A genetic test a few years ago told Catherine Afarian and her husband that their future child would have a 50 percent chance of inheriting brown eyes, 30 percent of having green eyes, and 20 percent blue. That same test indicated that she has a decreased risk for Alzheimer’s, and an increased one for colorectal cancer.
Afarian’s “genetic experiment,” as she calls her son, unsurprisingly ended up with brown eyes. Her risk results though were a bit unexpected: the Alzheimer’s results were a relief because she has a family history; the cancer results were a good thing to know because she doesn’t.
Afarian is the spokesperson for 23andMe, a privately held direct-to-consumer, or DTC, genetic-testing company based in Silicon Valley. The company is at the forefront of a growing movement to bring the rapidly evolving world of genetics into the hands of consumers, making their information accessible and affordable for the first time.
“As a company, we fundamentally believe your DNA is yours, you own it, and you should have access to it,” she says. “It’s our mission to tell you everything science can.”
However, when it comes to genetics, science doesn’t know everything. And since what science can tell us about genetics is constantly changing, accurate interpretation of the results is potentially out of step with the rapid growth of testing technology.
23andMe and the World of Genetic Testing
23andMe and other DTC genetic-testing companies have boomed in recent years, with hundreds of thousands using the services to learn about their DNA. In 2007, 23andMe’s first genome service cost $999 and provided 14 genetic reports; today it is $99 and offers 254 different reports.
These reports are limited to diseases or conditions that researchers have some information about. 23andMe offers reports in four categories: carrier status, disease risk, drug response, and traits. These range from cystic fibrosis to Parkinson’s to antidepressant response to sex-hormone regulation. “Asparagus metabolite detection,” under traits, will rank the odds of smelling asparagus in your urine.
“Asparagus metabolite detection,” under traits, will rank the odds of smelling asparagus in your urine.
A genetic test through a doctor would typically be either a specific test for a specific mutation to confirm a diagnosis, or a broader diagnostic test looking for markers across the genome associated with disease states. But 23andMe analyzes about 1 million of the more than 10 million single nucleotide polymorphisms in the human genome and reports findings for a range of characteristics.
Selecting certain SNPs from the genome helps 23andMe keep costs low. Consumers simply mail in their saliva and 23andMe sends it to a certified lab. Two to four weeks later, the reports are available securely online.
“The assumption is that at some point [23andMe] will move to whole sequencing — but at a price point for consumers,” Afarian says.
The growth of these consumer tests holds great scientific promise, but also raises the question of uncertainty on the interpretation side.
For 23andMe, inaccuracy in the testing is not a concern. “The information 23andMe provides is incredibly accurate,” Afarian says. “If we tell you you’re a C-C there, you are. From there, the next step is interpretation — what does science know about it?”
It turns out the answer isn’t so clear.
(In)accuracy of Interpretation
“There is a huge gap in information about genomic services,” says James O’Leary, chief innovation officer at Genetic Alliance, a nonprofit advocacy organization dedicated to transforming health through genetics. “New technologies develop quickly and it’s unclear to people how to access them, what the purposes are, and what is reasonable in terms of results.”
Even if the tests themselves are accurate, it’s important for consumers to take much of the interpretation with a grain of salt.
“There is a huge gap in information about genomic services.”
“Everyone will have results. Everyone has mutations. Whether they are medically actionable or not is a different story,” O’Leary explains.
Not only are mutations not necessarily indicative of a condition, they’re just part of the story. “A lot of the information that is given back to patients on those types of lifestyle impacts of genetics are not very influential risk factors,” O’Leary continued. “The genetic portion doesn’t account for a large portion of risk; genetic information doesn’t make a lot of sense without other lifestyle and environmental factors.”
Afarian recognizes the limits as well. “It’s the basic nature of genetics that there are very few cases where genetics are deterministic, meaning if you have a gene, you will have the condition,” she said. Her son could have had blue eyes, and Afarian’s risk factor results don’t mean that she will or won’t get those diseases. “At the end of the day, age is the greatest risk factor for Alzheimer’s. Fundamentally, if you don’t want to get Alzheimer’s, don’t get old.”
In rare cases, however, mutations are indicative of far higher risk, and are medically actionable. An oft-cited example is a harmful mutation in the BRCA1 or BRCA2 genes, which greatly increases the risk of developing breast or ovarian cancer. This is the mutation that famously caused Angelina Jolie to get a preventative mastectomy earlier this year. Whereas in many cases mutations will only increase risk by a fraction of a percent, a mutation on the BRCA1 or BRCA2 genes increases the risk several-fold. If there is a family history of cancer that suggests someone may have a mutation in one of these genes, he or she can take a genetic test to check, and then determine how to manage their risk.
