The Breakthrough Prize Foundation announced the winners of the 2025 Breakthrough Prizes in Life Sciences today, April 5, 2025. The prizes honor achievements by researchers working in the fundamental sciences. This year, the committee awarded eight scientists three Life Science prizes for their research in diabetes and obesity, multiple sclerosis, and DNA editing.

Daniel Drucker, Joel Habener, Jens Juul Holst, Lotte Bjerre Knudsen, and Svetlana Mojsov share a Breakthrough Prize for their work on the foundational research to the pharmaceutical development of the GLP-1 drugs to treat type 2 diabetes and obesity.

For their contributions to understanding the causes and underlying biology of multiple sclerosis, Stephen Hauser and Alberto Ascherio share a Breakthrough Prize.

Finally, David Liu was awarded a Breakthrough Prize for developing base editing and prime editing, two DNA editing technologies that can correct mutations that cause genetic diseases.

These researchers’ accomplishments represent important advances in life sciences and in improving human health and wellbeing.

Discovering a small peptide hormone with boundless potential

By Allison Whitten, PhD

Today’s wildly successful GLP-1 drugs got their start in an unexpected place: the pancreas of the deep-sea anglerfish, known for the fishing pole-like rod jutting out from its head. In the early 1980s, endocrinologist Joel Habener at Harvard Medical School and Massachusetts General Hospital cloned the gene for glucagon — a peptide hormone that raises blood sugar levels — using mRNA from the pancreatic islet cells of anglerfish caught nearby off the coast of Massachusetts. With this new data in hand, his team soon noticed an additional mysterious sequence in the DNA that could produce another peptide. “We didn't know if it even existed, but it was predicted to be produced by the DNA sequence,” said Daniel Drucker, an endocrinologist at the Lunenfeld-Tanenbaum Research Institute and former postdoctoral fellow in Habener’s lab. “It was similar to glucagon, but different.” They decided to call it a glucagon-like peptide (GLP).

After further investigations in collaboration with Svetlana Mojsov, a chemist at The Rockefeller University who was then working at Massachusetts General Hospital, the scientists introduced the genetic sequences into rat pancreatic islet cells. They showed that the stretch of amino acids called GLP-1 (7-37) stimulated the production of insulin — the peptide hormone that moves glucose into cells to decrease blood sugar levels — when blood glucose levels were elevated (1). Across the Atlantic Ocean in Copenhagen, Denmark, Jens Juul Holst independently confirmed that a similar form of GLP-1 stimulated insulin production in pigs and that it was present in their intestines (2).

It didn’t take long for researchers to recognize the enormous potential for GLP-1-related drugs to treat people with diabetes who cannot produce enough insulin. Yet, the road to drug development quickly met a hurdle, as the natural form of GLP-1 rapidly degrades in the body within a few minutes.

Fortunately, researchers at the Veterans Affairs Medical Center in New York discovered a similar but more stable hormone called extendin-4 that exists in the venom of Gila monster lizards (3). This led to a synthetic version called exenatide that became the first GLP-1 receptor agonist approved by the FDA to treat type 2 diabetes in 2005.

Meanwhile, Lotte Bjerre Knudsen and her team at Novo Nordisk were also spearheading efforts to develop a longer-lasting GLP-1 receptor agonist that binds to albumin in the blood to protect it from degradation. Their first drug, liguratide, was approved to treat type 2 diabetes in 2010. Knudsen and her colleagues also recognized and began studying the powerful weight loss effects of liguratide, and they discovered that it binds to neurons in the arcuate nucleus, a region of the brain involved in regulating food intake and energy expenditure (4). Liguratide was the first GLP-1 receptor agonist to be approved to treat obesity in 2014, and Knudsen’s team then built on these efforts to develop semaglutide, which would go on to achieve even greater weight loss effects in patients with type 2 diabetes or obesity.

“[Knudsen] was the first to take on that challenge to convince her colleagues at Novo Nordisk that this was worth exploring, and it's worth remembering that when she undertook that project — and it was probably in the late 2000s — there was no market for obesity drugs,” said Drucker.

We wouldn't be in the position of getting recognition if it wasn't for the efforts of literally thousands of scientists and investigators, and tens of thousands of patients who volunteered for these trials. 
- Daniel Drucker, Lunenfeld-Tanenbaum Research Institute

Today, many people know these revolutionary GLP-1 receptor agonist drugs by their brand names: Victoza, Ozempic, Rybelsus, Wegovy, Mounjaro, Zepbound, and more. This year, one of the three Breakthrough Prizes in Life Sciences is shared by Habener, Mojsov, Drucker and Holst for their basic science discoveries of GLP-1, and Knudsen for her work in translating that work into GLP-1 receptor agonist drugs to treat type 2 diabetes and obesity. Drucker pointed out the important contributions from many others along the way too. “We wouldn't be in the position of getting recognition if it wasn't for the efforts of literally thousands of scientists and investigators, and tens of thousands of patients who volunteered for these trials,” he said.

