy were noted. At the end of
1914, as a result of Behring's constructive assistance, the injection of serum was established as preventing disease. Starting
in April 1915, the mistakes in dosage and the shortage of supplies were overcome and the numbers of sick fell dramatically.
Behring was declared "Saviour of the German Soldiers" and was awarded the the Prussian Iron Cross medal.
|Historical engraving showing how the medicinal serum was obtained from immunized horses.|
Courtesy of Aventis Behring
An Attempt to Develop a Therapeutic Method against Tuberculosis
After Robert Koch had failed with his tuberculosis therapy in 1893, Behring began to search for an effective
therapeutic agent against this disease. However, very soon, he had to admit that combating tuberculosis using a healing serum
was not feasible. Therefore, he concentrated on working on a preventive vaccination, which, however, required precise knowledge
of the mechanism of infection. In Behring's view, the tubercle bacillus was transmitted to children through the milk of a
mother or a cow infected with tuberculosis. He then started treating milk with formaldehyde, so as to eliminate this source
of infection. This procedure was not accepted due to the bad smell of the milk. Moreover, the transmission of tubercle bacilli
through the respiratory tract was proven to be more likely than through the digestive system, as had been claimed by Behring.
From 1903, Behring worked on active immunization through attenuated tuberculosis infectious agents, which
he then tried on cows, however, with only moderate success. His aim was to obtain a protective and therapeutic agent for humans.
A number of agents (tuberculase, tulase, tulaseactin, tulon) failed to make a breakthrough. At the beginning of World War
I, Behring halted his efforts to combat tuberculosis and dedicated himself entirely to the further development of tetanus
Behring's Relationship to Paul Ehrlich
Paul Ehrlich was Behring's colleague at Robert Koch's institute. Here, he was able to work out a reliable
and reproducible standardization method for diphtheria serum. However, in later years, tension developed between the two researchers.
Differences with Ehrlich's pupil, Hans Aronson, resulted in bad feelings, which increased when Ehrlich's Royal Institute of
Experimental Therapy was founded at Frankfurt/Main. The previous friendship between the two researchers never fully succumbed,
through the mediation of Friedrich Althoff. However, it was subsequently demonstrated that the only photograph showing Behring
and Ehrlich together, which appeared on the cover of a Berlin newspaper on the occasion of their 60th birthday in 1914, was
a photomontage made up of two separate photographs.
|Report of the Berliner Illustrirte Zeitung (Berlin Illustrated Newspaper) about Emil von Behring and Paul
Erlich and their work on the occasion of their 60th birthday.|
Photo: Courtesy of Aventis Behring
Behring lived entirely for his idea of revolutionizing medicine through serum therapy. This idea hung
above him and motivated him, in his own words, "like a demon." His enormous concentration on his work often drove him to physical
illnesses, as well as to deep depressions, which forced him to take time off work for a sanatorium stay from 1907 through
Acknowledgements and Honors
In 1903, Emil von Behring was given the title of "Wirklicher Geheimer Rat mit dem Prädikat Excellenz"
by the German emperor Wilhelm II. The diploma says: "This is in order that Behring should remain in unbroken loyalty to Myself
and the Royal Family and to fulfill his official responsibility with continuous eagerness, whereby he who has the right connected
to his present character, will receive the highest protection by Myself". A splendid uniform was provided along with the title.
In 1901, when the Nobel Prizes were awarded for the first time, Behring received the Prize in Physiology
|A detail (right) and the diploma for the first Nobel Prize in Physiology or Medicine, awarded to Behring
Photo: Courtesy of Aventis Behring
Behring Jubilee in 1940
On December 4, 1940, the Philipps University Marburg celebrated the 50th anniversary of the original publication
of Emil von Behring's decisive discovery of serum therapy. Top leaders of the National Socialist Party, the rectors of numerous
German universities, representatives of the Behringwerke and many scientists and friends of Emil von Behring from abroad were
also present. The celebration, which continued over a few days, began with lectures and addresses by officials, both of the
state and party. Finally, a foundation certificate for a new Institute for Experimental Therapy was handed over. The professors
then moved from the university auditorium (Aula), to unveal a new Behring Memorial close to the St. Elisabeth Church.
The celebration was followed by a two-day scientific meeting, presenting the state of the art of immunology and the fight
against infectious diseases.
The Background of the Celebration
In the view of the National Socialists, Else von Behring was regarded as a "half-Jew", as her mother came
from a Jewish family. With the help of a number of friends she was able to get her sons accepted by Hitler as "Aryans" and
not stigmatized as "half-breeds". After the death of Else von Behring in 1936, no obstacles were left for the Nazi party to
use Emil von Behring as a glorified representative of national socialist "Germanic" science. During the ceremony there were,
however, some signs of tension. Although one of Behring's sons participated in the ceremony, he was not greeted by any of
the official speakers. Only the Danish researcher, Thorvald Madsen from Copenhagen, who had previously been chairman of the
Health Organisation of the League of Nations, dared to mention Behring's friendly connection with researchers from enemy countries,
such as those at the Institute Pasteur in Paris. Courageously, he also recalled the great bacteriologist Paul Ehrlich, despised by the Nazis due to his Jewish origin,
who had played a significant role in Behring's successes.
*The exhibition is from October to December 2001.
Translated by Gabriella
Nichols, Department of Anatomy, Philipps University Marburg, Germany.
Published with the support of