Walter Gilbert

American scientist Walter Gilbert (born 1932), who shared the Nobel Prize for Chemistry in 1980, became world famous for his groundbreaking research in the field of molecular biology. Admired by both fellow scientists and laymen, his efforts substantially advanced the field of genetic engineering. Because of his work, scientists have been able to manufacture genetic material in laboratories. When receiving his Nobel award, he was cited for developing a method for determining the sequence of nucleotide links in the chainlike molecules of nucleic acids. Later, he formed several commercial biotechnology firms, and he became involved in helping map the human genetic blueprint.

Early Life

Walter Gilbert was born on March 21, 1932, in Boston, Massachusetts, to Richard V. Gilbert, an economist, and Emma Cohen, a child psychologist. His father worked for the Office of Price Administration during World War II as part of President Franklin D. Roosevelt's administration. His mother proved to be an intellectually stimulating influence in the two-child household. When Gilbert was a boy, she would administer intelligence tests to his sister and him, and she educated him at home during his earliest years, teaching him how to read. In 1939, the family moved to Washington, D.C., where Gilbert attended public schools.

As a boy, Gilbert took an active interest in science, joining mineralogical and astronomical clubs. Naturally curious, he began performing his own experiments, once with nearly catastrophic results: when he was 12 years old, while his family lived in Virginia, he attempted a chemistry experiment that ended in an explosion of shattered glass. He suffered a slashed wrist and his mother had to take him to the hospital. According to her account, Gilbert was only concerned with determining what went wrong with the experiment.

In high school, he became fascinated with inorganic chemistry and nuclear physics. A youth of advanced intelligence, he would often skip school to go to the Library of Congress so he could read about Van de Graaf generators and atom smashers. "I decided to try and find out about these subjects, but there was nothing available in school," he recalled. "My grades were still good enough that the school didn't object too much." He also maintained his interest in astronomy and, as a teenager, he won a regional science fair in Washington, D.C. by making a telescope that photographed sun spots.

After high school, he attended Harvard University, where he majored in chemistry and physics. While in college, his interests became focused on theoretical physics. As a graduate student, he studied the theory of elementary particles and the quantum theory of fields. After one year of graduate school at Harvard, he transferred to the University of Cambridge in England for two years and received a doctorate degree in physics in 1957. His thesis involved dispersion relations for elementary particle scattering. While at Cambridge, he met James Watson, a young American scientist who had established a name for himself in scientific circles--and imprinted his name in genetic textbooks forever--with his groundbreaking work with DNA. That same year he returned to Harvard for a year of post-doctorate study. He also married Celia Stone, a poet he first met in high school. They would have two children, John Richard and Kate. After that, he became an assistant professor of physics at Harvard University. In the late 1950s and early 1960s, he taught several courses in theoretical physics.

Entered Molecular Biology Field

In 1960, Gilbert reached a turning point in his life when he worked with Watson and Francois Gros on an experiment that involved the identification of messenger RNA. (The experiment uncovered new information about messenger RNA--essentially, the "messenger that relayed information from DNA to the areas in the cell where proteins are manufactured.") Gilbert found experimental research exciting, and from that point on, he continued working in molecular biology, which was a new and exciting field at the time. In 1961, Gilbert gained a great deal of notoriety when he published his first paper on messenger RNA in Nature Magazine. He soon became a tenured biophysicist at Harvard.

Following his work with RNA, he did research into protein synthesis, again uncovering new information that would advance the field. In the mid-sixties, he worked with Benno Müller-Hill. Their collaboration resulted in the isolation of the lactose repressor, the first example of a genetic control element. Again, his research findings advanced the field as well extended his notoriety to the international level. Later in that decade, working with David Dressler, he helped invent the rolling circle model, which describes one of the two ways DNA molecules duplicate themselves.

The 1970s were also an active and fruitful period for Gilbert. In that decade, he developed a technique of using gel electrophoresis that read nucleotide sequences of DNA segments. Also, he isolated the DNA fragment to which the lactose repressor is bound, studied the interaction of the bacterial RNA polymerase and the lactose repressor with DNA, developed recombinant DNA techniques, and helped develop rapid chemical DNA sequencing. In 1974, he became an American Cancer Society Professor of Molecular Biology. Late in the decade, he worked with Lydia Villa Komaroff and Argiris Efstratiadis on the bacterial strains that expressed insulin. The work he started with DNA would eventually lead to the Nobel Prize in Chemistry in the next decade.

Entered the Business Arena

In 1979, Gilbert formed an alliance with businessmen and other scientists to help found Biogen, a commercial genetic-engineering research corporation. Reportedly, he approached this enterprise with the same enthusiasm he brought to his academic and research pursuits, learning as much as he could about patent laws and exploring management issues. For several years, Gilbert served as chief executive officer. However, he was often at odds with the company's board of directors and he resigned in 1984. Later, he would lend a hand in starting several other biological companies, including Myriad Genetics. A few years after he left Biogen, he founded the Genome Corporation, a company involved in human genome research. But the company went out of business after the stock market crash of 1987. Despite the failed venture, Gilbert's interest in genome research never flagged. When he left Biogen, he went back to Harvard, where he became a major and very high profile supporter of the Human Genome Project, a government-funded enterprise looking to build a complete map of the gene sequences in human DNA.

