Mark Goulian freely admits that when he was a freshman at Harvard in 1981, he was cocky. Goulian (pictured left) wanted to study high-energy physics because it was interesting, certainly, but also because it was hard. "I wanted to reach that goal because it was difficult," says Goulian, now an assistant professor of physics at the University of Pennsylvania. "In retrospect, it was a ridiculous reason to do something."

Despite his appointment in the physics department, Goulian has staked his career on biology, emphasizing cell signaling. The journey to find that specialty took 20 years, two theoretical physics postdocs, and finally a biology fellowship at Rockefeller University. Later this year, at his tenure decision, he'll find out if his meandering career path is likely to continue in a straight line for a while. However it turns out, he seems likely to adapt.

Great Expectations

As an undergraduate at Harvard, Goulian was intrigued by the quest for a grand unified theory, so he went on to do graduate work in Harvard's high-energy physics program. Physicists tend to split early between two tracks--theoretical and experimental--and like most cocky young physicists, Goulian pursued a career in theory. It was a misstep that would haunt him for years.

Goulian spent his graduate school years developing mathematical formulas to describe string theory, at the time considered the leading candidate for a grand unified theory. Looking back, Goulian says he should have known he was off track because he wasn't passionate about his work. "It's very easy when you get on academic track to start following a program, and you don't necessarily step back and think, 'Why am I doing this?' "

Second Thoughts

After getting his Ph.D. in 1990, Goulian continued on to a postdoc at the University of California at Santa Barbara. There, he continued his theoretical studies of high-energy physics, but his growing dissatisfaction finally overwhelmed him. "I started getting depressed. I wasn't that interested in what I was doing. My work was going well--I'd written a paper that got a little of attention. (The paper) was interesting to people, but it wasn't that interesting to me." He considered leaving science altogether, but a conversation with another postdoc changed his mind. "He said the obvious thing: 'If I could do anything else in physics, what would it be?' " Goulian had always had an interest in condensed matter physics, a field that ranges from crystal growth to membrane physics. "It was doing real science, describing real phenomena … stuff I had not been doing as a high energy physicist."

He benefited from a quirk of the field: High-energy physics grants are generally awarded to groups rather than individuals, so they tend to allow more flexibility than single-investigator grants. His advisors supported his decision to switch fields, going so far as to extend his postdoc position to a third year to give him time to make the transition.

Goulian got his first taste of biology while studying membrane theory. Physicists tend to regard membranes as two-dimensional structures with random thermal fluctuations. Goulian modeled what would happen to the random fluctuations in the presence of impurities in a bilayer membrane. He also modeled whether and how the bilayer could mediate interactions between two impurities. Biologists call them proteins, not impurities, and protein interaction is an important field of study because transmembrane proteins direct cell signaling and other vital processes. The work would be critical to Goulian's career, though he had no way of knowing it at the time. Satisfied with the results, he moved on to other projects.

In 1993, Goulian took a postdoc at Exxon to solidify his place in the condensed matter field, doing theoretical work on crystals and polymers. Near the end of his time at Exxon, he found his interest waning again. "It was clear that this stuff was okay,” Goulian says, “but I hadn't really found my passion."

Discouraged, he considered alternatives, including management consulting and computer science; even going so far as interviewing with IBM's speech-recognition department.

Then an ad for a new program at Rockefeller University’s Center for Studies in Physics and Biology piqued his interest. His earlier work with biological membranes and the paper that resulted from that work helped him get into the program. But after two postdocs, another change didn't seem wise. "I was thinking this was career suicide." But the idea appealed, and his ongoing frustration made him a bit reckless. "It was an opportunity to live in Manhattan and figure out what I wanted to do with my life. (That attitude) loosened me up quite a bit." When he arrived in 1995 as a research fellow, he immediately set about doing theoretical work on biomembranes, following up on his work at UC Santa Barbara. Six months later, that old feeling arose again. "It still was not quite right," he says.

A Moment of Clarity

Finally, something clicked. Perhaps it was the shock of moving into a biology department and away from the familiar environs of physics. At Rockefeller "there was no physics department to run and hide in," he recalls. And it was difficult to be a theorist in biology, which tends to be driven by experimental science. Experiments beckoned, and he finally realized the source of the problem that had been haunting him: he wasn't happy as a theorist. "I was a closet experimentalist," he says.

Soon after, he joined the lab of cellular biophysicist Sandy Simon, where he promptly began a project that was too ambitious and mostly failed. But he learned quickly. "I got a very broad exposure to cell and molecular biology. I fell in love with microbiology and cell signaling. I hadn't been that excited since I was in college."

Goulian worked on several projects, but his next revelation came while he was sitting in front of a microscope, waiting for the results of electrophysiology measurements. He passed the time by reading a molecular biology manual on a nearby bookshelf. "I knew a little molecular biology, but I had no notion of what you could do experimentally,” he says. “It reminded me of electronics--the idea that you had these tools to splice things together in an ordered way, that you could reengineer things in the cell to do something else." It brought to mind an electronics course he'd taken in college. "I enjoyed the course and always had a certain affinity to electronics. Cells struck me as very simple analogies." Soon after, he began a side project to study cell signaling in E coli.

Lesson Learned

In 1999, his career path finally illuminated, Goulian began to cast about for a job. He got an offer from a biotech company, but he also interviewed at Penn's physics department. He didn't try to make a hard sell. "I was very honest. I said that I worked in cell signaling, and I'd only be using physics indirectly. I didn't want them to hire me for the wrong reasons. But they knew that I had the background and could teach the classes, and I could make ties to faculty in the biosciences to help them bridge the gap between departments."

He is up for tenure this year. Though he has published extensively on cell signaling, Goulian hasn't completely abandoned his background in physics. Much of his work involves biophysics and fluorescent analysis. But he his firmly entrenched in biology now, despite his academic title of assistant professor of physics.

"If there's a moral in this," he says, "it's to find what you love to do. It sounds trite, but it's very hard to do." You can take his word for that.

Jim Kling writes from Seattle.

Jim Kling is a freelance science and medical writer based in Bellingham, Washington.