MY MATERNAL grandmother had Alzheimer’s disease. Before she died, she forgot our names, our faces and, eventually, how to speak and think.But my grandfather’s heartbreak was the most painful to witness. I remember watching the two of them on the sofa together in the months before she died. My grandfather, a sometimes severe man not overly disposed to expressions of tender emotion, cooed into my grandmother’s ear: “My bride, oh my bride. I love you. Do you hear me? I love you.” She just stared down blankly, folding napkins.
That scene was burning in my brain last week when I received an e-mail from a company that offers extensive genome scans directly to the public. The e-mail told me that my tube of spit had been analyzed and the results were in. I logged onto my account and began to scan the report for my estimated genetic risk for 17 diseases and conditions.
Breast cancer, colon cancer, Type 2 diabetes: normal. Strangely relieving. Obesity: a little above average (I do not come from thin people).
Heart attack, multiple sclerosis, rheumatoid arthritis, macular degeneration: all a little below average. Even better.
And then there it was, in an orange “warning” box on my Web browser: a significantly higher-than-average lifetime risk for late-onset Alzheimer’s disease, the most common type of this devastating disorder. The average risk of late-onset Alzheimer’s is about 17%. Mine is 29%, owing to the DNA letters I carry in a gene called APOE, which contains coding instructions for a protein involved in processing cholesterol. It comes in different forms, or alleles -- and in my case, one of the copies I carry confers higher risk.
Before I could process a coherent thought, I burst into tears. Alzheimer’s might be decades away for me -- I am not yet 30, and the late-onset disease strikes after 65 -- but that risk allele didn’t pop up in my genome out of nowhere. In all likelihood it came from my mother, who just turned 60. My mother -- who already has high cholesterol, a known risk factor for Alzheimer’s disease.
I was surprised by my reaction. It wasn’t exactly news, was it? Family history alone told me that my mom is at higher risk of Alzheimer’s just by being her mother’s daughter. And the risk is not excessively high; this is by no means a guarantee that either of us will succumb to the disease.
But something about the plain and simple statement of my own genetic fact seemed shocking and terrifying.
“Genetic information has a special power,” says Dr. Robert Green, professor of neurology, genetics and epidemiology at Boston University School of Medicine. “It has a feel of fate about it, a sense of inevitability, that sense that, ‘Oh, you are marked.’ ”
The test I received was from Redwood Shores, Calif.-based Navigenics, the latest company to offer personalized genome scans directly to consumers. Its launch last week follows fast on the heels of the Google-backed start-up 23andMe and Iceland’s deCODEme, which both debuted in November.
The companies, which scan the entire genome for telltale DNA variations linked to traits or diseases, are the splashiest manifestation yet of tests the public can buy to learn their genetic risk for a range of conditions including breast cancer, glaucoma, baldness, more.
Cost of knowing
They don’t come cheap. Navigenics charges $2,500, plus a $250 yearly fee for scientific updates. The other two charge about $1,000. Navigenics justifies its higher price because it offers unlimited genetic counseling.
But the companies say their services offer something precious: the chance for people to take control of their health and destiny. “The whole goal here is to tell people whether they are at increased risk so they can do something about it,” says Dietrich Stephan, Navigenics co-founder (with Dr. David Agus of the Cedars-Sinai Medical Center) and a research director at the Translational Genomics Research Institute in Phoenix.
Some scientists agree the tests could carry special behavior-changing clout -- more than a public service message could ever do. “The public knows what is good for them. They could tell you like robots what it is. But they’ve become desensitized to it,” says Colleen McBride, chief of social and behavioral research at the National Human Genome Research Institute. “One could argue that genetics is like über-personalization . . . it is reasonable to think that it could get their attention.”
But many doctors and researchers have voiced concerns over this technology hopping straight from lab bench to Web browser. They say the science of genomic medicine is in its infancy, yielding research-grade information not yet suitable for public consumption. And some raise issues of privacy.
