At medical and scientific conferences in the last few years, the iPad has been the most popular raffle prize donated by conference sponsors. At the most recent genomic medicine conference I attended, the raffle prize was a free personal genome sequence, delivered to the winner on an iPad! As the cost of sequencing is dropping faster than the cost for computing power and storage, the genome sequence will soon cost less than the iPad that's used to deliver it.
There are many other indicators of the mind-boggling pace of technology advances and plummeting price for genome sequencing. Recently, the National Institutes of Health (NIH) has requested grant applications for pilot studies to determine the potential role of whole genome sequencing during newborn screening, when virtually every baby born in the United States has a small blood sample taken by a heel stick. Having a complete genomic profile from birth would obviate the need for any future blood or DNA sampling in order to obtain genetic testing information; one would only access the data from a patient's electronic health record, personal health vault, or their smart phone.
Besides the stunning technical advances, application of large-scale sequencing has led to unexpected and game-changing biological and medical insights. At the top of my list for these changes has been the realization in oncology that a tumor's genomic profile of mutations is more important in determining the appropriate choice of chemotherapeutic agent than the organ in which a tumor originates (eg, breast or lung), necessitating a complete revamping of cancer taxonomy for diagnosis and treatment and promising much improved survival rates.
Another potentially widespread application for rapid sequencing is identification of infectious agents involved in hospital outbreaks, where it is now possible to determine exactly when, where, and by whom the infection was introduced to the hospital. Such molecular microbiology by genome sequencing may soon be done as a routine screening procedure prior to hospital or emergency department admission on all patients.
Increasingly, genome sequencing has been used to identify the etiology of diseases in children with complex, undiagnosed conditions. In the most famous of these cases, Nick Volcker, a young boy in Wisconsin with a severe Crohn-like disease was not only diagnosed by sequencing as having a mutation in a gene on the X chromosome, but knowledge of the specific gene causing his clinical symptoms led to the correct treatment and a complete cure. The story of using DNA sequencing to save the life of a gravely ill child was documented in a series of articles in the Milwaukee Journal Sentinel that was awarded a Pulitzer Prize.
In 2012, Stephen Kingsmore's group in Kansas City pushed the envelope of genome sequencing to show that sequencing and genome interpretation could be performed in less than 50 hours in babies in the neonatal intensive care unit (NICU), arriving at accurate medical diagnoses and appropriate treatments far faster than the sequential testing procedures for individual disorders usually followed in this setting. This demonstration of “stat sequencing” has made the potential clinical relevance of genome sequencing a reality for many previous skeptics.
But how do physicians and healthcare providers make sense of the vast amount of new genomic data and its potential clinical implications? Although we still don't know what much of our genome does, there are many clinical situations where sufficient evidence now exists for the use of genomic information to optimize patient care and treatment. Therefore, it is timely to see a comprehensive textbook and practical guide to the use of this information across a broad spectrum of adult diseases—from individual differences in drug response, cardiac and cancer risks, to Alzheimer and other neurological and psychiatric disorders. I applaud both the timing and the effort of the editors and the authors of this volume, as well as the American College of Physicians for their role in supporting this effort.
The organization and style make this a very practical handbook for internists, primary care physicians, and other healthcare providers, with concise presentations of key information needed for diagnosis, management, and treatment across approximately 200 different clinical conditions.
Physicians today are increasingly dealing with patients who have surfed the Web to obtain information potentially relevant to their health. In the next few years, patients will increasingly individualize this research based on knowledge of their unique genomic profile and expect their physicians and healthcare system to act as “Genome Health Navigators” to provide precise and optimum health and wellness guidance.
David H. Ledbetter, PhD
Executive Vice President & Chief Scientific Officer
Geisinger Health System