Athree-decade scientific career is something to be proud of. Dr. Paul Zamecnik ought to know. He's logged not just one but two of them—one before and one since retirement. His first 30-year stint ended when he reached Harvard's mandatory retirement age in 1979. He didn't rest on his laurels but merely switched employers. Today, almost 30 years later, he's still working full-time and has no plans to stop.

A 1934 graduate of Dartmouth Medical School, Zamecnik (pronounced ZAM-ess-nick) can claim more than mere longevity. Early in his career, he rubbed shoulders with Drs. James Watson and Francis Crick, who won the Nobel Prize in 1962 for identifying the structure of DNA. And Zamecnik has continued to make important scientific contributions as the decades have ticked by. In 1996, he won the Albert Lasker Award—known as "the American Nobel"—for a career, according to the award citation, "characterized by sheer scientific originality and brilliance."

In the 1950s, Zamecnik helped unravel themystery of how proteins are made—inventing the first cell-free system for studying protein synthesis and identifying transfer RNA. Two decades later, he pioneered antisense technology, a method of attacking harmful viruses and bacteria by blocking the expression of specific genes. Today, as he nears his 96th birthday, he's still an active scientist at Massachusetts General Hospital (MGH); his current focus is developing treatments for tuberculosis. Some people, Zamecnik concedes, might think, "Why isn't that guy in a retirement home?" But Karen Pierson, one of his three children as well as a technician in his lab, has a simple explanation for her father's refusal to leave the bench: "He loves to work."

As a DMS student in the 1930s, Zamecnik had planned to go into clinical medicine. That would have been the safer choice, he admits. But then he discovered that he enjoyed research. Within months of Zamecnik's 1929 enrollment (at age 16) in Dartmouth College, the stock market crashed and the nation entered the Great Depression. "In a way I was blessed," he says. "I went through the Depression without

Photo by Jon Gilbert Fox

Zamecnik had his first experience with research at Dartmouth in 1934—and 74 years later, just shy of his 96th birthday, is still doing research full-time at Mass General.

out being much affected by it because I was in school most of the time." He remembers spending a lot of time studying as both an undergraduate and amedical student, but he still managed to take advantage of the outdoor opportunities available in the New Hampshire mountains. He stayed at cabins owned by the Dartmouth Outing Club, and he provided medical assistance at one of the earliest downhill ski races in the country, on Mount Moosilauke.

It was during his second year at Dartmouth Medical School that Zamecnik first encountered scientific research. He tried to grow frog tissues in culture, following the lead of the renowned scientist Alexis Carrel, who ran a lab at the Rockefeller Institute in New York City. "He was a famous man in his day," says Zamecnik. "Won a Nobel Prize [in 1912]. Had his picture in the papers." In 1932, Carrel made headlines for keeping cells from a chick embryo alive for 20 years.

After finishing DMS's then two-year program, Zamecnik went on to Harvard to complete his M.D. In 1936, as he approached graduation, he applied for an internship in surgery at MGH. The problemwas that just about everyone else in his class wanted the same internship.

"So I found myself on a waiting list," he says.

Fortunately for Zamecnik, a Harvard instructor mentioned a residency in oncology at Huntington Memorial Hospital. Zamecnik met with the hospital's director, Dr. Joseph Aub, for an interview. But "instead of quizzing me about medicine and plumbing the depths of my ignorance," Zamecnik says, Aub asked the young trainee if he'd be willing to teach his daughters to ski—assuming that, as a Dartmouth graduate, Zamecnik must be a good skier. Despite his limited skills on the slopes, Zamecnik told Aub he'd be happy to oblige.

There was a strong commitment to research at Huntington, so Zamecnik had a chance to delve deeper into the world of discovery. "You didn't have many patients to care for," he says. "The [rest] of your time you were allowed to spend in the laboratory."

But after a year and half there, still thinking he'd ultimately practice medicine, Zamecnik began to worry that he needed more clinical training. So he and his wife, Mary, whom he'd married in 1936, moved to Cleveland, where he did an internship in medicine at University Hospitals. He liked the internship and his colleagues but realized that he really did prefer research and that he didn't want to commit to a life split between the lab and the clinic. Practicing medicine "draws you in," he says. "It's your first priority."

Zamecnik was also motivated by the lack of medical knowledge at the time. "A medical doctor saw the patient, listened to his chest, banged him on the back a little bit, quizzed him, then blessed him and allowed the curative powers of nature to take over," he says. He thought he could make a greater contribution by advancing the science behind medicine than by treating patients.

So he took some time off from residency to attend biochemistry classes and began a small research project on the side.

Soon he became interested in a question that, years later, would lead to one of his most significant discoveries. During an