In the future, Drucker hopes that these drugs will positively impact countless more lives. “Maybe we'll be using them for substance use and addiction related disorders, and peripheral artery disease, and metabolic liver disease, and Alzheimer's disease, and all kinds of arthritis and inflammatory conditions — and maybe their utility [will] be far greater than we ever imagined.”

Uncovering the causes of multiple sclerosis 

By Dika Ojiakor, PhD

In 1894, the French neurologist Pierre Marie proposed that multiple sclerosis (MS) — a chronic neurodegenerative disease in which the body’s immune cells attack the insulating, lipid-rich substance surrounding nerve fibers — was caused by an infection and that a vaccine could one day be used to prevent it (5). The hypothesis could explain the geographical variation in the prevalence of the disease and the sudden rise in cases in regions where it was rare or had never previously been observed.

In the 1990s, after working for several years as a physician in developing countries, Alberto Ascherio, an epidemiologist and nutritionist at Harvard University, decided to shift his focus to neurodegenerative diseases like MS. “You realize that you can probably have much more impact if you can discover the causes of the disease rather than treating one-by-one the people who get sick,” he said. 

In 2001, he began investigating whether infection with the Epstein-Barr virus (EBV) — a common herpesvirus that more than 90 percent of human adults carry — increased the risk of MS in later life. At the time, despite evidence suggesting a link between EBV infection and MS, the cause of the disease remained unknown (6). 

To test his hypothesis, Ascherio and his team designed a conceptually simple study. “How do you find out that a virus is causing a certain disease?” he asked. “You start with people who were not infected with the virus. Then you follow them over time. And then, you need to prove that those who get the virus will get the disease, and those who don’t get the virus don’t get the disease.” 

But proving that a common infection like EBV causes a relatively rare disease like MS required a “very large number of people,” Ascherio said. Fortunately, his research team found participants uniquely suited for their study: active-duty US military personnel. Recruited at a young age, US military personnel have their blood tested for HIV upon entering service and every two years thereafter. The military also archives the leftover serum from these tests. Ascherio reasoned that he could use the stored serum samples as well as medical records of military recruits to investigate the link between EBV and MS risk over a long period of time.  

He and his team obtained serum samples from over 10 million young adults enlisted in the US military over the span of 20 years. They then determined EBV status at recruitment and monitored the onset of EBV infection and MS during active duty. Following years of meticulous epidemiological analysis, the researchers showed that EBV infection increased the risk of developing MS by a factor of 32 (7). 

The finding paves the way for the use of antiviral drugs to potentially treat MS, an option that Ascherio believes is “certainly worth pursuing.” It also opens the possibility of developing an EBV vaccine that could one day help prevent the disease. 

Ascherio shares this year’s Breakthrough Prize with Stephen Hauser, a neuroimmunologist at the University of California, San Francisco. Through decades of research, Hauser reshaped the understanding of MS by identifying B cells, rather than T cells, as the main drivers of nerve damage in the disease (8). Hauser demonstrated that B cells produce the antibodies that target myelin — the protective coating around nerve fibers — and activate T cells to attack it, triggering both inflammation and disease progression. 

It’s obviously an honor to be recognized for our work; but most importantly, I think it will help for the next breakthrough. 
- Alberto Ascherio, Harvard University

Working closely with industry partners, Hauser helped develop and test multiple B cell-targeted therapies for MS, which have transformed the treatment of both relapsing and progressive MS and are now considered the global standard for managing the disease. 

Reflecting on being named one of this year’s Breakthrough Prize recipients, Ascherio said, “It’s obviously an honor to be recognized for our work; but most importantly, I think it will help for the next breakthrough.” 

Editing the code of life

By Stephanie DeMarco, PhD

Just four DNA bases code the genome — sequences of adenines, guanines, cytosines, and thymines. But a single mutation in one of these bases can be the cause of many genetic diseases. Whether it’s a switch from a cytosine to a thymine to cause progeria or a swap from an adenine to a thymine in sickle cell disease, a single point mutation in the genetic code can have a massive impact on a person’s health.

Innovations like CRISPR have made the prospect of editing mutations out of DNA a tantalizing one, but as a therapeutic, the technology has a few drawbacks. Notably, editing DNA with CRISPR can get messy. For example, cutting both strands of the DNA double-helix introduces a greater chance of bases getting incorrectly inserted or deleted from the genome. It can also be an inefficient process in cells that are not actively dividing.