Some researchers say it’s unclear whether people will understand the genetic risk data and what they will do with it. Is this just a bit of harmless fun? Will it improve long-term health outcomes? Or will hypochondriacal patients march to their doctors and demand truckloads of unnecessary tests, harming themselves and the healthcare bottom line -- while others incorrectly see their results as destiny and adopt worse lifestyle habits? (What’s one more T-bone if you are fated to die of a heart attack anyhow?)
“On the one hand we are excited by technology and its promise, but on the other hand, we want to make sure that the public’s health doesn’t get hurt,” says Dr. Muin Khoury, director of the National Office of Public Health Genomics at the Centers for Disease Control and Prevention in Atlanta.
No matter how grave the concerns, genetic research is speeding ahead. Almost every week these days, genetics researchers are coming up with new DNA variations linked to some disease or another.
Some scientists think the information should be available for people to use.
“I personally started getting very frustrated doing all this research when there was nothing waiting on the other side of the fence waiting to implement it,” says Stephan, the Navigenics co-founder.
Now, with the advent of an enormously successful research tool called the genotyping chip, it is finally inexpensive enough to offer these scans to the public (see accompanying story).
Navigenics, 23andMe and deCODEme all use such chips to analyze DNA in spit or cheek swab samples sent in by customers, using them to detect as many as 1 million DNA variations known as SNPs: single nucleotide polymorphisms.
Very few SNPs have been associated with disease, and even fewer still reliably so. But as science progresses and links more SNPs to diseases, the companies aim to update their databases.
When 23andMe first launched, it offered information on about 20 diseases and traits (including earwax type and bitter-taste perception). Today, that number is 58 (deCODEme offers 26 and Navigenics 18 -- 17 each for men and women, including prostate and breast cancer respectively).
for On 23andMe’s website, each disease is listed as either “Established Research” -- findings generally confirmed in at least two studies of 1,000 people or more -- or “Preliminary Research,” findings that have yet to be repeated and validated.
“We want to buck the paternalistic attitude,” 23andMe co-founder Linda Avey says of the company’s rapid addition of new conditions even when the science is tentative. “And if anything, what we are hearing back from our customers is ‘We want more.’ ”
In addition, 23andMe and deCODEme give their customers the opportunity to search their raw results -- all those hundreds of thousands of SNPs, and check them for the latest genetics result. So when a new study is published suggesting that smokers who carry two DNA letter “T"s at position “rs1051730" in the human genome tend to smoke more cigarettes and get more lung cancer -- as was published April 3 in the journal Nature -- customers can head straight to their accounts, type in “rs1051730" and see where they fall.
Navigenics has taken a more conservative approach. If, for example, I want to get my entire genome scan, which I certainly do, I must sign a waiver acknowledging that any of the SNP-disease associations I might Google myself are likely to be spurious. Only then will the company send me the file on an encrypted disk.
“We will take responsibility for the information we believe is real,” Stephan says. “For everything else, you can have your genome to play with. But without our blessing, the potential for misinformation is extremely high.”
It might not be smart, but I just can’t help myself. I want to know everything.
For the conditions with full reports, there are ample resources to help explore results. All three companies’ websites are packed with explanatory graphics, background information, the biology of diseases, links to disease associations and expert medical opinions. At every turn, the sites try to make clear that risk profiles are estimates, not diagnoses. “It is really complicated information in a lot of ways,” 23andMe co-founder Avey says. “That’s our challenge. How do we distill this information down and write it in language that everyday people can understand?”
The Navigenics site emphasizes strategies to reduce your risk and offers free, unlimited access to genetic counselors to make sure that people understand the ocean of numbers in front of them. Also, there are tips for talking to your doctor and advice for taking the printouts to an appointment.
My DNA turned up a heightened risk of glaucoma -- almost three times the average. As it happens, I just got a reminder card in the mail to see my optometrist for a check-up. Even though genetics plays a very small role in development of the disease, I’ll be sure to let him know, so he can poke my eye and check for increased pressure. Why not?
Do scans help or harm?
But no amount of transparency, caveats, tutorials or access to genetic counselors can satisfy the concerns of many critics: bioethicists, doctors and health economists who worry that the newness and unreliability of these genetic data make the services, at best, a waste of money and, at worst, a threat to public health.
