Herbert Wayne Boyer

• Born: July 10, 1936
• Place of Birth: Derry, Pennsylvania

AMERICAN BIOCHEMIST

Boyer, along with Stanley Norman Cohen, developed the basic techniques used in genetic engineering. Boyer and Cohen were the first to use restriction endonucleases to cut DNAs from two different sources, splice them together to make a recombinant DNA molecule, and express the recombinant DNA molecule after insertion into E. coli cells.

PRIMARY FIELDS: Biology; genetics

PRIMARY INVENTIONS: First recombinant DNA organism; human insulin

Early Life

Herbert Wayne Boyer was born in 1936 in the western Pennsylvania town of Derry. After graduating from Derry High School, where he played football, Boyer commuted to St. Vincent College in Latrobe, Pennsylvania, where he majored in pre-med biology, receiving a BS in biology and chemistry in 1958. He then attended graduate school at the University of Pittsburgh. In 1959, he married Marigrace Hensler. Boyer completed his PhD work in 1963, after which he did three years of postgraduate work focusing on biochemistry at Yale University in the laboratories of Edward Adelberg and Bruce Carlton. While conducting postdoctoral research, Boyer was active in the civil rights movement.

Life’s Work

In 1966, Boyer accepted an assistant professorship of biochemistry and biophysics at the University of California, San Francisco (UCSF). His research focused on the isolation and characterization of EcoR1, a restriction endonuclease enzyme from Escherichia coli (E. coli) that cuts molecules of deoxyribonucleic acid (DNA) at very specific nucleotide sequences. Boyer discovered that EcoR1 creates DNA molecules with short (four-nucleotide), single-stranded, complementary, “sticky” overhang ends.

In 1972, Boyer teamed up with Stanley Norman Cohen, a professor, research scientist, and physician at Stanford University who had been studying the insertion of small, circular, nonchromosomal DNA molecules called plasmids, which reside and replicate in a variety of bacteria, into E. coli. Cohen had realized that two DNAs cut with Boyer’s EcoR1 restriction endonuclease could easily be spliced together because of the complementary overhangs. In 1973, Boyer, Cohen, Annie Chang, and Robert Helling cut, combined, and ligated two different plasmids and inserted them into E. coli, marking the construction of the first recombinant DNA using restriction endonucleases as well as the beginning of the era of genetic engineering, also known as gene cloning. Now scientists could recombine DNAs at will and insert them into other organisms. In 1974, Boyer and Cohen, along with Chang, Helling, John Morrow, and Howard Goodman, succeeded in constructing a recombinant DNA molecule from the DNA of a plasmid and the ribosomal RNA-coding DNA of Xenopus laevis, the African clawed frog. After insertion of the recombinant plasmid/Xenopus DNA into E. coli, the recombinant DNA was transcribed into Xenopus laevis ribosomal ribonucleic acid (rRNA). This was the first demonstration of a eukaryotic DNA molecule (the rRNA gene from Xenopus laevis) being expressed in a foreign organism, E. coli. Boyer and Cohen next patented their gene-splicing technique.

In 1976, Boyer was promoted to professor of biochemistry and biophysics at UCSF, a position he would hold until his retirement in 1991. In April 1976, Boyer and Robert Swanson, a financier and venture capitalist who studied chemistry and management at the Massachusetts Institute of Technology (MIT), incorporated Genentech (Genetic Engineering Technology), a company whose first focus was to synthesize the human insulin gene, recombine it with a plasmid, and insert it into E. coli with the hope that the E. coli would synthesize human insulin. Swanson conceived of the project because the incidence of diabetes in the United States was increasing while the availability of bovine and porcine insulin was decreasing. Swanson and Boyer joined forces with Arthur Riggs, a geneticist at the City of Hope, a clinical research hospital in Duarte, California. By 1978, the Genentech/City of Hope team had successfully cloned and expressed the human insulin gene in E. coli. Genentech licensed the production and marketing of human insulin to Eli Lilly. Genentech, one of the leading biotechnology companies in the world, became a publicly traded company in 1980. In 1985, it became the first biotechnology company to produce and market its own medicinal product, human growth hormone (hGH), marketed under the name Protropin.