Won the Nobel Prize

The next decade started with Gilbert receiving the most prestigious honor a scientist can attain. His innovative work and long list of achievements up to that point culminated in 1980 when he received a share of that year's Nobel Prize in Chemistry. Still a Harvard professor at the time, he shared the award with Professor Frederick Sanger, of Cambridge University in Great Britain, and Paul Berg, of Stanford University in California. They were honored for independently developing a method for determining the sequence of nucleotide links in the chainlike molecules of the nucleic acids DNA and RNA. Their work added a great deal to the worlds knowledge about how DNA, as a carrier of the genetic traits, directs the chemical machinery of the cell. Working separately in their own labs, Gilbert and Sanger developed different methods to determine the exact sequence of the nucleotide building blocks in DNA. Together, their work resulted in the creation of effective tools that enabled continued investigations into the structure and function of the genetic material.

Sought the Origin of Genes

After Gilbert resigned from Biotech in 1984, he returned to Harvard University. Beginning in 1985, he worked as a professor in the university's departments of physics, biophysics, biochemistry, and biology. Former students fondly recalled studying under him. Gilbert's labs and classrooms provided an exciting atmosphere where all were considered equals, including the world famous educator himself. Students enjoyed working with Gilbert, as they found that he encouraged camaraderie, demonstrated humor, and possessed an infectious personality.

Gilbert also worked in Harvard's Department of Molecular and Cellular Biology where, with fellow staff members, he became involved in research, discovery, and training in biological areas including cellular biology, biochemistry, neurobiology, genetics, and bioinformatics. This led him to research involving molecular evolution and the development of the theory of the intron/exon gene structure. Essentially, Gilbert set out to discover the origins of genes and how they evolved. It is believed that such a theory, if eventually proven correct, could impact drug design, as it may allow scientists to recognize and manipulate the working parts within proteins.

Essentially, the purpose of the research was to discover where genes may have come from and what the first genes were like. In the course of the work, Gilbert came up with terms for the interrupted pattern in which genes are stored. In the intron/exon theory, exons refer to the working parts, while introns refer to the regions in between where the cell has to splice out. If the theory is proven correct, some believe the history of life on earth could be deduced from the DNA of modern genes. The intron/exon theory is somewhat controversial and has not gained total acceptance. In response, Gilbert employed extensive computer and statistical analysis to try and support it. Fellow scientist Philip Sharp, a molecular biologist at the Massachusetts Institute of Technology, who first discovered the primordial introns, an accomplishment that won him a Nobel Prize in Physiology or Medicine in 1993, remarked that solving the mystery may be impossible, but he gave Gilbert a vote of confidence: "That won't stop Wally Gilbert, of course.... [He] captured the imagination of the field, and still has it, I think.

What Gilbert has tried to do is to find out how the first genes were assembled in the "organic soup oceans that once covered the entire world and gave rise to life." Obviously, this is a daunting task. Modern genes contain a great deal of information, and to determine precisely how they evolved by examining their structure would be a lengthy and complex process. However, Gilbert feels the first genetic elements were simple components that predate the modern exons. The early exons became mixed and matched and constructed into long chains that would make increasingly larger genes. He believes that by studying the structure of modern genes, we could see find the early components and then determine how the mixing and matching process occurred. In his theory, the introns would be the elements that could make the mixing and matching possible.

Outside Activities

Outside of his interests in science, Gilbert enjoys Chinese cooking, playing the piano (a skill he learned later in life), and studying and collecting ancient art, particularly Greek sculpture.

Further Reading

• Hilts, Philip J., "Reading the History of Life in the Text of Modern Genes, The New York Times, November 12 1996.
• "A Conversation with Walter Gilbert," Discover, November 1998, http://www.findarticles.com/cf_0/m1511/11_19/57564251/p1/article.jhtml (February 10, 2003).
• Cromie, William J., "Scientists Ponder Sequence of Genes," Harvard University Gazette, http://www.news.harvard.edu/gazette/2001/04.05/07-genes.html (February 10, 2003).
• Gilbert, Walter, "Walter Gilbert-Autobiography," Nobel e-Museum, http://www.nobel.se/chemistry/laureates/1980/gilbert-autobio.html (February 10, 2003).
• "Nobel Prize in Chemistry to Nucleic Acid Investigators," Nobel e-Museum, http://www.nobel.se/chemistry/laureates/1980/press.html (February 10, 2003).
• "Walter Gilbert (1932- )," Access Excellence @ the National Health Museum, http://www.accessexcellence.org/AB/BC/Walter_Gilbert.html (February 10, 2003)
• "Walter Gilbert," International Center for Scientific Research, http://www.cirs.net/researchers/Chemistry/GILBERT.htm (February 10, 2003).