The same medication given to two different patients could help one and kill another, due to genetic variance.
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What Karen Daggett of Frazee, Minnesota didn’t know about herself almost killed her. Several years ago, she and her husband were out for a Valentine’s Day dinner when she began to feel so ill that she was rushed to an emergency room. “The doctor told my husband that it was good he brought me in when he did, because my body was shutting down,” Daggett recalls. “Even 12 hours later, I would have died.” Subsequent DNA testing at Mayo Clinic revealed that Daggett lacked a gene allowing her liver to metabolize many medications, including one she had recently begun using to control an irregular heartbeat. She had become dangerously dehydrated as the unmetabolized drug accumulated in her body.
The revelation led to an adjustment of Daggett’s medications and to new light being shed on several unexplained ills—including a baffling resistance to the effects of pain medications—that had plagued her and other family members for years. Daggett’s experience highlights the way that the increase in knowledge about individuals’ genetic makeup can personalize medical treatment and improve patient outcomes. “It’s really what we think is the future of medical care and medicine in the United States,” says Dr. Keith Stewart, director of the Mayo Clinic Center for Individualized Medicine, one of the nation’s leaders in moving genomics from the laboratory to clinical care since it was established in 2012. “Every single American should have their genome sequenced.”
Precision medicine (also known as individualized or personalized medicine) is an approach that tailors medical decisions, treatments, and recommended lifestyle practices (such as diet and exercise) to individual patients based on his or her unique genes. It’s one of the most promising healthcare innovations on the horizon, and one that recently received a substantial boost in support. In January 2015, President Obama announced a $215 million research effort known as the Precision Medicine Initiative to enable the National Institutes of Health and related groups to make this type of healthcare more widespread.
The life-saving potential of genetic testing is most familiar in terms of its ability to diagnose and manage inherited diseases such as cystic fibrosis, hemophilia, and breast cancer. (The actress Angelina Jolie brought widespread attention to such testing in 2013 when she shared her choice to undergo a preventative double mastectomy after learning that, in addition to a family history of cancer fatalities, she carried a BRCA1 gene mutation that greatly increased her odds of developing breast cancer.)
But determining hereditary disease risk is only one of genetic testing’s potential benefits. Doctors can also use DNA sequencing with cancer patients to more precisely identify what kind of cancer is present, and which treatment options have a better chance of being effective. On a far broader scale, genetics can also impact how a person responds to different drugs, a branch of precision medicine known as pharmacogenomics.
The RIGHT study (short for the Right Drug, Right Dose, Right Time), done at Mayo Clinic, showed that 99 percent of all patients studied have some sort of genetic variant that impacts the way the body processes medications. To understand what this means, on a basic level, think of your body as a bathtub and your medication as the water flowing from the faucet. Without a drain stopper, the water would flow right through you with no effect; a different stopper might lead the water to drain too slowly or convert to poison, leading to toxic buildup. Now imagine the “stopper” functions differently for each medication you take. This means virtually all of us at some point may be prescribed a medication or typical dosage that, at best, acts as a placebo and, at worst, may cause serious side effects, such as those suffered by Karen Daggett.
After learning of her genetic variance, Daggett encouraged every member of her extended family to get DNA testing. The same variation was subsequently found across four generations of her family, leading many of her relatives to adjust their own medications (with the help of their physicians), including her sister, who had just been diagnosed with breast cancer and whose course of treatment was promptly modified to account for her own missing gene. “I want to encourage everyone to get this kind of genetic testing done,” says Daggett, “because it can be a matter of life and death.”
How feasible is it that we’ll all be basing our healthcare decisions on our personal genetic profiles in the near future? Perhaps more so than you’d think, especially as several Minnesota companies and institutions, including Mayo Clinic and Minneapolis-based pharmacogenomics company OneOme, are working to accelerate the integration of individualized medicine into routine healthcare.
For almost a decade, simple, mail-order genetic testing that looks at a small subset of an individual’s DNA (collected through a saliva sample), has offered the curious layperson access to a limited amount of entertaining insight (i.e. one’s odds of being able to detect the scent of asparagus pee), but practical testing that would give healthcare providers thorough enough genetic data to make diagnostic and pharmaceutical decisions is still in something of a nascent stage. Yet advances in how quickly genes can be sequenced, along with reductions in cost, are accelerating genomics’ accessibility and applicability at an impressive rate. (The first whole human genome sequencing, completed in 2003, took more than 3 years and cost at least $500 million. Today, it costs about $1,000 and takes fewer than three days.)
Mayo Clinic is currently working toward a late-2017 release of an educational app with a San Francisco-based tech company called Helix to provide more detailed and practically useful genetic analysis directly to consumers. The Helix platform is essentially a digital hub for patients to store their genetic data, which can then be accessed by any number of apps that would analyze the data for various purposes.
After providing Helix with a DNA sample via a mail-order saliva-collecting kit, customers can choose from a number of different “partner” applications from companies ranging from Mayo Clinic to National Geographic to Mount Sinai, each focused on a specific area of insight, including nutrition, ancestry, personalized fitness plans, family planning resources, and even individualized wine tasting recommendations.