For one thing, Khoury says, despite the high-tech wizardry of genome scans, most of the advice available so far is just common health sense: Don’t smoke, do exercise, eat a healthy diet, maintain a healthy weight, keep your blood pressure and cholesterol in check, and go for your regularly scheduled tests. What’s more, most of the risks revealed by these tests are pretty small. The really potent genetic effects are probably obvious from family history alone.
“If someone asks me, shall I take [the test],” Khoury says, “I would say ‘No, you don’t need it. Tell me about your family history. If you have a family history of skin cancer, stay away from the sun. If you have osteoporosis, take calcium supplements.’ We know what to do.”
Dr. H. Gilbert Welch, professor of medicine at Dartmouth Medical School, is also wary. A longtime critic of what he sees as an epidemic of over-diagnosis in the U.S. healthcare system, he thinks genome scans will make matters worse, especially because most doctors have little genetics training.
“I think a broad-spread application of personalized genetic testing would create havoc and would likely lead to more harm than good,” he says. “It will make people anxious, and it would probably push doctors to more aggressive interventions simply because of lack of information and a feeling they had to do something.”
Then there’s the issue of privacy. In the U.S., there is still only limited protection from genetic discrimination. The Genetic Information Nondiscrimination Act, which would protect individuals against discrimination based on their genetic information when it comes to health insurance and employment, is stalled in the Senate, though it has passed in the House of Representatives.
The Washington, D.C.-based Genetics and Public Policy Center is also pushing for the Food and Drug Administration to regulate consumer genetic testing.
The center’s director Kathy Hudson says that though these three genome-scanning companies appear scientifically stringent and transparent in their messages, there are no laws to prevent businesses from over-selling results or providing inappropriate tests, as some have done.
Ultimately, it will take extensive research on people receiving genome scans to reveal whether they offer real, long-term health benefits or evidence of harm. Will learning that a propensity to heart attacks lurks in your DNA finally give that extra push to cut back on the T-bones, take the stairs and finally stop smoking? Will knowing that you are loaded with cancer risk alleles hurry you to early screening?
One such study began last year. Headed by McBride and Lawrence Brody at the National Human Genome Research Institute, it will offer subjects the opportunity to be tested for eight conditions, including skin, colon and lung cancer; heart disease; and Type 2 diabetes.
The team will follow subjects from their earliest interviews all the way to their doctors’ offices, kitchens and gyms to try and determine who seeks testing and why, if they understand their results and what they do with them.
Navigenics announced Tuesday that it will be partnering with scientists at the Mayo Clinic to study how its customers use the results. Customers like me.
So what am I going to do? I don’t quite know yet.
Had I seen an increased risk of breast cancer you can bet I’d be feeling myself up every other Tuesday and pushing for an early start to mammogram screening.
My lifetime estimated risk for obesity is 36%, just above the population average of 32% -- a higher risk because I carry two copies of the “fat gene” FTO, discovered last April. Obesity is a risk factor for several diseases -- cancers, heart disease -- so I’ll work hard to keep my weight within a healthy range, and will probably have to keep working all my life.
Does this genetic information give me the motivation to ride my bike to work and not eat that last cookie? Sure. But did I already have that motivation? In spades.
I’ve told my parents about the Alzheimer’s results, and I am pushing my mother to talk with her doctor about taking statins to bring down her high cholesterol.
She half-laughs me off because she is already doing lots of the “right” things. She has low blood pressure; takes multivitamins and folic acid supplements; eats healthfully, including lots of fish and olive oil; keeps her mind and body active with knitting, a busy social life and regular exercise.
So maybe I should sit back and chill. Maybe the statins would hurt her in the long-run. But when scary orange boxes glare at you from your computer screen, it’s hard. You just want to do something.
That is the potential power of these tests. Whether that power urges us toward healthy change, paranoid medical flailing or nothing at all, is still an open question. But as private genome scanning companies drive the science of genomic medicine forward, we’ll find out soon enough.