Where, in your opinion, has the Human Genome Project had the most surprising impact?
In February 2001, Science and Nature published two papers that provided the first detailed look at a nearly complete sequence of the human genome. On the 10th anniversary, Focus asked research leaders at Harvard Medical School to weigh in on the mapping of the human genome. We asked:
Where, in your opinion, has the Human Genome Project had the most surprising impact?
What do you think? Join the conversation below.
David Altshuler
The greatest impact of the Human Genome Project has been in illuminating previously unsuspected biological processes and contributors to disease.
For example, I was taught that the typical “gene” consisted of a protein-coding region and a small amount of nearby regulatory DNA. The rest was “junk.” Today we know that the majority of the functional DNA in the human genome falls outside of this narrow depiction of a gene. A great task for the next generation is to untangle the biological functions and disease relevance of noncoding DNA sequences.
I learned about “genetic” diseases, but in most cases the specific genes and pathophysiological mechanisms were unknown—a black box. Today, using the unbiased approach of genetic mapping in families and populations, we know of genes and mutations for thousands of rare familial diseases, and increasingly for common, complex diseases. In the vast majority of cases, the specific genes mapped by genomic methods were previously unsuspected as playing a role.
Some have expressed disappointment that, 10 years after the sequencing of the human genome, medicine remains a highly imperfect science, without magic bullets for disease. My own view is that progress in medicine is held back by the fundamental and largely unexplored complexity of human biology and disease. By providing comprehensive tools that expand our thinking beyond the “usual suspects,” genomics has built a foundation for and accelerated the ultimate arrival of more effective prevention and therapy for disease.
No doubt, progress will still take a long time. But how long would it have taken without the genome project?
David Altshuler is professor of genetics and of medicine at Harvard Medical School and a physician at Massachusetts General Hospital. He is also a founding member, deputy director and chief academic officer of the Broad Institute of Harvard and MIT.
Raju Kucherlapati
We are in the golden age of human genetics and genomics. The sequencing of the human genome not only provided the blueprint for human life but the work in the past 10 years has provided great information about the genetic diversity in human populations and individuals. The past decade also has seen a dramatic reduction in the cost of DNA sequencing and many other ancillary technologies. The combination of technology developments and biological and medical discoveries is enabling us to assess risk, provide accurate diagnosis and—for those individuals who are already diagnosed with a disease—the prognosis and, in many instances, use genetic and genomic information to determine the most optimal treatment for the patients. These aspects can together be called personalized medicine. If I had to identify two of the most surprising areas of impact, I would say first the dramatic reduction in the cost of sequencing, and second the adoption of the use of genetic and genomic information in clinical settings.
Sequencing individual human genomes is now offered in commercial settings for $10,000 or less. This cost is anticipated to go down further in the next few years. This development has significant impact on developing better risk assessment and diagnostic tools that are being widely embraced by commercial entities and the medical and patient communities.
One of the most surprising aspects of personalized medicine is the acceptance of the importance of genetics in making treatment decisions, as evidenced by the current involvement of many pharmacy benefit managers, such as Medco, and drug store chains, such as CVS Caremark, Walgreens and Walmart. Together these organizations serve tens of millions of individuals, and they could have a high impact on how genetic information is used by the general population.
Raju Kucherlapati is the Paul C. Cabot Professor of Genetics at Harvard Medical School and a professor of medicine at Brigham and Women’s Hospital.
Matthew Meyerson
The Human Genome Project (HGP) has exerted an unexpected impact on cancer therapy. Now it is possible to discover and diagnose the major genome alterations that cause cancer and to select patients for genome-targeted therapies where available. One dramatic example has been the development of the first targeted therapy for metastatic melanoma, a deadly and poorly treatable disease. One year after the HGP announcement, a group of scientists in Cambridge, England, identified mutations in the BRAF gene for a protein kinase in about 60 percent of melanomas. This past year in clinical trials led by Keith Flaherty at Massachusetts General Hospital, the first B-Raf kinase inhibitor drug was shown to be effective for the treatment of melanomas bearing BRAF mutations.
A similar dramatic transformation has occurred in the treatment of non-small cell lung cancer. Here, genomic knowledge enabled researchers at both Mass General Hospital and the Dana-Farber Cancer Institute to identify mutations in the EGFR gene for a different protein kinase. Treatment with EGFR inhibitors has dramatically benefited patients whose lung cancers harbor EGFR mutations, opening the door to a floodgate of new targeted therapies for genomically defined subpopulations of lung cancer patients.
Because of these developments, the diagnosis of cancer for selection of therapy is beginning to move from the location and appearance of the tumor to detection of the genome aberrations that may be targets for therapy.
Matthew Meyerson is a professor of pathology at Harvard Medical School, co-director of the Center for Cancer Genome Discovery at Dana-Farber Cancer Institute and a senior associate member of the Broad Institute.
