César Milstein
Encyclopedia
César Milstein FRS
(8 October 1927 – 24 March 2002) was an Argentine
biochemist
in the field of antibody
research. Milstein shared the Nobel Prize in Physiology or Medicine
in 1984 with Niels K. Jerne and Georges Köhler.
, Argentina
, to a Jewish family. He graduated from the University of Buenos Aires
and obtained a PhD
under Professor
Stoppani (Professor of Biochemistry
) in the Medical School
on kinetic studies
with the enzyme
aldehyde dehydrogenase. In 1958, funded by the British Council
, he joined the Biochemistry
Department at the University of Cambridge
to work for a PhD under Malcolm Dixon
on the mechanism of metal activation of the enzyme phosphoglucomutase
. During this work he collaborated with Frederick Sanger whose group he joined with a short-term Medical Research Council
appointment.
technique for the production of monoclonal antibodies
—a discovery recognised by the award of the 1984 Nobel Prize for Physiology or Medicine. This discovery led to an enormous expansion in the exploitation of antibodies in science and medicine.
Milstein himself made many major contributions to improvements and developments in monoclonal antibody technology—especially focusing on the use of monoclonal antibodies
to provide markers that allow distinction between different cell types. He also foresaw the potential
wealth of ligand-binding reagents that could result from applying recombinant DNA
technology to monoclonal antibodies and inspired the development of the field of antibody engineering.
Milstein's early work on antibodies focused on the nature of their diversity at the amino acid level as well as on the disulphide bonds by which they were held together. Part of this work was done in collaboration with his wife, Celia. The emphasis of his research then shifted towards the mRNA encoding antibodies where he was able to provide the first evidence for the existence of a precursor for these secreted polypeptides that contained a signal sequence. The development of the hybridoma
technology coupled to advances in nucleic acid sequencing then allowed Milstein to chart the changes that occurred in antibodies following antigen encounter. He demonstrated the importance of somatic hypermutation
of immunoglobulin V genes in antibody affinity maturation
. In this process, localised mutation of the immunoglobulin genes allows the production of improved antibodies which make a major contribution to protective immunity and immunological memory. Much of his work in recent years was devoted to characterising this mutational process with a view to understanding its mechanism and, indeed, he contributed a manuscript for publication on this topic less than a week before he died.
Quite apart from his own achievements, Milstein acted as a guide and inspiration to many in the antibody field as well as devoting himself to assisting science and scientists in less developed countries. It is also worth mentioning, that even though the Nobel Prize would have made him a wealthy man, Milstein did not patent his enormous discovery since he believed that it was mankind's intellectual property. According to his beliefs, his work did not have any economic interest, only scientific.
He was elected a Fellow of the Royal Society in 1975, was a fellow of Darwin College, Cambridge
from 1980 to 2002, awarded the Louisa Gross Horwitz Prize
from Columbia University
in 1980, won the Copley Medal
in 1989, and became a Companion of Honour in 1995.
Milstein died early on 24 March 2002 in Cambridge
, England at age 74 as a result of a heart condition from which he had suffered for many years.
Royal Society
The Royal Society of London for Improving Natural Knowledge, known simply as the Royal Society, is a learned society for science, and is possibly the oldest such society in existence. Founded in November 1660, it was granted a Royal Charter by King Charles II as the "Royal Society of London"...
(8 October 1927 – 24 March 2002) was an Argentine
Argentina
Argentina , officially the Argentine Republic , is the second largest country in South America by land area, after Brazil. It is constituted as a federation of 23 provinces and an autonomous city, Buenos Aires...
biochemist
Biochemist
Biochemists are scientists who are trained in biochemistry. Typical biochemists study chemical processes and chemical transformations in living organisms. The prefix of "bio" in "biochemist" can be understood as a fusion of "biological chemist."-Role:...
in the field of antibody
Antibody
An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...
research. Milstein shared the Nobel Prize in Physiology or Medicine
Nobel Prize in Physiology or Medicine
The Nobel Prize in Physiology or Medicine administered by the Nobel Foundation, is awarded once a year for outstanding discoveries in the field of life science and medicine. It is one of five Nobel Prizes established in 1895 by Swedish chemist Alfred Nobel, the inventor of dynamite, in his will...
in 1984 with Niels K. Jerne and Georges Köhler.
