Genetic Testing: Innovation, Regulation, & Culture
A look at the influences behind the most exciting tool in modern medicine
Physicians utilize medical history, health metrics, and test results to tailor treatments to individuals, but an additional source of patient data is now being put to use: genetic information. More accessible genetic testing has made it feasible for nearly anyone to gain access to this ultimate source of health data, which can be used to predict disease risks, improve diagnoses, personalize treatment, and, ultimately, make healthcare more effective. When the Human Genome Project was completed in 2003, sequencing a single human genome cost nearly $100 million, which limited the practice to universities and research labs. But dramatic advancements in DNA sequencing technology have since led to a near-100,000 fold reduction in costs. In 2014, the American biotechnology company Illumina released the first system capable of sequencing the entire human genome for under $1,000, less than the average cost of an MRI scan in the United States. These low costs have prompted some hospitals in the U.S. to use whole genome sequencing in diagnostics. As prices continue to drop, advanced genetic testing services will likely be available in hospitals around the country.
The widespread implementation of in-hospital whole genome sequencing may be years away, but today, anyone can have their genome sequenced without ever stepping foot in a hospital. Using only a mailed-in saliva sample, direct-to-consumer genetic testing services offer customers information about genetically inherited conditions, probabilities of developing diseases later in life, and expected responses to certain medications. Founded in 2006, 23andMe was one of the first American biotechnology companies to offer affordable genetic sequencing and interpreting services to the public. Substantial investment in marketing quickly made 23andMe a household name. Their tagline: “Based on your DNA, we’ll provide specific health recommendations for you.” Time named 23andMe’s at-home genetic testing product invention of the year in 2008, touting it as “a $399 saliva test that estimates your predisposition for more than 90 traits and conditions ranging from baldness to blindness.”
But in 2013, the FDA ordered 23andMe to stop marketing their DNA testing products. In a warning letter, the FDA expressed concern with the company’s claims that it could assess patients’ risks of cancer and drug responses, and warned the company of the potential consequences of false positive or false negative health assessments. The FDA believed that a high probability for a disease could lead to unnecessary worry, while a low probability for a disease might give some a false sense of security. Their letter cautioned, “if the BRCA-related risk assessment for breast or ovarian cancer reports a false positive, it could lead a patient to undergo prophylactic surgery, chemoprevention, intensive screening, or other morbidity-inducing actions, while a false negative could result in a failure to recognize an actual risk that may exist.” The FDA also mentioned that patients who learn of potential negative interactions between their genes and medications may adjust their doses or quit taking medications altogether without consulting their physician.
23andMe failed to respond to the FDA’s multiple requests for supporting data, and eventually stopped offering genetic interpretation services. Today, the company’s website simply states: “23andMe provides ancestry-related genetic reports and uninterpreted raw genetic data. We no longer offer our health-related genetic reports.” But much of the damage has already been done. Hundreds of thousands of individuals have had their genomes sequenced and interpreted by 23andMe. Without consultation from medical professionals, some may have jumped to incorrect conclusions about the results of these tests. Consider someone who learned of a high probability of developing a terminal illness; it could have influenced every aspect of that person’s life: what jobs to take, how much to save for retirement, or the decision to have children.
Edit: on October 21, 2015, 23andMe announced that it will provide some health-related genetic interpretation services recently approved by the FDA. The company is optimistic that additional tests for diseases like Parkinson’s and Alzheimer’s will be approved soon.
In 2013, The New York Times featured a famous example of genetic testing’s impact in medical decisions: an op-ed written by Angelina Jolie entitled “My Medical Choice.” After her mother died of breast cancer at age 56, Jolie took a genetic test that revealed her to be a carrier of a mutated BRCA1 gene. BRCA1 is a tumor suppressor gene; mutations in this gene result in up to an 87% risk of breast cancer and a 50% risk of ovarian cancer. Not satisfied with these odds, Jolie underwent a preventive double mastectomy, decreasing her chances of breast cancer to under 5%. Jolie expressed that the results of the test made her feel empowered, but also stressed the seriousness of her decision. Two years later, Jolie had her ovaries and fallopian tubes removed as well. The high-profile surgeries have led to what Time Magazine called “The Angelina Effect.” In the year following the story, demand for BRCA1/2 testing nearly doubled.
The UK-based biotechnology company Gentle Labs recognized the impact that genetic testing can have on medical decisions, and took this into account when developing its services. In addition to conducting multiple studies to ensure the validity of genetic interpretations, the company employs physicians with expertise in medical genetics to clearly communicate the significance of test results to customers via private video teleconferencing. Customers diagnosed with certain diseases are advised to seek medical screening or treatment when necessary, and carriers of disease-causing genes are warned about the possibility of passing the genes on to their children. Gentle Labs also gives its customers online access to their genetic information so that they can discuss it further with their primary care physician. At $1,990, the service is nearly five times the cost of 23andMe’s now-defunct genetic testing product, but Gentle defends the higher cost by highlighting the value of its post-test counseling services.
