Spit gets a bad rap. But imagine if just a vial of the much-maligned fluid held a roadmap to our future health.
That (in vastly simplified terms) is the vision of the Coriell Institute for Medical Research, a nonprofit biomedical research institution in Camden that is pioneering the use of genetic testing as a means of identifying personal risk factors for certain diseases.
And spit? That’s Coriell’s favored medium for harvesting DNA from volunteer subjects. “It’s less invasive than a needle and blood,” I am told.
The institute launched the Coriell Personalized Medicine Collaborative (CPMC) in December 2007 with an initial goal of enrolling 10,000 individuals in the study; it is better than halfway to the goal.
Many of the subjects are referred by CPMC partners, including Cooper University Hospital (across the street from Coriell); Virtua Health in Marlton; Fox Chase Cancer Center in Philadelphia; and Ohio State University Medical Center in Columbus, Ohio. The project is privately funded and free to participants.
Coriell is already a leader in gene studies. The institute, founded in 1953 by Dr. Lewis Coriell, has been researching gene samples from around the world for more than 55 years. More than 2 million vials of cells collected over the years are stored in rows of shiny cryogenic steel tanks filled with liquid nitrogen and housed in the Coriell Biobank. Among other things, the collection was used in the Human Genome Project, a worldwide program to identify the more than 20,000 genes in human DNA.
For the CPMC study, participants provide a DNA sample and a personal health history; after a period of lab analysis, they learn of their personal risk for ailments such as coronary artery disease, melanoma, prostate cancer and diabetes.
But there’s a catch. “We only tell you results that are potentially actionable,” says Courtney Kronenthal, the center’s director of communications and development, who is tasked with explaining the research to individual participants. By actionable, they mean diseases that can be headed off at the pass through lifestyle changes (such as diet and exercise), medication or regular screening.
CPMC’s testing, however, can reveal an individual’s genetic predisposition to other diseases for which no treatment is currently available, such as amyotrophic lateral sclerosis (Lou Gehrig’s disease) and Alzheimer’s. A board of scientists, ethicists, physicians and others meets regularly to review the latest science and determine which findings should be revealed to the study subjects, and which should be withheld.
The larger objective for Coriell is to help integrate such testing into the arsenal of modern medical tools. “The overarching goal of our project,” says Coriell president and CEO Michael Christman, “is to try to understand the best practices in the implementation of genetics in medicine.”
My own participation in the study began in November 2010. Before my first visit to Coriell, I entered the secure CPMC website to fill out a complete family- and personal-health history. That took about 45 minutes and itself was a revelation. Both my parents are deceased, and I had never considered how little I knew of their health histories.
Later that month, I made the trip to Camden. Kronenthal briefed me on the study and its potential risks (anxiety, potential misinterpretation of the results, fear that my children might be at risk for similar diseases). Then there are the benefits: If a predisposition for an actionable disease were identified, I could make the appropriate lifestyle changes and inform my personal physician of the need for vigilance. What’s more, the testing could help with personalized drug selection and dosage by detecting any sensitivity to several specific drugs, such as Plavix, which is used to prevent blood clots in heart patients.
Then it came time to spit in the tube. Kronenthal advised me to rub my cheeks to help generate the desired amount of saliva. “Fill it to the line,” she said, before leaving my saliva glands and me for a few minutes of privacy. She had one last proviso: “Bubbles don’t count.”
It took me eight good spits to deliver my quota into the 3-inch tube. In the weeks that followed, Coriell’s lab technicians isolated my DNA from the rest of my fluid sample and injected it into a special gene chip for genetic analysis. The chip was rotated for 16 to 18 hours in a carousel-like incubator that allowed my DNA to bond with the reference DNA on the chip. Next, the chip went through a fluidics station for washing and staining. Finally, a laser scanner captured the information from the chip for analysis.
All I had to do was wait.
When my results became available three months later on the CPMC website, they were, to say the least, surprising.
Kronenthal had explained that more than 99 percent of human DNA sequences are identical, but each of us has about 1 percent that is unique. Each of these unique sites in our genome is called a single nucleotide polymorphism, or SNP (fondly referred to as “snip”). If you think of your genome as the instruction manual that tells your body how to function, then a snip is a sort of typographical change that may or may not alter those instructions.
I entered the CPMC website with a fair degree of confidence of what secrets my snip might hold. My family history (parents, sister, aunts, uncles, cousins) is replete with heart disease and various cancers. I always figured that would be my fate and have tried to eat and exercise with those factors in mind.
Before letting me near my results, the website offered further explanation of the research (even a video) as well as a repeat of all Kronenthal’s warnings. I could even opt to see a Coriell counselor before viewing the results. (Study participants also have no-charge access to a network of pharmacogenomics-trained pharmacists to help explain drug-related findings.)
