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This story is a supplement to the feature "Jeremy Nicholson's Gut Instincts: Researching Intestinal Bacteria" which was printed in the July 2008 issue of Scientific American.
One of the hottest biomedical fields right now is metabolomics—the study of the metabolites and other chemicals that the body and its bacteria produce. The goal is to find out how the compounds can serve as indicators of health and disease. For the Insights story, "Going with His Gut Bacteria," in the July 2008 Scientific American, Melinda Wenner talked with Jeremy Nicholson of Imperial College London. One of the founders of the field, Nicholson thinks that metabolomics may prove that the best medicine actually targets intestinal flora rather than cells of the body. Here is an edited excerpt from the interview.
You were one of the first scientists to study the metabolome, the collection of chemicals produced by human metabolism. Was it hard getting people to take the idea seriously?
Nobody was in the slightest bit interested. I had terrible difficulties getting funding throughout the 1980s in this area. I remember sending a paper to Nature in 1987 that showed how you could use nuclear magnetic resonance and computational pattern recognition to look at urine from animals that had been poisoned with lots of different sorts of drugs. The editor said, "There's no interest [in this] to anybody whatsoever." That would have been 10 years in advance of the first paper that would really call itself metabolomics or metabonomics.
Over the 10 years that followed, I built up a hell of a laboratory, so when our work started to get noticed, we were already one of the best-equipped labs in the world.
Why was no one interested back then?
I don't think it was necessarily willful resistance; there was a lot of other stuff going on. In the '80s molecular biology had just come in. You couldn't get a grant in the U.K. unless you were doing molecular biology, because everybody thought that was going to solve everything. Then, also, in the late '80s you had the idea of genomics coming in.
Why do you think that the metabolome is more likely than the genome to give scientists the answers they want?
Genomics only takes you part of the journey to real biological discovery. The genome is a blueprint for life, but it doesn't tell you how the thing works. If you had a blueprint for a nuclear power station, it would tell you exactly how to build one, but it wouldn't tell you anything about quantum mechanics, physics, the idea of nuclear fission, radioactive decay or anything that made it work. You can look at the genome the same way. It may well have a blueprint for building life, but it doesn't tell you how the parts fit together.
And your work has shown that the environment makes a huge contribution to your health.
People talk about the genes that make you fat, but really, if you sit on your butt eating pork rinds and Big Macs and watching television, you will get fat, no matter what your genes say. What you do to yourself is really important. Metabolism captures environmental signatures as well as genetic. Your environment involves things like drugs you're exposed to, the pollutants you're exposed to, the products of your gut microbes, the metabolic products of your diet—so when we do a broad-screen metabolic profile, we're capturing all of that information, plus information that links to genome variation. For me, metabonomics is the most holistic of the "-omics." In principle, it can capture the signature of everything.