By Rolfe Winkler
Joel F. Habener, a Harvard University academic whose research paved the way for revolutionary weight-loss drugs Ozempic, Mounjaro and others, which analysts forecast will be the biggest blockbusters in pharmaceutical history, died Sunday in Newton, Mass. He was 88.
Eileen Martin, a friend of Habener's, said he died peacefully at home. She didn't give a cause.
Habener led research that discovered a hormone dubbed GLP-1. The hormone regulates blood sugar levels and would later become the key ingredient in Novo Nordisk's Ozempic and Eli Lilly's Mounjaro -- drugs that proved a major advance in diabetes treatment and so effective at regulating appetite that people who take them have called them miracle cures for obesity. Others taking the drugs say they cure addictions to nicotine, alcohol and gambling.
Two crucial discoveries
Habener and his collaborators made two crucial discoveries, the existence of the hormone itself, which they found in a bottom-feeding fish, and later the hormone's function as a so-called incretin, a substance that stimulates insulin production. It would take years and additional discoveries made by others to synthesize the hormone into an effective drug and to determine doses that didn't make patients vomit.
The drugs that mimic GLP-1 and other, similar hormones have driven Eli Lilly's market capitalization above $1 trillion and also lifted the fortunes of Novo Nordisk. The flood of dollars going to Denmark, where Novo is based, at one point forced the Danish central bank to keep interest rates artificially low to prevent its currency from spiking in value.
Habener was elected to the National Academy of Sciences, received the Canada Gairdner International Award, the Breakthrough Prize and the Lasker Award, and has been nominated for a Nobel Prize.
Sneaking into Disneyland
Joel Francis Habener was born in Indianapolis on June 29, 1937. His father, Arthur, was an engineer working on bombsight technology, but was laid off when World War II ended, and he moved the family to Anaheim, Calif. Habener recalled in a 2025 interview how, during high school, he and his friends sneaked into Disneyland while it was still under construction to play on rides.
He studied medicine at UCLA where the highlight of his studies was a fellowship program doing autopsies. Habener did dozens of them over the course of a year, cementing his interest in research. He also met a lab technician, Ann, who would become his wife. "That was a lucky break," he recalled.
When he arrived in Massachusetts for his first fellowship studying parathyroid hormone, Habener found a ready source of thyroid glands to study from a local Cambridge slaughterhouse that supplied calf meat. Habener recalled how he and a colleague would arrive at the facility where a table full of severed calf heads awaited them.
In 1978, Habener set up his own lab at Harvard's Massachusetts General Hospital, looking to capitalize on a new technology for cloning genes by studying pancreatic and other hormones. Recombinant DNA technology, as the method was called, allowed researchers to quickly identify the structure of hormones that are encoded by genes.
But the method required splicing DNA of different organisms and using bacteria to propagate samples. That created fears among some researchers that lab leaks might harm the public. The city of Cambridge restricted the technology as a result. Two of Habener's postdocs found an alternative. They weren't allowed to experiment with mammals, including rats, so they isolated tissue samples from anglerfish, the carnivorous bottom-feeders with razor sharp teeth. Inside the pancreatic tissue of these fish, the team found the genetic blueprint for unidentified hormones. One of these was GLP-1.
At first they didn't know the hormone's function. Research spearheaded in the mid-1980s helped determine that a truncated form of GLP-1 spurred insulin release, setting off a two-decade journey to turn the hormone into an effective diabetes treatment.
Avoiding nausea
The first problem scientists encountered was that the human body breaks down GLP-1 quickly. It took years to discover formulations that would remain in the bloodstream long enough to have a therapeutic effect. The second problem, as several early studies showed, was that GLP-1 given in large doses caused patients to vomit, foreshadowing the primary side effect of today's blockbusters. The solution was starting out with a small dose and working up.
The first treatment to closely match the human hormone, Novo Nordisk's once-daily shot Victoza, received approval from the Food and Drug Administration in 2010. Ozempic would prove more effective for weight loss and only needed to be taken once a week. It was approved in 2017.
Habener is survived by his younger brother Stephen. His wife Ann passed away in 2017.
Write to Rolfe Winkler at rolfe.winkler@wsj.com
(END) Dow Jones Newswires
December 29, 2025 13:27 ET (18:27 GMT)
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