Fall 2013

Richard DiMarchi: This is a century of biology as much as the last century was a century of physics and engineering. If you think back to the progress that was made from the time that Lindbergh crossed the Atlantic to the time that Armstrong was stepping on the moon, which is about 40 years, you can see what is phenomenally possible in this decade in our understanding of disease and health. If we can make those same leaps in our ability to treat diseases, this world is going to be very, very different.

My core interest as a chemist, the large molecule chemist focused on macromolecules, I'm passionate about life and the molecular basis of life. In understanding how someone ages. In understanding how someone goes from health to disease. In understanding how we can prevent diseases opposed to treat disease.

One of the things I try to do in my research laboratory is to build interest and confidence. Nothing motivates like success. Nothing demotivates like failure. Trying to connect with the students, understand their level of interest, their need for independence is a vital ingredient in tying them to a research project where they're likely to be successful.

The purpose of a university is to inspire and to educate and I take that responsibility very seriously. Every student is different but they're similar. They are like the fingers on your hand. In isolation, they have only small value but in the context of one another, is where you really get the synergy and the creativity that a university can provide. If you recruit incredibly talented motivated people, then it's just a matter of creating environment where they feel excited about the problem that they're working on and they're self-driven.

I spent nearly 25 years at Lilly Research Labs and it was phenomenal. The technology, the people, the resources: but you know, there's a time in life when one needs to evolve. I've always believed that a person's life can be divided in three phases. A point where you learn, the point where you earn, and the point where you come back to return. I've just been following that philosophy and living it to great fulfillment. I just can't think of a more wonderful time of life and an environment like Indiana University is just so conducive to people's intellectual and personal growth. It's just an honor and a privilege to be here as a faculty member.

Transcript

Richard DiMarchi
Distinguished Professor, Standiford H. Cox Professor of Chemistry,
and Jack and Linda Gill Chair in Biomolecular Sciences

Rocking the World of Chemistry

Among biomolecular scientists, Richard DiMarchi is a rock star.

 

The Indiana University Distinguished Professor would never describe himself that way. But the term fits when you’re talking about someone who holds more than 100 patents, has co-authored more than 150 scientific papers, and whose research has led to effective drug treatments for diabetes and osteoporosis, and potentially for obesity as well.

And all because of an IU education, a talent for thinking differently, and the support of a few generous and far-sighted donors.

The Revolution Starts Here

The last 35 years have witnessed a biotechnology revolution. Richard DiMarchi has been right in the thick of it.

The 1970s were an exciting time to be a protein chemist. Young DiMarchi was recruited to IU’s PhD program by then-chair of the chemistry department, Gene Cordes. “I thought I was headed to a fellowship at Stanford,” says DiMarchi, “but Gene convinced me that if I wanted to study protein chemistry, this was the place to do it. He was right.”

In the early ’70s, biotechnology was in its infancy. “Protein science was mostly an academic discipline then, with limited commercial application,” DiMarchi explains. “But during that time, we learned how to make protein-based molecules. That gave us the ability to manufacture therapeutically useful proteins at commercial scale and acceptable cost.”

That capability opened up a world of possibilities for the young chemist. He converted his IU doctorate into post-doctorate studies at The Rockefeller University and then a 22-year career with Lilly Research Labs, eventually becoming global vice president of biotechnology and product development. There, DiMarchi realized that if you can make proteins synthetically, you can explore their structural properties and start to grasp their biological function.

“The more we understand their biology, the more we can anticipate how we might use these proteins as drugs,” he says. Tinkering with proteins to vary their structure and function proved to be one of DiMarchi’s real talents. As a result, he became a seminal figure in the discovery and development of a number of important protein and peptide-based medicines.

Worldwide Impact

If you know someone with insulin-dependent diabetes, there’s a good chance that DiMarchi’s research has helped improve their quality of life.

While at Lilly, he had an “aha!” moment regarding the hormone insulin, which regulates glucose in the bloodstream. In the 1980s, Lilly had developed an rDNA-based process to biosynthesize human insulin in quantity, a huge breakthrough that provided a virtually unlimited supply for diabetics. (Prior to that, insulin had to be isolated from pigs and cattle.)

DiMarchi realized that if he switched the positions of two amino acids, he could create a new version of insulin—an analog—that actually performed better than the natural form.

The resulting drug, called Humalog®, became the first biosynthetically optimized hormone approved for human use. Millions of diabetics now take it to regulate their blood sugar.  

Humalog’s commercial success led to interest in other protein-based medicines. For example, through another counter-intuitive leap, DiMarchi and research associates at Lilly developed an osteoporosis drug called Forteo®, which actually builds bone mass and helps prevent recurring fractures.

“In many ways,” he explains, “what we do is just molecular architecture. We’re sculpting molecules to have a certain shape, a shape that bestows upon them a particular biological function that benefits people suffering from a particular health problem.”

The Academic Life

In 2003 DiMarchi left Lilly to become the Standiford H. Cox Professor of Chemistry and the Jack and Linda Gill Chair in Biomolecular Sciences at Indiana University. Why? He wanted to train the next generation.

Sierra Seifert
Postdoctoral fellow Chenguang Ouyang (left) and graduate student Sara Brandt at work in DiMarchi’s lab.

“A big part of why I’m at IU, as opposed to a pharmaceutical company or a biotech, is my associates, and particularly the students that I’m training. Drugs will come and go, but the individuals you educate are your true legacy. My graduate students and postdoctoral associates have been centrally important to what we’ve accomplished. My own role is just a fractional portion. It’s the people I’ve worked with who will carry on when I’m gone.

“I’ve also taught introductory biochemistry to probably more than a thousand undergraduates: How many of those have gone on to graduate school, medical school, or other disciplines associated with the biological sciences? I don’t know, but I consider them part of my legacy.”

IU has another appeal, too. “The pharmaceutical and biotech industries are not suited to the kind of experimental work that a university can do—pure exploration, the sorts of crazy things that make other people say, ‘That just won’t work.’ And most times, it doesn’t. But it’s those few successes that constitute the breakthroughs we must have to make progress.”

And that’s where his endowed positions come in.

“There has been no successful revolution, whether political, cultural, or scientific, that hasn’t been appropriately funded,” he argues. “I think the medical advances of the last 50 years will pale in comparison to what we will accomplish in the coming century. Who’s going to fund this work? It’s highly expensive. When people like Linda and Jack Gill or Standiford Cox step forward, they provide the essential resources to educate the students and advance the experimental work in the laboratory. It is the most valuable capital we have, because it comes with no strings attached. That means we can do the wild and crazy things and make the discoveries that we otherwise might not make.”

Still Going Strong

In his 10 years at IU, DiMarchi and his colleagues have not only advanced the chemical science of creating macromolecules, but also brought six different promising drugs to human trials with three pharmaceutical companies. He’s hopeful these drugs will prove beneficial to people suffering from adult-onset diabetes, obesity, and lipid disorders.

So what’s next for the rock star? “I’m excited by the scientific advances that allow us to do molecular architecture we could only dream of 30 years ago,” he says. “The core technology drives the work. Our question now is, can you produce molecules that have non-natural building blocks to create superior drugs?

“We’re currently focused on obesity. This is the disease challenge of our time. Twenty percent or more of the adult population, globally, is clinically obese. I believe the research we’re doing is steadily chipping away at a medicinal solution. This is what propels me to come to work in the morning.”

Rock on, professor. Rock on.

 

Want to know how you can support the next generation of biomolecular rock stars? Contact Tom Recker, assistant dean of advancement for the College of Arts and Sciences, at 812-855-1963 or .

 


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