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InterviewYellow Beret program graduated 10 future laureates and Fauci

How a Nobel-winning ‘accidental scientist’ changed the world by saving himself

Robert Lefkowitz documents his career, culminating in a discovery used in 50% of FDA approved drugs in new memoir, ‘A Funny Thing Happened on the Way to Stockholm,’ out this month

  • This photo of Dr. Robert Lefkowitz in his office at Duke University captures a pose that all of his trainees will undoubtedly find familiar: feet up on the desk, smile on his face, exulting over the latest data. (Courtesy)
    This photo of Dr. Robert Lefkowitz in his office at Duke University captures a pose that all of his trainees will undoubtedly find familiar: feet up on the desk, smile on his face, exulting over the latest data. (Courtesy)
  • Dr. Brian Kobilka, left, with Dr. Robert Lefkowitz at the post-Nobel Prize lecture they gave. (Courtesy)
    Dr. Brian Kobilka, left, with Dr. Robert Lefkowitz at the post-Nobel Prize lecture they gave. (Courtesy)
  • Dr. Robert Lefkowitz shakes hands with former president Barack Obama in 2012 prior to departing to Sweden to accept the Nobel Prize. (Courtesy)
    Dr. Robert Lefkowitz shakes hands with former president Barack Obama in 2012 prior to departing to Sweden to accept the Nobel Prize. (Courtesy)
  • Dr. Robert Lefkowitz, speaking at center right, with Dr. Anthony Fauci at center left. The two served together for a decade on the Council of the Association of American Physicians during the 1990s. (Courtesy)
    Dr. Robert Lefkowitz, speaking at center right, with Dr. Anthony Fauci at center left. The two served together for a decade on the Council of the Association of American Physicians during the 1990s. (Courtesy)

Dr. Robert Lefkowitz vividly remembers the life-changing early-morning phone call he received from Stockholm almost nine years ago. At age 69, after decades of research work, he learned that he had finally received the ultimate honor, the Nobel Prize.

Now the Jewish-American scientist and 2012 laureate in chemistry is reflecting on his lifetime of achievement in a new memoir, “A Funny Thing Happened on the Way to Stockholm: The Adrenaline-Fueled Adventures of an Accidental Scientist.”

“For anybody who’s won a Nobel Prize, that call is an amazing experience,” Lefkowitz told The Times of Israel. “You know in that moment your life is about to change forever.”

Lefkowitz — and his former postdoctoral fellow Brian Kobilka, who shared the prize with him — got to attend the Nobel ceremony and banquets, the culmination of a 10-day stretch of festivities in Sweden that he compares to Super Bowl Sunday. Lefkowitz — who has been on the faculty of Duke University Medical Center since 1973 — was honored by the university’s legendary men’s basketball coach, Mike Krzyzewski, at a ceremony in which students chanted, “He’s so smart!” He threw out the first pitch at a minor league baseball game in Duke’s hometown of Durham, North Carolina, but, alas, a similar opportunity did not work out with his beloved New York Yankees.

Lefkowitz has been a Yankees fan since his days growing up in the Bronx. He graduated from the prestigious Bronx High School of Science and Columbia University, where he attended both undergrad and medical school. In the 1960s, with a fellow new doctor named Anthony Fauci, Lefkowitz participated in a unique Vietnam War-era government program for recent med school graduates.

Dr. Robert Lefkowitz, center, with his parents at his graduation from Columbia Medical School. (Courtesy)

A chapter in the book describes Lefkowitz’s family connections to the Holocaust. Although his grandparents escaped Poland decades before World War II, other family members perished in the Shoah. Lefkowitz visited his forebears’ hometown of Czechostowa, Poland, encountering an abandoned Jewish cemetery that included gravestones of family members.

Lefkowitz co-authored the book with another former postdoc of his, Randy Hall. He said he hopes that fellow scientists will read it, but also lay readers and, perhaps, young people interested in becoming a physician-scientist like himself.

The Yellow Berets

It was the Vietnam War that turned Lefkowitz into a researcher. He had married his first wife, Arna Gornstein, and started a family. He said that he was reluctant to be drafted into what many considered an illegal, immoral war and an alternative presented itself in the US Public Health Service, a program through which recent med school grads could work for the government for two years. In Lefkowitz’s case, the work was at the National Institutes of Health.

Dr. Robert Lefkowitz with the ‘Yellow Berets’ in a 1968 US Public Health Service photo of the staff of the National Institute of Arthritis and Metabolic Diseases,as it was then known. Two other Yellow Berets pictured would later go on to win Nobel Prizes: Harold Varmus, top row, third from left, and Mike Brown second row, second from left. (Courtesy)

Although participants were jokingly nicknamed the Yellow Berets, admittance was rigorous. Those accepted in the same year as Lefkowitz included three other future Nobel laureates  — Harold Varmus, Michael Brown and Joseph Goldstein — and Fauci. In its eight years of existence, the program enrolled 10 laureates-to-be.

Decades later, Fauci and Lefkowitz served successive terms as president of the Association of American Physicians. Lefkowitz said that Fauci — whom he calls “a good friend” — works “tirelessly” overseeing the COVID-19 response in the US, and is “pretty remarkable” given that he is 80 years old.

