So, what's in it for me? That question probably crossed many minds five years ago following the news that scientists had successfully assembled the first draft of the human genome -- the genetic blueprint of a human being. The answer for most of us was ''not much."
What a difference five years can make. Today, we are witnessing a revolution in the understanding of health and disease, spurred on by the sequencing of the human genome and the subsequent creation of a map of human genetic variation. And, like most historic movements, this revolution has been given a name: personalized medicine.
At its most basic, personalized medicine refers to using information about a person's genetic makeup to tailor strategies for the detection, treatment, or prevention of disease. That may sound like a straightforward task, but it actually poses major scientific challenges when one considers that there are 3 billion letters in the human DNA code. This ''instruction book" is 99.9 percent identical between any two humans. But how do we set about analyzing the 0.1 percent differences that holds clues to the variations among humans in susceptibility to disease?
Taking aim at that crucial 0.1 percent, a six-nation consortium, led by the US National Human Genome Research Institute and involving researchers from the Broad Institute of Harvard and MIT, recently produced a map of common patterns of human genetic variation, also known as haplotypes. Though the first phase of this ''HapMap" was just completed in February, early uses have already led to the discovery of genes involved in susceptibility to common diseases, including diabetes, heart disease, osteoporosis, lower back problems, and blindness. Each one of these gene discoveries sheds new light on the biological basis of disease, which in turn provides new targets for therapies and new options for prevention.
Designing new drugs
Data on human genetic variation can be used to pinpoint genes responsible for the wide variability in people's responses to many common drugs -- a field referred to as pharmacogenomics. For example, a recent study published in the New England Journal of Medicine identified a gene that plays a central role in determining whether someone is likely to develop a dangerous reaction to warfarin, a blood-thinning medication often prescribed for people at risk for blood clots or heart attacks. Researchers are now trying to translate those findings into a genetic test that could help doctors adjust warfarin doses to each patient's genetic profile.
Driven by advances in biotechnology and computer software, this newfound knowledge is swiftly making its way into the clinic. Thousands of cancer patients are already benefiting from a half-dozen targeted drugs, such as Gleevec, Iressa, and Tarceva, that are known to work better in people with certain genetic profiles. In fact, researchers from Massachusetts General Hospital and Dana-Farber Cancer Institute have developed a promising genetic test to identify the lung cancer patients who could benefit most from Iressa and other drugs that attack cancer in a similar way. These therapies represent the leading edge of a wave of many similar ''designer" drugs that are expected to emerge from the research and development pipeline.
In another landmark move for personalized medicine, the US Food and Drug Administration recently approved the first laboratory test designed to use genetic information to help doctors select the most appropriate medications and doses of medications for their patients. This AmpliChip test analyzes two genes that code for enzymes involved in the metabolism of about 25 percent of all prescription drugs. Common variations in the gene sequence can cause an individual to metabolize these drugs more quickly or more slowly than average.
The FDA action has implications far beyond this individual product because it clears the regulatory pathway for the development of similar ''DNA microarrays." These tests employ technology similar to a computer microchip, but contain thousands of DNA probes rather than electronic circuits.
When DNA or RNA that has been isolated from a patient's blood, tumor, or other tissue is placed on the microarray, it is possible to determine what genes are turned on or off in that sample, and even what gene variations are present in that patient, by analyzing how his or her DNA or RNA binds to the chip.
Bumps in the road
Clearly, the era of personalized medicine is underway. But are we really ready for this revolution? Many healthcare professionals have not been trained to interpret and use the results of sophisticated genetic tests. Much remains to be done to enhance the knowledge of genetics and genomics among doctors, nurses, pharmacists, and social workers, as well as to facilitate the availability of referral networks of medical geneticists and genetic counselors. Universities, hospitals, and professional societies are all vital to this effort.
The public is also in urgent need of education and guidance. Even the savviest consumer is likely to have difficulty interpreting the onslaught of advertisements from companies trying to hitch their wagons to the personalized medicine star. These ads run the gamut from established medical laboratories offering tests for genes involved in susceptibility to serious diseases, such as breast cancer, to Internet opportunists making wild claims about being able to tailor diets or face creams to a person's DNA profile.
There is no way for consumers to gauge whether a genetic test is scientifically valid, let alone whether it is appropriate for them or reimbursable by their insurance companies. The lack of oversight of such tests leaves the average person vulnerable to misuses or mispresentation of what personalized medicine truly is.
Still, personalized medicine remains one of the most compelling opportunities we have to improve the odds of staying healthy. By 2010, it is likely that predictive genetic tests will be available for as many as a dozen common conditions, enabling individuals to take preventive steps to reduce their risks of developing such disorders. Doctors will also begin tailoring prescribing practices to each patient's unique genetic profile, choosing medications that are most likely to produce a positive response.
By 2020, the impact is likely to be far more sweeping than any of us can envision today. New gene-based designer drugs will be developed for diabetes, heart disease, Alzheimer's disease, schizophrenia, and many other conditions that take a high toll on our society.
If technological development continues at the current dramatic pace, it is possible that each of us will be able to have our genomes sequenced for $1,000 or less, possibly right in the doctor's office using microchip technology. That information can then be used to guide prescribing patterns and develop a lifelong plan of health maintenance customized to our unique genetic profiles. Achieving the $1,000 genome will be no small feat. Currently, it costs about $10 million to sequence a human-sized genome, so highly innovative DNA sequencing technologies are vital to turning this dream into reality.
To realize the full potential of personalized medicine, we must venture beyond the fields of science and medicine and into the ethical, legal, and social arenas. For example, without legislative protections against genetic discrimination in health insurance and the workplace, many people will be reluctant to undergo potentially life-saving genetic tests or to participate in the clinical trials needed to develop genetically targeted therapies. In February, the Senate passed the Genetic Information Nondiscrimination Act of 2005 by a vote of 98-0. The president has indicated strong support, but the bill remains before the House of Representatives, with no hearings scheduled. Given that more than 800 genetic tests are now available and hundreds more are on the horizon, we need this legislation.
Other tough questions that we as a society need to ask ourselves are: Will access to genomic technologies be equitable? Will knowledge of human genetic variation reduce prejudice or increase it? What boundaries will need to be placed on this technology, particularly when applied to enhancement of traits rather than prevention or treatment of disease? Will we succumb to genetic determinism, neglecting the role of the environment and undervaluing the power of the human spirit?
We obviously do not have all the answers yet. It will take much thoughtful research and vigorous debate among scientists, health-care professionals, ethicists, legal scholars, patient advocates, and ordinary citizens to chart the wisest course.
Dr. Francis S. Collins is director of the National Human Genome Research Institute, part of the National Institutes of Health in the US Department of Health and Human Services. He led the Human Genome Project, which was the international effort to sequence the human genome.