Unlike most people studying molecular genetics, who study vast quantities of molecules at once, Carlos Bustamante [pictured at left] has pioneered techniques to study the physical properties of the individual molecules. In doing so, he demonstrated that identical enzymes doing the same job may act differently for some unknown reason. Bustamante's initial experiments--stretching and moving single DNA molecules--have led to his current research: how a lone enzyme copies a DNA sequence. But it wasn't always easy for the University of California, Berkeley, professor and Howard Hughes Investigator. Bustamante has traveled far and learned what it takes to become a scientist in the demanding world of biomedical research.

The Journey

Bustamante was born and raised in Lima, Peru. After completing high school, he attended Cayetano Heredia University and received his B.S. in biology in 1973. In addition, he received his M.S. in biochemistry from San Marcos University in 1975. However, he realized that he had to leave Peru to seek the training necessary for him to become a research scientist. He soon left his native country to attend the University of California, Berkeley, as a Fulbright scholar.

Struggles With American Culture

"The first year was very traumatic," Bustamante admits. "If I had to do it again--knowing how hard that first year was--I would really have to think about doing it again." Friendless, without a firm grasp of English, and unfamiliar with American culture (especially the humor and the comparatively reserved nature of interpersonal relationships), he still had to meet Berkeley's difficult graduate demands.

In spite of the difficulties, Bustamante felt appreciated in Berkeley's liberal atmosphere. "In many respects, it was refreshing to see that I was being accepted regardless of where I came from and regardless of my accent. That kind of diversity and plurality ... is what makes places like Berkeley so wonderful, and that's why people like to come here."

However, moving from Peru's generally more conservative culture to Berkeley's "anything goes" lifestyle sometimes presented its own unique challenges for Bustamante. He struggled to adjust to American culture. As a graduate student in 1975--fresh after the women's liberation movement--he offered his bus seat to a woman who cursed him for doing so. Another time, he was stunned to witness a group of topless women protesting a policy that allowed only men to be shirtless.

Despite seeing such unconventional behavior, Bustamante remained stoic and successfully dealt with his new environment. "I thought if that's what it took to be a scientist, then I had to do it. So I did." Eventually, his circumstances improved: he gained friends, became proficient in English and American culture, and received his Ph.D. in biophysics in 1981. During his graduate student days, he married his girlfriend and she eventually joined him from Lima.

In the Lab

After completing a postdoc at the Lawrence Berkeley Laboratory, he earned a professorship at the University of New Mexico (UNM) in Albuquerque, where he taught from 1982 to 1990. It was at UNM that Bustamante took notice of the incredible elasticity DNA molecules display as they are separated by molecular weight. Inspired, he wanted to define the physical properties of DNA molecules.

Bustamante continued that work in his next position at the University of Oregon in Eugene, and also when he returned to Berkeley as a professor in 1998. Bustamante's UNM research, which quantitatively measured the elasticity of a single DNA molecule, demonstrated that large molecules could be physically manipulated. This idea evolved into his lab's current study of the spatial arrangement of molecules during transcription (the copying of one strand of DNA into a complementary RNA sequence by the RNA polymerase enzyme) and how molecular motors generate force in real time. To do such precision work, Bustamante's lab uses some unusual techniques and instruments.

Those Wonderful "Toys"

Bustamante's lab has pioneered some of those DNA manipulation techniques and has modified existing instruments to carry out their specialized work. They use high-resolution scanning force microscopy to examine the minute processes of transcription. This microscope, also called an atomic force microscope, probes the topography of the surface, like a record player "reads" a record's grooves. Also vital to the work is optical (laser) tweezers, which manipulate objects at the molecular level. This newer technology is an improvement over the magnetic tweezers used in the first experiments.

Making Science Worth It

Those high-tech devices allow Bustamante to explore his professional curiosity. "I was never very happy with the view that comes from studying many, many molecules at the same time, which is how many processes have been studied both in chemistry and biochemistry."

Imagine taking millions of people, mixing them up, and then averaging them together. The results would miss much of the innate variability found among individuals and miss a great deal of what those people are really like. So, Bustamante says, that's how it is with molecules inside the cell. And that's what he has found: Individual molecules may act differently.

To Bustamante, it's those (admittedly) rare eureka moments that "make science worth it." Although he feels fortunate to be a professor, especially at Berkeley, he has found an unpleasant side to the life of an academician. Bustamante detests "bureaucratic paper pushing," which, he feels, takes away from his "play" time in the lab.

But the work itself isn't all Bustamante enjoys about his professional life. He also enjoys hearing when one of his students has good news. Bustamante's lab employs 40 people, so he's constantly meeting with them to look at results, ask questions, and make suggestions.

Life Lessons

Bustamante hopes to impart some of the life lessons he has learned to those in his lab. Recognizing his lack of discipline as a student, he has worked hard to correct it. To succeed as a scientist or student of science, he has found that hard work, creativity, organization, self-confidence, drive, and discipline are essential. He also believes that some fallacies persist in the scientific community about what makes a good student. "We have to realize that what makes the difference between a good student and bad student is not intelligence--or anything like that--or capabilities or creativity...I would really say what distinguishes them is not their intellectual ability at all." Instead he has found that "nothing beats working hard and studying hard." Speaking from personal experience Bustamante has found that anybody can do it, regardless of nationality or ethnic background.

Clinton Parks is a writer for MiSciNet and may be reached at cparks@aaas.org.

Clinton Parks is a writer for MiSciNet and may be reached at cparks@aaas.org.