BRCA1 and BRCA2 reports are offered through 23andMe, but it is a more limited screening. Since a family history can determine whether an individual ought to take the genetic test at all, and because it is a complex and serious illness, BRCA testing is probably better suited for a doctor-administered genetic test.
Recreational or medical?
While much of DTC genetic testing began largely for entertainment — traits like eye color, hair type, earwax consistency — the growing emphasis on complex health and disease factors could make the knowledge gap a greater concern.
“It’s important to recognize that for many people this truly is ‘recreational genetics,’ ” says Howard Levy, an assistant professor in the Division of General Internal Medicine and McKusick-Nathans Institute of Genetic Medicine at Johns Hopkins University. “If they’re getting the data and making medical decisions without medical counseling, that could be a problem. If it’s just cool stuff to know — tracking ancestry, cocktail-party conversation, for fun — and they are not making medical decisions, maybe that’s not a bad thing.”
However, the fact that 23andMe results include all types of conditions means consumers are getting both “entertaining” and health care-related reports.
“Because so many results are of uncertain significance, it’s an incredibly challenging thing to deal with and figure out what it means as a consumer,” O’Leary says. “We’re finding out new information about the genome all time; managing that outside the health care context is really difficult for people.”
23andMe aims to alleviate some of this difficulty by providing interpretation for the results. Their reports cite scientific studies and use a star system to indicate the level of credibility. As new studies come out, 23andMe sends an email incorporating new information to keep people engaged in their genetics.
But this is where the pace of genetics research gets tricky.
This isn’t a problem with the scientists and clinicians at 23andMe. “What it comes down to,” Levy says, “is if we’re going to live on the cutting edge of knowledge, new discoveries are acted on right away. The downside is that new discoveries sometimes make a mistake.”
Levy says he is more open to DTC genetic testing than most physicians; that it comes down to a philosophy of autonomy versus paternalism, and he’s a fan of autonomy. Yet engagement relies on continued participation and accountability on the part of the consumer as well. Keeping up with the information, Levy says, is equally the responsibility of the consumer and the genetics-interpretation company.
Levy does recommend that consumers bring their results to their doctor as well, something that 23andMe and many genetics professionals encourage, particularly if consumers are considering a lifestyle or medical change based on their test results. “[An individual] could cause serious permanent harm to themselves by misinterpreting the information they get,” Levy says.
Doctors and the Education Deficit
As of now though, studies show that the majority of test consumers don’t share results with their doctors. In fact, sharing the results with a doctor has two significant roadblocks: cost and experience.
While the actual DNA testing is quickly becoming inexpensive and ubiquitous, professional interpretation still requires time and expertise. This ironically makes the physician follow-up more of a limiting factor in understanding results than the tests themselves.
The second problem is that even doctors and specialists in the field sometimes don’t know or can’t keep up with genetics research. “There’s a significant educational deficit — on the consumer and also the physician side,” says Michael Dougherty, director of education at the American Society of Human Genetics. “If you take [DTC results] to the physician, generally they don’t know what to do with it.”
“There’s a significant educational deficit.”
As a result, medical groups are working to increase education of the public and of physicians regarding genetics and its growing role in medicine. Dougherty explains that while doctors should refer patients to specialists if they suspect the individual has a genetic condition, genetic specialists are unfortunately in short supply. This makes it important for physicians to become more familiar with the field. “Where the greatest [educational] need exists is with frontline health providers — nurses physicians, primary-care physicians, nutritionists, et cetera,” he says. “It will become incumbent increasingly on primary-care physicians to recognize when the genetic test results are moving beyond area of their expertise.”
In addition to education programs, data through DTC tests themselves can also contribute to ongoing genetic research to help better understand results. Ninety percent of 23andMe test consumers opted in to participate in the research, allowing 23andMe scientists to view their anonymous data and identify hundreds of new genetic associations and identify targets for potential new drugs and treatments.
The opportunity to contribute to that research is one of the things 23andMe values most. “I’d like to think that some treatment 20, 30, 40 years from now — I’d like to think my family participated in making some of those things available,” Afarian said.
As our conversation was wrapping up, I asked if there was anything she’d like to add.
“Well it sounds like you’re not a customer,” she said. “I would love to send you a kit!”
I’m not sure I could handle the uncertainty.