The Lasker Awards, a prestigious set of prizes given for advances in medicine and public health research, were given on Thursday to scientists whose research helped lead to the discovery of a new class of obesity drugs, infectious disease specialists who worked on the drivers of H.I.V. infection and how to stop it, and a scientist who discovered a way the body protects itself from infectious diseases and cancer.
The Laskers are highly regarded in the fields of biomedicine and are sometimes seen as foretelling recipients of the Nobel Prizes in the sciences.
This year’s Lasker-DeBakey Clinical Medical Research Award went to three scientists for their work on GLP-1, the hormone that led to drugs like Wegovy (the same compound is the basis for Ozempic), which have transformed the treatment of obesity. They are Dr. Joel Habener, Svetlana Mojsov and Lotte Bjerre Knudsen.
Each of the three honorees played a role at a key moment: finding the new hormone; finding the biologically active shorter form of GLP-1; and, finally, showing that the shorter form elicits weight loss.
Of course, as almost always happens in science, many others also played key roles, and the Lasker Foundation mentioned some as part of its citation. And one of the honorees, Dr. Mojsov, is receiving what many deem a long overdue recognition.
The story of GLP-1 begins with Dr. Habener, an endocrinologist who arrived in the mid-1970s at Massachusetts General Hospital, where he decided to work on diabetes.
Most of the focus had been on insulin, which lowers blood sugar levels. But there is another hormone, glucagon, that raises it. Dr. Habener decided to try to find the gene for glucagon, hoping it would lead to a way to squelch the hormone and so lower blood sugar.
Working with anglerfish, he discovered a gene for another mysterious protein that resembles glucagon.
The next year, in 1983, another scientist, Graeme Bell of the Chiron Corporation, found the same mysterious protein in hamsters. He called it glucagon-like-peptide-1, or GLP-1.
A young scientist at Massachusetts General Hospital, Dr. Mojsov, was intrigued by GLP-1. She realized that after GLP-1 was made, it was cut by enzymes in the cell to make it into a form that was biologically active. But where was it cut? And after it was cut, where in the body was the active protein found?
Dr. Mojsov speculated, based on her deep knowledge of protein chemistry, that the first six amino acids of the protein chain were sliced off after GLP-1 had been made. Then she proved her speculation using what was, for the time, a very sophisticated chemical methodology.
Next, she synthesized this shorter molecule, the active form of GLP-1.
Now she could ask, Where in the body is it?
The answer, she learned, was that it is secreted in the intestines.
Collaborating with Dr. Gordon Weir, and others in Dr. Habener’s lab, she discovered that GLP-1 acts only on the insulin-producing cells of the pancreas and that it exquisitely regulates blood sugar.
“Gordon called me and said, ‘You won’t believe how active this is,’” she recalled. “‘Very, very small amounts still stimulate insulin production. I have never seen that before.’”
“The final excitement,” she said, was when a colleague, Dr. David Nathan, infused her GLP-1 into patients. He gave her blood samples from the patients to analyze. Some received GLP-1, and others did not.
It was absolutely clear which patients had received GLP-1.
Dr. Mojsov recalled looking at her research assistant and saying, “This is going to be a drug.”
But there was one problem: GLP-1 lasted only fleetingly in the body.
“Its half life was about three minutes,” said Dr. Jeffrey Friedman, an obesity researcher at Rockefeller University and a member of the Lasker committee.
No one, at the time, was thinking of obesity.
That changed when Lotte Bjerre Knudsen, a researcher for Novo Nordisk, saw a research paper by Dr. Stephen Bloom of Hammersmith Hospital in London. In his paper, published in 1996, he reported that when he had injected GLP-1 into rats’ brains, they lost their appetites.
GLP-1 molecules, she realized, had an effect — weight loss — that was separate and distinct from their effect on blood sugar. And that effect could be demonstrated if only the hormone could be made to last longer.
She set to work, coupling GLP-1 to a fatty acid that binds to albumin.
The result was liraglutide, a drug that lasted 13 hours in the body. At first, Novo Nordisk tested it as a diabetes treatment. But Dr. Knudsen insisted on testing it separately as a treatment for obesity.
It was modestly effective.
In 2014, liraglutide, known as Saxenda, was approved for obesity — the first GLP-1 obesity drug.
That opened the door, said Richard DiMarchi, a chemistry professor at Indiana University who worked on successors to GLP-1s.
Novo Nordisk scientists then developed GLP-1 analogs that lasted a week, which led to the semaglutide, or the diabetes drug Ozempic. It was followed by Wegovy, for obesity, which caused an average 15 percent weight loss.
That amount of weight loss was unprecedented, Dr. DiMarchi said. Until then, obesity researchers had thought a 10 percent weight loss was an impossible dream. It was their sound barrier, Dr. Di Marchi said. And now it had been breached, with semaglutide-based drugs expected to face a growing range of competitors in years to come.
The Lasker-Bloomberg Public Service Award will be presented to Quarraisha and Salim Abdool Karim, a pair of South African infectious disease specialists, in recognition of their work to end Africa’s H.I.V. epidemic. The Abdool Karims have led decades of work from their home in Durban, where they founded the Centre for the AIDS Programme of Research in South Africa and have nurtured two generations of African scientists.
The Abdool Karims met as young researchers in apartheid South Africa. They were activists against white rule, determined to use science to address the country’s vast health disparities.
While studying in New York in the late 1980s, they saw the ravages of untreated H.I.V. In South Africa, the apartheid government was suppressing discussion of the virus, Salim Abdool Karim said.
So they went home and conducted the first studies that showed that H.I.V. was spreading fast among South Africans — and that young Black women were most vulnerable. Their findings grimly foretold the devastation that was to come.
“We were scientists taking on the challenge not just for South Africa but for all of sub-Saharan Africa, but we weren’t doing it in New York or Washington, we were doing it while immersed in these vulnerable communities that was our source of inspiration,” Qurraisha Abdool Karim said.
The Abdool Karims have supervised years of research into prevention technologies such as vaginal gels carrying drugs to kill H.I.V., and potential vaccines. These efforts failed, repeatedly, thwarted by the virus. In a recent conversation, Salim Abdool Karim jokingly called H.I.V. “a career killer,” adding, “It’s lucky nobody told us when we started” that 35 years later they would still be trying to prevent the virus from spreading.
Quarraisha jumped in, quietly pointing out that while the failures had been discouraging, they always added to the body of knowledge. “Every time we had negative results, we went back into the lab and said, ‘OK, what did we learn?’” she said.
Recently the Abdool Karims’ research center was part of a clinical trial of a twice-yearly injectable antiviral drug that produced a stunning success — total protection against new infections in young women who had received the shot. Quarraisha said the results were such a shock after so many years of trying that she hadn’t had words to talk about it at first.
“That was a wonderful challenge,” she said.
The Albert Lasker Basic Medical Research Award was awarded to Zhijian Chen of the University of Texas Southwestern Medical Center for his discovery of a way the body senses foreign DNA, like DNA from viruses, inside cells.
Dr. Chen, who goes by James, learned that there is an enzyme that detects foreign DNA or aberrant cancer DNA and attaches to it. That signals the immune system to go on the attack, with an inflammatory response. But it is also a process that can go awry in autoimmune diseases when the enzyme mistakenly attaches to normal cellular DNA.
The Lasker committee said Dr. Chen’s discovery “holds promise for fighting infectious diseases and cancer, and for managing autoimmune diseases.”
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