MILWAUKEE - Glinda Stephan was a little girl when Joseph's disease claimed her mother's legs and then her life. Since then, each of her five siblings has developed symptoms of the inherited disease, which can leave its victims with slurred speech, numb limbs and blindness.
When a test became available, Stephan resisted taking it. "There is no cure for it and nothing you can do," said the 47-year-old Rice Lake, Wis., resident. "What good does it do to know?"
That is the central question facing medical science today as technology based on the mapping of the human genome promises to revolutionize health care in much the same way that immunizations and antibiotics changed the practice of medicine.
For Stephan, the answer came sooner than expected. Her son, Garrett, struggled with worries that his mother had the disease and had passed it on to him. Why should he bother going to college? No way would he risk passing the disease on to a child. "That's when I said we would get tested," Glinda Stephan said.
Specialists gave her an exam, took a blood sample and told her to wait for the results.
She waited and prayed.
It was a genetic test that searched for the rare medical condition afflicting Stephan's family. In much the same way, genetic tests could be developed for many types of human ailments.
And while those test results could lead to preventive measures and more effective treatments, they also raise new questions for patients with a genetic predisposition for a deadly disease and health care insurers who will pay - or avoid paying - for treatment.
Follow-up genetic research to the National Institutes of Health's Human Genome Project, which attempts to identify the more than 30,000 genes in human DNA, promises to give doctors advanced tools that allow them to tailor treatments to patients.
Specific genes have been detected that underlie prostate cancer and certain kinds of breast cancer, cystic fibrosis, heart ailments and blood-clotting problems. The goal is to find the genes, develop systems to interpret the mountains of information and manufacture gene tests that can be used in the doctor's office.
Genetic research has provided tests that can tell whether a person is likely to develop breast cancer, colon cancer or Huntington's disease. More gene-based tools are on the way to show whether someone is vulnerable to other maladies.
The day could soon arrive - as it has overseas - when genetic tests for certain conditions are available over the counter.
This personalized medicine is becoming possible as researchers decipher what once were unsolved mysteries deep within a patient's genetic code. The revealed information indicates which drugs are best for a specific person, how much to prescribe and which medications are likely to cause life-threatening side effects.
"Every institute at the National Institutes of Health funds genetic research. And they would not be investing this much money if they felt there would not be some payoff," said Alan E. Guttmacher, deputy director of the National Human Genome Research Institute at the NIH.
Some foresee the day when every newborn is genetically screened for hundreds of possible diseases. This information, along with other genetic data, could be compressed into a data-storage device and worn on a chain around the neck. Call it DNA on a disc.
The day of the disc will arrive, said Lance Fors, chairman and chief executive of Third Wave Technologies Inc., a Madison, Wis., company manufacturing genetic test kits that physicians could use in their offices. The Third Wave genetic tests - as with other companies' - also aim to help remove physicians' guesswork on proper medication dosages.
The knowledge that a person has genes linked to heart disease could be extremely valuable. Many lives could be saved if genetic tests could identify those at risk and target them for preventive treatment, said Ulrich Broeckel, director of the Human Genetic Resource Center at the Medical College of Wisconsin in Wauwatosa.
Although a few effective genetic tests are available, it could be years before genetic research reaches its full potential as the underpinning of medical treatment. The more researchers learn, the more complexities they uncover.
"There can be one gene mutation or hundreds that account for a disease," said Jim Burmester, senior scientist at the Marshfield Clinic, where a project is under way to examine 40,000 longtime patients and then compare their medical records to their genomes.
But the gene genie is out of the bottle. Myriad Genetics of Salt Lake City has a pilot project to market genetic tests directly to consumers in Atlanta and Denver. For years, the biotech company offered genetic tests through physicians to find mutations in two genes strongly linked to inherited breast cancer.
These mutations cause only a small number of breast cancer cases - fewer than 5 percent. But if breast cancer runs in a family, women might want to know whether they carry a gene mutation called the BRCA mutation. Some healthy women have had breasts removed to head off the disease.