About ten years ago, David Liu, a chemist at the Broad Institute of MIT and Harvard, and his team were determined to find a way to fix a point mutation in the genome without making a double-stranded break. In a project led by then postdoctoral researcher, Alexis Komor, the researchers developed a brand new gene editing technology: base editing (9).

Building off of knowledge from CRISPR, base editing involves directing a mutated Cas9 enzyme to a specific place in the genome using a guide RNA. The Cas9 binds to the DNA, but it does not induce any breaks. Instead, Liu and his team tethered it to a cytidine deaminase, which converts cytosines to uracils (which, when it occurs in DNA instead of RNA, the cell interprets as a thymine) and guanines to adenines. To ensure that the non-edited DNA strand would match up with the edited strand, the team engineered the Cas9 to cut the non-edited strand. This causes the cell’s repair machinery to use the edited strand as a template and cement the updated DNA change into its genome.

Liu and his team, led by then postdoctoral researcher Nicole Gaudelli, also developed adenine base editors that could convert thymines to cytosines and adenines into guanines (10). Gaudelli used an enzyme evolution approach to develop these base editors because there was no known naturally occurring enzyme that could perform these base conversions. With these two base editors now available, researchers could correct about 30 percent of all known single-base disease-causing mutations (11).

But what about diseases caused by the eight other kinds of single-base changes or changes in more than one base? The answer, Liu said in a conversation with the Sheekey Science Show on YouTube, came in the form of a then-prospective postdoctoral applicant: Andrew Anzalone.

“When I asked him what are you thinking of working on, he pulled out this kind of audacious idea … which proposed that perhaps we could use a reverse transcriptase to directly copy an edited DNA sequence from an extension on a guide RNA into a nicked target DNA site,” he said. “It was a wild idea, and there were all sorts of reasons why it might have failed.”

That idea would become prime editing, which with a number of what Liu called “small miracles” allowed them to precisely edit sections of DNA (12).

This prize also highlights, during a time in which support of science in this country faces unprecedented dangers, that science saves and improves lives. 
- David Liu, Broad Institute of MIT and Harvard

Since base editing’s development in 2016, it has already shown success in clinical trials. For example, base-edited CAR T cells successfully treated a 13-year-old girl with T cell leukemia. Prime editing, a more recent advance with its development in 2019, is not far behind. The FDA cleared Anzalone and Liu’s biotech company, Prime Medicine, to begin clinical trials using prime editing to treat chronic granulomatosis disease in May of last year. 

Writing in an email about his feelings around having won this prize, Liu said, “It’s humbling for our lab to be recognized in this way — especially the efforts of our students, collaborators, and postdocs such as Alexis Komor, Nicole Gaudelli, Andrew Anzalone, and many others who made base editing and prime editing possible. This prize also highlights, during a time in which support of science in this country faces unprecedented dangers, that science saves and improves lives.”

References

1. Drucker, D.J. et al. Glucagon-like peptide I stimulates insulin gene expression and increases cyclic AMP levels in a rat islet cell line. Proc Natl Acad Sci USA  84, 3434–3438 (1987).
2. Holst, J.J. et al. Truncated glucagon-like peptide I, an insulin-releasing hormone from the distal gut. FEBS Lett  211, 169–174 (1987).
3. Eng, J. et al. Isolation and characterization of exendin-4, an exendin-3 analogue, from Heloderma suspectum venom. Further evidence for an exendin receptor on dispersed acini from guinea pig pancreas. J Biol Chem  267, 7402–7405 (1992).
4. Secher, A. et al. The arcuate nucleus mediates GLP-1 receptor agonist liraglutide-dependent weight loss. J Clin Invest  124, 4473–4488 (2014).
5. Murray, J. Infection as a cause of multiple sclerosis. BMJ  325, 1128 (2002).
6. Larsen, P.D. et al. Epstein‐Barr nuclear antigen and viral capsid antigen antibody titers in multiple sclerosis. Neurology   35, 435 (1985). 
7. Bjornevik, K. et al. Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis. Science  375, 296–301 (2022).
8. Hauser, S.L. et al. B-Cell Depletion with Rituximab in Relapsing–Remitting Multiple Sclerosis. N Engl J Med  358, 676–688 (2008).
9. Komor, A.C. et al. Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage. Nature   533, 420–424 (2016).
10. Gaudelli, N.M. et al. Programmable base editing of A•T to G•C in genomic DNA without DNA cleavage. Nature   551, 464–471 (2017).
11. Landrum, M.J. et al. ClinVar: public archive of interpretations of clinically relevant variants. Nucleic Acids Res  44, 862–868 (2016).
12. Anzalone, A.V. et al. Search-and-replace genome editing without double-strand breaks or donor DNA. Nature  576, 149–157 (2019).