What is the Future of Diagnostic Medicine?

It´s 2015, and I want you to meet someone. Her name is Betty. She is 25 and healthy, although an uncle has had some heart problems. Her doctor suggests that she have her genome sequenced. Betty worries that if the results are bad, her insurance company will drop her, but Congress has finally outlawed such discrimination. The test results aren´t good: They show three gene variants known to increase risk of heart attack fivefold. Betty and her doctor immediately begin a prevention
program based on diet and exercise, of course, but also medication selected to work specifically with her genetics.

Fifty years pass. Betty notices no heart trouble, but one day her arm starts to hurt. Too much gardening, she figures, but her doctor knows better with a glance at the genetic results in her file. He diagnoses a mild heart attack and puts together a customized treatment. Betty lives into the 22nd century.

Today, though-in 2005-Betty is just a dream. She is the poster girl for personalized medicine, a creation of Francis Collins, the National Institutes of Health researcher who helped map the human genome. Collins, along with Craig Venter and his company, Celera, identified the 25,000 genes that serve as the construction manual for the human body. Although geneticists had already been able to home in on diseases caused by a single mutated gene-disorders such as cystic fibrosis, sickle-cell anemia, Huntington´s disease and Tay-Sachs-laying out the entire sequence of our DNA allowed them to begin exploring diseases with more complex roots.

Mapping the human genome gave scientists a view of the entire canvas of our genes, including the small aberrations called single-nucleotide polymorphisms, or SNPs (â€snipsâ€), that occur in everyone´s DNA. Some of these deviations are harmless, but others, when they interact, create instructions that produce some of our most serious disorders: cancer, heart disease, diabetes, Parkinson´s, schizophrenia, and on and on.

Now there are dozens of companies painstakingly comparing DNA samples from people who are sick with those from people who aren´t, looking for SNPs associated with those disorders. If they pinpoint aberrations exclusive to the disease sample, they can create reagents-and thus tests-that identify the SNPs from blood or DNA swabs.

Celera´s scientists, for example, have discovered SNPs in the past two years that indicate at least twice the normal risk of heart attack-putting people who carry the aberrations at the same risk as diabetics, smokers and those with high cholesterol. Such is the cruel science behind seemingly healthy people dropping dead of a heart attack at age 47. The promise of personalized medicine is to be able to find those people who would otherwise have no reason to worry, monitor them
closely, and get them started on a preventive regimen.

I would love to take Celera´s test, but it won´t be ready for at least a year. And although there are about 800 genetic tests available right now, most of them screen for diseases that rarely show up in humans. The 13 tests I took-from DNA Direct, Genelex and Kimball Genetics-are for common conditions that turn up in every walk of life, and they´re all for single-gene mutations. Celera and other companies are focusing on the multiple-gene problems, but that will take years, so researchers are also looking at the grunts that do your individual genome´s dirty work. I am speaking now of proteins.

Built with instructions from genes, proteins go on to build your entire body. When the instructions are bad, the proteins do bad things-disrupting normal biological functions and causing disease. The emerging field of proteomics is about identifying these proteins, and it´s an important secondary tactic in the push for personalized medicine, because any given gene may or may not become active, but the presence of a certain protein can tell you unequivocally whether you´ll get a certain disease. Already many doctors test for high levels of C-reactive protein, a biomarker for inflammation that plays an early role in heart disease.

Other proponents of personalized medicine, including Geoffrey S. Ginsburg, director of Duke University´s Center for Genomic Medicine, say that getting the science right is just one hurdle to making gene-based predictive tests part of the standard physical. Federal health agencies exercise little to no oversight of testing protocol or accuracy, or even of how a patient´s DNA should be safeguarded. None of the companies I bought tests from were suggested to me by a doctor; I did my own research, checking the reputations of their labs and that they´re run by bona fide geneticists. But for all I know, one of the labs with my DNA could be planting it at a murder scene right now. Then there´s the insurance issue: Few companies pay for genetic testing. And while the U.S. Senate has passed laws forbidding discrimination based on a patient´s genetic test results, the House has yet to follow suit.
I just hope my insurance company doesn´t read this.