His research into recombinant DNA provided a foundation for the biotech revolution, leading to a long list of lifesaving treatments.
Arthur D. Riggs, a biochemist whose pioneering research into the mechanisms of human DNA led him to a series of breakthrough advances, including the invention of artificial insulin and monoclonal antibodies, died on March 23 in Duarte, Calif. He was 82.
City of Hope National Medical Center, where Dr. Riggs spent most of his career, said the cause of his death, at City of Hope’s Helford Clinical Research Hospital, was lymphoma.
Dr. Riggs’s impact on the field of biotechnology was nothing less than revolutionary. He was one of a handful of researchers who could claim to be among the $500 billion industry’s founding fathers.
He is probably best known for his role in the invention of artificial insulin. Working alongside Keiichi Itakura and Herbert Boyer, he developed a way to use recombinant DNA technology — essentially, the ability to splice together strands of DNA — to turn E. coli into microscopic factories for the production of humanized hormones.
Dr. Riggs explained the process by using the analogy of a strip of magnetic tape, as one would find in a cassette.
“A cassette tape has the instructions for playing the music,” he told an interviewer from City of Hope in 2013. “It has a beginning and an end, and there’s a code that says: With this code you have this tone. One bit will tell you what note to play, and the next bit will tell you another note.”
If you cut the strip and splice in tape from a different recording, it will sound different when you play it back. The same, more or less, goes for DNA.
“When you take a gene from a mouse and put it into a bacterial gene, you cut out a piece of the mouse tape and you put it into the bacterial tape,” he said. “So you cut and splice. Recombinant DNA technology is just how to cut and splice and put genes where you want them.”
Dr. Boyer and another researcher, Stanley Cohen, had already developed the basic technology behind recombinant DNA. Dr. Riggs’s insight was to see how that technology could be used to tweak bacteria to produce artificial hormones for human use.
“We chose insulin because it looked doable, and there was a need,” he told The Los Angeles Business Journal in 2021. “At the time, diabetics were being treated with cow insulin because there was no source of human insulin. And cow insulin resulted in a high rate of allergic reactions.”
Starting in the mid-1970s, he and his team, working alongside scientists at Genentech, a Bay Area start-up, raced against two other groups — one at Harvard and one at the University of California, San Francisco — to be the first to perfect the process.
They began by synthesizing somatostatin, a hormone only one-tenth the size of insulin, to try to prove that their idea worked. They soon hit a snag: Although the bacteria would produce the hormone, it would quickly degrade. Then Dr. Riggs realized that they could attach the somatostatin to a much larger protein while it was still in the bacteria and separate them later.
Once they mastered somatostatin, in 1977, they needed only a year to do the same with insulin. In 1982, after a lengthy review and approval process, a commercial version, Humulin, was approved by the Food and Drug Administration. It was the first significant biotech product to receive the agency’s approval.
The discovery made Genentech, and Dr. Riggs, rich. But unlike many of his fellow biotech pioneers, he declined the opportunity to make even more money working in the for-profit sector; he was under contract to Genentech, but after that arrangement ended in 1984, he returned to City of Hope full time.
He lived in the same house for 50 years and rarely sat for interviews. He gave most of his money away in the form of anonymous donations to City of Hope. His beneficence, to the tune of $210 million, was finally revealed last year, when he made an additional $100 million donation to the hospital.
“City of Hope convinced me that if my donations were made public, I could encourage others to follow suit,” he told The Los Angeles Business Journal.
Dr. Riggs later developed the foundations for monoclonal antibodies, again using recombinant DNA technology to trick bacteria into producing proteins that mimic human antibodies. That development has led to major advances in treating cancer and other diseases.
In the 2000s he turned to the question of epigenetics, the study of how markers attached to a gene alter the way that gene is “read.” Over the course of an organism’s life, a gene will gain or lose certain markers, a process influenced by behavior and changes in one’s environment.
Epigenetics is an emerging and still poorly understood field. But even after retiring in October 2020, Dr. Riggs continued his research, certain that it would lead to even more lifesaving breakthroughs.
“I could have retired into a South Pacific mansion and enjoyed myself on the beach,” he said in 2021, “but I would have been bored within a week.”
Arthur Dale Riggs was born on Aug. 8, 1939, in Modesto, Calif., where his family owned a farm.
After they lost the property in the Great Depression, his father, John Riggs, moved the family to San Bernardino, where he built and operated a trailer park. Despite having only an eighth-grade education, John Riggs was sufficiently adept at engineering to be able to design the park’s electrical and plumbing systems himself; in his spare time he built autogiros, which combine elements of an airplane and a helicopter.
Arthur’s mother, Nelly (Calkins) Riggs, a nurse, encouraged her son's early interest in science, buying him a chemistry set when he was young and shuttling him to the library, where he spent hours reading science fiction.
He received a degree in chemistry from the University of California, Riverside, in 1961 and a Ph.D. in biochemistry from the California Institute of Technology in 1966. After a postdoctoral fellowship at the Salk Institute in San Diego, he arrived at City of Hope in 1969.
He married Jane Merrill in 1960. She survives him, as do his sister, three children and three grandchildren.
“I’m disappointed that I never quite made it as a space-traveling scientist or a space cadet,” Dr. Riggs said in his City of Hope interview. “But in my field, I’ve been able to do things that are just as exciting.”
He added, “When I sit back and think about it, I just continue to be amazed at what the field has done in general and that I’ve been able to be part of it. It’s absolutely incredible.”
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