I plunged in, expecting the worst as I clicked on the report for coronary artery disease. But according to the report, I have “two copies of the non-risk variant”—meaning each of my parents had given me a gene that did not suggest a higher risk for the disease. I found similar results for melanoma, prostate cancer and hemochromatosis (iron overload).
Then I turned to diseases where I had no family history: lupus, type 1 and type 2 diabetes and age-related macular degeneration. In each case I had at least one gene variant that suggested a heightened risk. Whoa!
My next step was to talk with Tara Schmidlen, one of Coriell’s two board-certified genetic counselors. I shared with her my surprise at the results, which were entirely contrary to my expectations.
“That is one of the most common comments that I hear from people that I counsel,” said Schmidlen.
Her explanation: CPMC only looks at a single gene variant at a time. In any individual, there might be many more genes that could be implicated in a given disease, but CPMC has “elected to just give you what we know for certain right now, based on the literature,” said Schmidlen.
Among the uncertainties is how to combine evidence from multiple genes. “Should we add them together? Should we multiply them? Do some of them cancel other ones out?” Schmidlen asked. “That’s the part of the science that’s currently being worked out for a lot of diseases.”
At this point, CPMC provides only a partial picture of genetic predisposition—what Schmidlen refers to as “a piece of the puzzle.” Other important pieces include family history and environmental factors.
In other words, the CPMC report is not a green light for me to start bingeing on double bacon cheeseburgers. “Absolutely not,” Schmidlen declared.
In fact, the coronary artery disease that has historically stalked my family does indicate that I am at risk, no matter what the genetic test says. Indeed, says Schmidlen, family history is often “the more significant risk.”
But what about when there is no family history and the genes indicate a heightened risk?
Again, the genetic picture is incomplete, and family history might provide a more significant piece of the puzzle. But the genetic information can be considered a call to action, or at least awareness.
In the case of lupus, for example, an individual with the risk variant should develop an awareness of the symptoms, which range from common issues like fatique and hair loss to oddities like a telltale butterfly-shaped rash. If a risk of hemochromatosis is detected, a blood test might be in order. The diabetes risk might encourage a change in diet, greater attention to weight management and possibly a blood-sugar test. A melanoma risk should certainly prompt a skin exam and increased use of sunscreen.
“Some of the diseases are more actionable than others,” said Schmidlen.
In time, Schmidlen believes the science will be able to paint a more complete picture of an individual’s future health. “As we go forward, hopefully we can add more pieces to the puzzle,” she said. “The plan is to release additional variants for each of these diseases in some sort of multi-gene model so we can give you more information.”
Christman says the study is sufficiently funded to go on for many more years—perhaps indefinitely, if resources allow. Patients already in the study will be offered additional information as it becomes available and will be invited to participate in ancillary studies.
For now, I guess I can feel safe—relatively speaking—in ordering that cheeseburger. Just hold the bacon.
SIDEBAR: Direct-to-Consumer DNA Testing—at a Price
Focused genetic testing to screen for specific diseases (such as breast cancer) or suspected birth defects is not new. What is new is predictive testing, which analyzes a person’s entire collection of DNA for clues about that individual’s future health.
While the Coriell Institute considers such predictive genetic testing to be in the research stage, several companies—including Navigenics, 23 and Me and Genetic Testing Laboratories Inc.—have for a number of years offered home-testing kits for personal genetic screening through their websites. The testing ranges from $99 to $399.
These direct-to-consumer services came under federal scrutiny in July 2010 when the Government Accountability Office revealed to a House Energy and Commerce Subcommittee that four different genetic-testing companies yielded often contradictory results from the same individual’s DNA.
Critics of the services say more research is needed to increase the reliability of predictive testing.
What’s more, there are no universally accepted procedures within the medical community for analyzing test results. Also, critics say, personalized counseling is an essential part of the process.
“I’m not really so sure that it’s reasonable to charge someone for this at the moment,” says Coriell president and CEO Michael Christman.
Coriell is conservative in its approach to genetic testing. For now, it only reports to subjects on eight actionable diseases and several prescription drugs. The web services, on the other hand, report on a wide array of diseases and medications. On its website, 23 and Me claims its testing can “discover risk factors in 97 diseases.”
Dr. Arnold Pallay, a family practitioner and medical director of Changebridge Medical Associates in Montville, is a proponent of predictive genetic testing. He is also director of the new Personalized Genomic Medicine program at Atlantic Health’s Morristown Medical Center and Overlook Medical Center in Summit.
Pallay, who for at least 10 years has performed genetic testing in his office and more recently at Morristown and Overlook, agrees the direct-to-consumer tests have the potential to confuse their subjects. He would prefer if the services did more “direct-to-provider-based testing. I would like to see it offered in the provider’s office primarily.”
While focused tests are only ordered in specific instances, Pallay recommends predictive testing for everyone curious about their genetic makeup. He says testing at his practice runs from $300 to $700 and “often is not covered by insurance.”