Over the past three years, AAAS member Michael Snyder has become a guinea pig for his own research, volunteering to regularly draw blood so his Stanford lab could track his genomes. His genetic profile, called an iPop, or integrative personal omics profile, revealed that he had a high risk of developing diabetes. "My sugar shot through the roof, and we caught it early," says Snyder, director of the Stanford Center for Genomics and Personalized Medicine, whose project was detailed in a recent article in Pacific Standard. Armed with the new information gleaned from his iPop, he was able to change his diet as the disease progressed and prevent serious damage.
Snyder's project is one of many unlocking clues tucked away in our DNA.
Scientists believe that chronic diseases—such as diabetes, heart disease, cancer, and Alzheimer's—are caused in part by genetic factors. By studying our genomes, they hope to figure out what variations lead to these diseases, as well as how doctors can treat patients more effectively. Researchers already know about a few thousand genome variations that lead to true medical consequences—and add to that knowledge base every year.
This intense study of our genomes has paved the way for personalized medicine, the tailoring of medical treatment to the individual characteristics of a patient, according to the President's Council on Advisors on Science and Technology.
Our bodies respond to medications slightly differently: While one treatment or medication may work well for one patient, it may not be the best solution for another. By studying a patient's genome, doctors can know who will benefit from a prevention or therapeutic treatment, sparing expense and side effects for those who won't. So, for example, if someone's a poor metabolizer of a drug (because they carry a known genetic variant that reduces efficiency), doctors can alter the dosage or perhaps offer a completely different medication, explains AAAS Fellow Rex Chisholm, a professor in cell and molecular biology at the Center for Genetic Medicine and Surgery at Northwestern University.
Sequencing genomes can also yield valuable information for healthy people. Armed with specifics on their DNA, people can foresee risks and make more informed lifestyle choices.
That's been the focus of Snyder's lab, which is looking beyond genomes to other health markers, such as microbiomes (the microbes that flourish in our guts and even in our mouths and on our skin that help keep us healthy). Scientists are realizing the importance of these microbiomes for our overall health and studying the relationship between specific diseases and these beneficial microbes that dwell inside of us.
Those microbiomes are just some of the billions of markers that his lab is tracking. "We don't know which of the billions of markers we're following right now are going to be the most informative," Snyder says. Eventually, routine tests for regular patients will be some subset of that.
Such longitudinal studies—where patients give a regular blood sample—would help clinicians trying to catch disease early by showing changes relative to a particular individual's baseline healthy state. "To me, that's the nature of personalized medicine," says Snyder.
Among the biggest advances in personalized medicine is understanding and treating cancer, explains AAAS member Alan Shuldiner, director of the Program in Personalized and Genomic Medicine at the University of Maryland in Baltimore.
"These days, if you have cancer, there's a good chance you'll get your genome sequenced, and that information will lead to the possible drugs that you might take," Snyder says. It's also clear that cancer is a genetic disease, in terms of predisposition.
That's why actress Angelina Jolie—whose mother died of breast cancer—used genetic testing to inform her decision to undergo a double mastectomy. The tests revealed that Jolie carried the BRCA1 gene and an 87 percent risk of breast cancer.
It's also clear that everyone's cancer is different. "There are some common themes, but in general they're pretty different," says Snyder, who says that personalized treatment will be standard of care in the not-too-distant future.
More new developments focus on mystery diseases or conditions. In some cases, sequencing can reveal a disease that's known and hadn't been suspected; in other cases, there's a completely new disease. For half of those mystery cases, researchers can at least get a short list of possibilities to narrow the field.
And as researchers gather more cases—people whose diseases or conditions share the same characteristics and whose genomes share the same mutation—databases grow.
