N.B.: An abbreviated version of this perspective is scheduled to appear in the Iowa City Press-Citizen. On February 15, 2013, I will be participating in a televised and webcast discussion of personalized medicine as part of the University of Iowa's WorldCanvass series.
DNA (deoxyribonucleic acid) – it is literally the stuff of life. Three billion instances of four nucleotides (abbreviated GATC) (in the haploid genome) define our humanity, and slight variations across those three billion instances are responsible for all our differences, including our susceptibility and predisposition to diseases. Thus, understanding how DNA regulates biological processes is key to the mechanics of life and to treating disease at its most fundamental levels.
In 2003, after multiple years of painstaking work, two groups, one public and one private, each succeeded in sequencing the DNA of one individual – a human genome – at a cost of roughly three billion dollars. This technological tour de force required collaborations among research laboratories across the country, vast arrays of robotic machines to identify DNA snippets and massive amounts of computing power to assemble the snippets into a complete genome sequence via a technique known as shotgun sequencing.
In the intervening ten years, the cost to sequence a genome has dropped below ten thousand dollars. In other words, for the price of a minivan, you could have your family's DNA sequenced today. More importantly, technological advances will soon push that price below $1000, with $100 sequencing soon to follow. Very soon, having your DNA sequenced is likely to cost less than what most of us spend on gas for our cars each month.
In many ways, the dramatic reductions in DNA sequencing cost are due to advances in some of the same technologies that have given us powerful, yet inexpensive mobile telephones and other electronic devices. Automated DNA sequencers rely on robotics for sample management, advanced computing for coordination and data management, and miniaturization and nanotechnology for biological process and sample analysis.
Beyond the potential for scientific insight, these dramatic declines in DNA sequence costs have been in part due to perceived business and healthcare opportunities. Many companies, including ones created by faculty and students at the University of , see personalized medicine as a new frontier, much in the way that advanced imaging – x-ray computerized tomography (CT), positron emission tomography (PET) and magnetic resonance imaging (MRI) – transformed assessment and diagnosis in the 1970s and 1980s. To spur research and innovation, the X Prize Foundation has offered 10 million dollars to the first group to sequence 100 human genomes highly accurately at a cost of $1,000 or less.
Toward Personalized Medicine
What are the implications of inexpensive DNA sequencing for each of us? We can read the letters in each of our personal books of life. However, we do not yet understand fully how those letters collectively define the operating manual for our cells and our bodies, but biomedical research is bringing us closer to commonplace medical treatments.
Today, if you visit your primary care physician, he or she compares your current health to that of a typical human of your age and gender. Therein is the problem. There is no mass production of typical humans; each of us is custom made and slightly different, unique among the roughly seven billion people on this planet. We celebrate those differences, for they define our humanity. In that sense, every child's mother is right when she calls her child special and precious, for we are, in so many wondrous ways.
Biologically, DNA variations and the genes expressed lead to our differing appearance, behavior, physiology and metabolic processes. When combined with our varied lifestyles, environments, exercise patterns and food preferences, it is no surprise that we have different physical reactions to the same drugs and medical treatments. None of us is typical, yet today's medicine treats us as if we are.
When you visit your physician in a few years, to what might he or she compare your current health? Ideally, it would be you at your very best, perhaps at age 25 when you were in peak physical and mental condition, at your optimum weight, and living a healthy lifestyle. More to the point, your physician would then tailor your treatment based on a deep understanding of your unique genetic characteristics, your current condition, physical environment, and your body's particular reactions to those treatments. This is the promise of personalized medicine – earlier and more effective treatment tailored specifically for you.
Our DNA is the personal operating manual that directs our cells and physiology. Understanding that is essential to personalized medicine, but it is not enough. We also need inexpensive and routine diagnostics that can compare the "current you" and the "healthiest possible you" to determine what is wrong.
All of this is analogous to how we now diagnose automobile problems. In addition to inspecting the vehicle, all mechanics read the data captured by the vehicle's onboard monitoring electronics. That data include the vehicle's history of operation and all deviations from the factory-defined standard. While you drive, the vehicle continually monitors itself, raising alarms if there are problems.
Just as the best car repair is the one you never need, the best health care is treatment you never need because you are well. The next best case is early intervention that alerts you and your caregivers before serious issues develop. Late intervention when you are very sick is both damaging to you and expensive for all of us.
As with DNA sequencing, new technologies are bringing the medical diagnostics version of personal monitoring ever closer, allowing each of us to track our physiology and lifestyle. There are already smartphone apps that can measure heart rate and lung function, wearable devices that monitor exercise and sleep functions, and wireless meters for glucose monitoring. Some individuals in the quantified self community are now measuring their bodies in ways that were heretofore only possible in a research environment. Via microfluidics, nanotechnology, robotics, advanced computing and other technologies, the Star Trek tricorder is on the horizon.
Like all new technologies, genetic medicine brings a new set of societal questions. If DNA sequencing uncovers an untreatable genetic defect, do you want to know? It is not a hypothetical question; we are already facing this ethical dilemma for selected diseases. Because you are genetically similar to your siblings, what are the implications for them if you fit a particular disease profile? What is the appropriate ethical and economic balance between personalized health care treatment and cost, particularly if you choose a lifestyle that worsens your health, given a genetic predisposition to a disease? How do we protect individual privacy in a world of "big data" and inexpensive health monitoring devices?
As a comprehensive research university that combines the sciences, engineering and medicine with the liberal arts and humanities, the University of Iowa (UI) brings insights and expertise to all aspects of genetics-based personalized medicine. The UI is a major participant in scientific and biomedical research, as well as the transfer of research ideas into practice via new companies created by its faculty, research staff and students. It is also engaged actively in helping shape the ethical, social, legal and economic frameworks that will govern this transformation.
This exciting new world of personalized medicine is ripe with the promise of improved health for our citizens, by helping our children remain healthy, by allowing our seniors to live independently for longer periods, and by ensuring our citizens in rural areas can monitor their health in detail.
I believe the future is bright. Via personalized medicine, we can improve the quality of life and reduce health care costs for everyone, while respecting and protecting our individuality.
Remember, we are all special. Our DNA tells us so.