WASHINGTON, Sept. 21 — Half a century of biomedical advances paved the way for today’s powerful weight-loss drugs like Ozempic. But what was that journey like for the scientists behind it?
Joel Habener of Massachusetts General Hospital and Svetlana Moysov of Rockefeller University, who received the prestigious Lasker Award for their role in the study, told AFP how they made a discovery that is changing the way we think about weight.
The pair will share the award, seen as a harbinger of future Nobel Prize wins, and a $250,000 honorarium with Lotte Bjelle Knudsen of Novo Nordisk, which makes Ozempic.
Early Molecular Biology
Obesity has become a global health crisis, affecting 900 million people worldwide, including more than 40% of Americans and nearly a quarter of Europeans.
But when Mr. Habener, now 87, began his career as a physician-scientist in the mid-1970s, his curiosity was focused on diabetes.
He was particularly interested in glucagon, a pancreatic hormone known to increase blood sugar levels — the opposite effect of insulin, which is already used to treat diabetes.
Habener believed that by understanding and modulating the effects of glucagon, new ways of managing diabetes could be discovered.
To pursue this, he turned to the emerging field of molecular biology, aiming to isolate and clone the gene that codes for glucagon.
Fortunately, he turned to fish.
But he soon ran into an obstacle: the National Institutes of Health banned his planned research into mammalian genetics.
This prompted him to turn his attention to studying anglerfish, which have a unique endocrine organ other than the pancreas.
“It was a godsend in terms of simplicity,” he recalled, describing his eureka moment when he isolated the precursor protein that gave rise to glucagon and a second glucagon-like hormone.
Although Habener didn’t realise its significance at the time, it turned out to be a fish version of GLP-1, the basis of today’s diabetes and obesity medications.
“That’s the beauty of discovery research,” he says. “By exploring the unknown, surprises emerge.”
Identifying the potential of GLP-1
Moysov, who emigrated from Yugoslavia, further developed the earlier findings of Habener and others and made several important contributions.
She meticulously studied the hormone’s structure, accurately predicted the active form of GLP-1, and devised an innovative chemical method to synthesize it.
She also proposed that GLP-1 would be released in the intestine and act to induce insulin production. Together with Habener and others, she proved this theory through laboratory and human experiments and demonstrated its potential therapeutic effects.
“I was convinced it was a drug that could help with diabetes,” says the 76-year-old doctor, but at the time there was no scientific evidence that hormones could regulate weight.
Subsequent research by Habener, Moisov and colleagues first demonstrated that GLP-1 has the ability to slow gastric emptying, interact with receptors in the brain, suppress appetite and even have an effect on drug addiction.
A new era of treatment
Since the 1990s, Knudsen, head of Novo Nordisk’s GLP-1 therapeutics division, and her team have built on these breakthroughs, developing treatments for diabetes (Ozempic) and obesity (Wegovy) that extend the drugs’ therapeutic effects from a few hours to more than a week.
“We now know that GLP-1 actually has a much broader range of health benefits,” says Moisov, though she scoffs at the “miracle drug” label.
Obese patients “have a significant loss of not only weight but also muscle mass, which is also a very serious problem,” she stressed, “and I don’t think they should be taking it for cosmetic reasons.”
GLP-1 drugs are now approved to treat cardiovascular disease, and there is emerging evidence that they may have a preventative effect against dementia.
The exact mechanism is still unknown, but Habener suggests that a commonality may be their ability to suppress inflammatory pathways.
As for the future, Moisov is optimistic: He predicts a new generation of similar drugs will emerge that further minimise side effects and target a wider range of diseases. — AFP
