Lefkowitz on Failure and Success in Medical Research

Nobel Prize-winner traces the highs and lows of his career in a public conversation

Part of the Lefkowitz Wins Nobel Prize Series
Robert Lefkowitz discusses his research on cell receptors with President Richard H. Brodhead. Photo by Jared Lazarus/Duke University Photography
Robert Lefkowitz discusses his research on cell receptors with President Richard H. Brodhead. Photo by Jared Lazarus/Duke University Photography

A Duke research scientist who has earned the greatest rewards of success spent an hour Thursday talking a lot about failure.

In a public conversation with President Richard H. Brodhead before an estimated 250 people, 2012 Nobel Prize winner Dr. Robert Lefkowitz spoke about the importance of failure in his research, a side of successful medical scholarship that rarely gets attention.

"Science is 99 percent failure, and that's an optimistic view," said Lefkowitz, a Howard Hughes Medical Institute investigator who has spent his entire 39-year research career at Duke.  His research on cell receptors provides the basic science foundation for an estimated half of all drugs used for medical treatment.

Lefkowitz first planned to be a clinical physician, but a two-year research hitch at the National Institutes of Health gave him a taste of research.  The first year, he said, he did nothing but fail.

"It almost drove me out of research.  After that first year, I made arrangements to return to clinical training.  But by the end of the second year, I had tasted some success and would have preferred to stay on in research," he said.   

"The fact is I hadn't yet learned to deal with the frustration that comes with failure.  But if you are asking big questions you have to be prepared to fail.  That's one of the most difficult things for young researchers to come to grips with."

Learning from disappointment was essential to his ultimate success, Lefkowitz said.  "As with everything in science and life, you have to find your own way.  For me I focus on what is working.  It's a lot easier for me, now that I have a group of people working in my lab.... The bottom line is more you go through failure and come back through it, the more helpful it is."

He said that at the end of each year he reviews his lab's results and if there's too much success, "I'm not a happy person."

"It means we're not asking the right questions," he said. "However, I think a lot of my fellows in the lab would agree we're asking the right questions right now, because we're facing a lot of failure!"

The public conversation in Griffith Film Theater followed the format Brodhead has initiated with the Duke Idea tours in which he discusses critical issues with Duke faculty around the country before alumni audiences.

Brodhead said that after he saw how the campus was "lifted up in reflected glory" after Lefkowitz won this year's Nobel Prize in chemistry, he thought "why do that just in San Francisco; Why not do it in our hometown with our homeboy?"

Lefkowitz said one of the pleasures of the award was that he could bring this to Duke, noting that he is a "Dukie through and through."

Speaking with relaxed humor, Lefkowitz talked about early resistance he faced from established researchers when he started achieving results on cell receptors.  When he started the work, the idea that cell receptors even existed was still controversial.

He also discussed the more than 200 students who have passed through his lab, many of whom have gone on to become leading researchers in their own right.  He shared the Nobel Prize with Brian K. Kobilka of Stanford University School of Medicine, a former Duke faculty member who trained at Duke under Lefkowitz.

Brodhead recalled that Lefkowitz had told him one question he asks of some potential students is, "Are you lucky?"

"What I'm looking for is real work ethic and a sense of optimism, and these things are not easy to evaluate in a day," Lefkowitz said.  "I believe in self-fulfilling prophecies: You make your own luck.  If you believe you are lucky, you will end up better than people who believe life is raining on them."

Lefkowitz mused that he and Kobilka have, vastly different personalities, strengths and weaknesses, but succeeded in the lab together.  "Everyone has strengths and weaknesses.  The role of the mentor is to help students find out what their true gifts are and enable the students to tap into that and play to their strengths while addressing the adverse consequences of their weaknesses."

While Lefkowitz and Kobilka both had been repeatedly mentioned as possible Nobel winners, the award came in chemistry, not medicine. Lefkowitz doesn't have a Ph.D. and isn't a chemist -- at least not officially.

But earlier this week, Lefkowitz received a letter from the CEO of the American Chemical Society (ACS), the largest national professional association in chemistry.  The letter invited him to join ACS and included a personal check from the CEO made out to the ACS that would cover Lefkowitz's initiation dues.

Then a few days ago, the chair of Duke's Department of Chemistry invited him to join the department faculty.  Lefkowitz noted he was thrilled by the offer and accepted "as long as I don't have to go to the faculty meetings."

Below: Nobel Prize-winner Robert Lefkowitz takes questions from the audience during a public conversation Thursday in Griffith Film Theater.  Photo by Jared Lazarus/Duke University Photography

Robert Lefkowitz takes questions