For those of you who like stories with simple plots and tidy endings, I must confess the tale of the Human Genome Project isn't one of those. The story didn't reach its conclusion when we unveiled the first draft of the human genetic blueprint at the White House on June 26, 2000. Nor did it end on April 14, 2003, with the completion of a finished, reference sequence.

Instead, human genome research is an epic drama being played out year after year, in sequel after exciting sequel, as scientists continue to make new discoveries about the role of our DNA instruction book in health and disease.

The First Law of Technology says we invariably overestimate the short-term impact of a truly transformational discovery, while underestimating its longer-term effects. Indeed, that appears to be true about the sequencing of the human genome. Many news articles are coming out right now reflecting upon what has—or hasn't—happened in the decade since we announced the first draft sequence. Cynics tend to view the immediate health benefits from genomic research as a glass half empty, but I see a glass half full—and growing fuller every day.

For me as a physician, the great appeal of the Human Genome Project was the opportunity it offered to seek answers to some of medicine's biggest puzzles. Today, as I look across all fields of biomedical research, it is clear that genomics is helping to piece together many of those puzzles. Whether their work focuses on cancer, diabetes, infectious diseases, mental illness or other conditions, researchers are using tools that have sprung out of the Human Genome Project to identify the molecular causes of disease and to develop new strategies for diagnosis, treatment, and prevention.

The cost of sequencing the first human genome was about $400 million. Today, the cost of sequencing one genome stands at $9,500, and, within the next four or five years, we expect to reach the point where we can sequence an individual's genome for $1,000 or less. This impressive decline in cost has fueled a rapid expansion in the medical applications of DNA sequencing and related technologies.

Back in 2000, I went out on a limb and forecast that within a decade there would be predictive, genetic tests available for about a dozen conditions, that it would be possible to take steps to reduce the risk for some of these conditions, and that pre-implantation genetic diagnosis would be widely available. And essentially all of that has materialized.

About five years ago, researchers began using an approach called genome-wide association studies to uncover genetic variants associated with the risk of common diseases. The first success, published in 2005, was the discovery of a variant in the gene for complement factor H that proved to be a major predictor of age-related macular degeneration, a leading cause of blindness in older people. No one had previously suspected that particular gene, which plays a role in inflammation. This underscores the power of researchers being able to scan the whole genome, and not just limit their searches to their own best hunches.

In the years since then, researchers have turned up hundreds of variants associated with risk of Crohn's disease, heart disease, diabetes and dozens of other conditions. However, when considered individually, most of these variants are rather weak in their contributions. So, one of the big challenges facing scientists today is: Where is the rest of heritability hiding? Might it lie in areas of our DNA instruction book we've yet to fully understand, the "dark matter" of the genome?

Another area ripe for genomic exploration is cancer. Among the earliest public calls for the Human Genome Project came from Renato Dulbecco, who, in a 1986 article in Science, made the case for sequencing the genome on the basis of what it would do for cancer research. Dulbecco's vision is now coming true in the form of efforts like The Cancer Genome Atlas (TCGA) project, which is building comprehensive catalogs of the key genomic changes in 20 major types and subtypes of cancer.

Already, in its pilot phase, this NIH-supported project has produced comprehensive molecular classification systems for ovarian cancer and glioblastoma, which is the most common form of brain cancer. This information may help doctors do a better job of matching individual patients with the therapies that are most likely to work well for them. What's more, the findings may lead to new therapies directed at the molecular changes underlying various subtypes of cancer.

Some of this is already happening today. Take the case of Beverly Sotir, a nonsmoker diagnosed with advanced, non-small cell lung cancer several years ago. Beverly received standard chemotherapy, but her tumors kept growing. Then, last July, based on a genetic analysis of her tumor at Dana-Farber Cancer Institute in Boston, she signed up for a clinical trial of a new genome-based drug called crizotinib.

The results were dramatic. In the first six months of treatment, some of Beverly's tumors shrank by more than 50 percent, while others disappeared. And she continues to do well.

Unfortunately, crizotinib works in only about 5 percent of patients with lung cancer. Why is this? Response to this drug depends on whether or not a patient's tumor has specific genomic changes, called ALK fusions. Beverly's tumor did, and so, like three-quarters of patients with similar profiles, she responded well. These patients demonstrate the potential of personalized medicine—of the value of matching the right treatment with the right patient at the right time.

Clearly, we need a lot more stories like Beverly's, not only for cancer, but for Alzheimer's disease, asthma, depression, heart disease, obesity and so many other conditions. It is my hope and expectation that over the next one or two decades—or however long it takes—genomic discoveries will lead to an increasingly long list of health benefits for all the world's peoples.

Image of Collins and Clinton announcing the human genome draft in 2000 courtesy of NIH


Francis S. Collins, MD, PhD, is director of the National Institutes of Health. As a physician and geneticist, he led the Human Genome Project to completion in 2003. His latest book, The Language of Life: DNA and the Revolution in Personalized Medicine (HarperCollins), was published earlier this year. He received the National Medal of Science in 2009.

Image credit: National Institutes of Health

[The views expressed are those of the author and are not necessarily those of Scientific American.]