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Nobel in Duke's DNA: Paul Modrich becomes second standing faculty member awarded the Nobel Prize

<p>For the second time in four years, a Duke professor in biochemistry was awarded the Nobel Prize in Chemistry.</p>

For the second time in four years, a Duke professor in biochemistry was awarded the Nobel Prize in Chemistry.

Paul Modrich’s Nobel Prize win is a huge victory not only for him and for Duke, but also for all fields of basic research, administrators and colleagues said.

Modrich—James B. Duke professor of biochemistry, member of the Duke Cancer Institute and Howard Hughes Medical Institute investigator—was awarded the 2015 Nobel Prize in Chemistry Wednesday, along with Aziz Sancar of the University of North Carolina at Chapel Hill and Tomas Lindahl of the Francis Crick Institute in the U.K. The researchers were honored for their discoveries of three different fundamental mechanisms of DNA repair—a critical process in maintaining the integrity of many organisms’ DNA. The research has potential applications in fighting cancer and other diseases.

Modrich is the second standing faculty member in Duke’s history to win a Nobel Prize and also the second professor from the department of biochemistry, after Dr. Robert Lefkowitz, James B. Duke professor of medicine and professor of biochemistry and immunology, received the same award in 2012 for his work on G-protein-coupled receptors.

“I have to say this acknowledgment is shared by graduate students and others in my lab. I want to thank the biochemistry department at Duke for giving me a scientific home,” Modrich said during a press conference held Wednesday at UNC to honor the Nobel Prize winners. Modrich called into the conference while away on vacation in New Hampshire.

Modrich has been a Duke faculty member since 1976 and has studied the molecular machinery of DNA for most of his career, prompting Richard Brennan, James B. Duke professor of biochemistry and chair of the biochemistry department, to describe him as “a homegrown Duke biochemist.” Modrich’s discovery of the mismatch repair mechanism demonstrated how errors made during DNA replication are corrected and paved the way for further understanding of cancer and many other diseases.

“This is the most exciting kind of honor that any university can get,” said Michael Schoenfeld, vice president for public affairs and government relations. “The fact that Professor Modrich was elected for the most prestigious science prize in the world is a great honor for him, but also a great honor and reflected glory to Duke and to all of the faculty and students who have worked with him over the years.”

Nancy Andrews, dean of the School of Medicine, noted that Modrich’s work “is of fundamental importance to understanding cancer and other serious diseases.”

“This is an extremely proud moment for Paul and his laboratory and for all of Duke and shines a spotlight once again on the outstanding science here,” she wrote in an email.

Although the applications of Modrich’s work to cancer medicine and many other fields of biomedical research are significant, Lefkowitz noted that Modrich’s win is also a boost for basic science, which is the pursuit of understanding essential scientific processes and phenomena without focusing on immediate applications or treatments for diseases.

“It is simply driven by the curiosity of a scientist to understand a basic process,” he said.

Second win

Robert Lefkowitz said that becoming the first Nobel laureate at Duke was a “remarkable experience that changed [his] life.” As Modrich is the second Duke faculty member to win the award in four years, Lefkowitz expressed his hope that the number of Nobel laureates coming out of Duke might start to catch up to that of the older top-10 universities.

“It’s impressive—we’ve never had anybody and now we have two,” he said.

Despite the close proximity of two of this year’s Nobel Prize winners and the academic collaboration between Duke and UNC, Dr. Michael Kastan, executive director of the Duke Cancer Institute, noted at the press conference that having two researchers from Duke and UNC in the same field win the same award is a coincidence.

Modrich’s and Sancar’s work with different DNA repair mechanisms was independent, though Sancar, Sarah Graham Kenan professor of biochemistry and biophysics at UNC, said at the press conference that they have published three papers together and are friends. Sancar also noted that he has nominated Modrich for the Nobel Prize in each of the past 10 years.

“Even though we all hate Duke, I was expecting Paul [Modrich] to get it,” Sancar joked.

Schoenfeld said the awards reflect not only the strength of research at Duke, but the strength of research in the Triangle area.

“It’s a very exciting day for Duke, and it’s equally exciting because one of the other recipients is a professor at UNC,” Schoenfeld said.

The importance of basic science

Modrich has been an investigator at the Howard Hughes Medical Institute—a nonprofit organization with an endowment of $19 billion dedicated to funding scientists—since 1994. HHMI Senior Scientific Officer Bodo Stern explained that the mission of the HHMI is to provide long-term support to scientists, rather than focus on specific projects.

“We supported his work in studying the basics of mismatch repair, and nobody could’ve guessed that it would have had anything to do with cancer, but it laid the foundation to find later that these proteins are important in colon cancer,” he said.

Kastan described the implications of Modrich’s work in colon cancer at the press conference Wednesday. Given the essential role mismatch repair plays in correcting DNA errors, defects in this mechanism are the cause of the most common form of hereditary colon cancer and may also lead to certain neurodegenerative diseases and other cancers.

The other researchers who received the prize discovered related mechanisms for DNA repair. Lindahl’s research provided the initial insight that DNA requires more complex repair mechanisms than were previously known. He also discovered a type of repair mechanism known as base excision—in which pieces of DNA are removed during the repair process. Sancar’s research focused on DNA repair in response to ultraviolet radiation damage.

Stern added that Modrich is the type of scientist the HHMI wants to support, given his decades of work delving into a specific biological problem and the impact of his discovery. Modrich’s success also exemplifies the importance of basic science, or discovery science, in a scientific community that increasingly focuses on research that can have near-term applications, Stern said.

“It’s definitely a notion that’s a little bit in retreat, but we are really emphasizing to others that support for basic science is really the foundation for any translational science,” Stern said. “Mainly because we don’t really know where the breakthroughs will happen or where new therapies will come from, so it really is important to fund basic science broadly.”

Brennan emphasized that all three Nobel Prize wins demonstrate the enormous impact that discovery science can have on later outcomes and human health.

“That should be a major wake-up call to the rest of the research community in the U.S.—the fact that they won the Nobel Prize working on basic science,” he said. “I hope the NIH and our senators from North Carolina understand how important it is to fund basic research, because you never know what’s going to come out of it.”

In addition to potentially influencing colleagues and politicians, Modrich’s win will serve to highlight the importance of basic science to young scientists and companies looking to invest in research, Brennan explained. He hopes adding another Nobel laureate to Duke’s faculty will attract more scientists to the University.

“It was the reason why we came here to Duke,” he said. “We saw these great people and now it’s even better.”