Genomic discoveries to clinical applications: Are we reaching an inflection point toward precision medicine?

Each year at the annual American Society of Human Genetics (ASHG) meeting I follow certain rituals. During the first “poster session”, I quickly peruse all of the vendor booths on the floor to assess something of the overall flavor of the commercial space’s focus. During the next two poster sessions I cruise all of the aisles of the scientific posters and scan the  titles.  This is sort of a daunting challenge requiring months of aerobic training as the number of posters presented at ASHG is huge -more than 3,000 this year.  From this, I gain some insights on where genomic science is focused. I find that this ritual provides a valuable overall snapshot of the state of the field of human genetics.  Over two decades of watching, broad trends have included linkage studies for gene discovery using microsatellites, mapping of the anatomy of the genome, cataloging of human genetic variation, SNP genotyping/genome wide association studies, and the explosion in sequencing technologies.

This year, at least by my eye, there was a qualitative difference in both the commercial and scientific offerings. ASHG, which has typically focused on discovery science, had much more of a feel of clinical application.  Numerous vendors from academic and private industry were promoting clinical sequencing services, microarray technologies, and health informatics software relevant to managing genomics data.  Posters covered a very wide spectrum of topics but many dealt either with interrogating clinical data for genomic discovery or the clinical application of genomic technology in the context of ongoing health care delivery.  In short, ASHG had the feel that the genomics community has reached an inflection point in the trajectory towards a vision of precision medicine.

There are several underlying factors that could have facilitated this sea change. First, inexpensive genotyping and sequencing have made studies of genotype/phenotype correlations accessible to the scientific masses.  Second, health informatics systems have matured to the point (I say this with some hesitation as at least my home institution’s electronic health record [EHR] system is hardly as mature as I would like it to be) that useful information might be gleaned from EHRs about  large numbers of properly consented individuals.  Finally, and I think most importantly, the climate of fear regarding the integration of genomic discovery research into mainstream clinical care has abated.  The center of gravity of discussions around genomics ethical, legal, and social issues has shifted from “Should the genomics research enterprise integrate with clinical care?” to “How can genomics research synergize with clinical care to benefit the widest population possible while minimizing harm?” Also, it seems that the boundaries of public tolerance for personal information sharing in electronic media have changed largely because of the penetration of social media in society.  Additionally, at least in the U.S., there seems to be a strong trend towards interest in learning about personal determinants of health (think fitness trackers that follow your every move) that is likely benefiting genomics research participation.

More directly, programs like the National Human Genome Research Institute’s eMERGE, CSER and IGNITE have funded projects that are informing the field with preliminary data across a variety of domains relevant to a future where medicine becomes more individualized. On the regulatory front, the FDA has embarked on a new initiative to overhaul processes for evaluating genomic technologies. Several large health systems, such Geisinger and Kaiser have invested heavily in population scale sequencing initiatives to learn how such information might be used to improve the well-being of their customers.  Finally, the announcement regarding NIH’s Precision Medicine Initiative seems to have crystallized the realization across academic health systems that genomics is about to come to main street, and not just to a few enclaves of genomics expertise. Genomics has a long way to go on the trajectory towards application in population health, however these projects are helping to tackle some of the more challenging issues facing the integration of genomics into mainstream clinical care.

Remarkable as this sea change is, it is incumbent on those of us at the interface of public health, health care, and genomics to continue to demand that the genomics community not lose the trees for the forest. In order to benefit the widest number of individuals possible, precision medicine must be predicated on a firm foundation of evidence of health benefit for each application and intended use.