The doctor hands you your newborn son, and with him a readout of his genetic propensities toward diseases, conditions, and reactions to medicines. Before you get him home, you will know his odds of contracting macular degeneration in his middle age and how susceptible he will be to melanoma before his 60th birthday.
Sound far-fetched? Courtney Kronenthal believes it will be routine by as early as 2017. What scientists know about the genomic makeup of human beings — and what patients are doing with their own knowledge — is evolving by the day.
Scientists have cracked the genetic code, and much of what those long strings of letters mean in the real world. It’s just a matter of educating the people and the doctors who treat them.
Kronenthal, the director of communications and development at the Camden-based Coriell Institute, will be one of several featured speakers at BioNJ’s Diagnostics & Personalized Medicine Innovation Summit and Funding Roundtable on Wednesday, March 14, beginning at 7:30 a.m. at Princeton University’s Carl Fields Center. Cost: $90. Visit www.bionj.org.
Kronenthal will join G. Steven Burrill, CEO of Burrill & Company; Sam Chawla, global director for diagnostics and life science tools at UBS; Joseph Hammang, senior director of worldwide science policy at Pfizer; Paul Kildal-Brandt, global alliance leader at Janssen Diagnostics; and Aydogan Ozcan, associate professor of electrical engineering and bioengineering at UCLA, to discuss the future of personalized medicine — that which is tailored to individuals, based on genomic study.
Kronenthal, a native of California’s Bay Area and the first in her family to graduate from college, leaned toward science while growing up, but was drawn to the field of genetics by a sudden outbreak of cancer in her circle. “For some reason, cancer became very apparent in my life,” Kronenthal says. “An aunt was diagnosed with cancer, then a grandmother.” A spate of other relatives and acquaintances followed suit. “It just came out of nowhere. I thought ‘What is this?’”
Kronenthal earned her bachelor’s in biological science from UC-Santa Barbara in 2001, then attended the Boston University School of Medicine. She earned her Ph.D. in genetics and genomics in 2007.
While studying, Kronenthal realized that her passion was not in lab work. She greatly preferred talking about genomics and the potential it has to revolutionize medical treatment. She joined Coriell, a nonprofit scientific research organization founded six decades ago that now focuses on stem cell and genome-informed research, as director of communications in 2007.
The 99 percent club. You and I are 99 percent identical. So are you and everyone else. The human genome — the genetic hereditary code that scientists cracked in 2003 — breaks down our genetic makeup into nucleotides designated as G, A, T, and C, then repeats these letters billions of times to spell out our DNA code.
As it turns out, Kronenthal says, 99 percent of this billions-long string is the same for everyone. Our individuality is based on the less than 1 percent of the genome string where that varies. This makes one person susceptible to heart disease, another hypersensitive to certain drugs, others more prone to balding, and so on.
From a scientist’s point of view, Kronenthal says, this small percentage is great news. Handling less than 1 percent of something the scale of the genome is significantly more manageable that trying to find the one place in the galaxy of letters where the G and the A switch places and make someone more susceptible to cancer.
Potentially actionable conditions. For the past few years, the Coriell Institute has been conducting a study on about 5,000 volunteers. The participants provided saliva samples that since have been analyzed according to genome-informed research.
The institute returns genome-informed data to these participants and, to a degree, fills them in on what their genomic alphabet says about them as individuals.
Kronenthal says the institute has taken the relatively conservative first step of informing participants about “potentially actionable conditions.”
These are conditions that a person could head off by changing behaviors or diet. Melanoma is one example — if a participant’s genome suggests a heightened susceptibility to skin cancer, that person could take precautions such as staying in the shade and using sun block.
The conservative approach of this first step has gotten some flak, Kronenthal admits. Some people believe the institute should lay out everything up front, but Kronenthal defends the approach by saying that giving information that a person could directly do something about makes that person more aware of fixable problems and gets the process of public education rolling.
The good news is that what is considered actionable grows all the time. Every time participants come back to the study, Kronenthal says, more potentially actionable conditions have been identified and, thus, more participants become more informed (and empowered) by the new knowledge.
Power to the patient. An unanticipated outcropping of Coriell’s study, Kronenthal says, is that as participants learn more about their DNA, they are pushing their doctors to be more aware of their genomes. Doctors, in turn, are suddenly faced with a Rosetta stone to a patient’s entire genetic makeup, and the decision is either use it or ignore it
As a result, Kronenthal says, doctors are learning more about how to treat patients by using genomes. It could be the first time in history that patients are driving medical professionals to know more about advances in medicine.
The CSI effect. Education is paramount, Kronenthal says. The public needs to know that genome-informed medicine is not make-believe or science fiction. But the doctors need to be told this too. Despite how far the field of genomics has grown, she says, most do not understand what the subject is all about.
In legal circles, “the CSI effect,” named after the popular forensics-detective television show, refers to the phenomenon of juries dismissing solid genetics-based evidence because they think the science is as advanced as it is on TV. Consequently, juries do not believe real evidence to be solid because the prosecution has not been able to turn small samples of DNA into detailed digital readouts of defendants. “We take saliva samples, and I can’t count the number of times someone has said ‘this is like CSI,’” Kronenthal says.
The genomics version of the CSI effect is that many of those who do know about it feel as if having the GATC readout means that everything can be cured. The reality is less glamorous and less futuristic than television programs might lead some to believe, Kronenthal says. Scientists, in fact, are still trying to figure out how all those letters really work together.
“Let’s say there are five sites on the genome that influence a condition, like lung cancer,” Kronenthal says. “If I have all five of these markers, does my risk for lung cancer increase fivefold? If I have two that increase my risk and two that decrease my risk, will they cancel each other out? We just don’t know that yet.”
Pharmacogenomics. Kronenthal believes that pharmacogenomics — the practice of tailoring medicines specifically to an individual’s genomic fingerprint — will be the first practical, routine use for genomics-informed medicine.
Already, some drugs, like warfarin (a blood thinner sold under the brand name Coumadin), are coming with genetic testing guidelines that allow doctors to determine ahead of time whether a patient could take a specific drug. Drugs, Kronenthal say, work by activating or deactivating some sort of process in the body. With what scientists know about the genome now, they can tell whether a specific patient’s DNA is written to activate or deactivate when a drug enters the system.
The case that spurred this genetic pre-test is that of Karen Schmale, a St. Louis woman who was given Coumadin as a treatment for blood clots in her lungs.
After one week she was unable to walk and was given an emergency blood transfusion. Her system did not allow the drug to deactivate what it needed to and, thus, Schmale was unable to rid her body of excess Coumadin.
Kronenthal sees the genetic testing guidelines now associated with warfarin as a watershed, the kind of thing that will soon enough compel patients to challenge doctors to run genetic tests before prescribing medicines.
And this is good, she says. As patients take more accountability for their own lives and treatments, doctors will have to step up and listen, or risk being left behind on possibly one of greatest advancement in recent medicine.