More than 99 percent of the human genome has been sequenced, and many of its estimated 30,000 genes are now known. Almost daily, we hear about technological advances in genetics—sequencing more, better, faster; testing for millions of genetic variants at once on a silicon chip; offers to sequence a portion of your DNA, or even your whole genome—for $350,000 at current prices. And, of course, research findings: genetic variants associated with diabetes, asthma, autism and more.
But the promise of the Human Genome Project in understanding and curing disease is still far from our grasp. The research findings seem scientifically grounded, but are they truly significant? Should we do anything about them, or is our genetic destiny already determined?
Getting answers is difficult, in part, because the current research paradigm is flawed. First, genes interact with environmental factors to cause disease, and teasing out these interactions requires studies with hundreds of thousands of participants. Most studies rely on smaller cohorts, collected for specific purposes, and lack the statistical power to detect such interactions. We're left with many small fiefdoms of researchers and patients that can't contribute to the greater understanding. Second, while existing studies may carefully document the patient's characteristics (phenotype) in relation to the disease in question, they don't capture other characteristics—other diseases, environmental influences, lifestyle factors—and the opportunity to use the data to the fullest is missed.
Perhaps the greatest flaw is that patients typically don't benefit directly from the research, and may never know what was discovered using their samples. One reason for this may be the somewhat paternalistic view that genetic findings are too complex for the average person to fully comprehend (or for the average researcher to make understandable to laypeople). Another reason may be that the researchers themselves aren't completely confident in their findings, and fear that participants lack sufficient knowledge to take them "with a grain of salt." In fact, many genetic findings don't stand up to the test of reproducibility, and, after additional studies, may not be confirmed.
This has not deterred commercial efforts to provide anyone (who can afford it!) with their own genetic information. In this unregulated situation, in which ethical and social issues are ignored, people may subject themselves to information that is difficult to interpret, unclear, lacking context and potentially frightening. There are also efforts at a growing number of hospitals to bank patients' DNA using blanket consent forms upon admission. Although researchers may learn from such samples, participants gain nothing, and information captured from them at one point in time is of limited use.
We can do better. With electronic medical records and the informatics tools we have, our ability to capture data is greater than ever, and growing. If properly utilized, these tools can lead to better health care and better research.
Children's Hospital Boston wants to change the face of genetic research, so that it directly benefits the participants. Our paradigm, which we term the Gene Partnership Project, or GPP (see Making Genetics Count, page 8), will maximize the significance of research findings by studying large populations of patients, capturing all available phenotype and environmental information and, most importantly, giving relevant findings back to patients as they become available. Rather than ask patients (or their guardians) to donate DNA samples on a blanket consent form, we seek to build "informed cohorts"—large groups of subjects who are engaged and informed about the research they're participating in.
To fully engage patients as partners, we must first put them in control of their health information. Children's is implementing a personally controlled health record (PCHR) system called Indivo, a Web-based electronic record that is under patients' control and which integrates information from all their visits to Children's and, we hope in the future, other health care settings. Patients will also have the opportunity to learn about and join different research studies through their PCHRs and to receive individualized communications of the findings. Through a computer architecture developed by the Children's Hospital Informatics Program, these communications will be done in a manner that protects patients' privacy and identity. An Informed Cohort Oversight Board with expertise in genetics, ethics, research and communication will vet the communications to ensure that they are thoughtful and meaningful.
Partnering with researchers makes people more willing to volunteer for studies because it increases trust. There is much to gain. Starting in childhood gives us a unique opportunity to identify the effects of genetic variants before environmental exposures and lifestyle habits alter the picture. At the same time, Indivo will allow us to tap into environmental and lifestyle information that patients may provide. (Going forward, we envision having access to environmental data from other sources, such as public health records on infectious outbreaks or chemical exposures.) And participation can potentially continue for life, to the benefit of all involved.
This paradigm starts to fulfill the promise of "personalized medicine" and is truly genetics for the people. As we share the fruits of research with our patients, our long-term vision is to make our software, architecture and data available to academic institutions around the world. To move genetics forward and to personalize medicine, everyone needs to share.