Walking Before Running: Genomic Medicine 10 Years After the Human Genome Project

It has been said that the folks at the National Human Genome Research Institute (NHGRI) never pass up the chance for well-deserved celebration – and I should know, I was one of them.  Probably at least a few readers have noticed that the Human Genome Project (HGP) has celebrated a number of milestones and anniversaries over the years – and 2013 is no exception.   April 14, 2013 marks the 10^th anniversary of the completion of the Human Genome Project, and as one might expect, NHGRI has a number of commemorative events planned.  Though most individuals outside of the genomics research community think only of the most obvious output of the HGP – the actual linear sequence of A’s, G’s, C’s and T’s that make up the human blueprint , the project comprised much more than that.  Additional components included sequencing of several important model organisms, creation of maps of the human genome that have greatly facilitated the work of discovering mutations causal of disease, and development of technologies to make genomics research cheaper, faster, and more accurate.  Reflecting on the last decade of progress in basic and biomedical research made possible by genomics, it is not too difficult to conclude that the HGP was a great public investment in science made in the second half of the 20^th century.

The April 10 issue of the Journal of the American Medical Association also celebrates the 10^th anniversary of the completion of the HGP.  The issue has a sampling of research studies that showcase the advances genomics is bringing to a diversity of areas of biomedicine, include cancer care, geriatric medicine, reproductive care, and microbiology.  Additionally, there are a series of short pieces that explore aspects of genomics that are related to the implementation of genomics in clinical and public health arenas.  The issue also contains an education-oriented article reviewing some of the currently available clinical molecular diagnostic tests in terms that a clinician not steeped in genomics can follow.

Readers of this blog will probably find several of the original research articles relevant to the field of public health genomics. For example, one of the articles identifies variants associated with long QT syndrome as the likely causal factor for at least some cases of unexplained intrauterine fetal demise.  If replicated in a larger population-based study, this could have implications for the provision of prenatal screening, and potentially provide some insights on a health problem of considerable importance at a population level. Another article showcases the growing prowess of metagenomics for investigating infectious disease outbreaks through a retrospective dissection of the microbial genomics of the 2011 German toxigenic E. coli outbreak.  Not novel?  Consider that it was achieved directly from fecal samples without an intermediate culture step to isolate the potentially causal organisms.  The development of robust, open-ended, and culture-independent molecular diagnostics platforms for infectious disease could have a profound effect on clinical as well as public health laboratory practice.

Those with an interest in health disparities will likely find the article on Alzheimer’s disease of interest, though not because it is yet another genome-wide association study (GWAS).  Rather, because it is the largest GWAS study conducted to date for Alzheimer’s in African Americans, a population that is notoriously understudied in most modern biomedical research.  The findings, like most GWAS findings, are of little immediate clinical or public health use.  However they hint at differences in the genetic architecture of Alzheimer’s that may in part account for long observed epidemiologic differences between white and African American populations.

Several of the opinion pieces in the JAMA theme issue touch on issues important to public health genomics, including the role of clinicians in guiding effective use of genomic test results, and the preparedness of health informatics infrastructure in the U.S. for genome scale data.  However, the piece that is likely to be of the most interest is an article exploring the value of genomics to the health care system in the U.S. and abroad .  This article points out a variety of important conditions that must be met before health insurers, and the broader health care system, are likely to embrace genomic advances.  As well the authors discuss the need to attend to the effects that very costly, yet potentially transformative new technologies might have on health across different population groups.

Despite the considerable interest of this JAMA theme issue,  I confess to being  somewhat dissatisfied.  Undoubtedly, many of my clinical colleagues as well as those in the public health community will feel the same way.  Absent are large prospective studies demonstrating dramatic improvements in morbidity and mortality, or substantial cost savings, arising from the ability to harness the genome to combat the top 10 causes of death in the population.  However, all of us (myself included) should remember on this 10^th anniversary after the end of the HGP, that we haven’t harnessed the genome.  In fact, we have really just begun to scratch the surface of understanding how the sequence of 6 billion base pairs leads to health and disease.  Studies of clinical effectiveness, from both clinical and public health researchers, will come.  In another few decades (yes, decades), I predict that we will be amazed at how much genomics  has contributed to improving the health of individuals and populations.  I would love very much to be there for that party.