Lefkowitz says the hybrid physician-scientist is increasingly rare. He laments that only one percent of physicians are identified with any research today.

“The problem recently is where will the next Tony Fauci come from,” Lefkowitz said.

The receptors that snagged a Nobel

Much of Lefkowitz’s own research over the past 50 years has had to do with a part of a cell called receptors, which he said are necessary for a drug or hormone to work.

“I devoted my career,” he said, “trying to understand and clarify, study the nature of hormone and drug receptors. When I started out, there was no consensus such things existed.”

Dr. Robert Lefkowitz, speaking at center right, with Dr. Anthony Fauci at center left. The two served together for a decade on the Council of the Association of American Physicians during the 1990s. (Courtesy)

In a step forward, he proved the existence of one kind of receptors called beta adrenergic. “Adrenergic,” he explained, is derived from “adrenaline.”

The early 1980s were adrenaline-raising times as Lefkowitz’s team competed with rivals from other institutions, including the Hebrew University of Jerusalem.

“Trying to clone the gene for the beta receptor gets highly technical and very difficult,” Lefkowitz said. “In the book, there are some chapters about how intense the competition was.”

Not only did Lefkowitz succeed, he discovered that beta adrenergic receptors are part of a larger family called G-protein-coupled receptors or GPCRs. His studies of GPCRs are what ultimately earned him the Nobel Prize, according to the Nobel website.

This photo of Dr. Robert Lefkowitz in his office at Duke University captures a pose that all of his trainees will undoubtedly find familiar: feet up on the desk, smile on his face, exulting over the latest data. (Courtesy)

“Other scientists got in the game, using technologies we developed,” Lefkowitz said. “It became clear the family is numerous, with 1,000 different receptors. They mediated all physical processes in humans and other mammals… how we see, how we smell, how we taste… at least three of the five senses.”

Of the long-term implications, Lefkowitz said, “I think the most important one is, these receptors are very druggable” and a focus of about half of all FDA-approved drugs in the US.

He also discovered a process involving receptors called desensitization, describing this as a mechanism through which a receptor is turned off from receiving a signal from a hormone or drug. This discovery has “led to the development of novel types of drugs,” he said.

‘A Funny Thing Happened on the Way to Stockholm,’ by Dr. Robert Lefkowitz and Randy Hall. (Courtesy)

Both of his findings — GPCRs and desensitization — occurred during the same 12-month span, from 1986-87.

“It’s amazing sometimes how things really do come together,” Lefkowitz said. “We made two really important, seminal discoveries in that year.”

Throughout his career, he recalled, “people had been telling me, ‘Bob, for sure you’re going to win the Nobel Prize.’ … [Years] went by. It did not happen.” By the mid-2000s, he said, “I pretty much came to the conclusion that I was not going to get the prize.”

That changed on an October morning in 2012, with a 5 a.m. phone call from Stockholm.

“I had a pretty good idea before I even got on the phone,” Lefkowitz said. “Sure enough, it was the head of the chemistry prize committee.”

“It was an amazing experience to get the call,” Lefkowitz added, noting that for the rest of the day “the phones are ringing … there are press conferences and people calling to congratulate and 1,500 emails from co-workers.”

In his first-person biography on the Nobel website, Lefkowitz notes that in 2012, he was among the 33 Nobel winners to date who were Jewish and had attended New York City public high schools, with many having family roots in the Eastern European Jewish migration from 1881 to 1924. The list includes a fellow 2012 laureate, Dr. Alvin Roth, a co-winner in economic sciences.

Super Nobel Sunday

The Nobel ceremony takes place on December 10, the anniversary of Alfred Nobel’s death and a national holiday in Sweden. Before the trans-Atlantic trip, Lefkowitz participated in a tradition for American Nobel laureates — a meeting with the president before going to Sweden. Lefkowitz got to meet then-president Barack Obama, which he called a great privilege and pleasure.

Dr. Robert Lefkowitz shakes hands with former president Barack Obama in 2012 prior to departing to Sweden to accept the Nobel Prize. (Courtesy)

As for his 10 days in Sweden, Lefkowitz remains in awe, from the endless balconies of the great hall where the ceremony is held to the subsequent banquet for 1,500 people, and the separate banquet the next night hosted by the Swedish king and queen.

The prize itself consists of an 18-karat gold medal and a diploma featuring Swedish calligraphic writing and art. A painting of his prize hangs in his office at Duke.

Laureates give two speeches — a Nobel lecture focusing on their prize-winning achievements and a talk in which they can address other themes, akin to an acceptance speech. In Lefkowitz’s acceptance speech, he criticized an unnamed American political party for denying science, from climate change to vaccines. The live TV commentary in Swedish stated that he had criticized the Republican Party.

Dr. Brian Kobilka, left, with Dr. Robert Lefkowitz at the post-Nobel Prize lecture they gave. (Courtesy)

“At no point did I say ‘Republican Party,’” Lefkowitz noted, adding that the Swedish media “follow our politics closely enough.”

“A lot of people think Trump invented an anti-science bias in government,” Lefkowitz said. “It’s not true at all. It preceded him. He raised science denial to an art form, but it existed well before him. Unfortunately, it has been a staple of the Republican Party for some time.”

In contrast, he said in his talk, “Swedish heroes are scientists and intellectuals. They take such pride in Nobel winners.”

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