Patrick O. Brown

Education

Brown received each of his degrees from the University of Chicago, including his B.S. in 1976 and M.D. in 1982. His Ph.D., granted in 1980 while under the guidance of Nicholas R. Cozzarelli, involved the study of DNA topoisomerases.

Academic career

After getting his medical degree in 1982, Brown completed a 3-year pediatric residency at Children's Memorial Hospital in Chicago but decided he could have a greater impact through basic research. In 1985, Brown took a 3-year postdoctoral fellowship at the University of California, San Francisco with J. Michael Bishop and Harold Varmus (who shared the 1989 Nobel Prize in Medicine for their discoveries about how genes can ignite cancerous tumors). At UCSF, Brown and colleagues defined the mechanism by which retroviruses, such as the HIV virus, integrate their genes into the genome of the cells they infect, which helped lead to development of new drugs to fight the disease.

In 1988, Brown became an investigator of the Howard Hughes Medical Institute and an assistant professor in the department of biochemistry at Stanford University School of Medicine, where he continued to investigate retroviral replication. In the early 1990s, Brown began developing a new technology to enable systematic investigation of the behavior and properties of whole genomes—called DNA microarrays. "I had a mental image of a DNA microarray, even including the red and green fluorescent spots, a few years before I'd figured out the details of making them," Brown told The Scientist.

Brown and his colleagues created a robotic dispenser that could deposit minute quantities of tens of thousands of individual genes onto a single glass slide, a "DNA microarray" or "gene chip." By flooding the slide with fluorescently labeled genetic material derived from a living sample, a researcher could see which genes were being expressed in cells. Shortly after their first description of DNA microarrays, the Brown laboratory published a "how-to" manual on the Web that helped these robotic devices become standard equipment in life science labs throughout the world, in an effort led by Joe DeRisi, Michael Eisen, Ash Alizadeh, and others.

Brown and his colleagues developed experimental methods for using DNA microarrays to investigate basic principles of genome organization, gene expression, cell regulation and specialization, physiology, development and disease, and the microbiome, along with statistical and computational tools for visualizing and interpreting the resulting large volumes of data. This work was especially revealing for the molecular portraits of many human cancers including lymphomas such as DLBCL, breast cancers, and other tumors, as part of diverse global collaborations including David Botstein, Michael Eisen, Lou Staudt, Ash Alizadeh, and others. Microarray technologies are widely used for comparing gene expression patterns and other genome features among individuals and their tissues and cells, providing information on disease subcategories, disease prognosis, and treatment outcome.

Starting in the late 1990s, Brown began publicly voicing concern over what he called "a fundamentally flawed process of scientific publishing," in which academics typically published results of publicly funded research in private, commercial publishing houses that charged subscription fees for access to journals. "We viewed this entire process as being patently unfair. Not only were scientists in poor countries being denied access to the latest and best information out there, but the public who supports this research was being denied access as well. We felt there simply had to be a better way to do it," Brown told a University of Chicago medical journal.

Brown began a collaboration with other scientists, including Harold Varmus (then director of the National Institutes of Health), David J. Lipman (then director of the National Center for Biotechnology Information), and Michael Eisen of Lawrence Berkeley National Laboratory, to overhaul the scientific and medical publishing systems to make papers available on the rapidly developing Internet platforms such as Usenet and the World Wide Web. "Why should publishers be able to control what I can do with information that was published by my scientific colleagues whose motivation was exactly to have their discoveries contribute to future discoveries?... We had already existing tools that we could use to so to speak hyperlink things so that you could reorganize information in systematic ways, but they weren't really being exploited by the conventional scientific literature," Brown said in an interview with BioMedCentral Biology. The magazine Nature reported that the scientists' open-access movement could "spell the end for many print titles"; Brown called subscription-based scientific journals "anachronisms."

In 2001, Brown, Eisen and Varmus co-founded the Public Library of Science (PLOS) to make published scientific research open access and freely available to researchers in the scientific community. Funded by a grant from the Gordon and Betty Moore Foundation, the non-profit organization advocated for designing alternative systems to fund for scientific publishing.

In 2002, Brown was elected to the United States National Academy of Sciences, identifying him as one of the top 2000 scientists in the nation. He is a member of the National Academy of Medicine and a Fellow of the American Association for the Advancement of Science.