Nearly half of those sequences have come out of TIGR, making the organization's current president, Claire Fraser, one of the hottest biologists of the last two years (as was noted in this publication last spring—see Science Watch, 12[2]:1-2, March/April 2001). Recently four articles on microbial genomes coauthored by Fraser in the last two years could be found within the Hot Papers database, joined most recently by a report on the sequence of chromosome 2 of the plant Arabidopsis thaliana. Indeed, since 1981 Fraser has published two dozen articles that have collected over 100 citations each, another four with more than 1,000 each, and one, the Haemophilus influenzae sequence published in Science, which has garnered an amazing 2,100-plus citations in just six years (see the table on page 4).

Fraser received her bachelor of science degree in biology from Rensselaer Polytechnic Institute in 1977 and her doctorate four years later from the State University of New York (SUNY) at Buffalo, where she studied with her future spouse, TIGR founder J. Craig Venter, now of Celera Genomics and well known, of course, for his role in the sequencing of the human genome. After a one-year postdoc at SUNY Buffalo, Fraser moved on to the Roswell Park Cancer Institute and then spent eight years at the National Institutes of Health (NIH), where she was named chief of the Section of Molecular Neurobiology at the National Institute of Alcohol Abuse and Alcoholism in 1989. Fraser joined TIGR at its inception in 1992 and became president and director of the Institute in 1998. She is also a professor in the Departments of Pharmacology and Microbiology at the George Washington University School of Medicine.

From her home in Potomac, Maryland, 
Fraser spoke with Science Watch correspondent Gary Taubes.

The first microbial genome sequenced at TIGR was Haemophilus influenzae. How was Haemophilus chosen to be number one?

It was [1978 Nobel laureate] Hamilton Smith's suggestion to sequence Haemophilus as the first test project. Craig [Venter] had met Ham at a conference in Spain and invited him to be a member of TIGR's scientific advisory board. And so Ham came down with some of the members of his lab from Johns Hopkins and sketched out the project for us. Haemophilus was the species he had worked on for most of his career—the organism from which he isolated the first restriction endonucleases. It was a favorite of his, and was as reasonable a place to start as any. The E. coli project was already being pursued by Fred Blattner. The Haemophilus genome is about half the size of E. coli, a difference that would work in our favor. And since there were no microbiologists at TIGR, there was nobody to argue for or against Haemophilus, so that was the one we chose as a test.

How many microbial genomes have been completed so far, and how many have come out of TIGR?

The total number of published microbial genomes is around 60. TIGR has completed 25 of them, of which 21 have been published so far. Several are in the manuscript-preparation phase. We have actually reached a bottleneck in terms of the manuscript writing. At the moment, we've been funded to do over 40 microbial genomes in total.

What's the decision process in choosing which genomes to pursue?

It's very much determined for us by the various funding agencies. We did Haemophilus and Helicobacter pylori with money from Human Genome Sciences. Neisseria meningitidis was done with money from Chiron. Every other project has been done with federal funds, primarily from the NIH and the Department of Energy (DOE). At NIH, the National Institute of Allergy and Infectious Diseases and the National Institute of Dental and Craniofacial Research have both targeted key human pathogens, and DOE has been interested in organisms of environmental relevance, either because they represent extremophiles or because they have potential for bio-remediation. For us, it's been almost a 50-50 split between NIH-funded and DOE-funded projects.

In a recent paper in Emerging Infectious Diseases you suggest that there is unlikely to be a valid model organism for the microbial world. Why is that?

If you look across all of the organisms that have been studied with whole-genome sequencing so far, there is a very small subset of the total number of genes that is shared by a majority of the species. Other than DNA polymerases and ribosomal proteins and some of the most basic housekeeping genes, you would be hard-pressed to find genes involved in metabolic processes that are shared by a large number of species. Even among the heterotropic organisms that need organic nutrients to survive, you can't find a large number that share the same basic metabolism. When you look beyond some of the basic functions to more specific functions related to the unique biology of individual species, then we see very, very different sets of genes appearing. continued