By Brian Herman, Published on March 30, 2015, Featured in: Healthcare
President Obama’s proposed Precision Medicine Initiative promises unprecedented support for the rapidly growing field of genome-based medical therapies.
The initiative will fund research into developing treatments tailored to patient genetics, especially to combat cancer. It will also support collection of 1 million mapped genomes along with information on the health and lifestyle of each participant. The initiative is an extraordinary opportunity to further our understanding of the connection between genes, disease and treatment.
The sum requested for the project — $215 million — indicates that the federal government means business. But a number of serious ethical questions remain about the sharing of genome information and its protection.
Precision medicine refers to treatment tailored to a patient’s individual variability. Genetic discoveries have exponentially broadened the scope of such possibilities as researchers discover links between a person’s genetic profile and disease. A number of these discoveries have translated into clinical application and treatment.
To grow this research and the clinical therapies it will generate, researchers need large-scale databases of individually sequenced genomes that can be plumbed for data and analysis. The president’s initiative will offer an unprecedented opportunity for the gathering of such a database.
But the amassing of information as sensitive as a person’s individual genome requires extraordinary care and consideration. Certainly, geneticists, biomedical ethicists, and researchers are all in agreement that consistent policies need to be in place, but opinions differ when it comes down to the nitty gritty. Waiting too long to provide concrete guidance may end up deterring the one element every genome research project needs: willing participants.
One area of particular concern is how much information gleaned from mapping a genome researchers are obliged to give to a study’s participants.
This is anything but a theoretical question. According to researchers, it is highly likely, even inevitable, that mutations will be found when mapping a genome. Large genome-mapping research projects will uncover scores of mutations. Researchers — and participants — need certainty as to what information should be given, or “returned,” to participants regarding these so-called “incidental findings.” Thus far, there is a consensus only that policies must be in place for each study, that participants must be advised of these policies in advance, and that they must have the option not to receive returns.
When it comes to exactly what kinds of information should be returned, the situation is less clear. Those grappling with these issues point out that these questions are complex. Just one example is whether genetic information that is of significant value to the participant’s offspring should be considered returnable. And although most agree that researchers should not be obliged to return results on aberrations about which little or nothing is known, there is less certainty about the return of information on those genes science does understand.
Key players are engaged with the issue. A 2014 “Primer” based on a 2013 Presidential Commission for the Study of Bioethical Issues advises that researchers are ethically obligated to develop a plan that balances the clinical significance of findings against “the benefits, risks, and costs of disclosure, including the risk that seeking or analyzing incidental and secondary findings might distract from the central goal of research.”
Primer also states that “disclosing certain incidental findings might lead participants to obtain lifesaving medical interventions, or help participants make informed medical decisions.” It still remains for each individual research team to define and weigh the variables.
Other interested bodies have made recommendations, including the Public Population Project in Genomics and Society in 2013 and more recently, the National Human Genome Research Institute. The issues were also addressed in a series of NIH-funded projects and most recently a November 2014 symposium of the University of Minnesota Consortium of Law and Values.
Nearly all agree on the general principle that participants should be offered genetic information if the findings reveal an established and substantial risk of a serious health condition and the findings are clinically actionable. Debate continues on what findings qualify and how to manage the process.
When it comes to clinical genome sequencing, the American College of Medical Genetics and Genomics has issued guidelines and a growing list of genes that clinical labs now have an obligation to look for, though patients may opt out. Whether this route is also appropriate for research remains to be decided.
A related big issue is whether large-scale data repositories — a building block of the Precision Medicine Initiative — share obligations to offer incidental findings to source individuals.
Without more ethically-defensible certainty, consistency and specificity, it won’t take long for perceptions of unfairness to arise. The end result will impact the pool of those willing to offer their genomic material for research.