Originally published on March 30, 2015
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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.