Arthur D. Riggs, Ph.D., the world-renowned diabetes expert who developed the technology that led to the first human synthetic insulin for the treatment of diabetes, died March 23 after battling cancer.
Riggs’ major scientific discoveries achieved over more than a half-century of research, paving the way for development of the monoclonal antibody therapies that are the foundation of modern treatments for cancer, autoimmune diseases, blindness and a host of other diseases. His breakthrough work in diabetes enabled mass production of insulin for people living with the disease. Today, synthetic insulin is used by hundreds of millions of people.
He was 82.
Riggs was already recognized for his novel research into the inner workings of DNA when he joined City of Hope as a research scientist in1969. In 1977, his research led to the creation of the first artificially synthesized gene and human protein, the important hormone inhibitor somatostatin, followed not long after by the first ever synthesis of human growth hormone. A year later, he was able to apply this disruptive technology to produce human insulin from bacteria — a breakthrough that saved countless lives and led directly to the launch of the $500 billion global biotech industry.
As a scientist and leader at City of Hope over the next 53 years, Riggs continued to perform groundbreaking research and make major contributions across the life sciences. His 1975 paper on mammalian epigenetics — how behaviors and environment can cause changes that affect the way genes work — remains one of the most frequently referenced on the subject. It was one of more than 200 scholarly papers on which he is an author, in addition to holding 20 patents. He was recognized for this lifetime of achievements by his election to the National Academy of Sciences in 2006.
“Arthur Riggs is one of the scientific giants of the age and should be a household name for his contributions to diabetes alone,” said Robert Stone, president and CEO of City of Hope and Helen and Morgan Chu Chief Executive Officer Distinguished Chair. “His research also led to the development of monoclonal antibody therapies that today treat cancer and other diseases. His amazing scientific accomplishments go far beyond one condition, though, both in his own work and in that of the dozens of talented researchers for whom he was a devoted mentor. City of Hope today owes an enormous debt to him, as do countless people whose lives have been changed by his discoveries.”
Arthur Dale Riggs was born on Aug. 8, 1939, to a farming family in Modesto, California. The family soon moved to San Bernardino, where his father, who had given up farming, built and managed a mobile home park. Riggs learned to build and fix things from his father, an inventive and mechanically adept man who once designed and built his own helicopter.
“Helping my father was a great learning experience,” he recalled in an interview in 2010. “But I also remember sometimes telling my father that I had homework to do in order to avoid digging ditches. I would then read science fiction rather than do my homework.”
Riggs’ lifelong passion for chemistry and biology was sparked by his mother, a nurse, who gave him a chemistry set at the age of 10. He also exhibited early the imagination that goes hand in hand with scientific research.
Drs. Arthur Riggs and Keichi Itakura first engineer human insulin in the laboratory
After graduating from San Bernardino High School, Riggs attended the University of California Riverside, where he earned a degree in chemistry in 1961. He was awarded his Ph.D. in biochemistry in 1966 by Caltech, where he and fellow student Joel A. Huberman wrote a now classic paper on mammalian DNA replication. Notably, their thesis advisors — including Herschel (H.K.) Mitchell, Ph.D. — declined the usual practice of having their names attached to the paper. Instead, they insisted that Riggs and Huberman be the sole names on the paper, because of the originality and independence of their research.
That spirit of independent inquiry remained with Riggs throughout his career, beginning with postdoctoral work while still at Caltech. In 1968, he proposed a theory on DNA modification that suggested that epigenetic changes and metabolic memory have major roles in the pathophysiology of diabetes. This work virtually created the field of epigenetics, which has important applications in treating serious genetic diseases. It remained a major focus of his research for decades.
After postdoctoral work at the Salk Institute on the regulation of DNA in bacteria, Riggs came to City of Hope. Attracted by the diabetes researchers at City of Hope, along with the potential to apply his work to diabetes, he continued his research in the nascent field of recombinant DNA technology with a mission to help find a cure for the disease.
In 1976, he attended a lecture at City of Hope on DNA gene splicing given by a young University of California Berkeley scientist named Herb Boyer, who had just formed a two-person company called Genentech. Riggs and his colleague Keiichi Itakura, Ph.D. agreed, under City of Hope’s banner, to collaborate with Boyer’s nascent company on a project using E. coli bacteria as a “host” for synthesizing human proteins. In 1977, they succeeded in reverse-engineering the genetic code for a protein called somatostatin, an important inhibitor of many human hormones — and then did the same for human growth hormone — developing versions of the genes that would function inside the bacteria. It was a historic first that demonstrated that it was possible to “manufacture” complex human proteins.
The following year, Riggs and Itakura undertook the more daunting problem of achieving the same bacterial synthesis of human insulin, a far more complex protein than somatostatin or human growth hormone. This groundbreaking work enabled the large-scale production of synthetic insulin, which became the first genetically engineered product approved by the Food and Drug Administration. The Juvenile Diabetes Research Foundation bestowed its Research Award on Dr. Riggs in 1979 for this work, and the synthetic insulin he helped create is still used by hundreds of millions of people every day. The work also served as a catalyst for the biotech industry and the development of industrial biomedical technology.
“You cannot overestimate the importance of this seminal work, not simply to people with diabetes, but also in helping to found the field of biotechnology,” said Peter Dervan, Ph.D., Bren Professor of Chemistry, Emeritus, at Caltech. “Before Arthur Riggs, synthesizing human proteins was only an idea, and the potential of the biotechnology industry not yet evident. What Riggs and his colleagues did transformed aspirations into practice and provided a road map to an entirely new branch of applied molecular biology that has delivered untold benefits to humankind.”
