Researchers are identifying the genes that could cause disease in our own bodies. But how much do we really want to know about what lurks within us?


Five years after the Human Genome Project succeeded in mapping a rough draft of our complete genetic design, a new breed of genetic code breakers is discovering that it points the way to moneymaking enterprises.

There are now some 830 genetic tests to identify more than 1,000 ailments, and the number of tests is swelling as researchers continue to sleuth out genetic mutations that hold the key to our health — or lack thereof. “We are now at the beginning of seeing the fruits of the Human Genome Project enter into health care, and that is potentially hugely valuable to patients and their providers,” says Kathy Hudson, PhD, director of the Johns Hopkins Genetics and Public Policy Center.

That value has also attracted a growing number of genetic tradesmen to the field, from academics with impeccable résumés to dedicated entrepreneurs to a 21st-century version of the snake oil salesman. These pioneers of the testing business have been making up rules as they go along — because, like in the Old West, genetic testing is brand-new territory, where there are no rules.

Done properly, a genetic test can accurately pinpoint a potentially devastating health threat such as cancer. Coupled with advanced pharmaceutical technology, testing sometimes can identify the drug your body can best use to beat that same threat.

Meanwhile, predictive genomic tests can warn of dangers that lie dormant inside our bodies, and they can alert us that we may be predisposed to diabetes or breast cancer. Because this field is so new, regulations are still being developed, and the field is way ahead — and, critics would add, sometimes far afield — of mainstream medicine.

Some genetic-testing companies require tests to be ordered and interpreted by doctors. Others appeal directly to — and deliver results directly to — consumers. Critics say that, in the wrong hands, the results of a predictive test would be useless. Geneticists contend that the worst abusers offer hocus-pocus diagnoses that are more in line with medieval medicine than modern health care.

One point, though, everyone can agree on: Genetic testing will usher in a new era of personalized medicine. It will eventually eliminate the crapshoot involved in deciding which drugs will work in which individuals, while giving all of us a much clearer guide to the particular health threats lying in wait as we grow older.

THE FUTURE OF MEDICINE
Back in 2000, the Human Genome Project finished what was then the working draft of a map of more than three billion paired chemicals that form the blueprint for human design. Each of us comes equipped with 20,000 to 25,000 genes inherited from our parents. They influence the color of our eyes, our height, and, most importantly for health care, our predisposition to disease.

Since then, scientists have been making steady headway in identifying specific genetic mutations, or biomarkers, that can trigger dozens of diseases, including breast cancer, lupus, sickle-cell anemia, and cystic fibrosis.

They’ve also figured out when and how those mutations can lead to actual disease. Each of us has two copies of every gene (except for sex chromosomes in males), one from each parent. A dominant disorder shows up when one of those two genes is defective, explains John Compton, who left his job as a researcher at the National Institutes of Health to launch GeneDx, which sleuths out genetic mutations that cause rare disorders. “With a recessive disorder, like cystic fibrosis, you need both copies of the gene to be defective,” Compton adds. “If just one is defective, you don’t have the disease.”

“The search for mutations is the future of medicine,” says Mara Aspinall, president of Genzyme Genetics, one of the most established testers in the field.

Mapping genetic mutations will help identify which people respond to which drugs, Aspinall explains. The average drug works for only 50 percent of patients. Some cancer patients undergoing chemotherapy, for instance, get only the side effects, and not the benefits, of the drugs. Now there are drugs being developed that are highly targeted at specific forms of a given disease. “Not lymphoma, but follicular lymphoma,” Aspinall says. “This will take drugs that are very marginal, only treating a subpopulation, and raise response rates to 90 percent.”

Genelex, a testing company that started out with paternity tests, now offers a DNA test it says offers insight into how an individual will metabolize — or process — drugs for a laundry list of conditions, such as depression, anxiety, seizures, high blood pressure, and heart disease. “This kind of testing is going to become routine,” says Howard Coleman, founder and chairman of Genelex.­ “We saw a 350 percent increase last year, and we’re on track to do that this year.”

IDENTIFYING HIDDEN WEAKNESS
Of course, the testing isn’t limited to pairing drugs with patients. At a cost of anywhere from several hundred to a few thousand dollars, genetic profiles also can identify potential trouble spots ticking inside our bodies.

A little more than a year ago, DNA Direct went online with the first of what is now 10 genetic tests. HealthCheckUSA in San Antonio has a host of DNA tests, including one for celiac disease, an autoimmune intestinal disorder that can be treated with a restrictive diet. But the most popular tests are the ones that scan for scarier biomarkers.

“I would say that the one that has the greatest interest from consumers is for breast and ovarian cancer,” says DNA Direct founder Ryan Phelan. That’s not surprising, she adds, given the amount of media attention that both cancers command — and given the role that genetic mutations play in those diseases. A mutation can up the odds for breast cancer to a statistically chilling 85 percent, and 45 percent for ovarian cancer.

To be tested, people visit a lab in their area, where blood is drawn, tagged with a unique identifier (to protect the person’s identity), and sent to DNA Direct’s testing center. The test is actually performed by Myriad Laboratories, a highly regarded institution that Hudson credits with a solid reputation for good science. The people who have the genetic mutations that predispose them to cancer are given a 50- to 70-page web-based report that spells out what the dangers are and how they can take that information to their doctor.