One such database is the NUgene Project, a research biobank founded at Northwestern University that Chisholm helped develop. So far, some 10,500 participants have agreed to contribute blood samples used to extract DNA for genetic variation research. With access to electronic health records, researchers learn about the participants' disease history. Records from NUgene and eight other biobanks linked through the eMERGE consortium allows researchers from many centers to combine efforts as they study genetic variations associated with hypothyroidism, dementia, heart disease, and more.
At the University of Maryland, a recent pharmacogenomics discovery already in use has to do with Plavix, a medication for heart disease. Patients entering the cardiac catheterization lab are offered genetic testing, and within four to five hours cardiologists can have genomic results that help them tailor medication doses to that patient. Shuldiner says that another pharmacogenetic application developed at the University of Maryland is a set of two genetic tests that can predict the most appropriate dose of warfarin, a treatment used to prevent blood clots from forming in blood vessels. That test will have a one day or less turnaround time at a price tag of about $100 to $200 and will help lessen the risk of either under-dosing or over-dosing patients and exposing them to unnecessary side effects.
This kind of personalized medicine is already in practice, says Shuldiner, and we can expect to see more examples in the future. Shuldiner guesses it may only be a few years before many people see sequencing in their routine health care. "The field has moved to a point where many of genomic and genetic discoveries are ready for translation into patient care," says Shuldiner.
Dollars and sense
Among the biggest questions surrounding personalize medicine is the cost of this kind of custom-tailored care. According to Snyder, the bulk of the cost isn't the sequencing itself — that's only about $3,000 per genome. What's costly is the interpretation, which takes hours of studying variants and currently runs about $15,000 to $20,000 for a healthy person, though that will get faster and less expensive as systems become automated, explains Snyder. People would also need to do about three follow up tests that will cost about $800. In most cases, costs depend on the application. Genetic testing to predict response to Plavix for heart disease costs about $100 to $200 for a single genetic test.
Another question is who pays for it? Many of these genomic tests are not yet reimbursed by insurance companies.
"Who would pay you to get your genome sequenced while you're healthy?" asks Snyder. "Even though it makes a lot of sense, our financial system is not set up in a way to reward people to do that." Insurance companies typically won't pay for someone to have their genome sequenced, even though they should, Snyder explains, because of the possibility of a person switching insurance companies.
However, most researchers and clinicians believe the cost is justified.
"In the long run, we hope that these pharmacogenetic interventions will actually save health care costs, and that's the key behind personalized medicine," Shuldiner says. "Most of us believe that personalized medicine can't cost the health care system more money, it needs to save money in the long run." In that line of thinking, the upfront costs of genetic testing will be compensated for in health care savings through prevention of complications or incorrect dosages. For instance, explains Shuldiner, in the case of Plavix, about quarter of our population would not genetically respond to the medication and have a higher risk for a reoccurring heart attack. "So if we could prescribe a more effective medication to that 25 percent of the population, we could prevent them from having a reoccurring heart attack and prevent them from readmission to the hospital," Shuldiner says. Likewise, over-dosing warfarin would put patients at risk for life-threatening bleeding that would land them back in the hospital.
In cases where a person is healthy, information gleaned from genomic tests could save money in treatments down the line if a condition or disease is caught early on.
Our future health
In the future, this growing field will produce more companies specializing in sequencing patient's genomes. Snyder started a small company, Personalis, which does genome interpretation. We'll also see more people volunteering to have their genome sequenced, like Snyder, by enrolling in studies.
But according to a 2011 Nature article, which laid out a strategy for going forward with genomics, widespread use of genomic medicine to improve health care. It might not become commonplace until after 2020.
Before then, the science must translate into clinical practice to better treat patients, says Chisholm, who's also a member of the Genome Medicine Working Group within The National Human Genome Research Institute, which held a series of meetings, starting in 2010 to help understand what it takes to move genomic medicine forward.
"I think a lot of people will say 'personalized medicine is our futureCOMMAAPOSTROPHE" Shuldiner says, "but I'd go one step farther and say it's here today, and we need to find ways to advance what we already know in patient care in a more rapid and efficient way."