Despite the enormous publicity surrounding the synthesis of human insulin and the subsequent creation of dozens of biotech companies all pursuing the limited scientific talent in the field, Riggs declined to join any of them. Instead, he returned to his research at City of Hope and continued to make important discoveries in epigenetics and other areas of life sciences over the course of his career.
“Art Riggs was an influential figure in my own development as a scientist," said Bruce Beutler, M.D., director of the Center for the Genetics of Host Defense, UT Southwestern Medical Center. "I had finished college and was working with Susumu Ohno, downstairs from Art’s lab, prior to attending medical school. I remember watching day by day in 1977 as Keiichi Itakura synthesized the insulin gene from a library of nucleotide triplets; then seeing Art and his group express the insulin protein in bacteria, and show that it was active. I had a strong sense that history was being made. I was very much in awe of him. Yet, he was perfectly approachable and friendly. It wasn’t until later that I learned of his many other accomplishments, particularly in the realm of epigenetics. He presented a wonderful example to follow, and was one of the greatest scientists of our time.”
Crucially, he recognized that antibodies could be used as treatment for many diseases. Riggs developed recombinant DNA technology capable of producing humanized monoclonal antibodies that are the foundation for an entire class of drugs that today comprise the standard immunotherapies for cancers of the lungs, prostate, breast, brain and other organs, as well as for previously untreatable ailments from age-related wet macular degeneration (a major cause of blindness), multiple sclerosis and HIV to autoimmune conditions including rheumatoid arthritis, Crohn's disease, ulcerative colitis and plaque psoriasis.
“Art was one of the most brilliant scientists of our day. He had a remarkable ability to think outside the box and was not afraid to put forth bold ideas, many of which shifted existing paradigms and opened wholly new areas of exploration in basic and applied biology,” said Peter Jones, Ph.D., chief scientific officer at Van Andel Institute in Grand Rapids, Michigan. “We first met in 1979, and over the years, swapped ideas, reveled in science and marveled at its beauty. Along with his commitment to groundbreaking science, Art and his wife were immensely generous with their resources and dedicated to improving the environment and medicine. City of Hope and, indeed, the entire scientific community, were so lucky to have such a gentleman scientist in our midst.”
Renowned not only for his scientific prowess but also his selfless leadership and ability to motivate and develop top research talent, in 1981 Riggs was named chair of the Division of Biology at Beckman Research Institute of City of Hope; in 2000, he was named the institute’s director. In 1994, he became the founding dean of City of Hope’s Irell & Manella Graduate School for Biological Sciences. In 2016, he was named chair of the Department of Diabetes and Metabolic Diseases Research at City of Hope.
Throughout his tenure, Riggs demonstrated his commitment to teaching future generations of scientists in order to keep City of Hope at the forefront of research into diabetes. In an interview in 2019, Riggs described his collegial management style, which he credited to his experience with his doctoral advisors at Caltech.
“My philosophy for scientific leadership is to make suggestions, almost never orders,” Riggs said. “This is what my mentors did … My office door is open [and] I do try to be as nice as I can to everybody.”
Riggs served as director of City of Hope’s Diabetes & Metabolism Research Institute until he reached his 81st birthday. He relinquished that position to Debbie C. Thurmond, Ph.D., but remained focused on research, as well as remaining the Samuel Rahbar Distinguished Chair in Diabetes & Drug Discovery.
In addition to devoting himself to research at City of Hope, Riggs also devoted much of the wealth he realized from his discoveries to support its mission. Insisting on anonymity, he gave more than $200 million of his own money to City of Hope over the course of two decades. Near the end of his life, he made a further gift of $100 million, bringing the total of his gifts to more than $310 million during his lifetime. In honor of his philanthropic and scientific contributions to City of Hope, the research institute he founded and managed for so many years was renamed the Arthur Riggs Diabetes & Metabolism Research Institute.
“It is a humbling honor to take responsibility for this institute that Riggs so lovingly and painstakingly built,” said Thurmond, Ruth B. & Robert K. Lanman Chair in Gene Regulation & Drug Discovery Research. “It’s entirely fitting that it should carry his name, even as we carry on the work he began for the benefit of people with diabetes. His philanthropy is an extension of the generosity of spirit he has shown to me and everyone else who has ever walked through these doors.”
Riggs agreed to have his contributions acknowledged publicly in the hope it would place a spotlight on City of Hope’s accomplishments over the last half-century and encourage similar support from other major donors. His insistence on anonymity for years was in keeping with his principles for living an ordinary life and shunning any of the trappings of wealth and the attention it would bring. He lived for 50 years in the same home he bought when he came to City of Hope, and refused to spend money on expensive cars or other luxury items, in part because he did not want his family’s lives to be affected by wealth. A colleague once asked if Riggs had ever had the desire to do even a little splurging, to which he replied, “Well, I do always have the latest iPhone.”
Riggs also was a fan of basketball — so much so that it helped guide his career. In a 2010 interview, Riggs said one reason he chose Mitchell as his graduate school mentor was “because I enjoyed playing basketball, and he was the coach of an intramural basketball team.”
“Art was soft-spoken, gentle, kind and sometimes, very shy,” said Keiichi Itakura, Ph.D., professor emeritus with City of Hope's Center for RNA Biology and Therapeutics. “But when it came to science and sports, he was very determined and didn’t hold anything back. He never wanted to retire and would still come to us with research ideas. I am grateful for all of the long-lasting memories of our time together whether it was in the lab, on the racquetball court or spending time in nature.”
Riggs is survived by his wife, children and grandchildren.
“The extraordinary work Art has done lives on in all of us who are committed to carrying on his legacy of eradicating diabetes and cancer, particularly the scientists he trained and influenced who follow in his footsteps, and in the countless lives his life’s work has touched in such a profound way,” Stone added.
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