Arthur Riggs (geneticist)

American geneticist (1939–2022)

Arthur Dale Riggs (August 8, 1939 – March 23, 2022) was an American geneticist who worked with Genentech to express the first artificial gene in bacteria. His work was critical to the modern biotechnology industry because it was the first use of molecular techniques in commercial production of drugs Riggs served on the board of trustees at the Keck Graduate Institute of Applied Life Sciences. In 2006, Riggs was elected to the National Academy of Sciences. After the family lost their farm during the Great Depression, they moved to San Bernardino, California, where Riggs attended San Bernardino High School. He helped his father, who managed a trailer park, to build and fix things. His mother, a nurse, gave him a chemistry set to encourage his interest in chemistry and biology. obtaining a Ph. D. in biochemistry in 1966.

As graduate students at Caltech, he and Joel A. Huberman collaborated on work that later led to a classic paper on mammalian DNA replication, which was published in 1966. They wanted to use radioactive nucleotides to tag replicating DNA and then use photographic film to produce physical images that capture what happens during replication. Their advisors were not interested in the experiment when Huberman and Riggs proposed it, and the students continued the work on their own. Using their method, they were able to measure the rate of DNA replication. The results indicated that chromosomal DNA contained many sections, which replicated independently, and that replication occurred in both directions at each section's origin. The results were important and helped to extend scientists' understanding of mammalian DNA replication. Herschel Mitchell and Giuseppe Attardi, their advisors, felt that the papers should be published under Huberman and Riggs' names, without their advisors', because they had done the work independently. opening up new areas of research and theory. Riggs and Itakura collaborated with Herbert Boyer at Genentech, and used recombinant DNA technology to become the first to produce a human protein in E. coli. Following the advice of Riggs and Itakura, the group successfully produced the hormone Somatostatin in 1977 as a proof of concept before they attempted to work with the more complicated insulin molecule. They were able to link somatostatin to a larger protein, beta galactosidase, produce it in E. coli, isolate it, and then separate the somatostatin from the galactosidase. Somatostatin was the first mammalian hormone to be produced in a bacterium.

In 1973, Riggs hypothesized that X chromosome inactivation might act in ways analogous to restriction enzyme complexes such as E. coli. He eventually published a theoretical paper on the topic that correctly predicted a key mechanism for DNA methylation epigenetics. In the 1980s, Riggs became convinced that the type of splicing approach used with recombinant DNA also could be used to produce antibodies. Riggs worked with Shmuel Cabilly on "fundamental technology required for the artificial synthesis of antibody molecules." Once again, Riggs and his group characterized the genes for antibodies and cloned them into bacteria. They were able to describe and patent a method for making humanized monoclonal antibodies, using mouse antibodies. They created a gene sequence that would "trick" or induce bacteria into manufacturing humanized antibodies rather than mouse antibodies. This technology has been used to produce "smart" cancer drugs such as Herceptin, Rituxan and Avastin. In 2009, Riggs published on studies conducted with Gerd Pfeifer on the "methylome" of the genome of a human B cell, examining the DNA methylation pattern of the entire genome in an attempt to find patterns of the epigenetic mark 5 methylcytosine. DNA methylation is believed to pass information from parent cells to daughter cells, functioning as a secondary, high fidelity information encoding system. The blood donated for the isolation of the B cells was that of Riggs himself. "It could have been anyone's DNA, but as a pioneer in DNA methylation epigenetics, there is something special to me about it being my methylome". Riggs continued to work on the epigenetic programming of the cell, designing proteins that can bind to DNA in highly specified ways, wherever desired.

Riggs was closely involved in institutional expansion at City of Hope. In the 1990s, he helped establish the City of Hope Graduate School of Biological Sciences (renamed the Irell & Manella Graduate School of Biological Sciences as of May 15, 2009) and served as its founding dean from 1994 to 1998.