Phillip A. Sharp Biography (1944-)

Nationality
American
Gender
Male
Occupation
biologist

Phillip A. Sharp has conducted research into the structure of deoxyribonucleic acid (DNA --the chemical blueprint that synthesizes proteins) which has altered previous views on the mechanism of genetic change. For his work in thisarea, Sharp was presented with the 1977 Nobel Prize in medicine along with Richard J. Roberts. Sharp was born in Falmouth, Kentucky, on June 6, 1944 to Katherin Colvin and Joseph Walter Sharp. He attended Union College in Barbourville, Kentucky, where he received a B.A. degree in chemistry and mathematics in 1966. Sharp earned his Ph.D. degree from the University of Illinois in 1969.

Sharp and Richard J. Roberts discovered in 1977 that, in some higher organisms, genes may be comprised of more than one segment, separated by material which apparently plays no part in the creation of the proteins. Previously, mostscientists believed that genes were continuous sections of DNA and that thestring of coding information that makes up each gene was a single, linear unit. Sharp and Roberts, however, distinguished between the exons, thesequences that contain the vital information needed to create the protein, and the introns, incoherent biochemical information that interrupts the protein-manufacturing instructions. Each gene is apparently composed of fifteen to twenty exons, in between which introns may be located. During proteinsynthesis, exons are copied and spliced together, creating complete sequences, while the introns are ignored.

This discovery had not been made earlier largely because scientists had conducted most of their genetic research on prokaryotic organisms, such as bacteria, which do not have their genetic material located in clearly defined nuclei. Studies of bacteria had indicated that gene activity resulted in the transcription of double-stranded DNA into single-stranded messenger ribonucleic acid (mRNA); this is translated to the corresponding protein by ribosomes. Prokaryotic organisms have no introns, however, and therefore could not supply evidence for the existence, or the significance, of noncoding regions of DNA. Roberts and Sharp carried their research out on adenoviruses, the virus responsible for the common cold in humans. Although these are also prokaryotic organisms, Roberts and Sharp were able to take advantage of the fact that virusesreproduce themselves using the mechanisms of eukaryotic cells. Since their genome has some similarities to the genetic material in human cells, their protein synthesis was therefore relevant to the study of the cells of higher organisms.

In their experiments, Sharp's team created hybrid molecules in which they could observe mRNA strands binding to their complementary DNA strands. Electronmicrographs allowed the scientists to identify which parts of the viral genomes had produced the mature mRNA molecules. What they discovered was that substantial sections of DNA were ignored in producing the final mRNA. This unexpected result gave evidence of a greater complexity of mRNA synthesis in eukaryotic organisms than in prokaryotic ones. Further research indicated that themRNAs of eukaryotic organisms are synthesized as large mRNA precursor molecules; the introns are spliced out by means of enzyme activity to produce the mature mRNA that manufactures proteins. They found that a single gene could produce a variety of proteins--some defective--as a result of different splicingpatterns.

It is now believed that many hereditary diseases are caused by imperfect splicing of the genetic material, leading to the creation of faulty proteins. This may occur if the copying and splicing of the exons is not carried out accurately. One such disease is beta-thalassemia, a form of anemia prevalent in some Mediterranean areas that is caused by a faulty protein responsible for theformation of hemoglobin. Because of the insight Sharp's and Roberts's research has produced into the mechanisms of cell reproduction, it has important ramifications for research on malignant tumors and the viruses responsible fortheir development. It has also led to an investigation of methods for stopping the replication of the human immunodeficiency virus type 1 (HIV-1), with potential benefits in the search for a treatment for AIDS.

Sharp and Roberts's work has also led to new theories on the nature of evolutionary change; rather than being the cumulative effect of genetic mutation over time, it is now believed that it may be the result of the shuffling of large segments of DNA into new combinations to produce new proteins.

In 1990, before his earlier work had led to his Nobel Prize, Sharp was offered, and accepted, the presidency of the Massachusetts Institute of Technology.A short time later, he decided not to accept the position in order to devotehis time exclusively to research. He has remained active in the field of academic administration, however, and has lobbied for research funding. He has also been active in industry; he was one of the founders of Biogen, a corporation started in Switzerland and now operating in Cambridge, Massachusetts, that has employed techniques developed in genetic engineering to produce the drug interferon.

Recent Updates

November 14, 2005: U.S. President George W. Bush announced that Sharpwill receive one of three 2004 National Medals of Science for Biological Sciences at a White House ceremony. The National Medal of Science is the nation'shighest honor for science. It recognizes individuals in a variety of fieldsfor pioneering scientific research that has led to a better understanding ofthe world around us. Source: National Academies, www.nationalacademies.org, November 18, 2005; National Science Foundation, www.nsf.gov, November 16, 2005.

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