Biography 36: Patrick Henry Brown (1954- )
Pat Brown was born in Washington, D.C. He was a good student but didn't have the all-fired certainty that he was going to be scientist. He was curious about how things worked and interested in helping people. It seemed natural for him to get both a Ph.D. in 1980 in biochemistry and an M.D. in 1982; both degrees were from the University of Chicago.
Although still undecided about a full research vs. medical career, Brown started his residency training in pediatrics at the Children's Memorial Hospital in Chicago. During his 3-year residency, while working with his patients, Brown realized that his curiosity about how things worked could help alleviate the need for understanding how genetic disorders develop. What exactly makes one person different from another and is there a practical way to distill these differences?
Brown went back to research. In 1985, he started a 3-year postdoctoral fellowship with J. Michael Bishop at the University of California, San Francisco. After his postdoc, Brown started his own lab and became a Howard Hughes Medical Institute investigator. He eventually settled in as an Associate Professor in the Department of Biochemistry at Stanford University School of Medicine.
Brown never forgot the idea of "genetic differences." He began thinking about the feasibility and usefulness of comparing the DNA of whole organisms ? one to another. Scientists get information about genetic similarity, evolutionary history, and conservation of function when they compare the DNA sequences of individual genes. Brown wanted to scale this up so that the entire gene complement of an organism could be compared with that of another. This would give information about variation in genetic expression and development that cannot be obtained with individual sequence comparisons. He began to think of this idea as a DNA array ? laying down DNA samples into columns and rows.
From the very beginning of this project, Brown had a very clear vision of what was needed. Sample preparation had to be cheap and easy to produce without user-unfriendly equipment. His first collaboration with an engineer failed because the mechanization of producing a DNA array became too "engineered." In the end he settled on the still-elegant fountain pen design. A solution containing DNA is sucked up into a pen and then printed onto a glass slide. With computerized automation, these DNA arrays can hold up to 80,000 samples ? more than the estimated total number of genes that make up a human being.
In 1995, Brown published the first of many papers that use DNA arrays to analyze patterns of expression. He had held workshops on how to build DNA arrays and has made the protocols available at his web site.
Brown is an advocate of freedom of information and is on the PubMed Central Advisory Committee. The Committee is trying to deal with the issues of electronic exchange, storage and dissemination of scientific information by providing and promoting free electronic exchange.
When he's not working, Brown likes to spend time with his family especially his kids. He also likes to run and has participated in local marathons.
In the 1990s, DNA arrays provided the means to analyze patterns of gene expression at different timepoints in a living cell.
Pat Brown draws an analogy between the genome and a script that tells a cell how to behave.
Pat Brown talks about developing microarray technology for genome-wide analysis.
Pat Brown discusses the early technology behind the microarray.
Pat Brown talks about using microarrays to discover the differences between cancer cells and healthy cells.
Pat Brown talks about how the 30,000 spots on the microarray represent genes.
DNA microarrays provide the means to analyze patterns of gene expression at different timepoints in a living cell.
Igor Dawid and Thomas Sargent explain how they developed subtractive mRNA hybrization to find genes expressed by different cell types. Pat Brown and Steve Fodor show how genomes can be screened with DNA arrays and GeneChips™
Why use DNA arrays?
The first DNA arrays were made of solid gold.