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Vernon Ingram

 
Scientist: Vernon Martin Ingram

German–British–American biochemist (1924–)

Ingram, born Immerwahr in Breslau (now Wrocław in Poland), was brought to Britain as a refugee from Nazi Germany as a child. He was educated at Birkbeck College, London, where he obtained his PhD in 1949. After working briefly at Rockefeller and Yale he returned to England and joined the staff of the Medical Research Council's molecular biology unit at the Cavendish Laboratory, Cambridge, in 1952. In 1958 however he moved to the Massachusetts Institute of Technology where he has served as professor of biochemistry since 1961 and as John and Dorothy Wilson Professor of Biology since 1988.

By the mid 1950s it was clear to Francis Crick that it should be possible, and was indeed essential, for molecular biology to be able to show that mutant genes produced changes in the amino acid sequences of proteins. Although such a claim was central to the supposed revolution in molecular biology, there was, as Crick realized in 1955, no direct evidence that proteins are in fact coded by genes.

Consequently Crick and Ingram attempted to reveal such a change in the lysozyme of fowl eggs. However, although they succeeded in distinguishing differences between lysozymes from such different birds as duck and pheasant, they failed to find any difference in lysozymes between two hens of the same species. At this point however Max Perutz gave Ingram some sickle-cell hemoglobin (hemoglobin S) to work with. (Hemoglobin S, possessed by sufferers of a crippling anemia, had been distinguished from normal hemoglobin A by Linus Pauling and his student Harvey Itano in 1949.) Ingram split the hemoglobin into smaller units by using the enzyme trypsin to break the peptide bonds. He then separated these units by electrophoresis and paper chromatography. This allowed him to show that hemoglobin S differs from normal hemoglobin at just one site where the amino acid valine replaces the glutamic acid of the A form. Although it came as a surprise that the alteration of one amino acid in over 500 could produce such major effects, it also dramatically established that molecular biology was not just an abstract and remote branch of structural chemistry.

Ingram went on to show that this and other point mutations of hemoglobin could be used to trace the evolutionary history of vertebrates, work reported in his The Hemoglobins in Genetics and Evolution (1963).

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Vernon M. Ingram
Born 19 May 1924(1924-05-19)
Breslau, Germany
Died 17 August 2006 (aged 82)
Boston, Massachusetts
Residence Germany, United Kingdom, United States
Nationality German
Fields Biologist
Institutions MIT
Alma mater University of London
Doctoral advisor Fred Barrow

Vernon M. Ingram, Ph.D., FRS (19 May 1924 — 17 August 2006) was a German American professor of biology at the Massachusetts Institute of Technology.

Contents

Biography

Ingram was born in Breslau, Lower Silesia. When he was 14, he and his family left Nazi Germany because of their opposition to Nazism and settled in England.

During the Second World War, Ingram worked at a chemical factory producing drugs for the war effort and at night studied at Birkbeck College at the University of London. He received a bachelor's degree in chemistry in 1945 and a PhD in organic chemistry in 1949.

After receiving his doctorate, Ingram worked at postdoctoral appointments at the Rockefeller Institute and Yale University. At Rockefeller, he worked with Moses Kunitz on crystallizing proteins. While at Yale, he studied peptide chemistry with Joseph Fruton. In 1952, Ingram returned to England and started working at the Cavendish Laboratory at the University of Cambridge, studying protein chemistry.

In 1956, Ingram, John A. Hunt, and Antony O. W. Stretton determined that the change in the hemoglobin molecule in sickle cell disease and trait was the substitution of the glutamic acid in position 6 of the β-chain of the normal protein by valine. Ingram used electrophoresis and chromatography to show that the amino acids of normal human and sickle cell anemia hemoglobins differed due to a single mutated gene. Much of this work was done with the support of Max Perutz and Francis Crick. Ingram won the William Allan Award from the American Society of Human Genetics in 1967.

This was the first time a researcher demonstrated that a single amino acid exchange in a protein can cause a disease or disorder. As a result, Vernon Ingram is sometimes referred to as "The father of Molecular Medicine." [1]

Ingram joined the MIT faculty in 1958, intending to stay for only one year. He found that he enjoyed it there so much that he stayed on. While at MIT, Ingram collaborated with Paul Marks of Columbia University on hemoglobin research. He was also interested in embryonic hemoglobin and how it differed from that of adults.

