Our Scientists

Two days after Michael Eisen received his Ph.D. from Harvard University in 1996, he got a call from an old friend. The friend had often heard Eisen claim that someday he wanted to be a baseball play-by-play announcer. "If you're serious," he told him, "there's a minor-league team in Tennessee that wants to talk with you."

Thirty hours later, Eisen was on a plane to Nashville. He rented a car at the airport and drove an hour south to the town of Columbia. "When I walked through the gates they handed me a roster and a microphone and said, 'You're on the air in ten minutes.'"

Eisen's summer as a radio announcer for the Columbia Mules didn't stop him from reporting for a postdoctoral fellowship in HHMI investigator Patrick O. Brown's lab at Stanford University in the fall. But broadcasting is an apt metaphor for the approach Eisen has taken to science: He constantly strives to ensure that advances made in his lab reach as broad an audience as possible, and he has created new opportunities for other researchers to do the same.

At Stanford, Eisen developed software and techniques to analyze data from DNA microarrays—tools invented in Brown's lab that are used to measure the activity of thousands of genes simultaneously. Microarrays are now used by many labs around the world and have been an important tool for determining distinct "genetic signatures" for diseases such as cancer. "We were generating data on a scale never generated before," says Eisen.

But sifting through the mountains of data that Brown's lab was collecting was only part of the challenge. What Eisen and his lab mates really needed was more biological context for their data. "When you're working on just one gene at a time, you can know everything there is to know about that gene," he says. "But when you shift to studying the entire genome, you can only know a tiny fraction of the relevant information you need to interpret an experiment."

Eisen and Brown decided that if they could place all the research articles that were relevant to a particular microarray experiment in a single online location, then interpreting the results would be much easier. "People recognized the value of the Internet as an information distribution medium, but they hadn't yet realized how valuable it would be if the information were searchable and immediately available," Eisen says. However, they quickly ran into a problem. Although more and more scientific publishers were posting their articles online, most were charging substantial fees for access.

Eisen and Brown realized that the only way to solve the problem was to get scientists to change the way they publish their findings. "Becoming a publisher was the last thing on our minds," says Eisen. "But we slowly became convinced that we needed to create a new model of scientific publishing and show people that it could work."

The result was the Public Library of Science (PLoS), which Eisen, Brown, and Nobel Prize–winning cancer biologist Harold Varmus cofounded in 2001. Now the publisher of seven online peer-reviewed scientific and medical journals, PLoS permits free, unrestricted use and distribution of the articles it publishes, as long as the original work is properly cited. Eisen says PLoS has demonstrated that open access is a logical way to take advantage of the Internet's capability to disseminate information to anyone who needs it.

The time and energy that Eisen devoted to launching PLoS have not detracted from his research career. Since 2000, he has been a computational and evolutionary biologist at the University of California, Berkeley and the Lawrence Berkeley National Laboratory. Eisen's lab, which includes geneticists, biochemists, biologists, ecologists, and computer scientists, uses fruit flies in the genus Drosophila as a model to study how the form and behavior of animals is determined by their genome sequences. Specifically, they are interested in the sequences that determine when genes are turned on and off during development——with the long-term goal of understanding how changes in these sequences alter how species look and act.

Realizing that patterns and principles are more likely to emerge when scientists compare the genomes of related species than by studying the stream of As, Ts, Gs, and Cs in a single genome, Eisen helped spur a major international effort to sequence the genomes of 12 species of Drosophila. His lab led the labor-intensive analysis of the data that project generated. The information from the "12 Genomes Project," published in 2007, is serving as a rich resource for Drosophila researchers.

Eisen's team analyzes these genomes, and those of other flies, and performs detailed experimental dissections of gene regulation in Drosophila embryos. "We are trying to take advantage of natural sequence variation," says Eisen. "You can think of these genomes as experiments that evolution has already done for you."

The function of regulatory DNA in fruit flies may seem far removed from medical applications, but Eisen insists that there is a "direct and important" link. "In just a few years, everyone will be able to know their genome sequence. At that point, a great challenge is going to be understanding the consequences of genetic variation. Our interest in the long run is to apply what we learn in Drosophila to understanding variation in the human genome."