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Expectations exceed understanding in unraveling the genome

From the September ACP Internist, copyright © 2010 by the American College of Physicians

By W. Gregory Feero, MD, PhD

Recent high-profile articles in the lay press have criticized the lack of immediately tangible health benefits from genomics research investment. Expectations for immediate clinical benefit from genomic discovery, fueled by both scientists and the media, have outstripped even the blistering pace of genomic discovery. The gap between discovery and application is particularly notable in general medical practice, where only a handful of evidence-based applications, such as genetic counseling/testing for hereditary breast and ovarian cancer syndromes, have entered routine care.

The paucity of current tangible health benefits from genomic discovery contrasts considerably with the quite sanguine outlook for rapid development of clinical benefit from genomic discovery held and promoted by some prominent members of the genomics community a decade ago. Articles in both the scientific and lay literature from around 2000 predicted clinicians would routinely draw on an understanding of their patients’ genomes to tailor care within the decade. Clearly we aren’t there yet.

Expectations exceed understanding in unraveling the genome

The genome and its function are understood to be more complex by the day. Though this wealth of complexity is favorable for scientists, it is not so for the many individuals living with both rare and common heritable conditions. For these individuals new methods for better screening, prevention and treatment cannot come fast enough.

Recently the National Human Genome Research Institute hosted a planning conference to mull over future opportunities and challenges in genomics research. The breadth of topics discussed was considerable, discourse was intense yet polite, and many conversations lasted well into the night. A similar meeting in 2003 had been electrified by the promise of significant insights just waiting to be discovered, while the 2010 meeting was suffused with a sober appreciation of the complexity our genome encodes.

Understandably, the group was universally appalled that anyone with a real understanding of the pace of genomic discovery could be anything less than blown away by the scientific discoveries that have occurred in the last decade. A major topic of debate was the extent to which genomics research should shift focus to developing and implementing clinical applications based on early emerging genomic discoveries.

Some in the genomics community clearly felt that the expectation of near-term clinical benefits from genomics research has been heightened to unrealistic levels. They argued that the race to clinical benefits is more akin to an ultra-marathon than a 100-yard dash, and the majority of clinical benefits will not accrue for 50 to 100 years. Those of this opinion feel that the focus of the genomics community for the next several decades should remain squarely on understanding the function of the normal genome and how derangements in function lead to disease. They point to examples of breakthroughs like small molecule treatments for chronic myelogenous leukemia that came from a careful and rational approach to targeting a well-defined molecular entity with rationally selected small molecules, arguing that true advances in patient care will occur only when the molecular details of the human condition are under our belts.

At the other end of the spectrum, some meeting attendees argued that now is the time to shift to a more clinical focus, as genetic factors relevant to disease risk and drug therapy are being discovered daily. They pointed out that in some instances these basic discoveries are being marketed to consumers and clinicians within days of publication of the discovery with little, if any, clinical trial data to support the new application’s health benefits. Waiting to investigate such potential clinical applications is likely, this group believes, to result in societal harms as unstudied new technologies pass unfiltered into the hands of health care consumers. Additionally, the point was made that our clinical care infrastructure, including health information technology systems, is extremely slow to change, and that planning for integration of genomics should begin decades before expected routine use.

In reality both viewpoints are valid and in no way mutually exclusive. Programs in both basic genomic research and applied clinical research directed at promising genomic discoveries need to be grown. Very likely some of the needed growth will be transparent and to some extent cost-neutral; for example, in clinical research as genomics becomes more evidently important to drug development, genomic technologies will naturally become part of clinical trials.

On the other hand, expanded basic genomic research and clinical studies on applications without an immediate promise of profitability, such as use of family history or genetic testing for screening for risk of conditions like diabetes and heart disease, will require increased funding from public and private grant-making organizations. Balancing the priorities between basic and clinical genomics research in a time of general fiscal austerity may itself prove to be one of the greatest challenges facing the genomics community over the next 10 years.

W. Gregory Feero, MD, PhD, a family physician with a doctorate in human genetics, is Special Advisor to the Director of the National Human Genome Research Institute (NHGRI) and faculty at the Maine-Dartmouth Family Medicine Residency Program (MDFPR). The opinions expressed in the column are his own and not necessarily those of either organization.

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