The Accident Advantage - Vitals Magazine

Published: October 30, 2026

By Jeremy Martin

6 min read

Days before winter break in 2016, David Leib, PhD, and his research team at the Geisel School of Medicine at Dartmouth found themselves in a pathogenic pickle.

The team was using mouse models to investigate neonatal herpes simplex virus (HSV). HSV in newborns is rare, but it can cause profound neurological damage and, in some cases, death.

But recently, progress had stalled. The team couldn’t get the HSV dosage right, so on a whim they tried a different approach: Give the mice very low doses of virus—down to 100 viral particles—and monitor any effects.

“100 virus particles is almost like no virus at all,” says Leib, a virologist and chair of the department of microbiology and immunology at Geisel. “We call it a ‘homeopathic dose.’”

They didn’t expect much to happen. And initially, nothing did. The mice showed no HSV signs or behavioral changes before the research team left for winter break. But just in case, the team had set up specialized equipment to monitor the mice’s feeding, drinking, and movement while they were gone.

And when they reconvened in the new year, a month later, they noticed that, with time, something had shifted. The HSV mice were exhibiting signs of anxiety. Further testing revealed learning and memory deficits that hadn’t existed weeks before.

“The mice who received this tiny amount of herpes infection couldn’t remember which order the objects go on the screen,” Leib says, referring to a mouse-specific cognitive test his team conducted with a tablet. The mice struggled to learn and were slower to correct themselves, appearing unable to retain new information.

What had begun as a study of neonatal HSV infection had turned into something else entirely: The mice, it seemed, were showing early signs of dementia. This raised the startling possibility that a common virus might play a role in neurodegeneration, for which the precise mechanisms—and therefore, a prevention or cure—continue to evade experts.

Medicine is full of unexpected breakthroughs like Leib’s. A 2024 analysis of 1.2 million publications found that 58% report outcomes scientists didn’t anticipate. But accidental discoveries only become big breakthroughs if someone recognizes their significance—and has the freedom and support to dig deeper.

At Dartmouth, a place Leib calls “an epicenter of serendipity,” that freedom is increasingly a feature of the institution’s academic research philosophy.

Double Serendipity

Alexander Fleming was studying staphylococcus when mold—accidentally introduced into his petri dish—killed the bacteria, and penicillin was born. Viagra was engineered to treat chest pain. Ozempic began as a diabetes drug. Could the unexpected discovery made by Leib’s team lead to a similarly out-of-the-box advancement? The team would first need to see if their findings in mice also applied to people.

Through a partnership with the Birthing Pavilion at Dartmouth Health’s Dartmouth Hitchcock Medical Center (DHMC), Leib’s team found a window into human HSV: discarded suction bulbs, vaginal swabs, and obstetricians’ gloves from routine deliveries. By testing these items, they found HSV DNA on almost 7% of these items, suggesting an unexpectedly high level of exposure during labor and delivery. These are not causing the severe infections that affect 0.016% of births, Leib says, but are possibly analogous to the same silent, low-level exposure Leib’s team had given the mice.

Their findings, published in February 2025 in PLOS Pathogens, suggest HSV exposure in newborns may contribute to anxiety, cognitive decline, and neurodegenerative disease decades later. Maternal HSV vaccinations—which aren’t yet available but are in the development pipeline—could be an effective preventative.

Patients and study subjects—such as those in David Leib’s laboratory—often do memory tests for cognitive decline. Try memorizing the order of these three symbols, then test yourself at the end of this story.

Leib calls the discovery “a double serendipity”: an unexpected finding that led, almost accidentally, to a potential breakthrough in one of medicine’s most stubborn challenges.

“There is no doubt in my mind—and I think most scientists would agree—that serendipity is the driver of so much discovery,” says Leib. “[It] is the catalyst of science.”

Fertile Ground

Modern funding structures don’t always make room for these moments. A 2025 analysis of 100,000 National Institutes of Health (NIH) grants found that higher-risk research was less likely to be renewed than safer, more predictable work.

Dartmouth and Dartmouth Health have bet the other way—and are seeing the benefits. Every dollar donated to Dartmouth Cancer Center’s Prouty Pilot Grant Program—which supports high-risk, early-stage research—generates an additional $12 in federal grant support, made possible by data produced during the pilot period. Similarly, the Byrne Family Cancer Research Institute, launched with a $25 million lead gift in 2022 from the Jack & Dorothy Byrne Foundation, has since attracted $110 million in grants.