Boyer was vice president of Genentech until 1990, when he became a member of the board of directors. In 1994, he became a member of the board of directors of Allergan, Inc., a company that focuses on the discovery and development of innovative pharmaceuticals. He served as chairman from 1998 to 2001 and was elected vice chairman in 2001.

Boyer is the recipient of numerous awards, including the Albert Lasker Award for Basic Medical Research (1980), the National Medal of Science (1990), the Lemelson-MIT Prize for Invention and Innovation with Stanley Cohen (1996), the Albany Medical Prize (2004), and the Shaw Prize in Life Sciences and Medicine (2004). He was elected to the American Academy of Sciences in 1979 and to the National Academy of Sciences in 1985. In 1991, after a substantial gift by Boyer and his family, Yale University dedicated the Boyer Center for Molecular Medicine. In 2007, St. Vincent College renamed the School of Natural Science, Mathematics, and Computing the Herbert W. Boyer School. After retiring, Boyer became professor emeritus of biochemistry and biophysics at UCSF.

Impact

Boyer and Cohen’s collaboration that led to the development of gene-splicing and genetic-engineering techniques had a profound impact on biology by revolutionizing the study of genetics and molecular biology. Their development of these techniques allowed for the construction, insertion, cloning, and expression of recombinant DNA molecules in foreign hosts and spawned the development of the biotechnology and biopharmaceutical industries.

Although the polymerase chain reaction (PCR) eventually replaced cloning as a method to amplify specific DNA molecules, the cloning of recombinant DNA molecules gave scientists a method to amplify and isolate specific DNA molecules to provide enough copies for DNA sequencing and analysis of gene structure and function. These analyses provided scientists with basic knowledge of the structure of the gene, the nature of mutations, and the control of gene expression.

The expression of recombinant DNA molecules in foreign hosts provided a mechanism for the production by foreign hosts of a variety of human proteins and enzymes to treat human disease. The first medicinally valuable protein that became commercially available was human insulin, in 1982. Insulin was quickly followed by the production of other recombinant human proteins, including hGH, interferon, tissue plasminogen activator (t-PA), and factor VIII clotting factor.

The Boyer-Cohen techniques also led to the development of a variety of transgenic strains of animals and plants. Today, animals such as goats, sheep, pigs, and cows are engineered to produce a variety of human proteins and enzymes of medicinal value, including t-PA, lactoferrin, factor VIII, factor IX, and alpha 1-antitrypsin. Plants are engineered to be insect-resistant, virus-resistant, and pesticide-resistant, allowing for increased yield and a reduction in the use of pesticides. Plants are also engineered to increase nutritional value. Rice, for example, has been engineered to produce beta-carotene, the precursor of vitamin A.

Bibliography

Drlica, Karl. Understanding DNA and Gene Cloning: A Guide for the Curious. 4th ed. New York: John Wiley & Sons, 2004.

Gitschier, Jane. "Wonderful Life: An Interview with Herb Boyer." PLoS Genetics, vol. 5, no. 9, 2009, doi:10.1371/journal.pgen.1000653. Accessed 30 Aug. 2024.

Hall, Stephen S. Invisible Frontiers: The Race to Synthesize a Human Gene. New York: Atlantic Monthly Press, 1987.

"Herbert W. Boyer and Stanley N. Cohen." Science History Institute, 1 Dec. 2017, www.sciencehistory.org/historical-profile/herbert-w-boyer-and-stanley-n-cohen. Accessed 30 Aug. 2024.

Martineau, Belinda. First Fruit: The Creation of the Flavr Savr Tomato and the Birth of Biotech Food. New York: McGraw-Hill, 2001.