Donald F. Steiner, MD, 1930-2014

Pioneer of insulin production, improved treatment for diabetes

November 17, 2014

Donald F. Steiner, MD, a pioneer whose research improved lives for millions of diabetic patients worldwide, died at his home in Chicago on Tuesday, November 11, 2014. He was 84 years old, and had been a member of the University of Chicago faculty since 1960.

Steiner, MS '56, MD '56, the A.N. Pritzker Distinguished Service Professor Emeritus in the Departments of Medicine and Biochemistry & Molecular Biology at the University, revolutionized thinking about how the body produces insulin. In 1967, he showed that insulin, thought to be made from two separate protein chains, began instead as a longer single chain, which he named proinsulin. Steiner showed a small interior part of that single long chain was sliced out, leaving behind the two connected A and B chains that together compose the insulin molecule.

This fundamental discovery paved the way to understanding how other hormones, as well as neuropeptides in the brain and endocrine system, are made and processed. It established the field of protein-precursor processing. It also enabled the pharmaceutical industry to improve the purity of insulin preparations, leading to insulins that were less likely to provoke an immune response and paved the way for biosynthetic human insulin production.

"This was a remarkable piece of work, a truly creative and ultimately beautiful set of experiments," said diabetes specialist Arthur Rubenstein, MBBCh, who did post-doctoral training with Steiner and later served as chairman of medicine at the University of Chicago and recently stepped down from serving as Dean of the University of Pennsylvania's Perelman School of Medicine. "No one else at that time was thinking through such problems in the same way. He was in the upper echelons of innovative scientists of the era."

Steiner and Rubenstein found that the small part of proinsulin that was sliced away, which they labeled "C-peptide," provided a useful independent indicator of insulin secretion. Circulating proinsulin is also useful for the diagnosis of insulin-secreting tumors of the pancreas. Working with RNA from the insulin gene, Steiner later discovered an even larger precursor of proinsulin, which he labeled preproinsulin.

In 1987, working with Rubenstein and the late Howard S. Tager, Steiner described the first mutations in the insulin gene, now known as insulin Chicago. Such mutations -- there are now more than 30 -- are associated with neonatal diabetes as well as other syndromes that combine mild diabetes and elevated circulating insulin or proinsulin. Working with colleagues in Japan, Steiner subsequently found the first mutation of the insulin receptor. He also contributed to important work on understanding how insulin binds to its receptor.

The discovery of proinsulin is considered "one of the ten most significant scientific achievements ever to occur in Chicago," said Joseph Bass, MD, PhD, professor and section chief of endocrinology at Northwestern University's Feinberg School of Medicine. "Don's idea of a proinsulin radically changed our understanding of signaling peptides. His work was a critical step in the ultimate molecular cloning of this hormone. It is worth contemplating the many millions of people whose lives have been saved by the use of recombinant insulin."

Donald Frederick Steiner was born in Lima, Ohio, on July 15, 1930. Colleagues said his small-town roots shaped his personality.

"He grew up in a family with a strong belief in honesty, generosity and hard work," said Rubenstein. "He respected everyone and never demonstrated an ulterior motive. That, and his scientific brilliance, made him the perfect mentor. He taught me how to do things and then gave me the credit for doing them. That's one reason so many good people flocked to his lab, where he only made them better."

Steiner earned his BS in chemistry and zoology from the University of Cincinnati in 1952, followed by an MS in biochemistry and an MD from the University of Chicago in 1956. He completed his internship at King County Hospital in Seattle, followed by a residency and post-doctoral fellowship at the University of Washington. He was invited to return to the University of Chicago as an assistant professor of biochemistry in 1960. He rose quickly through the ranks becoming professor in 1968 and department chairman in 1973.

He served as Director of the University of Chicago Diabetes-Endocrinology Center (1974-78), as well as associate director (1977-81), director (2000-04) and co-director (2004-14) of the University of Chicago Diabetes Research and Training Center. From 1985 to 2006 he was a Senior Investigator in the Howard Hughes Medical Institute at the University of Chicago.

Steiner published nearly 400 peer-reviewed papers, and his work has been cited by other researchers more than 10,000 times. He won dozens of prestigious national and international honors and awards, often several per year. These include the Lilly Award and the Banting Medal for Scientific Achievement from the American Diabetes Association, the Joslin Medal from the New England Diabetes Association, Israel's Wolf Prize, and, from Japan, the Manpei Suzuki International Prize for Diabetes Research -- the largest financial award for diabetes research. This summer he was awarded the University of Chicago Alumni Medal.

Steiner was elected to membership in the American Academy of Arts & Sciences in 1972, the National Academy of Sciences in 1973, and the American Philosophical Society, the United States' oldest learned society, in 2004.

"In addition to his seminal contributions to science, Don Steiner has had a profound impact at the University of Chicago, particularly on the diabetes program," said diabetes specialist Kenneth Polonsky, MD, Dean of the Biological Sciences Division and Pritzker School of Medicine at the University of Chicago. "The broad implications of his discoveries of the pathways of insulin biosynthesis and secretion placed the University of Chicago at the forefront of diabetes research."

"We know a lot more about diabetes simply because of him," said Louis Philipson, MD, PhD, director of the University of Chicago's Kovler Diabetes Center. "He was an extraordinary mentor for so many people. He combined professional brilliance with the drive to solve hard problems and the capacity, once the job was done, to share the credit. He was a model of how science should be done and how a friend should behave."

Steiner also was an avid patron of the arts, especially the Chicago Symphony Orchestra, and helped support large and small theater companies and the opera, according to his cousin Steve Roess. He was a talented pianist and, in the late 1960s, meticulously assembled a harpsichord in his basement laboratory at the University. He also enjoyed sailing on Lake Michigan, and gardening at his lakeside Michigan cottage.

Despite his accomplishments, Polonsky said Steiner was "an extraordinarily kind, gentle and attentive person."

"He always had time for his staff and colleagues, would answer questions at length and in depth, and was absolutely devoted to this University," Polonsky said. "We miss him profoundly."

"He was an inspiration," said Graeme Bell, PhD, the Louis Block Distinguished Service Professor of Medicine and Human Genetics at the University of Chicago. "We wanted to be like Don Steiner."

Steiner is survived by Ellen Steiner, the wife of his late brother Phares; by his niece Adrienne Steiner, his nephew Paul Steiner, several cousins and many, many friends.

A memorial service is being planned.