Back in early 2010, molecular geneticist Michael Snyder, then a trim 54-year-old, decided to put his genetic blueprint under the microscope and make the results public. Swabbing saliva from his cheek with a sterile sponge and drawing blood to obtain his DNA samples, the Stanford scientist became the subject of one of the first clinical studies to analyze the blueprint of a healthy individual rather than someone known to be sick.
Snyder's study took advantage of recent technological advances that have now made it possible to rapidly and much less expensively sequence a genome—the instruction manual, contained in virtually every cell of a person, for making a human being. Containing some 3.2 billion pieces of genetic information, the genome determines a broad spectrum of human traits such as eye color, height, general health, and whether someone might be more likely to be a basketball player or a biologist.
What the Stanford researcher found surprised him. His genetic tests showed that he had a higher-than-average risk for developing adult onset, or type 2, diabetes even though he wasn't overweight, nor did he have any known family history of the disease. But during the 14-month study, in which Snyder's health was closely monitored using a battery of tests, his glucose levels spiked and remained high following a respiratory infection. Only after six months of increased exercise and a change in diet did Snyder's glucose levels drop back to normal, he and colleagues reported in the March 16 issue of the journal Cell.
The $1,000 mark. Without the genetic testing, Snyder says, he would not have known of his diabetes risk or been able to address it so quickly. And with the cost of genome mapping already as low as a few thousand dollars and likely to reach a much-ballyhooed benchmark of $1,000 by next year, Snyder and other scientists see the procedure as a crucial part of medicine for everyone, not just the affluent or the curious.
Many experts, though, like Eric Topol, director of the Scripps Translational Science Institute in San Diego, caution that science is only in the embryonic stage of understanding the composition and inner workings of the human genome. Essentially, each person carries two copies of each gene—one from each parent—in every cell (except mature red blood cells). Within these cells, genetic information is divided into 23 pairs of smaller packages, called chromosomes, that store the 20,000 or so genes in the human body, along with other bits of genetic information. The genes in turn are made up of deoxyribonucleic acid, or DNA, molecules whose two strands wrap around each other like vines, forming the iconic double helix structure. Using a four-letter alphabet, scientists have identified and labeled the four building blocks, or bases: adenine (A), thymine (T), guanine (G), and cytosine (C), which combine in each DNA molecule according to precise rules, somewhat like the rungs on a ladder. An A must always seek out a T on its partner strand, while a G must always pair with a C.
If the bases are the musical notes that make up the genome's keyboard, then their exact ordering determines whether the genetic symphony is harmonious or discordant. Just as extra or missing notes can wreck a musical passage, an extra or missing A or T can increase a person's risk of developing a particular disease or, in rare cases, cause an incurable illness.
The challenge with genome mapping is that large portions of the map reflect uncharted territory. Researchers understand the role of genes in the body fairly well: They dictate how proteins—the compounds necessary for building and repairing muscles and other tissue—are made. But protein-coding genes account for only 1.5 percent of the human genome. A lot of the action appears to be happening in the other 98.5 percent. Once referred to as "junk DNA," this vast but little-explored portion of the genetic blueprint is now believed to play a critical role in regulating gene activity and carrying out unidentified functions that contribute to a person's being predisposed to a disease.
"People will need to be prepared for the fact that these tests are so new that the physician may have limited ideas of what to make of it and what to do with it," says genetic counselor Barbara Biesecker of the National Human Genome Research Institute in Bethesda, Md.
To test or not? So should a person who is free of ailments consider getting his or her genome mapped now, or as soon as the procedure hits the $1,000 mark? The answer appears to be a definite maybe. For some rare diseases like Huntington's, a single, easy-to-spot mutation means that an individual will inevitably develop the fatal illness. Similarly, certain other gene mutations confer a 60 percent risk that a woman will develop ovarian or breast cancer in her lifetime, five times that of women who lack the flaw. Knowing this, the woman could undergo early screenings for these cancers or even opt for elective surgery before the disease gains a foothold.
Most mutations, though, aren't of the all-or-nothing type. Instead, they confer only a small increased risk of developing a particular disease. People should keep in mind that such test results have limited value, says Biesecker. Individuals also may not want to know their risk for diseases they can do nothing about. "I'm just really worried about people who don't know what they're signing up for and what information they could get back," she says.
Mapping a subset of the genome, though, can be of enormous help in determining which drugs a person may be acutely sensitive to, or not respond to, because of the way the body metabolizes certain compounds. Some of these drug-related genetic tests (though not a map of the entire genome) are covered by health insurance. For example, before prescribing the blood thinner warfarin, used to treat some types of stroke and heart disease, many doctors do genetic testing to determine the optimum dosage. Some breast cancer patients are similarly tested to see how much of a particular protein, associated with an aggressive form of the disease, their genes produce. A drug targeting that protein may then become part of the treatment. "For most cancers, though there is not a requirement for a genetic test, it is the obvious thing to do," says Snyder.
But when it comes to getting the entire genome mapped, even researchers intimately involved with the testing have declined. As Biesecker says: "Perhaps I'm too much of a cynic, but there's not too many things you can benefit from knowing ahead of time before you start having symptoms."
Jeffery Schloss, program director for technology development coordination at the National Human Genome Research Institute, adds that most people can glean better information from a family history—at least for now. But Harvard Medical School geneticist George Church disagrees. He is director of the Personal Genome Project, which aims to map the genomes of 100,000 volunteers willing to make public their genetic sequences, along with medical and health records. Church notes that new genetic mutations or combinations occur all the time and may not be apparent in family histories.
The process of getting your genome mapped is relatively simple: A blood sample taken in a doctor's office is mailed unrefrigerated to one of a handful of genome sequencing companies, which chemically extract and dry the genetic material into a tiny pellet. Within weeks, the genetic code contained in the pellet is cracked open using electrical or chemical techniques and a report is sent to the designated doctor, who can interpret, for example, what dosage of a particular drug to administer. The code may also be recorded on a flash drive.
The ease of the procedure and its dropping cost are likely to attract others to have their genomes mapped. Though experts still debate the benefits, improvements in interpreting people's genetic codes will likely make such testing an increasingly valuable tool in the delivery of more individualized and effective medical treatments.