The tests range from $325 to $2,760, depending on the extent to which the genes are examined.
"If a woman knows in advance, she can consult with her physician and take certain measures," said William Hockett, Myriad's vice president of corporate communications.
The University of Michigan Cancer Center in Ann Arbor is developing a database of tissue samples and genetic data linked to patient outcomes for a variety of cancers. Depending on genes, treatments could be very different for two cancer patients with the same type of cancer. The analysis will consider not just the genetic makeup of the patients, but also a molecular examination of the tumor and its genetic composition.
Through the developing science of pharmacogenomics - the study of how a person's genetic inheritance affects the body's response to drugs - a cancer patient could one day simply swallow a pill to block the gene proteins feeding a tumor's growth.
In prostate cancer, new genetic research shows which tumors are more life-threatening. "If you wait long enough, most men get prostate cancer. But in some men, it is aggressive and kills the man. For others, it just sits there," said Max Wicha, director of the UM Cancer Center.
Arul Chinnaiyan, assistant professor of pathology at Michigan, said he has identified 55 genes that are significantly linked to prostate cancer. With nearly 200,000 cases diagnosed every year, prostate cancer is the second-leading cause of cancer deaths among men, after lung cancer. And the aggressive, metastatic form kills more than 30,000 American men each year, he said.
Surgery and other prostate cancer treatments put men at risk for impotence and urinary incontinence. By screening out patients who don't have the genetic disposition for prostate cancer to turn deadly, an effective test would limit the risk only to those who really need to take it.
Even when genetic testing doesn't lead directly to treatment, a little knowledge can be a beneficial thing. Patients with a genetic risk of heart disease, for instance, would know to better manage their diets, exercise and stress. "If we can identify which diseases people have an increased risk of developing, they could make changes in their lifestyles to reduce those risks," Chinnaiyan said.
But "we don't know what the impact will be on health care costs," said the NIH's Guttmacher. "If people can live longer, they will need more medical care, so it is a pretty complex kettle of fish."
That's not the only kettle of fish opened by personalized medicine.
"The fear is that a health insurance company will get test results and refuse to insure someone," said Larry Rambo, Wisconsin and Michigan chief executive officer for Humana Inc., a health insurance company. "I cannot imagine that happening, and I cannot imagine the legal and regulatory systems allowing that to happen."
Still, no federal legislation protects against genetic discrimination in the workplace or in the sale of individual insurance policies, said Eileen Mallow, deputy assistant in the Wisconsin Office of the Commissioner of Insurance.
Wisconsin law forbids genetic discrimination in group health insurance but not in life insurance. No state law prohibits life insurance companies from asking a potential client to take a genetic test, said Robyn Shapiro, director of the bioethics center at the Medical College of Wisconsin.
The potential exists for employers to try to avoid hiring workers who they believe are likely to become heavy users of health care, miss work or retire early for health reasons. In the future, she said, some employers may use genetic tests to discriminate against employees who have not yet become ill.
"It is important for people to realize how important and specific this information is and the potential for discrimination," she said. "You should know the impact the test will have on your life.
Rambo said the health insurance industry expects to pay for more genetic tests as they come on the market.
Gene testing could save untold lives through prevention and early detection. But until the human genome is completely fathomed, the question remains: Should everyone know what diseases lurk in their futures?
Perhaps not everyone. But a genetic test answered the prayers of Glinda Stephan, the Rice Lake woman with a family history of a rare neurological disease.
When the results came in, Stephan asked a friend to join her on the 125-mile drive to the Marshfield Clinic, where she met a doctor and a genetic counselor. "They said, 'You can tell your son he can have grandbabies,'" she said. "I was just in shock. It was like a million pounds lifted off my shoulders."
This year, Stephan added a task to her holiday to-do list: buying Christmas presents for her granddaughter, Isabella Brynn, who was born Sept. 6.