Dr. Stewart cautions that some of the genetic insight currently on offer in the direct-to-consumer marketplace may be based on firmer science than others. Startups that claim to offer personalized DNA-based nutrition advice or skin-care product recommendations may be staking out market turf in advance of a rigorous scientific basis for their ambitions—though the science could eventually catch up to their claims.
Dr. Gregory Plotnikoff, who runs a small private practice on Loring Park called Minnesota Personalized Medicine, is a longtime practitioner of integrated medicine (formerly at Allina’s Penny George Institute) known for helping patients suffering from elusive diagnoses from complicated health problems. He’s a local pioneer in applying genomics to patient care—one tool among several he uses to solve mysteries that have stumped his patients’ previous practitioners. “Among physicians there are a limited number of people who are able to interpret genetic data,” he says. “There’s no accreditation program for this. We’re really still in the covered wagons stage of genomics, trying to gather and understand all the data.”
One thing we do know, however, is that genes are not destiny. “They’re possibilities,” says Plotnikoff. And the interaction between genes and the environment is critical to how those possibilities play out. “Identical twins never have identical health histories,” he explains. “If you have one twin who’s a vegan marathoner and one with a diet of Twinkies and Ho-hos, they’re going to have very different health profiles.” The most frequent concern Plotnikoff hears from his patients is that genetic testing is going to reveal something scary that they don’t want to know, such as an inevitable march toward cancer or Alzheimer’s. He reminds them that genes are not a crystal ball. “We don’t look for things that are scary; we look for opportunities and insights that can be helpful.”
Doctors specializing in personalized medicine, including Plotnikoff, are unfortunately few and far between. Minneapolis-based OneOme is working to close this gap by making similar genetic insights more widely available and addressing the education gap among physicians who may not have the tools or knowledge to unpack their significance. OneOme worked with the Mayo Clinic to co-develop the RightMed test (based on exclusively licensed Mayo Clinic pharmacogenomic research), which combines a patient’s genetic profile and prescription history with an algorithm-based platform to gauge his or her ability to metabolize a wide range of common medications for conditions including depression and anxiety, bacterial infections, pain, allergies, arthritis, diabetes, cancer, and sleep disorders. While Helix focuses on more basic, consumer-facing educational apps, OneOme is ordered by a physician, linked to a patient’s electronic health data, and designed to directly inform decisions being made by healthcare providers.
In 2015, there were more than four billion prescriptions written in the U.S. alone, and independent studies have shown that between 25 and 60 percent of them fail to work as intended due to how bodies metabolize medication. OneOme’s RightMed cheek swab test can be performed in a physician’s office or sent directly to the patient’s home. (Since it must be ordered by a physician, OneOme provides suggestions on how to initiate a conversation about testing with your healthcare provider on their website. While some insurance companies will reimburse for the $249 cost of the test, it was designed to be affordable for those paying out-of-pocket as well.) The patient then gets a clinical test report, which is integrated into her electronic medical record and available to all her current and future healthcare providers, dividing the list of more than 340 medications into three simple categories: use as directed, use with caution, and use with great caution.
Patients also receive access to more detailed information on each medication on the list, including potential side effects, adverse reactions, and interactions with other drugs based on the patient’s specific genotype. Because our DNA doesn’t change, the test only needs to be done once—OneOme continues to update each patient’s report as more data becomes available on new medications as well as those currently on the list. At present, prescribing medicine is something of a trial-and-error process, and pharmacogenomics has the potential to help physicians more quickly hone in on an effective drug and dosage. And if patients have the RightMed test (or something similar) done early in their lives, then the potentially life-saving information is already available when the need for a clinical decision arises.
While pharmacogenomics offers the most actionable insight currently available in the genomics field, the explosion of startups offering personalized products and services of all kinds implies that we’re on the brink of a brave new frontier, in which not only will we know ourselves (on the molecular level, at least)—so will many of the companies we do business with. Habit, a meal delivery service that claims to offer personalized meals nutritionally optimized for your unique genetic profile and health goals, and Instant Chemistry, which claims to test romantic partners for “complementary genes that have been associated with higher levels of physical attraction and long-term relationship success,” are just two of the rapidly proliferating startups in the genomics space whose promises are based on science that, while advancing, is currently tenuous at best.
“The promise there is great,” says Plotnikoff. “I love the idea of going to a restaurant and giving them my thumbprint and getting my personalized recommended menu. Someday we may have a 3D printer equivalent in our homes that we give a little blood or urine in the morning, and it will spit out the vitamins we need for the day.” But he also cautions against being overly dazzled by the seductions of technology. “Genomics is helpful, but we have to be very humble about its value. What really counts is how genes and the environment interact.” And there’s plenty we already know about the practices that support wellness across all genotypes. “The five fundamentals are breathing, eating, sleeping, moving, and loving,” says Plotnikoff. “All those things affect how your genes are expressed, and there’s danger in ignoring them.”
Join Dr. Gregory Plotnikoff, Senior Consultant Minnesota Personalized Medicine, Dr. Matthew Ferber, Director Mayo Clinic’s Clinical Genome Sequencing Labratory, and Paul Owen, CEO OneOme as they shed more light on precision medicine for our March edition of Convos on Tap.