With the exception of certain infectious diseases, few of humanity’s ailments have cures. More than 560,000 Americans will die of cancer this year, and despite the 250,000 coronary bypass surgeries doctors perform annually, heart disease is still the country’s number-one killer.
The hardest diseases to cure are the ones that take the longest to develop. They are the end result of decades of complex molecular interactions inside your body. Yet this complexity also presents an opportunity. Scientists have discovered that these interactions leave discernible fingerprints on the body. By unweaving the complex tapestry of molecular clues—changes in the body’s proteins, nucleic acids and metabolites, collectively called biomarkers—doctors hope they will soon be able to not only detect disease but predict a coming illness in time to take action.
Biomarkers are not new. Since 1986 doctors have monitor-ed prostate cancer by measuring blood levels of the protein known as prostate-specific antigen (PSA). But tests that rely on a single biomarker to detect disease are rare, because most disorders involve intricate changes in a collection of biomarkers.
Take schizophrenia: in January 2010 scientists will release a biomarker test that distinguishes schizophrenia from other psychiatric conditions. The test, which is being commercialized by Rules-Based Medicine, a laboratory in Austin, Tex., is based on the characteristics of about 40 blood-based proteins.
To find potentially useful biomarkers, researchers collect blood samples from thousands of healthy people and analyze them. Biomarker levels in these samples provide a baseline reading. Then they do the same for people with a specific condition such as diabetes or breast cancer. If reproducible differences emerge between the groups, scientists can use the patterns in the disease group to diagnose the same condition in others. By collecting samples over time, researchers can also go back and analyze early samples from individuals who later become ill to identify patterns indicative of early disease or high disease risk.
Biophysical Corporation, a sister company to Rules-Based Medicine, is one of several companies that has developed blood-based biomarker tests and marketed them to the public [see “The Ultimate Blood Test,” by Philip Yam; Scientific American, June 2006]. The company searches for up to 250 biomarkers suggestive of cancer, inflammatory conditions, heart disease and other illnesses. Mark Chandler, Biophysical’s chair and CEO, says that the real value of the tests lies in long-term monitoring. A person could “get a test monthly, just a finger stick, that would be able to say, we have had a serious change here that is indicative of an early-stage cancer,” he explains.
Yet not all experts are convinced that the age of biomarkers is at hand. Cheryl Barton, an independent U.K.-based pharmaceutical consultant who authored a Business Insights market analysis report on biomarkers in 2006, says she remains “a little bit skeptical about how clinically useful they are.” A study of 5,000 subjects published in the Journal of the American Medical Association in July 2009 found that six cardiovascular biomarkers were only marginally better at predicting heart disease than were standard cardiovascular risk factors, such as whether the subjects smoked or had diabetes.
Adding to the overall difficulty, a person might suffer from two or more diseases—prostate cancer and heart disease, for example. No one knows how multiple diseases might affect overall biomarker signatures or how profiles will change as other diseases develop. “When you get to be 65 or 70, almost everybody has other conditions,” Chandler says. “We don’t know how to deal with that right now.” And scientists still need to discern which biomarkers are truly relevant to disease—a difficult task when working with blood, which contains tens of thousands of proteins at concentrations spanning more than 10 orders of magnitude.
Some companies have simplified the problem by avoiding blood altogether. LabCorp recently commercialized a biomarker test that analyzes colon cells in stool for the chemical signatures indicative of colorectal cancer. “The stool is in intimate contact with the lining of the colon, so it becomes much more highly populated with these rare molecules than would get into the bloodstream from colon cancer,” says Barry Berger, chief medical officer of Exact Sciences, a Madison, Wis.–based biotechnology company that developed the test technology.
In time, scientists are confident that they will eventually crack the more difficult problem of finding distinct disease signatures in the noisy data. “The evolutionary process, being complex and unknown, does not always give us an easy route,” Berger notes, “but it definitely gives us lots of opportunities.”