Identifying their genetic vulnerabilities can help people in a variety of ways, Phelan says. For instance, identifying a gene that runs in the family can help parents make decisions about preventive measures that their kids might take. “If I’m a mother with breast cancer, I want to know for my children if I’m carrying a gene that puts them at risk,” she says. Knowing the genetic code that spawns your cancer can affect treatment decisions, too. Certain mutations are known to produce tumors that metastasize swiftly if cancer develops. A woman facing surgery might choose a radical mastectomy over a lumpectomy if she suffers from the type of breast cancer that carries added risks.

DEALING DEATH SENTENCES
The rapid proliferation of genetic tests has caught the eyes of medical geneticists and bioethicists, who have begun to ponder the consequences. Earlier this year, Hudson hosted a symposium on genetic testing. It included everyone from geneticists to testing executives.

“We became attentive to the increasing number of companies advertising genetic testing direct to consumers, usually over the Internet,” says Hudson. One of the key issues: “looping out” the health-care provider, or testing someone without the knowledge of his or her doctor. The group brought up concerns about advertising genetic tests, and some thought it should be illegal.

Genzyme works solely through physicians, the designated middlemen whose role it is to explain the outcome of specific tests. Phelan opened DNA Direct with doctors and genetic counselors on staff, ready to help customers interpret their test results.

“When somebody orders a test online, a genetic counselor calls,” Phelan says. “Obviously, testing has an impact on any woman or man, and we want to make sure the right person in the family is tested. At the end of the day, when we prepare the report, our counselor … will walk you through the report the same day.”

But anyone can go on Genelex’s website and order up its drug-metabolization test. In fact, the company’s foundation has been consumers, not doctors, Coleman says. “Up until recently, [our growth] has been largely driven by individuals,” he says. “But we’ve seen physicians get more and more involved, even over the last year.”

Coleman won’t, however, offer the public a specific test to determine genetic disease. “If you’re giving a test for Huntington’s [an untreatable, degenerative brain disease],” he says, “you don’t want to send the results in an e-mail, because, let’s face it, that’s a death sentence. It needs to be handled by a medical geneticist.”

Genetic testing conjures up plenty of scenarios as chilling as Coleman’s. What if a testing group simply issued written notices of their results, leaving people holding pieces of paper saying they are prime candidates for a lethal case of cancer — with no counseling about those results or on how to respond? An advertising ban would at least leave more of the testing in the hands of professionals who know how to interpret results and who can suggest steps to take.

But the idea of an advertising ban didn’t gain much traction with the geneticists.

“We basically concluded that free speech protections that apply to commercial free speech would never allow you to put restrictions on advertising,” says Hudson.

The complaints about testing beyond the ken of primary-care physicians didn’t do much better.

“We’re not entirely convinced that health-care providers are so good at ordering or interpreting genetic tests,” Hudson says. “The idea that you have to have a provider involved is not completely convincing.”

The Johns Hopkins Genetics and Public Policy Center believes that there should be more government oversight. “What we really need to have in place is a gatekeeper at the point at which these tests are entering commerce,” Hudson says. “We shouldn’t regulate access, but we shouldn’t have access unless somebody has said, ‘This test really works.’ ”

Case in point: One Internet site offers tests to determine whether someone is genetically predisposed to various addictions. Hudson openly scoffs at the claim that these tests can predict addictive behaviors, because the science isn’t there yet. “Some of these tests being offered have been around for decades; they’re scientifically validated, and their interpretation is very clear-cut,” Hudson says. “And there are other tests being marketed that are hocus-pocus.”

PRIVATELY HELD?
For now, the call for a physician’s involvement in every patient’s genetic testing may be disingenuous. After all, information in a doctor’s files becomes part of a patient’s medical record and is accessible by the insurance companies that pay the bills.

But a privately arranged genetic test, like one from DNA Direct, can remain private, Phelan says. “[Customers] don’t want the insurance company to know,” she says. “Genetic risk is not a preexisting condition, but at some point, the insurance company can say it is.”
Unless, of course, Congress stands in the way. The Senate overwhelmingly passed a bill last February that prohibits insurers or companies from discriminating against someone based on their genetic information. Essentially, the law would stop a company from demanding genetic tests or ­tailoring health insurance rates to a person’s genetic profile. While the House companion bill has been hung up in committee, federal lawmakers are following the path of more than 30 states, which have put local prohibitions in place.

Advocates say that the lack of a clear law outlawing genetic discrimination will discourage people from being tested — or even from signing up for the clinical studies needed to advance the field. Who, after all, would want to share information that their DNA carries an embedded risk of a potentially catastrophic disease? Individual Americans have repeatedly maintained that genetic information should remain completely confidential. In a recent survey by Johns Hopkins, 94 percent of people said they would want their genetic information kept private from their employers.

And pressure for new legislation is likely to keep building as genetic data becomes increasingly accessible. Researchers at Harvard Medical School say they have developed new technology that will eventually­ enable the sequencing of an individual’s entire genome for as little as $1,000. Over the next five to 10 years, a growing body of knowledge will give people an unprecedented look at their own physical blueprints.

“What won’t be available?” says Hudson. “A genome contains all the instructions for how our body behaves, is structured, and functions. We will find the genes that cause disease.”

And the tests that screen your body for every one of those genes will quickly follow. Exactly how the testers will be put to the test, though, is one of the few remaining mysteries in the field.



John Carroll is an Austin, Texas-based freelancer who writes regularly about health-care and biotech issues.