Metabolomics and Personalized Medicine

by Food and Drug Administration (FDA)

Many of us try to make the most of what nature has provided. We buy clothes that enhance the shape of our bodies. We pick colors that go with our skin tones. We choose hairstyles that flatter us based on the shape of our faces. So why not choose medicine to improve health based on our genetic makeup?

Researchers worldwide are hoping to make this medical possibility a reality one day. And they're making strides by studying the way the body's cells work using powerful technologies and sciences known as genomics, proteomics, and metabolomics. Genomics is the study of all the genes, proteomics is the study of all the proteins, and metabolomics is the study of all the molecules derived from metabolism (metabolites) in a living organism.

"New biological understanding to help us to combat disease will come from knowledge of genes, proteins and metabolites," says Yvonne Dragan, Ph.D., a research biologist and director of the Division of Systems Toxicology within the Food and Drug Administration's National Center for Toxicological Research (NCTR). The FDA, academic and medical institutions, and pharmaceutical companies are all working to learn more about these cellular components, which can lead to more effective treatments for people based on their genetic structures and acquired differences.

"The long-term goal is to be able to personalize medicine," says Dragan. "Metabolomics is one of many tools to help do that."

What Is Metabolomics?

Metabolomics, genomics, proteomics, and other "-omics" grew out of the Human Genome Project, a massive research effort that began in the mid-1990s and culminated in 2003 with a complete mapping of all the genes in the human body.

Scientists believe there are 30,000 to 40,000 genes in the human body. A gene is a piece of deoxyribonucleic acid (DNA). About 99.9 percent of the DNA sequence is identical in all people, according to the National Human Genome Research Institute (NHGRI). But the 0.1 percent difference is critical because it represents the genetic variations that determine a person's risk for getting a disease, how mild or severe the disease will be, and how he or she will respond to a treatment.

While genomics researchers are searching for variations in genes that cause disease, and proteomics researchers are seeking out abnormal protein patterns, metabolomic researchers are mining for abnormal metabolite patterns.

Metabolites are generated through metabolism — all the chemical reactions within the body that create and use energy, handle foods and other substances, and regulate our internal environment. Digesting food, eliminating waste, regulating body heat, and even breathing are all involved in the body's metabolism.

Experts believe there are at least 3,000 metabolites that are essential for normal growth and development (primary metabolites) and thousands more unidentified ones that are not essential for growth and development (secondary metabolites) but may help fight off infection and other forms of stress on the body.

Scientists are especially interested in certain very small metabolites, known as low-molecular-weight metabolites. These include amino acids, sugars, carbohydrates, and lipids, and they can provide important clues about a person's health.

By studying the changes and concentrations of these small metabolites within the body's cells, scientists can find unique patterns, or profiles. These profiles change when the body is fighting a disease, reacting to a drug, or responding to another form of stress. The NHGRI defines metabolomics as the evaluation of tissues and body fluids, such as urine, blood, plasma, saliva, and cerebrospinal fluid, for metabolite changes that may result from bodily responses.

Researchers conduct metabolomic studies using predominantly two methods: nuclear magnetic resonance (NMR) and mass spectrometry (MS). NMR can rapidly identify and quantify hundreds of metabolites in a sample of body fluid. MS complements NMR in that it can display, quantify, and generate profiles of thousands of metabolites with more sensitivity than NMR. The profiles are then run through powerful computers that process, store, and generate data in a form for scientists to visualize and interpret.

Some scientists prefer an older term, "metabonomics," instead of metabolomics. They make a distinction between the two terms, using the older term to refer more broadly to the underlying principles or rules that govern the production of metabolites. But they don't all agree on the difference, and the two terms are often used interchangeably. In general, metabolomics is the term more commonly used.

Researchers are both optimistic and cautious about predicting the potential of metabolomics. "The field of metabolomics is still in its infancy," says Richard Beger, Ph.D., biophysicist and director of the NCTR's Center for Metabolomics. But in comparison to using proteomics or other -omic technologies, "metabolomics is cheaper and faster," he says. And the sample for metabolomic analysis is obtained through a relatively noninvasive procedure.

Beger sees metabolomics as a likely first screening tool for disease because metabolites are found in body fluids, which are easy to collect and prepare for testing. "A fluid sample can be tested within 10 to 15 minutes," he says. Then any abnormal results can be confirmed with genomics or proteomics tests, which require special cellular samples to be prepared.

"Metabolomics is a relatively new field and I'm very careful about not being overly speculative," says Christopher Newgard, Ph.D., director of the Sarah W. Stedman Nutrition and Metabolism Center at Duke University in Durham, N.C. But Newgard is excited about the potential of metabolomics to provide information about a person's traits and characteristics (chemical phenotype), and the presence or absence of disease. "What you're actually doing is getting a profile of the chemical phenotype of the person or the organism that you're studying," he says. "What is it about that individual's ... genetic program that translates into how ... he or she actually ... feels at this moment?" Metabolomics has that immediacy, he says, as opposed to genomics, which involves predictions of the course of a disease or the outcome of treatment.

About the Author

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