On the cloudy morning of Monday, Oct. 10, 1994, Dr. Robert J. Lefkowitz was asleep at his home in Durham while, six time zones away, a call was being readied in Sweden.
That year rumors had been swirling that the Duke University Medical Center cardiologist and researcher was a top candidate for the Nobel Prize in Medicine. Since the early 1970s, his discoveries showed how the body sends and detects signals that regulate heartbeat, breathing, vision and other essential functions.
At lunchtime in Sweden, Nobel officials placed a call to the Triangle. But it was not for Lefkowitz.
Instead, the phone rang at the Chapel Hill home of Dr. Martin Rodbell, former director of the National Institute of Environmental Health Sciences (NIEHS). Rodbell would share the prize with Dr. Alfred Gilman—he was a year behind Lefkowitz when they were research fellows in the 1960s—on a topic so close to Lefkowitz's that the Nobel Committee could easily have put the Duke doc in the remaining third slot.
"That was very tough," Lefkowitz says.
In 2004, Lefkowitz continued to be a Nobel favorite, as he had been since the early 1990s. This time, he lost out to scientists whose work he made possible. Again, the Nobel Committee had left a potential third slot empty.
Then this past October, 18 years to the day from the first snub, the news came from Stockholm that Lefkowitz had finally won the Nobel Prize, not in medicine but in chemistry. Because he sleeps with earplugs, Lefkowitz could not hear the phone when it rang and says he was instead awakened by "the elbow" from his wife, Lynn.
Another official came on the line and told Lefkowitz that he was sharing the prize with his former Duke cardiology fellow Dr. Brian Kobilka, who joined the lab in the 1980s. He is now a professor at Stanford University.
Lefkowitz elaborated in his Nobel banquet speech, "For me one of the most poignant aspects relates to sharing this award with a former fellow of mine. This highlights an aspect of science which is very important to both Brian and me—the mentoring of young trainees."
Scientists are not known for being the best personnel managers, with most learning how not to run a laboratory group. Yet Lefkowitz is well known as a caring and motivating mentor, unlike most scientists. While training more than 200 research physicians and scientists during his 40-year Duke career, Lefkowitz led a laboratory team that revealed the molecular heart and soul of the processes most central to our existence.
As a result of Lefkowitz and his team's research, the potential now exists to develop new drugs for human diseases that are more targeted and have fewer side effects.
Around 9:30 on the morning of the Nobel Prize announcement, Lefkowitz was still in his office fielding phone calls from well-wishers and reading the first of 1,500 congratulatory emails. One even came from a fellow Nobel laureate with advice on how to manage the onslaught of attention. Down the hall, the laboratory and administrative staff assembled an impromptu brunch in a conference room. On one of three cakes, the bakery had misspelled "Lefkowitz" but got "Nobel" correctly. Lefkowitz emerged around 11:30 a.m. to join his "scientific family" for the obligatory champagne toast and dozens of pictures.
"There's no one more gracious and open," said Dr. Marti Delahunty, a Duke oncology researcher ,at the toast. She worked with Lefkowitz from 1998 to 2006. "He's always here and he cares. You can tell there's a lot of love here. It's a family."
Lefkowitz's closest friend is Dr. Ralph Snyderman, chancellor emeritus of Duke's Medical Center. He had expressed the same sentiment in his presentation speech for one of Lefkowitz's many awards: "It is hard to imagine how one individual could have possibly achieved so much while being so genuinely loved by his colleagues."
Lefkowitz and Kobilka's research is based on the chemical signals the body uses to regulate itself. Like boats docking to a pier, these signals touch the outside of our cells at points called receptors.
These receptors receive information from both the body and drugs. For example, the body could send signals to pump adrenaline in preparation for a sporting event. And half of the prescription and over-the-counter drugs sold today interact with receptors to perform certain tasks such as relieving pain and allevating asthma.
The Nobel Prize-winning discoveries of Lefkowitz and Kobilka brought this concept down to earth, with real-world applications. Their research involved a large family of receptors called G-protein-coupled receptors, or GPCRs (see "Biochemistry 101: a glossary" in sidebar). They exist in almost all living organisms including plants, insects, bacteria and fungi, dating back almost 1 billion years through evolution.
Lefkowitz describes GPCRs as locks that are fit by keys of particular shapes. These chemical keys occur naturally in the body or can be a drug. They open the door to one or more of the hundreds of processes that regulate almost every imaginable bodily function. Some chemical keys only fit certain locks, or receptors, like those controlling heartbeat or breathing. Others fit those that control mood or appetite. They can stimulate certain processes, block them or do something in between.
So what are real-life versions of these stimulators and blockers? Have you taken pseudoephedrine (Sudafed) for a stuffy nose? The drug works by stimulating the alpha-1 receptor on blood vessels in swollen sinuses.
How about atenolol (Tenormin) for heart conditions? You're blocking beta-1 receptors to make your heart beat more efficiently.
Smoke medical marijuana? The chemicals partially stimulate CB1 and CB2 cannabinoid receptors in the brain.