The Leib lab’s finding of a possible link between low levels of HSV and dementia is striking on its own, but the result, Leib says, was not happenstance. It was the product of persistent curiosity and Dartmouth’s unique ingredients: interactions and collaboration that go far beyond the norm.

For example, the fact that Leib’s HSV mice were monitored over winter break—the observation that set their discovery in motion—came from a chance encounter with Francesca Gilli, MS, PhD, an immunologist and neurologist at Geisel, who had lent equipment and lab space to Leib for an entire month.

“You bump into people from a lot of disparate areas” in the hallway and around town, says Leib, who has also tapped into experts across Dartmouth, as well as DHMC clinicians. Their response, Leib says, is invariably focused on being helpful.

“It’s not like, ‘Well, what’s in it for me?’ It’s like, ‘That’s really interesting. Let me help you with that,’” Leib says. As a result, “[it] pulls you in directions you couldn’t possibly expect.”

Throughout Dartmouth’s history, this sentiment has also led to discoveries with far-reaching impact. Geneticist Victor Ambros, PhD, came to Dartmouth in 1992 after being denied tenure at Harvard while studying “schmutz” in roundworm data. That schmutz was microRNA, and his discovery of its role in gene regulation earned him the 2024 Nobel Prize in Physiology or Medicine. Immunologist Jason McLellan, PhD, spent years stabilizing coronavirus spike proteins during his postdoctoral training at Dartmouth. His 2016 breakthrough while at Geisel became the foundation for most COVID-19 vaccines and led to his induction into the National Inventors Hall of Fame.

Neither discovery was planned. Both required an institution willing to let researchers follow the unexpected long enough for it to change medicine.

“At First, I Didn’t Believe It”

Nearly a decade after Leib’s initial HSV breakthrough, Tyler J. Curiel, MD, MPH, the Gmelich Professor of Cancer Immunotherapy at Dartmouth Cancer Center and Geisel, was on his own hunt.

His lab was looking for new ways to circumvent cancer’s defenses. Specifically, they wanted to strip tumor cells of a protein called PD-L1—a kind of molecular shield that helps cancer cells evade the immune system.

To find the right drug, they screened FDA-approved medications, a strategy that would let them skip years of safety testing and move faster toward the clinic.

“My working hypothesis was that the drug that you need is already out there,” Curiel says. “Somebody’s already made it. You just have to find it.”

Their screen flagged an unexpected option: telmisartan, a blood pressure medication in use for 25 years. It was FDA-approved, affordable, and widely available.

The idea that a blood pressure drug could also fight cancer would have been surprising enough. Then came the experiments to find out how it all worked. When Curiel’s team tested telmisartan in tumor cells genetically engineered to lack PD-L1—essentially deleting telmisartan’s supposed target—the drug kept working anyway.

“At first, I didn’t believe it,” Curiel says. “I kept saying, ‘We’re doing something wrong.’”

Further investigation revealed that telmisartan doesn’t attack cancer cells directly. Instead, it makes other cancer drugs work dramatically better. Specifically, telmisartan supercharges a class of drugs called PARP inhibitors, which treat cancer patients who have the BRCA gene mutation. Most patients lack that mutation, which has always limited who could benefit from PARP inhibitors.

Remarkably, telmisartan amplified the PARP inhibitors’ ability to damage a tumor not only in BRCA-positive cancers, but across many tumor types—even those lacking BRCA mutations. This means telmisartan could lead to drastically expanded treatment options for huge new swaths of cancer patients.

These findings were published in March 2026 in the Journal for ImmunoTherapy of Cancer, and Curiel and his colleagues are already leading two clinical trials testing this drug combination: one for metastatic, castrate-resistant prostate cancer, and another for platinum-resistant ovarian cancer.

Discoveries like this depend less on luck than on staying open to, and listening to, surprising signals. “When you see crazy stuff, a lot of times it’s just crazy,” says Curiel. “But every once in a while, it’s important.”

Leib puts it another way—borrowing from a line often attributed to the late futurist Isaac Asimov: “The greatest sound in a science lab isn’t ‘Eureka.’ It’s ‘that’s funny.’”

Anne Holden contributed to this report.