Walter Gilbert Biography

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World of Scientific Discovery on Walter Gilbert

Walter Gilbert developed a method for determining the sequence of bases (individual components) in DNA, for which he shared the 1980 Nobel Prize in chemistry with Frederick Sanger and Paul Berg. Gilbert was born in Boston, Massachusetts, to a psychologist mother and an economist father. Interested in science since childhood, he majored in chemistry and physics at Harvard and received his Ph.D. from Cambridge University in England in 1957 for work in mathematical physics.

While teaching at Harvard, Gilbert shifted to experimental biophysics through acquaintanceship with James Watson, co-discoverer of the double helix shape of DNA. They experimented with messenger RNA, the nucleic acid that carries gene information to a cell's ribosomes for protein production.

In 1965-66 Gilbert and Benno Muller-Hill explored what mechanisms a cell employs to turn genes "on" or "off." Using a radioactive tracing technique, they isolated a protein which turns off production of lactose-digesting enzymes in the bacteria E. coli. This verified the model of cellular gene expression proposed by François Jacob, André Lwoff, and Jacques Monod a few years earlier.

This work led to Gilbert's sequencing of the DNA bases in and near the same genes. In 1975, at the suggestion of Andrei Mirzabekov, a Soviet scientist, Gilbert used the chemical dimethyl sulfate to fragment a strand of DNA at sites of the bases guanine and adenine. He labeled the segments with radionucleotides, cut them with restriction enzymes, which break DNA at known locations, and separated the fragments by electrophoresis. Gilbert and Allan Maxam developed a similar method for the other two DNA bases, thymine and cytosine, using the chemical hydrazine. After identifying the base sequences in the fragments, Gilbert was able to reconstruct entire DNA strand sequences thus "reading the letters" in which genetic instructions were coded.

In the 1970s and 1980s, Gilbert found himself in the midst of social and medical controversy when he decided to use the information he had to further commercial biotechnology when he joined Biogen. He left Biogen amid acrimony in 1984 and resumed his professorship at Harvard, which he had left in favor of persuing his business interests. Gilbert started another biotechnology company, the Genome Corporation, in 1988 with the goal of mapping the human genetic code and possibly selling the resulting DNA data to any interested parties. The company went bankrupt after the stock market crash, but Gilbert began working with the U.S. government and several biotechnology companies to put together the Human Genome Project (HGP). The HGP began operations in 1990 and had roughly mapped 95 percent of the genome by 2001.

In 1996 Gilbert cofounded and became chairman of the board of NetGenics, a pharmaceutical biotechnology company in Cleveland, Ohio. He continues in that position, which he holds concurrently with his professorship at Harvard. In 1992, Gilbert also cofounded Myriad Genetics, Inc., where he is vice chairman and director.