By the 1980s, Ingram became interested in neuroscience and especially Alzheimer's Disease. His interest was sparked by the work his second wife, Elizabeth (Beth), was doing with mentally retarded people in the Boston area. She had heard that Down's Syndrome was a disease of the neurofilaments; this turned out not to be the cause, but it was noted that people with Down's Syndrome did develop Alzheimer's Disease by the time they were 40.

After retirement, Ingram continued his research, maintaining a small laboratory at MIT. He and his wife, Beth, were housemasters of Ashdown House at MIT for 16 years. Asteroid 6285 Ingram is named in their honor. [2] He was elected to the National Academy of Sciences in 2002. [3]

Ingram died in Boston, Massachusetts, on August 17, 2006 of injuries stemming from a fall.

See also

Selected publications

  • Ingram, V.M. (1956). "A Specific Chemical Difference between Globins of Normal and Sickle-cell Anemia Hemoglobins". Nature 178: 792–794. doi:10.1038/178792a0. 
  • Ingram,, V.M. (1957). "Gene Mutations in Human Hemoglobin: The Chemical Difference between Normal and Sickle Hemoglobin". Nature 180: 326–328. doi:10.1038/180326a0. 
  • Hunt, J.A.; V.M. Ingram (1958). "Abnormal Human Haemoglobins. II. The Chymotryptic Digestion of the Trypsin-resistant Core of Haemoglobins A and S.". Biochimica et Biophysica Acta 28 (3): 46–549. doi:10.1016/0006-3002(58)90517-1. 
  • Ingram, V.M. (1961-03-04). "Gene Evolution and the Hæmoglobins". Nature 189: 704–708. doi:10.1038/189704a0. 
  • Blanchard, B.J.; A. Chen, C. Kelly, K. Stafford, B. Stockwell & V.M. Ingram (2004). "Novel Compounds eliminate the Neurotoxicity of the Alzheimer Aβ Peptide". Abstr. Massachusetts Alzheimer’s Disease Research Center, Annual meeting. 
  • Ingram, V.M.; B.J. Blanchard, A. Chen, C. Kelly, K. Stafford & B. Stockwell (2004). "Blocking the Initial Molecular Mechanism of Alzheimer’s Disease". Abstr. International Congress on Alzheimer’s Disease, Philadelphia. 
  • Ingram, V.M. (2004). "The Role of Alzheimer Aβ Peptides in Ion Transport across Cell Membranes, in Subcellular Biochemistry: Alzheimer’s Disease". in eds. Harris, R., Fahrenholz, F.. Cellular and Molecular Aspects of Amyloid. London: Kluwer Academic/Plenum Publishers. 
  • Colby, D.W.; P. Garg, G. Chao, J. Webster, A. Messer, V.M. Ingram and K.D. Wittrup (17 September 2004). "Development of a Human Variable Light Chain Domain Intracellular Antibody against Huntingtin via Yeast Surface Display". J. Mol. Biol. 342 (3): 901–12. doi:10.1016/j.jmb.2004.07.054. 
  • Webster, J.M.; D.W. Colby, V.M. Ingram, K.D. Wittrup and A. Messer (November 2004). "Enhanced anti-Huntington’s Disease Intrabodies". Abstract Soc. Neurosci.. 
  • Blanchard, B.J.; A. Chen, K. Stafford, P. Weigele and V.M. Ingram (5 October 2004). "Efficient Reversal of Alzheimer Fibril Formation and Elimination of Neurotoxicity by a Small Molecule". Proc Natl Acad Sci USA 101 (40): 14326–32. doi:10.1073/pnas.0405941101. PMID 15388848. 

Inaugural Article: Efficient reversal of Alzheimer's disease fibril formation and elimination of neurotoxicity by a small molecule Barbara J. Blanchard, Albert Chen, Leslie M. Rozeboom, Kate A. Stafford, Peter Weigele, and Vernon M. Ingram PNAS 2004 101: 14326-14332

See also

References

  1. ^ "2002 National Academy Fellows". Genome Biology. 2002-05-02. http://genomebiology.com/researchnews/default.asp?arx_id=gb-spotlight-20020502-01. Retrieved 2006-10-25. 
  2. ^ Darren J. Clarke (2002-07-17). "Surprise! High-flying Tribute for Ingrams". MIT News Office. http://web.mit.edu/newsoffice/2002/ingram-0717.html. Retrieved 2006-10-25. 
  3. ^ "Three Faculty Named to NAS". MIT News Office. 2002-05-15. http://web.mit.edu/newsoffice/2002/nas-0515.html. Retrieved 2006-10-25. 

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anemia (condition – in medicine)
Mutation
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