Karen Kramer has lost track of the number of times she has lifted her shirt to show off her breasts. A dozen times? A few dozen? A hundred?
On a warm Sunday afternoon in late May, the slender, comely brunette did it yet again in a restroom at Suburban Hospital in Bethesda, Maryland. Her aim, as always, was to comfort rather than titillate. A vice president with Facing Our Risk of Cancer Empowered, or FORCE—an advocacy and support organization for individuals at high risk for hereditary cancers—Kramer was meeting with a cluster of women who carry a BRCA gene mutation, some of whom were petrified at the prospect of undergoing prophylactic mastectomies. Having been through the experience herself in 2009, Kramer knew just what to do. “Two women were so scared,” she says, “that three of us took our shirts off and showed them our chests.”
In the wake of Angelina Jolie’s revelation last month that, due to a genetic propensity toward breast cancer, she’d had a bilateral mastectomy, FORCE has been inundated with people wanting advice. “Calls to our toll-free help line have tripled or quadrupled,” says the group’s founder, Sue Friedman. But for all the fresh focus on breast cancer, the genetic issues at the heart of Jolie’s story have much, much wider implications for our society. Indeed, Lara Croft’s infamous breasts may be obscuring the degree to which genetic testing is poised to make many of us—male, female, young, old, rich, poor—into versions of the terrified women Kramer sought to comfort in that hospital restroom.
From cancer to Alzheimer’s to diabetes, advances in genetic science mean that many of us are soon going to know—or at least have the option to know—more about our risks for a wide range of illnesses than we’d ever thought possible. On the surface, that sounds like a good thing, and it is in many respects. But while knowledge may be power, genetic testing also brings with it tremendous practical and psychological fallout—fallout that American medicine may not yet be ready to handle.
True, the system is racing to adjust: there are now more than 30 master’s degree programs in genetic counseling, all of which are full every year; phone and online counseling services are popping up; and a growing number of health-care insurers are contracting with genetic counseling services. But for all of these efforts, our medical system remains very much in catch-up mode. As Lawrence Brody, an investigator with the National Institutes of Health’s Human Genome Research Institute, says of genetic testing: “We can order this stuff, but the number of people who can interpret and deliver it correctly is still pretty small.”
IN THE past two decades, the number of genetic tests available has jumped from a few hundred to nearly 3,000. Rebecca Nagy, president of the National Society of Genetic Counselors (NSGC), recalls that when she entered the field 15 years ago, it took a year to get the results of a BRCA test. Today, you get them back in a week or two.
What happens when a toddler’s exome is sequenced and the lab discovers the BRCA1 mutation?
As the cost of testing declines, says Brody, medicine is moving toward “multiplex testing for lots of things at once.” We’re at the point, he explains, where sequencing a person’s entire exome can be done for somewhere in the neighborhood of $1,000. “Whereas before it would have been really bizarre to have someone’s entire genome sequenced because it cost about the same as the GDP of several small countries, now it costs about the same as an MRI,” he says. “This puts it in the realm where such a test may be reimbursable and useful.”
With exome sequencing, a patient may go in with questions about his prostate and come out with a report showing increased risks for everything from blood clots to kidney disease. Such data points are known as “incidental findings,” and they are at the heart of the hottest ethical debate now raging in the field, says Nagy. “What results do you disclose to someone and what results do you withhold? And do you give patients that choice?” One commonly cited example: what happens when a toddler’s exome is sequenced to determine the cause of a developmental delay and the lab discovers that the child has the BRCA1 mutation? Should the lab withhold that information? What about the pediatrician?
Nagy explains that “a basic tenet of genetics is that patients should have autonomy”—meaning the right to choose what they do and do not want to know. But in March, the American College of Medical Genetics and Genomics issued a statement contending that, in the case of certain specific deleterious, actionable genes, doctors have an ethical obligation to alert patients to the discovered risks. Balancing this “duty to warn” with an individual’s right to autonomy is tricky enough on its own. But there are other complicating factors to consider. What if disorders are likely to impact other family members? (The courts, unsurprisingly, have already been dragged into this debate.) And what about all the mutations that will pop up but that we don’t yet understand? “The menu is probably more vast in terms of what you can look at than people are prepared for, and the results will contain more uncertainty than people are prepared for,” says Brody—and this goes for doctors and patients alike. “The medical system is not set up to say ‘We don’t know what this means’ in a ready fashion.”
Given these dilemmas, it’s no surprise that a lot of doctors feel lost. A study published this February in the NSGC’s Journal of Genetic Counseling found that, among 220 internists surveyed at two academic medical centers, “[m]ost rated their knowledge as very/somewhat poor concerning genetics (73.7%) and guidelines for genetic testing (87.1%). Most felt needs for more training on when to order tests (79%) and how to counsel patients (82%), interpret results (77.3%) and maintain privacy (80.6%).” This finding supports a conclusion many in the field more anecdotally suggest.
