WORLD OF MICROBIOLOGY AND IMMUNOLOGY Milstein, César391•
After Miller finished his experiments at the University
of Chicago, he continued his research as an F. B. Jewett
Fellow at the California Institute of Technology from 1954 to- Miller established the accuracy of his findings by per-
forming further tests to identify specific amino acids. He also
ruled out the possibility that bacteriamight have produced the
spots by heating the apparatus in an autoclave for eighteen
hours (fifteen minutes is usually long enough to kill any bac-
teria). Subsequent tests conclusively identified four spots that
had previously puzzled him. Although he correctly identified
the a-amino-n-butyric acid, what he had thought was aspartic
acid (commonly found in plants) was really iminodiacetic
acid. Furthermore, the compound he had called A turned out to
be sarcosine (N-methyl glycine), and compound B was N-
methyl alanine. Other amino acids were present but not in
quantities large enough to be evaluated.
Although other scientists repeated Miller’s experiment,
one major question remained: was Miller’s apparatus a true
representation of the primitive atmosphere? This question was
finally answered by a study conducted on a meteorite that
landed in Murchison, Australia, in September 1969. The
amino acids found in the meteorite were analyzed and the data
compared to Miller’s findings. Most of the amino acids Miller
had found were also found in the meteorite. On the state of sci-
entific knowledge about the origins of human life, Miller
wrote in “The First Laboratory Synthesis of Organic
Compounds” that “the synthesis of organic compounds under
primitive earth conditions is not, of course, the synthesis of a
living organism. We are just beginning to understand how the
simple organic compounds were converted to polymers on the
primitive earth...nevertheless we are confident that the basic
process is correct.”
Miller’s later research has continued to build on his
famous experiment. He is looking for precursors to ribonu-
cleic acid(RNA). “It is a problem not much discussed because
there is nothing to get your hands on,” he told Marianne P.
Fedunkiw in an interview. He is also examining the natural
occurrence of clathrate hydrates, compounds of ice and gases
that form under high pressures, on the earth and other parts of
the solar system.
Miller has spent most of his career in California. After
finishing his doctoral work in Chicago, he spent five years in
the department of biochemistryat the College of Physicians
and Surgeons at Columbia University. He then returned to
California as an assistant professor in 1960 at the University
of California, San Diego. He became an associate professor
in 1962 and eventually full professor in the department of
chemistry.
Miller served as president of the International Society
for the Study of the Origin of Life (ISSOL) from 1986 to - The organization awarded him the Oparin Medal in
1983 for his work in the field. Outside of the United States, he
was recognized as an Honorary Councilor of the Higher
Council for Scientific Research of Spain in 1973. In addition,
Miller was elected to the National Academy of Sciences.
Among Miller’s other memberships are the American
Chemical Society, the American Association for the
Advancement of Science, and the American Society of
Biological Chemists.See also Evolution and evolutionary mechanisms;
Evolutionary origin of bacteria and viruses; Miller-Urey
experimentMMilstein, César ILSTEIN, CÉSAR(1927-2002)
Argentine English biochemistCésar Milstein conducted one of the most important late twen-
tieth century studies on antibodies. In 1984, Milstein received
the Nobel Prize for physiology or medicine, shared with Niels
K. Jerneand Georges Köhler, for his outstanding contributions
to immunologyand immunogenetics. Milstein’s research on
the structure of antibodies and their genes, through the inves-
tigation of DNA (deoxyribonucleic acid) and ribonucleic acid
(RNA), has been fundamental for a better understanding of
how the human immune systemworks.
Milstein was born on October 8, 1927, in the eastern
Argentine city of Bahía Blanca, one of three sons of Lázaro
and Máxima Milstein. He studied biochemistryat the National
University of Buenos Aires from 1945 to 1952, graduating
with a degree in chemistry. Heavily involved in opposing the
policies of President Juan Peron and working part-time as a
chemical analyst for a laboratory, Milstein barely managed to
pass with poor grades. Nonetheless, he pursued graduate stud-
ies at the Instituto de Biología Química of the University of
Buenos Aires and completed his doctoral dissertation on the
chemistry of aldehyde dehydrogenase, an alcohol enzyme
used as a catalyst, in 1957.
With a British Council scholarship, he continued his
studies at Cambridge University from 1958 to 1961 under the
guidance of Frederick Sanger, a distinguished researcher in
the field of enzymes. Sanger had determined that an enzyme’s
functions depend on the arrangement of amino acids inside it.
In 1960, Milstein obtained a Ph.D. and joined the Department
of Biochemistry at Cambridge, but in 1961, he decided to
return to his native country to continue his investigations as
head of a newly created Department of Molecular Biologyat
the National Institute of Microbiology in Buenos Aires.
A military coup in 1962 had a profound impact on the
state of research and on academic life in Argentina. Milstein
resigned his position in protest of the government’s dismissal of
the Institute’s director, Ignacio Pirosky. In 1963, he returned to
work with Sanger in Great Britain. During the 1960s and much
of the 1970s, Milstein concentrated on the study of antibodies,
the protein organisms generated by the immune system to com-
bat and deactivate antigens. Milstein’s efforts were aimed at
analyzing myeloma proteins, and then DNA and RNA.
Myeloma, which are tumors in cells that produce antibodies,
had been the subject of previous studies by Rodney R. Porter,
MacFarlane Burnet, and Gerald M. Edelman, among others.
Milstein’s investigations in this field were fundamental
for understanding how antibodies work. He searched for muta-
tionsin laboratory cells of myeloma but faced innumerable
difficulties trying to find antigens to combine with their anti-womi_M 5/7/03 7:52 AM Page 391