Unfortunately, few genetic testing companies in the U.S. offer similar counseling services. While the FDA requires evidence to support genetic interpretation claims, there are currently no FDA guidelines regarding how those claims are communicated. Everyone should have the right to their own genome, but genetic testing companies should be held to a very high standard in terms of genetic interpretation and communication. Direct-to-consumer genetic testing ought to require post-test counseling so that patients do not make any rash decisions based on the outcome of one test. This could be done via video teleconferencing, as Gentle Labs does, or, more ideally, in a hospital, where a patient’s primary care physician could explain the test’s results in the context of the patient’s medical history and overall health.
Besides improved communication of test results, in-hospital genetic testing has many advantages over direct-to-consumer genetic testing. While direct-to-consumer genetic testing can be cost-prohibitive, in-hospital genetic testing is often covered by insurance if recommended by a physician. While not widely implemented, some of the best hospitals in the country now offer comprehensive genetic testing services, and are already showing signs of success. Children’s Mercy Hospital in Kansas City, Missouri uses on-site genetic sequencing equipment to diagnose sick infants in intensive care, which helps physicians determine the most effective treatments for each patient. While other hospitals may have to wait weeks before an off-site genetic testing service reports back results, on-site sequencing can be completed in just a few days.
Hospitals with on-site genetic sequencing equipment could also improve patient outcomes by utilizing genetic information in prescribing decisions. Today, most drug dosages are determined by a patient’s BMI, age, or kidney and liver function, but many other factors can affect how drugs function in the body, including a patient’s genetic makeup. For example, the effectiveness of the anticoagulant drug Warfarin is influenced by at least two genes: CYP2C9 and VKORC1. If these genes are not taken into account, physicians could prescribe inappropriate drug dosages, which could result in excess bleeding or dangerous blood clots. Because of these risks, genetic testing is usually required for patients in need of Warfarin or any other drug with known gene/drug interactions. In hospitals without on-site genetic testing services, physicians must send patients’ genetic information to an off-site sequencing service, which can delay treatment for weeks. On-site genetic sequencing equipment would allow patients to receive the care they need much sooner.
However, some patients may be concerned about having their genome sequenced in the hospital for the fear that their insurance company will use the results to set their rates of coverage. While the Genetic Information Nondiscrimination Act of 2008 outlaws health insurance discrimination based on genetic information, the law does not apply to life, disability, or long-term care insurance. In addition, hospitals may resist implementation of genetic sequencing equipment because of the lack of data regarding its cost-effectiveness. While simple tests for gene/drug interactions are usually inexpensive to perform, implementing equipment capable of synthesizing the entire human genome usually requires a multimillion dollar investment. Are the financial benefits of whole genome sequencing substantial enough to justify its costs? Will it improve patients’ health outcomes? How will it affect healthcare costs in the short and long term?
Fortunately, genetic testing may soon be financially feasible for any hospital. Philadelphia-based startup Biomeme has developed a $1,000 PCR thermocycler that allows researchers or hospital staff to conduct diagnostic laboratory tests in just 40 minutes. The company boasts that the device makes real-time PCR so easy, “a seven-year-old can do it.” Biomeme was able to keep the costs relatively low by taking advantage of the computing power of smartphones instead of building expensive hardware into its own device. All human genetic data is encrypted and stored in a HIPAA-compliant database, and Biomeme’s data management system is cloud-based and compatible with all major electronic health record systems. While the device’s diagnostic capabilities are not nearly as advanced as more expensive sequencers, they are quickly catching up. In addition to accelerating hardware and software development, Biomeme is conducting rigorous trials with the Drexel University College of Medicine in an effort to expand the medical applications of the technology.
Hundreds of thousands of Americans have had at least part of their genome sequenced; as direct-to-consumer and in-hospital genetic testing become more affordable and more capable, this number is expected to rise. While genetic testing yields many benefits to medicine, it is important to consider the novelty of the technology; there is still a lot of uncertainty about how genes relate to specific disease outcomes. Simple genetic tests can determine the probability of developing or passing on diseases like breast cancer with a relatively high degree of certainty; other diseases, however, result from interactions between genetic and environmental factors that are not as well understood. If misinterpreted, genetic tests cause unnecessary worry at best, and can result in unneeded medical treatment at worst. But when used properly, genetic tests offer valuable information that can improve patient health outcomes. If both patients and physicians recognize the uncertainties and risks of genetic testing, it could soon become one of the most important tools in modern medicine.
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