BACTERIAL CLUES: By analyzing the products of intestinal bacteria, Nicholson hopes to fashion new tools for diagnosis and new targets for drugs.
POPULATION BOOM: The human gut contains some 10 trillion individual bacteria in 1,000 different species.
FATHER OF DISCIPLINES: Nicholson's work has spawned two new fields: metabolomics, which studies the metabolites that cellular processes leave behind, and metabonomics, which characterizes the metabolic changes a biological system experiences in response to stressors.
GROWING ON HIM: On first noticing metabolic fingerprints that cells leave behind: "I was thinking of them as extremely annoying interferences with mammalian biochemistry. Now I'm almost becoming evangelical about the bloody things." Image: Sion Touhig
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Editor's Note: The extended Q&A with Jeremy Nicholson mentioned in the July magazine can be found here.
Jeremy Nicholson was only trying to be thorough. It was 1981, and the young biochemist was using a technique called nuclear magnetic resonance spectroscopy, which can identify chemicals based on the magnetic properties of atomic nuclei. In particular, Nicholson wanted to study how red blood cells absorb cadmium, a metal that causes cancer. Realizing that he would achieve the best results if he could mimic the cells’ natural environment, he added a few drops of blood to the cells and ran the test.
“Suddenly there was a huge variety of signals that we hadn’t seen before—there were these amazing sets of spectra coming out,” Nicholson recalls. A sample of blood or urine contains thousands of metabolites—signatures of all the chemical reactions occurring in the body at a given time. If he could find a way to identify those chemical signatures and their significance, he reasoned, he would be able not only to better understand different diseases—based on chemical reactions that had gone awry—but also to identify early warning signs and potential interventions. That kind of science, he decided, was his kind of science.
Today the 51-year-old Nicholson is one of the world’s foremost experts on the so-called metabolome, the collection of chemicals produced by human metabolism. Whereas the genome provides detailed information about a person’s genetic makeup, the metabolome is a few steps down the line—it reveals how genes interact with the environment, providing a complete snapshot of a person’s physical health. “The genome is really like a telephone directory without any of the names or addresses filled in. On a very basic level, it’s got a lot of numbers,” explains Nicholson, who now heads the department of biomolecular medicine at Imperial College London. The metabolome “helps to give value to genome information and put it in perspective.”
But first it has to be deciphered, and that is no easy task. The job requires the analysis of blood, urine, breath and feces within large populations. For instance, to find potential chemical signatures, or biomarkers, for high blood pressure, Nicholson and his colleagues analyzed the urine of 4,630 individuals from the U.K., the U.S. and Asia and compared the urinary metabolites with blood pressure data to determine if any consistent metabolic differences exist between individuals with hypertension and those without it.
It is kind of like doing science backward: instead of making hypotheses and then devising experiments to test them, he performs experiments first and tries to decipher his results later. He must sift through the range of chemicals produced by the genes people have, the food they eat, the drugs they take, the diseases they suffer from and the intestinal bacteria they harbor.
Those bacteria in particular have become Nicholson’s prime focus. They influence how our bodies break down food and drugs and may explain why food affects people differently. For instance, some people cannot derive benefit from one of soy’s components because they lack the gut microbes necessary to process it. Although deciphering which metabolites come directly from our gut microbes can be difficult, in some cases it is easy—they are the chemicals that are not produced by cells or ingested in food.
Nicholson focuses on these chemicals both because little is known about them and because they appear to be highly relevant: recent research suggests that gut microbes play a crucial role in human health and disease. They help us absorb nutrients and fight off viruses and “bad” bacteria; disrupting intestinal colonies, such as with a course of antibiotics, often leads to digestive sickness. In fact, Nicholson says, “almost every sort of disease has a gut bug connection somewhere.”