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Igor Dawid, Acting Scientific Director of the National Institute of Child Health and Human Development.
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Igor Dawid enjoying the flowers.
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Thomas Sargent, 1983.
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Figure from Sargent and Dawid's differential expression experiment in frog embryos.
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Patrick Brown and Vishy Iyer, former post-doctoral fellow, in the lab.
Audio Glossary
BRCA1/BRCA2, Microarray technologyVideo Interviews
Tom Sargent is the chief research microbiologist in Section on Vertebrate Development in the Laboratory of Molecular Genetics, NICHD, NIH.
Clip 1 (0:48)
Part I: Theories on how organisms end up with differentiated cells.
Clip 2 (1:16)
Part II: Theories on how organisms end up with differentiated cells.
Clip 3 (1:20)
The cell as a micro-computer that can interpret signals for different responses.
Clip 4 (1:18)
Sargent's gene library and comparisons with today's gene chips.
Clip 5 (1:01)
Molecules that regulate development are similar in different organisms.
Clip 6 (1:03)
Why use other animal models to study development?
Dr. Patrick Brown is an associate professor of biochemistry at the School of Medicine in Stanford University.
Clip 1 (0:46)
Talks about the aesthetic pleasure he gets from doing an experiment.
Clip 2 (0:35)
The first DNA arrays were made of solid gold.
Clip 3 (0:59)
The first DNAs used to make the arrays.
Clip 4 (1:50)
Differences between the DNA array system and GeneChips(R).
Clip 5 (0:30)
Why use DNA arrays?
Igor Dawid and Tom Sargent did some of the first differential gene expression studies using cDNA subtraction. Pat Brown and Steve Fodor have changed the way genomes can be screened with DNA arrays and GeneChips®. IGOR DAWID (1935-)
Igor Dawid was born in Central Europe in what was Romania but is now part of Ukraine. There wasn't any defining event or moment that set him on a scientific career, especially since there wasn't too much science taught in his high school. However, he recognized that science was interesting and important. After World War II, Dawid went to Vienna to study. The University of Vienna didn't have a biochemistry curriculum and given a choice between pure biology or chemistry, Dawid chose chemistry. He finished a Ph.D. in chemistry in 1960. By this time, he realized that to further his career, he needed to work in the United States. With help from his Ph.D. advisor, he obtained a post-doctoral position at the Massachusetts Institute of Technology. It was here that he pursued a growing interest in biochemistry. He read an article in a journal that talked about the isolation of a "factor" that induced tissues to change their fate. Even though the article was retracted a few months later, Dawid's interest was piqued and he decided to go to Woods Hole for a course in this growing field of tissue-specific genes. At Woods Hole, Dawid met James Ebert, the director of the Carnegie Institute and later the director of Woods Hole. Ebert invited Dawid to work at the Carnegie and in 1962, Dawid became a Fellow and worked with Don Brown. Brown was using the traditional embryologist's model, frogs, to study development. Frog embryos are large and changes are easily visible. Also, a lot was known about the various stages of development. Dawid adopted frogs as a model system and continued to use them when he moved to the National Institutes of Health in 1978. Tom Sargent joined his lab in the early '80s. And they began working on Sargent's idea of isolating differentially expressed mRNAs from different frog embryonic stages. The subtractive mRNA technique not only netted a lot of stage-specific mRNA, but worked surprisingly well in that the differential libraries had very little cross-stage contamination. Dawid is currently the Acting Scientific Director of the National Institute of Child Health and Human Development. His lab in the Laboratory of Molecular Genetics Division works on differential gene expression in frogs and zebrafish. Dawid has been the Editor-in-chief and now serves on the advisory board of the scientific journals Developmental Biology, and Proceedings of the National Academy. He has been the Associate Editor of other journals, Cell and Genes and Development. He enjoys classical music and is an opera buff. THOMAS DEAN SARGENT (1953-)