Biography
Milstein was born in Bahía BlancaBahía Blanca
Bahía Blanca is a city located in the south-west of the province of Buenos Aires, Argentina, by the Atlantic Ocean, and seat of government of Bahía Blanca Partido. It has a population of 274,509 inhabitants according to the...
, Argentina
Argentina
Argentina , officially the Argentine Republic , is the second largest country in South America by land area, after Brazil. It is constituted as a federation of 23 provinces and an autonomous city, Buenos Aires...
, to a Jewish family. He graduated from the University of Buenos Aires
University of Buenos Aires
The University of Buenos Aires is the largest university in Argentina and the largest university by enrollment in Latin America. Founded on August 12, 1821 in the city of Buenos Aires, it consists of 13 faculties, 6 hospitals, 10 museums and is linked to 4 high schools: Colegio Nacional de Buenos...
and obtained a PhD
PHD
PHD may refer to:*Ph.D., a doctorate of philosophy*Ph.D. , a 1980s British group*PHD finger, a protein sequence*PHD Mountain Software, an outdoor clothing and equipment company*PhD Docbook renderer, an XML renderer...
under Professor
Professor
A professor is a scholarly teacher; the precise meaning of the term varies by country. Literally, professor derives from Latin as a "person who professes" being usually an expert in arts or sciences; a teacher of high rank...
Stoppani (Professor of Biochemistry
Biochemistry
Biochemistry, sometimes called biological chemistry, is the study of chemical processes in living organisms, including, but not limited to, living matter. Biochemistry governs all living organisms and living processes...
) in the Medical School
Medical school
A medical school is a tertiary educational institution—or part of such an institution—that teaches medicine. Degree programs offered at medical schools often include Doctor of Osteopathic Medicine, Bachelor/Doctor of Medicine, Doctor of Philosophy, master's degree, or other post-secondary...
on kinetic studies
Enzyme kinetics
Enzyme kinetics is the study of the chemical reactions that are catalysed by enzymes. In enzyme kinetics, the reaction rate is measured and the effects of varying the conditions of the reaction investigated...
with the enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
aldehyde dehydrogenase. In 1958, funded by the British Council
British Council
The British Council is a United Kingdom-based organisation specialising in international educational and cultural opportunities. It is registered as a charity both in England and Wales, and in Scotland...
, he joined the Biochemistry
Biochemistry
Biochemistry, sometimes called biological chemistry, is the study of chemical processes in living organisms, including, but not limited to, living matter. Biochemistry governs all living organisms and living processes...
Department at the University of Cambridge
University of Cambridge
The University of Cambridge is a public research university located in Cambridge, United Kingdom. It is the second-oldest university in both the United Kingdom and the English-speaking world , and the seventh-oldest globally...
to work for a PhD under Malcolm Dixon
Malcolm Dixon
Malcolm Dixon was a British biochemist.He was born in Cambridge, UK to Allick Page and Caroline Dewe Dixon. He received his PhD in 1925, under Frederick Gowland Hopkins at the University of Cambridge....
on the mechanism of metal activation of the enzyme phosphoglucomutase
Phosphoglucomutase
Phosphoglucomutase is an enzyme that transfers a phosphate group on an α-D-glucose monomer from the 1' to the 6' position in the forward direction or the 6' to the 1' position in the reverse direction....
. During this work he collaborated with Frederick Sanger whose group he joined with a short-term Medical Research Council
Medical Research Council (UK)
The Medical Research Council is a publicly-funded agency responsible for co-ordinating and funding medical research in the United Kingdom. It is one of seven Research Councils in the UK and is answerable to, although politically independent from, the Department for Business, Innovation and Skills...
appointment.
Career
The major part of Milstein's research career was devoted to studying the structure of antibodies and the mechanism by which antibody diversity is generated. It was as part of this quest that in 1975 he, together with Georges Köhler (a postdoctoral fellow in his laboratory), developed the hybridomaHybridoma
Hybridoma technology is a technology of forming hybrid cell lines by fusing a specific antibody-producing B cell with a myeloma cell that is selected for its ability to grow in tissue culture and for an absence of antibody chain synthesis...
technique for the production of monoclonal antibodies
Monoclonal antibodies
Monoclonal antibodies are monospecific antibodies that are the same because they are made by identical immune cells that are all clones of a unique parent cell....
—a discovery recognised by the award of the 1984 Nobel Prize for Physiology or Medicine. This discovery led to an enormous expansion in the exploitation of antibodies in science and medicine.
