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The road to a Nobel Prize: Robert Lefkowitz writes memoir, reconnects with roots

<p>Robert Lefkowitz (right) shared the 2012 Nobel Prize in Chemistry with his mentee Brian Kobilka (not pictured).</p>

Robert Lefkowitz (right) shared the 2012 Nobel Prize in Chemistry with his mentee Brian Kobilka (not pictured).

Over dinner at the Brodhead Center after a Duke men’s basketball game, Robert Lefkowitz’s former research fellow Randy Hall said that Lefkowitz should write up his stories into a book. 

With fellow Nobel Laureate Richard Feynman’s “Surely You're Joking, Mr. Feynman! Adventures of a Curious Character” as inspiration, Lefkowitz, James B. Duke distinguished professor of medicine and a professor of biochemistry, pathology and chemistry, began weekly phone calls with Hall to write his memoir. 

Lefkowitz’s memoir “A Funny Thing Happened on the Way to Stockholm: The Adrenaline-Fueled Adventures of an Accidental Scientist” is set to be released in February of next year. The story builds up to the 2012 Nobel Prize in Chemistry, which he shared with his mentee Brian Kobilka. He also shares his experiences as a trained cardiologist who was diagnosed with a heart disease. 

“My book goes through my childhood, Bronx High School for Science, undergrad at Columbia, medical school, my time at the National Institute of Health and, of course, Duke is the major part,” Lefkowitz said. 

The past three years

Since I profiled him in 2017, Robert Lefkowitz has been successful in the rigorous process of renewing his Howard Hughes Medical Institute funding. With 44 years under his belt as an HHMI investigator, his goal is to make it to 50 in 2026.

He has also since completed his bucket list goal of reconnecting to his family history in Poland, where many of his relatives died in the Holocaust. In a chapter titled “Roots,” he discusses his grandparents, who immigrated from Częstochowa, Poland, in 1904. 

“I was carrying, in my back pocket an invitation to speak at the Polish Academy of Sciences,” Lefkowitz said. “I wasn’t really going to go, but you know, as I was turning 75, there aren’t that many years left if I’m going to visit. So I gathered up a couple of my cousins and my wife, and we went.”

As an avid Duke basketball fan, Lefkowitz emailed men’s basketball head coach Mike Krzyzewski while he was there. Krzyzewski wrote back and said that his family was not from the same town but was from the same general area in Poland, Lefkowitz said. 

The Nobel prize

Lefkowitz and Kobilka’s research on G-protein-coupled receptors (GPCRs)—the target of about one-third of all drugs today—earned them the Nobel Prize in Chemistry in 2012. Lefkowitz is currently researching biased signaling, which looks at how drugs working through the same GPCR can signal through different pathways. 

In investigating whether there is more than one active conformation, or shape, of a receptor which transmits a signal into a cell, Lefkowtiz described the amount of failure as “colossal.” He credits much of the hard work to Laura Wingler—a former post-doctoral student in his lab and current assistant professor of pharmacology and cancer biology at Duke. Wingler spearheaded a program using cutting-edge biophysical techniques to map the GPCRs with atomic-level resolution, something in which Lefkowitz had no experience five years ago.

“We wouldn’t have thought this was possible before because we always used to think there were two forms of a receptor, active and inactive,” Lefkowitz said. “[This research can lead to] the design of even more selective and effective drugs going forward.” 

A message for students

I pointed out to Lefkowitz that the last time I interviewed him for the Chronicle was when I was 18 and a first-year, and now I’m 21 and about to graduate. 

“The difference between 18 and 21 is huge,”  Lefkowitz said. “The difference between 74 and 77 is just a few more aches and pains—and perhaps you picked up a disease or two—but that's about it.”

“You’re all on the way up, and I’m on the way down. Such is life.”

Lefkowitz hopes students—especially those with budding interests in medicine, biology or research—can find some inspiration and takeaways from his memoir. Here is some advice he wanted to highlight:

  • Keep an open mind about how your career will take shape.
  • Being optimistic and open to the gift of serendipity means that you need to be looking for it. The nature of serendipity is that you can’t make it happen. 
  • Always be charged up for what is waiting for you. Go in every morning with a sense of expectation that something good is coming. “Most days it wasn’t true, but other days it was,” Lefkowitz said. “Some of the things I consider the most wonderful happenings might have just passed me by if it weren’t for the fact that I was looking every day for something wonderful and exciting.”
  • On persistence and grit: Research is mostly failure. “One of the most important things I do as a mentor is to help support my trainees through all the failures, because research is mostly failure.” You also sometimes need to know when to give up on something, at least for the time being.
  • Mentorship and lineages in science highlight the importance of young people’s wisely choosing mentors and seeking the counsel of people they respect. When you look at extraordinarily successful people, it’s almost invariable that they trained with someone successful. 
  • Research is a shared experience. Being able to share the journey provides an overwhelming sense of accomplishment—and it doesn’t have to be a Nobel.

A need for physician-scientists

“At 77 years old, if it wasn’t for the pandemic, I’m as active as I ever was,” Lefkowitz said.

Like everything else at Duke, Lefkowitz’s 5 p.m. “TGIF lab get-togethers” over porters and politics have moved onto Zoom. He’s still giving lectures around the world, albeit virtually. 

“The reality is that it’s not the same spontaneity as sitting there at 5:30 in the afternoon and one of the kids in the lab says, ‘Hey boss, take a look at this,’” Lefkowitz said. “That’s what I miss.”

An interesting aspect of his memoir, especially during the pandemic, is how physician-scientists can live with one foot in each of those two worlds, he said. How he and an entire generation of physician-scientists came about mostly boiled down to serendipity and an NIH program that shaped the American landscape of success in scientific research and discovery.

During the Vietnam War, the NIH Associates Training Program was created to allow young physicians to spend two or three years doing research under the guidance of senior NIH investigators instead of being drafted into the war. These young scientists called themselves the “yellow berets,” and if it were not for that experience, Lefkowitz would have ended up as a practicing physician. 

Nine physicians in this program went on to win Nobel Prizes. The class of 1968 alone included Lefkowitz; three other Nobel laureates; and Anthony Fauci, the now-famous director of the National Institute of Allergy and Infectious Diseases.

Lefkowitz’ memoir also described the “magical” Nobel week in Stockholm. The 10 days of celebration is generally preceded by a stopover to see the president of the United States. 

“At least you did before Trump,” Lefkowitz said. “He has not invited the Nobel laureates, who probably wouldn’t go—one of the many anti-science things.”

The year-and-a-half of primary writing was all done before the pandemic, but his memoir includes some excerpts on Fauci, who is now perhaps America’s most renowned public health figure.

“He’s my age and we’re good friends,” Lefkowitz said. “We were yellow berets together at the NIH in 1968 for two years. I tell some stories about Tony and have some pictures of us together in the book.”

In the half-dozen times Lefkowitz has been in touch with Fauci since the pandemic started, Lefkowitz always got an automatic response which read along the lines of “I’m overwhelmed and can’t answer personal emails.” And then an hour or two later, Fauci would send a personal response. 

“One of the things that emerges from this book is the importance of having physician-scientists,” Lefkowitz said. “Tony is the quintessential physician-scientist, but he’s about to turn 80.”

“The question is where is the next physician-scientist going to come from?”

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