But it isn’t just medical professionals who face information overload. With the rise of direct-to-consumer test kits that enable people to skip the middle man (i.e., doctors) and order up their own reports on a variety of genetic markers, consumers too will find themselves struggling to navigate scientific terrain that lends itself to major misinterpretation. Experts note that a lack of basic numeracy is a significant problem. (Many people do not understand, for instance, that having a 50 percent greater risk for a disease that the average person has a 0.25 percent chance of developing is not cause for alarm.) So is the misperception that these tests provide the sort of clear yes/no answers people have come to expect from paternity tests or DNA analyses in criminal cases. Just because a patient—or even an entire family—tests negative for a BRCA mutation does not mean that there isn’t something going on in the gene pool, explains Kala Visvanathan, who heads prevention services at Johns Hopkins’ clinic for patients at high risk of breast and ovarian cancers. On the flip side, a positive result doesn’t mean someone is definitely going to get sick. “It is only one piece of the puzzle,” says Visvanathan. “One of the things people still need to be educated about is the difference between having a disease and being at risk for a disease.”
There’s a level of denial in very young adults. But as people start pairing up and settling down, the stakes of not knowing get higher.
Social worker Katie Berry has a front-row view of all the agonies and thorny issues that this new medical landscape is raising. Through Columbia Presbyterian Hospital in New York, Berry counsels men and women at high risk for Huntington’s, an inherited neurodegenerative disorder that typically manifests in midlife with some brutal combination of physical, cognitive, and psychiatric decline. A person with the Huntington’s gene can expect to get sick at some point down the road. There is no cure and, unlike with breast cancer, no preventive measures beyond maximizing general health with the aim of delaying onset.
Berry works solely with individuals not yet experiencing symptoms. Some have already been gene-tested. Others know that the disease runs in their family and are grappling with whether to get tested—and when.
This issue of timing is one that arises with many genetic markers, and can vary based on factors such as the degree to which risk increases with age and on the availability of medical interventions. “Risks change over time,” says Visvanathan. “This is a moving target.” With ovarian cancer, for instance, many younger women must weigh the risks of delaying (or foregoing) an oophorectomy (removal of their ovaries) with the desire to have children. Even for those not interested in parenthood, there are different hormonal and sexual repercussions to consider at age 27 than at age 67.
With no preventive options available for Huntington’s, the question of when to test is often dictated by looming decisions about marriage or parenthood. Most of the patients who come to Berry are in their 30s or early 40s. “People who are in their teens and early 20s tend not to be thinking about these things,” she explains. “There’s a level of denial in very young adults.” But as people start pairing up and settling down, the stakes of not knowing get higher. (People with the Huntington’s gene have a 50 percent chance of passing it to a child.) “They know there is this sword of Damocles dangling over their heads,” says Berry. But until the test is done, they can cling to the hope that they dodged the genetic bullet. “They think, ‘It’s possible I’ll never get it. It’s possible I can continue to live the life I’m living now,’ ” she says. “Knowing creates a whole other reality—a hugely different reality.”
Indeed, the news that one’s genome contains a potential time bomb presents numerous, excruciating psychological hurdles. Breaking the news to family can be a particularly rough part of the process, and not simply because of the heartbreak it brings loved ones. Learning that a family member has a particular mutation can suddenly force brothers and sisters, children and parents to confront unsettling questions about their own genes—questions that many people would prefer not to have raised at all. To facilitate sharing, medical facilities are increasingly providing aid and guidance. Visvanathan’s clinic invites patients to have family come in and talk with the staff. “We try to take some of that burden,” she explains. Hospitals at places like Georgetown University and the University of Pennsylvania often provide patients with letter templates tailored specifically toward informing family.
Then there’s the long-term challenge of living with a genetic specter lurking in the background. At times, the anxiety can be crippling, says Berry. “People talk frequently about how they go through periods—and I suspect it’s true of anyone who faces a chronic illness or potentially fatal disease—periods that last days, weeks, months, or even years when there’s a hyper-alertness about the body.” Every twitch, twinge, or tickle spurs a raw terror that the illness has begun to take hold. “People say they’re convinced they have the disease even though there’s nothing obviously symptomatic about them,” Berry says.
FOR THE medical community, addressing these challenges will mean changing medical-school curricula and investing in continuing education. “It means us going out to physicians’ offices and helping them understand when it’s appropriate to refer a person to a genetic counselor,” Nagy says. “It’s making them feel comfortable that, once referred, their patients will come back to them for ongoing care.”
Much more broadly, the general public is increasingly going to need a grasp of genetic basics to better manage their health, says Visvanathan. “Maybe the genetic aspects of health need to be brought into schools,” she posits. “Informing people at a young age would be helpful.” Where and when this education should take place is, in fact, already under discussion. “I was at a conference last year in Boston where people were talking about how to educate elementary schoolkids,” Nagy recalls.
Equally important, there will be a need for more organizations to do the simple work of linking those facing similarly cloudy futures to one another. Having a support network of others who understand the fears, thoughts, medical peculiarities, and even the language of your disorder makes a huge difference, says Berry. “You see a positive effect when people realize that they are not journeying alone.” In some cases, just having a regular chance to vent provides a measure of relief. “We have heard from patients that they love the support group because it allows them to gather all that negative energy, worry, and anxiety and spew it out in a one- or two-hour period,” she says. “Then the rest of the month they don’t have to think about it so much.” But the anxiety never fades entirely, says Berry. “It’s always present, always niggling.”
Such is the burden of knowledge—and, more specifically, foreknowledge. It is a burden more and more of us are going to have to decide whether to assume and one that our medical system is just beginning to learn how to help us shoulder. “This really is a slightly different paradigm for medicine,” says Brody. “It’s going to take a lot of work.”