Harvard geneticist Stephen Elledge started his scientific career trying to figure out how to tinker with the DNA of human cells. Instead, he ended up eavesdropping on the process cells use to fix genetic mistakes.
This accidental work led to profound insights into DNA repair relevant to human birth defects, cancer, and aging.
On Tuesday, Elledge, 59, received the highest American honor for a scientist. He will share the $250,000 Albert Lasker Basic Medical Research Award with Evelyn Witkin, 94, of Rutgers University, who studied the DNA repair system in bacteria.
Elledge’s “insights into the basic mechanisms of the DNA damage response have profoundly enriched our understanding not only of the fundamental genetics of all cellular life, but also of how we conceptualize many diseases and conditions, especially cancer,” Jeffrey S. Flier, dean of Harvard Medical School, said in a statement.
As cells divide and reproduce, they have to make precise copies of their DNA. Typos can doom a fetus, lead to birth defects, and cause cancer as well as symptoms of aging.
Elledge, who is also affiliated with Brigham and Women’s Hospital, uncovered a sequence of events, called a pathway, that protect a cell once its DNA has been damaged or incorrectly copied.
“This pathway helps coordinate things,” he said.
The 70-year-old Lasker awards, often called the American Nobels, recognize scientists who have made major advances in the “understanding, diagnosis, treatment, cure, or prevention of human disease.” More than half of Lasker winners have gone on to win Nobels.
The two other winners are James P. Allison, an immunologist at the University of Texas MD Anderson Cancer Center in Houston whose work sparked the recent wave of cancer treatments that harness the immune system, and Médecins sans Frontiéres/Doctors without Borders for its efforts last year to combat the Ebola outbreak in West Africa. All four will receive their awards during a Sept. 18 ceremony in New York.
In a phone call Tuesday morning, Elledge said he was honored to be included and appreciates awards such as the Lasker for the positive attention they draw to science.
“It’s nice to be recognized and have . . . the really creative people who’ve worked with me over the years get recognition,” said Elledge, who is married to fellow Harvard geneticist Mitzi Kuroda.
Elledge received his PhD at MIT and started the work on DNA damage when he was a postdoctoral student at Stanford in the mid-1980s.
If a reproducing cell makes too many copying mistakes, it will die or enter a state called senescence, rendering it unable to reproduce. Senescent cells send out signals to the immune system that trigger inflammation, which can cause disease and are probably a key ingredient in aging, he said. Some scientists are using the pathway Elledge identified to study aging and its connection to diseases such as cancer.
The research also led to a deeper understanding of several mysterious and rare birth defects, in which a child’s DNA repair system was faulty.
And the work has led to insights into many forms of cancer, including the most common genetic forms of breast cancer.
Elledge, like many who grew up in the 1960s, said he was turned on to science and technology by a combination of chemistry sets and the space race.
As a boy, he quickly ran through the experiments that came with his chemistry set, so he began devising his own combinations. The day he created an exploding gas that left the kitchen ceiling with a large orange stain, which didn’t come off for years, marked the end of the early experimental period of his life, Elledge said.
He went on to major in chemistry at the University of Illinois, and was the first member of his family to go to college. Elledge switched to biology for graduate school after he saw the potential for understanding and manipulating DNA.
His first major technological innovation came at MIT, where he developed a new method of cloning that allowed scientists to identify and track proteins used by cells. Technological innovations, he said, often do more to advance science than many individual insights.
Witkin, speaking with the other winners on a telephone news conference Tuesday morning, said she started her study of damage repair in 1941, before it was clear that DNA contained a cell’s genetic code.
Asked about sexism she may have faced during her long scientific career, Witkin said she had been lucky. When she was pregnant in 1949, her boss at the Carnegie Institution of Washington, Vannevar Bush, asked her what she needed. Bush, formerly head of the engineering school at MIT, awarded her a generous leave and a part-time schedule for six years.
“I was astounded by his attitude,” she said. “I don’t think we’re seeing that kind of attitude yet. I don’t know that we ever will on a large scale.”
All three scientists spoke about the importance of public and government support for basic research, the kind in which immediate benefits to people might not be clear.
Allison never started out looking for insights into cancer. He just wanted to understand how T cells, the foot soldiers of the immune system, get called into action. But his basic research in the 1990s has led to a branch of cancer treatment that is offering hope to patients like former president Jimmy Carter, now being treated with immune therapy for skin cancer that spread to his brain.
Elledge, whose initial work was in yeast, said today’s medical advances wouldn’t be possible without the previous decades of basic research.
A lot of great science also happens by accident, he said. When he was in graduate school, he studied DNA repair in bacteria — the field launched by Witkin’s research — but had no intention of continuing to work in the area.
He instead stumbled upon a different protein, turned on when DNA copying goes awry.
He was planning to ignore that insight and then realized that it “was maybe a toehold into a pathway that no one knows anything about, that tells a cell when a problem exists,” he said. “I couldn’t imagine it would end up being as important as it would end up being.”