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A Man of Many Hats

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As an MD/PhD, Russ Altman is a member of that rare breed of individuals who really do have one foot planted firmly at the bench and the other in the clinic. Upon finishing his undergraduate studies in biochemistry at Harvard University in 1983, he headed off to Stanford University, initially thinking he would pursue graduate work in biophysics. But when he arrived, he heard about the university's medical information sciences program that appealed to his twin interests of computer science and biology. Years later, when Altman took over as director of the program in 2000, he renamed it the biomedical informatics program. Also the chair of Stanford's bioengineering department, Altman continues to maintain a small medical practice despite juggling his many research projects.

Altman's lab is currently focused on developing PharmGKB, a pharmacogenomics database that aims to be the Web destination for information about genes that are important for drug response. "We're building this database and we're doing informatics research on how to deliver services and how to analyze data relevant to pharmacogenomics," he says. He also directs Stanford's Helix Group, which uses simulation, machine learning, and natural language processing methods to conduct protein and RNA structure analysis. And as principal investigator for the NIH Center for Biomedical Computation at Stanford, Altman helps develop software tools to simulate biological systems in terms of the motions of their components.

In addition to dual roles of researcher and physician, Altman is also a mentor and advisor to many. He says his approach to advising is based upon what he considers to be an "old fashioned" interpretation of the PhD as a hunting license to define and solve a problem independently. Along those lines, he tries to stay as much out of his students' way as possible during the early stages of their journey to a doctorate. "I try not be too directive in the very beginning stages where they're looking for their thesis project. I have a ton of ideas but I really feel it's important for them to articulate what the problem is, why it's important, and how to go after it," Altman says. "I work with them on all of those things, but it would be too easy for me to feed them the problem and why it's important — and then they would just be technicians implementing the work. … That might be fine for getting a PhD, but then when they hit the real world, they have not done this activity that the world is expecting them to do."

What they're made of Altman says that his grad students really get to see what they're made of in year two or three of their graduate studies. "They have done the confidence builder projects, maybe they've been on one paper as a middle author, but now they have to commit themselves to three or four straight years working very deeply on a problem and defining what it is," he says. "It's hard, and I want them to be primarily responsible for it. And they are very stressed out, more than in any other time." Sometimes, he must act as a life preserver for a student by throwing in his own ideas about the direction their research should take, but this rarely yields the desired outcome of producing an independent and mature investigator.

Pressure and dedication take on a whole new meaning for those brave souls endowed with the desire to embark on the MD/PhD path to which Altman was drawn. He has some advice for those considering it: "The first thing I say to somebody like that is, 'You have to want to be a doctor to go to medical school, and you have to want to be scientist to go to PhD school,'" he says. "What I mean by that is: do not do one simply to give you a competitive advantage in the other, because the training for both are long and hard, and any kind of superficial reason to do it cannot weather how physically and intellectually difficult it is to finish them." And when it comes to looking for the right MD/PhD program, Altman says that the quality of the PhD training should be the deciding factor. "Medical school is basically the same for everybody. At the end of the day, everyone takes the same nationalized exam, so the quality of medical school training is pretty much even," says Altman. "But the quality of PhD training is highly
variable. Given that, I would choose your program based on offering first-class PhD credentials and then the MD program."

Former Altman postdoc Alain Laederach, now a research scientist at the Wadsworth Center for Developmental Genetics and Bioinformatics, says his favorite memory is a rather terrifying experience involving the grant proposal for the Simbios group within Altman's NIH center, which was around 250 pages long. "Three days before it was due, Russ decided we needed to completely reorganize the structure of the grant," says Laederach. "It was exactly what the grant needed, but it took a lot of guts to start cutting and pasting everything in such a major way three days before the due date. But we ended up getting it funded."

Laederach says that he learned  from Altman's approach to getting the most out of the latest computational approaches to solve real-world biological problems. "In Russ's lab, I learned to identify biological problems that are tractable computationally and identify the best approach," says Laederach. "I also learned to identify the medical applications of the biology, which is critical to obtaining funding from NIH."

Naming Names
Any number of scientific greats have been shaped over the years in Altman's lab. Here are just a few of those who earned their stripes with him.

Jeff Chang
According to Altman, Chang arrived in his lab with coding skills at a level he has yet to see since. Chang actually joined the lab as a sophomore and later proceeded to write a "trail blazing" thesis on natural language text mining, Altman says. He is currently gearing up for a postdoc at the Duke Institute for Genome Sciences and Policy.

Rich Chen
Chen joined the lab as an MD student originally intending to do a short rotation as a researcher. But, as fate would have it, a local Silicon Valley venture capitalist happened to see a presentation he and fellow labmate Ramon Felciano gave and offered the students several million dollars to start up the company now known as Ingenuity.

Ramon Felciano
During his stint with Altman, Felciano co-founded Ingenuity, where he acts as both chief technology officer and vice president of R&D. He has also led the development of many informatics and Web-based projects, including RiboWeb, a semantic application for Internet-based, collaborative molecular biology.

Sean Mooney
Mooney arrived in Altman's lab as a postdoc and started BioE2E, an organization geared toward grad students and postdocs interested in the entrepreneurial side of biotechnology. He is currently an assistant professor in the Department of Medical and Molecular Genetics at the Indiana University School of Medicine.

Soumya Raychaudhuri
During his stint at Altman's lab, this former MD/PhD student published nine papers, the record for the most papers by any student in the lab. Currently, Raychaudhuri is a research fellow in the program of medical and population genetics at the Broad Institute.

Olga Troyanskaya
Troyanskaya says Altman taught her to be suspicious of her results and how to pick the best collaborators, among many other lessons. Currently, she is an assistant professor at Princeton University's Lewis-Sigler Institute for Integrative Genomics, where she works on computational techniques for genomic data integration, microarray analysis, and pathway identification.

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