When asked about the future of scientific discovery, David Clapham doesn’t hesitate. “Some people think we’re almost at the end of science — I think that’s crazy. Just because we know all these genes, that doesn’t mean we understand them. There’s so much more to learn and develop, and I’ve always found that incredibly motivating.”

That motivation fueled a distinguished 50-year career in research science, including appointments as Aldo R. Castañeda Professor at Harvard Medical School, as well as scientific and leadership roles at HHMI. His passion for science — sparked by an itinerant childhood and cultivated through training in electrical engineering, biology, and medicine — led him to chase down the physiology of unusual cells throughout the human body, including the heart, brain, teeth, and sperm.

Where Electricity Meets Biology

Though his scientific interests may seem disparate, Clapham was — and remains — inspired by the ways they intersect. “We humans think we invented the use of electricity a few hundred years ago, but actually, biology started using electricity four billion years ago,” he explains.

“Bacteria essentially invented batteries by pumping ions asymmetrically across a cell’s membrane. That allows the cell to store energy as voltage and use it as needed for very fast changes,” he says. “Even the electric motors humans invented resemble those first used by unicellular organisms.”

After completing an MD/PhD program at Emory University, Clapham had the extraordinary opportunity to work with Erwin Neher and Bert Sakmann at the Max Planck Institute in Göttingen, Germany. Neher and Sakmann had recently invented the patch-clamp technique, a breakthrough that would later earn them the Nobel Prizeexternal link, opens in a new tab.

Under their guidance, Clapham learned to measure the opening and closing of individual ion channels at millisecond resolution. These ion channels control how neurons communicate with muscles and with one another. The patch-clamp technique opened up the entire human body — from gut to muscle to eye — to new, deeper levels of understanding.

A Career-Defining Breakthrough

Clapham completed his medical residency during an exciting time for electrophysiology. Bertil Hille and his lab had used patch clamp to make an important cardiovascular discovery. They found that potassium channels responsible for slowing and accelerating the heart could be activated by the molecule guanosine triphosphate (GTP). In his nascent lab at Brigham and Women’s Hospital in Boston, Clapham set out to understand how and why this happened.

With the help of Eva Neer, a biochemist across the hall, he began applying different purified G protein components directly to the inside surface of cardiac cells to determine which one caused activation. To Clapham’s great surprise, G-alpha — which was thought to be responsible for most cellular activity — did nothing. But G-beta gamma, for which expectations were low, immediately activated the cardiac potassium channels.

“It was like an explosion — one of the most dramatic moments I’ve ever had in science,” he says.

In Pursuit of Novel Ion Channels

In many ways, this discovery set the course for his entire career: identifying ion channels throughout the body. One of Clapham’s most significant findings came from directly recording the electrical activity of a cell’s inner mitochondrial membrane. This revealed that mitochondria take up calcium through a highly selective ion channel. The work transformed a long-observed physiological fact — that mitochondria absorb calcium — into a defined, measurable behavior that could be studied using patch clamp.

Later, after running a research lab at the Mayo Clinic and returning to Boston to serve as the Chief of Cardiovascular Research at Boston Children’s Hospital, there came another fascinating, and deeply unexpected, discovery: CatSper,external link, opens in a new tab one of the body’s most complicated ion channels. This channel allows mature human sperm to swim and navigate their way to the egg and breach its protective layers for fertilization.

Some of his neuroscience colleagues teased him for working on “lowly” sperm instead of brain cells, but Clapham was fascinated by these unusually powerful cells, which are essential for human reproduction. He credits his medical training for his ongoing interest in the entire body, including below the neck.

Joining HHMI Leadership

Nearly twenty years after his first appointment as an HHMI Investigator, Clapham took on a leadership role at the Institute, serving as Chief Scientific Officer from 2016 to 2022. For him, the highlight of both roles was hearing the nation’s top scientists distill their work and discuss how to solve problems.

“Science is not about making predictions and then trying to force that conclusion,” he explains. “It’s about staying open-minded as you conduct experiments. At the heart of HHMI, we care about understanding systems and supporting scientists wherever their data takes them — which is often somewhere wonderfully unexpected.”

Still Asking Questions

After leaving the Chief Scientific Officer role, Clapham devoted himself full-time to his lab. As a Senior Group Leader at HHMI’s Janelia Research Campusexternal link, opens in a new tab, he continued to make unexpected discoveries, including finding an ion channel that senses cold in tooth cells. In recent years, his main interests were ongoing work on ion channels in mitochondria, lysosomes, and primary cilia,external link, opens in a new tab organelles essential for cellular function.

Clapham retired in the fall of 2025 and admits that it’s difficult to step away when unanswered scientific questions remain — but then, they always will. He plans to continue feeding his curiosity by staying up to date on scientific advances. At the same time, he is eager to step aside and make room for the next generation of scientists.

His advice to them is simple: “Every project is a failure most of the time. You have to see problem-solving as fun. But only the truth, what is real, endures in science.”