Opinion editorial by James Evans, MD, PhD

Evans is director of clinical cancer genetics at UNC Lineberger. Article originally published in the June 27, 2010 issue of Newsday.

The Human Genome Project at 10 Years: A Teachable Moment

It has now been 10 years since humans deciphered the digital code which, in a very real sense, defines us as a species. It is hard to over-estimate the significance of that achievement but easy to misconstrue what it means and where its true promise lies.

The philosophical import of having the human genetic code in hand is remarkable. And we have learned much that is fascinating. For example, we scientists were surprised (and humbled) to discover that it takes only about 22,000 genes to build a human being – half the number it takes for corn to get on with its business. The Human Genome Project (HGP), which came in ahead of schedule and under-budget (at about $3 billion) has also shed light on some very big questions about human ancestry and evolutionary biology. But the HGP was not sold to the American people in order to answer evolutionary questions, ferret out how humans populated the globe or discover interesting factoids, no matter how fascinating or important these subjects might be. No, what the American people want from their investment is better medical care and it was this promise that fueled its funding and its popularity.

Now at the 10 year mark we are witnessing arguments about whether the HGP was worth the money and effort. Questions are being asked about where all that genomic medicine is that we were promised a decade ago. So this seems like a good time to take stock of where current and future genomic payoffs might reside and where we may have fallen short. But it is also a rare opportunity to illuminate more fundamental issues related to the nature of scientific progress, how the public and those who practice science communicate and what we really should expect from science.

The HGP has certainly yielded some practical benefit to clinical medicine. One of the near-term success stories is the field of pharmacogenomics, in which knowledge of one’s genomic information is used to guide drug choice and dosing. Specific agents, such as abacavir for the treatment of HIV and clopidogrel, a drug widely used to reduce the risk of heart attack, can be more precisely prescribed now that we understand how a patient’s genomic constitution influences their responses to these agents. Pharmacogenomic approaches will not be applicable to every drug - but for select agents, knowledge derived from the HGP is already improving the care of patients. In another near-term advance, our ability to better diagnose rare genetic diseases (which are no less tragic to those who have them simply because they are rare) is gaining tremendous traction due to knowledge and technology propelled by the HGP.

We have gained insight into the molecular underpinnings of many common diseases and found variants in the population that are related to one’s risk of almost every disease imaginable. This knowledge will provide long-term benefit in the form of new drug targets and through better understanding of those diseases. But any direct or practical payoff from such knowledge is years away. The idea that you will benefit in any tangible manner from knowing whether you are at an increased or decreased risk of, say heart disease, is a fools hope - in spite of early delusions by scientists and a fledgling direct-to-consumer genetic testing industry which would have you believe otherwise. For the simple fact remains that whether you are at double or half the population’s average risk for a given common disease isn’t very important…you are still highly likely to develop them. That’s why their called common diseases! Moreover, we’ve known for a long time how to prevent such diseases: eat right, exercise, don’t smoke, drink responsibly and wear your seatbelt. Your mom was right. As could have been predicted by any practicing physician 20 years ago, parsing an individual’s risk for disease adds little to information easily gained by taking a brief family history, asking a few questions and making you step on a scale.

As in all scientific pursuit, the true promise of the HGP lies in the gradual and incremental accrual of knowledge about our world. Ultimately, the better we understand ourselves and our world, the better we will be able to act on that knowledge and improve the conditions of our lives. Because of scientific progress, your life is unimaginably richer and more comfortable than that of any human who ever lived even a few generations ago. But the time-line is agonizingly long for the translation of scientific knowledge into practical benefit. The road to tangibly better lives from scientific insights is circuitous, unpredictable and filled with dead ends and U-turns. That is the nature of science and there are no short cuts.

The current debate about whether the HGP lived up to its promise is misguided. On one hand scientists trumpet one-off advances and try to convince themselves and the public that they represent a revolution. On the other, the public is impatient for the genomic medicine it thinks it was promised. It is time to reframe the debate in more productive terms. Both scientists and the public must come to terms with the true nature of science or we will continue to have this same pointless debate in other guises and in other scientific disciplines. Scientists need to resist the temptation to over-sell the short term benefits likely to be derived from basic insights and technological advances. This is especially important in the realm of medical care where the stakes are enormous, the variables many and our chances of being mislead are high. Inflating an unrealistic bubble of expectations not only ignores the reality of how science works, but it is bad politics on the part of scientists. For when the bubble bursts and the cool things we’ve been promised don’t materialize (where the hell is my hover car and my personal robot, anyway?) legitimate scientific pursuit suffers to the detriment of all. But it’s not all the scientists fault. The media must resist feeding the bubble of unrealistic expectations in search of the next good story. And finally, the public has a responsibility to understand the nature of science, shed simplistic expectations and fund basic research without expecting immediate benefits. Just as scientific knowledge has transformed our lives (mostly) for the better over and over again, the HGP too will transform medicine and was well worth the cost. Its payoffs will be pervasive but will be predictably incremental - evolutionary rather than revolutionary.