Milstein himself made many major contributions to improvements and developments in monoclonal antibody technology—especially focusing on the use of monoclonal antibodies
Monoclonal antibodies
Monoclonal antibodies are monospecific antibodies that are the same because they are made by identical immune cells that are all clones of a unique parent cell....
to provide markers that allow distinction between different cell types. He also foresaw the potential
wealth of ligand-binding reagents that could result from applying recombinant DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
technology to monoclonal antibodies and inspired the development of the field of antibody engineering.
Milstein's early work on antibodies focused on the nature of their diversity at the amino acid level as well as on the disulphide bonds by which they were held together. Part of this work was done in collaboration with his wife, Celia. The emphasis of his research then shifted towards the mRNA encoding antibodies where he was able to provide the first evidence for the existence of a precursor for these secreted polypeptides that contained a signal sequence. The development of the hybridoma
Hybridoma
Hybridoma technology is a technology of forming hybrid cell lines by fusing a specific antibody-producing B cell with a myeloma cell that is selected for its ability to grow in tissue culture and for an absence of antibody chain synthesis...
technology coupled to advances in nucleic acid sequencing then allowed Milstein to chart the changes that occurred in antibodies following antigen encounter. He demonstrated the importance of somatic hypermutation
Somatic hypermutation
Somatic hypermutation is a mechanism inside cells that is part of the way the immune system adapts to the new foreign elements that confront it . SHM diversifies the receptors used by the immune system to recognize foreign elements and allows the immune system to adapt its response to new threats...
of immunoglobulin V genes in antibody affinity maturation
Affinity maturation
In immunology, affinity maturation is the process by which B cells produce antibodies with increased affinity for antigen during the course of an immune response. With repeated exposures to the same antigen, a host will produce antibodies of successively greater affinities. A secondary response...
. In this process, localised mutation of the immunoglobulin genes allows the production of improved antibodies which make a major contribution to protective immunity and immunological memory. Much of his work in recent years was devoted to characterising this mutational process with a view to understanding its mechanism and, indeed, he contributed a manuscript for publication on this topic less than a week before he died.
Quite apart from his own achievements, Milstein acted as a guide and inspiration to many in the antibody field as well as devoting himself to assisting science and scientists in less developed countries. It is also worth mentioning, that even though the Nobel Prize would have made him a wealthy man, Milstein did not patent his enormous discovery since he believed that it was mankind's intellectual property. According to his beliefs, his work did not have any economic interest, only scientific.
He was elected a Fellow of the Royal Society in 1975, was a fellow of Darwin College, Cambridge
Darwin College, Cambridge
Darwin College is a constituent college of the University of Cambridge.Founded in 1964, Darwin was Cambridge University's first graduate-only college, and also the first to admit both men and women. The college is named after the family of one of the university's most famous graduates, Charles Darwin...
from 1980 to 2002, awarded the Louisa Gross Horwitz Prize
Louisa Gross Horwitz Prize
Louisa Gross Horwitz Prize for Biology or Biochemistry is an annual prize awarded by Columbia University to a researcher or group of researchers that have made an outstanding contribution in basic research in the fields of biology or biochemistry....
from Columbia University
Columbia University
Columbia University in the City of New York is a private, Ivy League university in Manhattan, New York City. Columbia is the oldest institution of higher learning in the state of New York, the fifth oldest in the United States, and one of the country's nine Colonial Colleges founded before the...
in 1980, won the Copley Medal
Copley Medal
The Copley Medal is an award given by the Royal Society of London for "outstanding achievements in research in any branch of science, and alternates between the physical sciences and the biological sciences"...
in 1989, and became a Companion of Honour in 1995.
Milstein died early on 24 March 2002 in Cambridge
Cambridge
The city of Cambridge is a university town and the administrative centre of the county of Cambridgeshire, England. It lies in East Anglia about north of London. Cambridge is at the heart of the high-technology centre known as Silicon Fen – a play on Silicon Valley and the fens surrounding the...
, England at age 74 as a result of a heart condition from which he had suffered for many years.
External links
- César Milstein biography at the Nobel FoundationNobel FoundationThe Nobel Foundation is a private institution founded on 29 June 1900 to manage the finances and administration of the Nobel Prizes. The Foundation is based on the last will of Alfred Nobel, the inventor of dynamite....
- The Official Site of Louisa Gross Horwitz Prize