Tom Sargent was born in Indianapolis, Indiana, (the same year as DNA). As a child he was always interested in science. When he was twelve years old, a family friend gave him the first edition of James Watson's textbook Molecular Biology of the Gene. Sargent pored over the text for months studying concepts that were meant for college-level students. Sargent found biology so fascinating he majored in the subject at Indiana University. When he graduated he went to the California Institute of Technology for graduate work. During this time, gene cloning was a "new" technology and the arrival at Caltech of Tom Maniatis, who was the first to clone a mammalian gene, inspired many graduate students including Sargent to switch to gene cloning projects. Sargent finished his Ph.D. in 1981 by cloning and characterizing a rat serum albumin gene. While at Caltech, Sargent and others, including Mark Davis and David Cohen, became interested in differential gene expression. For post-doctoral work, Sargent looked for an organism where he could easily make libraries of genes that were being expressed at different times in development. He sat in on a talk by Igor Dawid who was using frog embryos to study development. Sargent approached Dawid who hired him immediately as a post-doc. They developed the subtractive library system using frog mRNAs almost concurrently with Davis and Cohen, who used a similar method to look at T-cell specific gene expression. Sargent and Dawid published their results first. However, because so few genes had been cloned at the time, there weren't very many identifiable clones in their library; there were a number of "unknowns" and some epidermal keratin genes. Since then, the "unknowns" have been identified as being homeobox and other types of regulatory genes. Sargent has been and still works on epidermal development - the first tissues to form in frogs. Sargent is currently Chief Research Microbiologist in the Section on Vertebrate Development in the Laboratory of Molecular Genetics, NICHD, NIH. He also teaches genetics at George Washington University. In his spare time, Sargent indulges in his hobby of wood-working. 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. STEPHEN P. A. FODOR (1953-)
Steve Fodor was born in Seattle, Washington. His father was a physician and Fodor didn't plan on going to college because it was what people expected him to do. Instead he spent time working on a potato farm and indulging in one of his favorite pasttime - fly-fishing. Fodor did finally go to college. He graduated from Washington State University with a B.S. in Biology. After this degree, he stayed at WSU and received a M.S. in Biochemistry. Fodor then went to Princeton and in 1985 received his Ph.D. in Chemistry. Throughout his undergraduate and graduate career, Fodor was known to have "hands." He was able to tweak techniques so that things worked. Fodor did post-doctorate work at the University of California, Berkeley, and it was there in 1989 that he was recruited to Affymax Research Institute in Palo Alto. He was put in charge of developing a process to generate miniature high-density arrays of biological compounds. This led to the development of the first DNA GeneChip®, and the techniques to read and analyze these chips for large-scale genomic studies. The process has undergone a lot of refinement since the early days and the publication of the seminal paper Light-directed, Spatially Addressable Parallel Chemical Synthesis -- the first look at high-density microarray technology and combinatorial chemistry in the 1991 February issue of Science. He and his colleagues received the AAAS' 1992 Newcomb Cleveland Award for this work. Now the genomes of entire organisms like yeast are being put on a GeneChip® for analyses. The success of the GeneChip® also led Affymax to spin off another company, Affymetrix Inc., in 1993 to focus on GeneChip® production and analysis. Fodor is currently Chairman and Chief Executive Officer of Affymetrix Inc. He has won numerous awards for his work on and the development of GeneChip® including the 2002 Takeda Foundation Award, the 2002 Economist Innovation Award for Nanotechnology, and the 2002 Oxford Bioscience Award. Fodor also serves on the Board of Directors for Sunesis Pharmaceuticals, Inc., is Chairman of the Board for Perlegen, Inc., and serves on the Board of Trustees of the Carnegie Institute of Washington. | |
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LinksSerially Sectioned Frog Embryo MoviesFrom the Society of Developmental Biology at Purdue University, this site has movies of developing frog embryos. This page may take a while to load and you will need the Quick Time plug-in. Dr. Pat Brown's Lab HomepageBrown's web site has instructions on how to build your own DNA arrayer and scanner. There are also photos and science articles on DNA microarray technology. DNA Microarry, Genome ChipThis site has a collection of links, news and other information pertaining to DNA arrays and GeneChips®. Bibliography
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