Indiana University

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Friday, April 13, 2012

Last modified: Friday, April 13, 2012

Richard DiMarchi

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Distinguished Professor

Distinguished Professor and Standiford H. Cox Professor of Chemistry and Linda and Jack Gill Chair in Biomolecular Sciences
Department of Chemistry
College of Arts and Sciences
University Graduate School
Indiana University Bloomington
Appointed to IU faculty, 2003
B.S., Florida Atlantic University, 1974
Ph.D., Indiana University, 1979

The descriptions of Indiana University Distinguished Professor of Chemistry Richard DiMarchi by his peer group are rightfully duplicative. From scientist-executives at several of the world's largest pharmaceutical companies to trustees at some of the nation's greatest universities, reflections invariably include "counterintuitive," "creative," "innovative," "collaborative" and "compassionate." And then, of course, "successful."

"It seems a bit beyond belief, but at this time Merck, Lilly, Roche and Bristol-Myers Squibb are all independently advancing novel drug candidates inspired by association with DiMarchi," says Dr. Suad Efendic, a professor of molecular medicine and surgery at the Karolinska Institute in Stockholm with 20 years of collaborative history with DiMarchi.

He earned his Ph.D. at IU and returned to Indiana after post-doctoral study at the Rockefeller University to begin what would be a 22-year career at Lilly Research Labs. He joined IU in 2003 as the Linda and Jack Gill Professor in Biomolecular Sciences. DiMarchi has generated a long success story: holder of more than 100 patents, co-author of more than 150 scientific papers, seminal presence in multiple Eli Lilly medicines that annually sell in excess of $5 billion (Humulin, Humalog, Humatrope, Evista, Forteo, Glucagon), and co-founder of the IU-licensed Marcadia Biotech, purchased by Roche last year for a reported $537 million, and the La Jolla-based biotech Ambrx.

Considered one of the leading peptide chemists of his age, DiMarchi began his career as a senior research scientist at Lilly. When he left there in 2003 as vice president of biotechnology and product development, he was running one of the world's largest and most successful biotechnology laboratories, overseeing about 2,000 scientists. During the years between, while working at the interface of chemistry and biology, DiMarchi would stamp himself as a pioneer in biotech research, a "drug hunter" who faced down skepticism and established methodologies to create novel medications that could benefit millions of people worldwide.

While at Lilly he developed and commercialized the first rDNA human protein, Humulin. His seminal contribution was the identification that a subtle inversion of two amino acids in the natural sequence of native insulin removed a biophysical limitation that led to the discovery of an insulin analog -- to be trade-named Humalog -- that was a more precise drug than Humulin for glucose control.

In 1996, that new fast-acting insulin became the first rDNA-derived human protein analog approved as medicine. Because of the redesigned insulin molecule, physicians and patients could use Humalog to lower glucose with less risk of life-threatening hypoglycemia and, in turn, prevent long-term kidney, eye and other complications associated with diabetes. That single molecular alteration became a $1 billion-a-year drug and established a precedent for modified proteins that has since been replicated with other popular protein drugs such as erythropoietin, granulocyte-colony-stimulating factor and alpha-interferon.

"His work showed that we as chemists could design something as a therapeutic agent that was superior to a native hormone that had been perfected by evolution," says Peter G. Schultz, Scripps Family Chair Professor of Chemistry at the Scripps Research Institute in La Jolla, Calif.

"There was enormous skepticism that chemical optimization could improve upon the structure of a protein that had evolved selectively over the course of many centuries," notes David Clemmer, the Robert and Marjorie Mann Chair Professor of Chemistry at IU. "His lab was first in recognizing and promoting the fact that rDNA-synthesis could be utilized to prepare analogs of natural proteins that enhance the performance of these natural products. This was truly the beginning of the modern age in protein medicinal chemistry."

The success of Humalog accelerated the development of other insulin analogs, heightened commercial interest in altered forms of other protein-based medicines, and assisted in rendering the regulatory environment more favorable. Another counterintuitive success for DiMarchi was Forteo, the only osteoporosis therapeutic that builds functional bone mass, preventing the risk of recurrent fractures.

Successfully having made the transition from industry to academia, DiMarchi has now focused his IU-based research on GLP-1/glucagon co-agonism. These multifunctional peptides stimulate insulin secretion, suppress appetite and stimulate thermogenesis. This scientific concept constitutes one of the most promising approaches to address the global epidemic of obesity and diabetes.

"He is one of a small group of scientists who has literally conceived of a drug, developed it and experienced its successful marketing," says John D. Diekman, a Princeton University trustee and founder/managing partner of the Menlo Park, Calif.-based 5AM Ventures, which originally financed Marcadia. "He has the unusual ability to convert cutting-edge science into scientific inventions and, subsequently, into real products used by millions of patients."

DiMarchi is, to quote Richard Giedroc, chair of the Department of Chemistry at IU Bloomington, "a nontraditional academic scientist who is simply passionate about translational research yet maintains the highest standards of the academy in professional integrity and scientific rigor."


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