Our Health: More Examples
Toxicity is one of the major hurdles to developing new drugs, but genetic research is helping to solve that vexing problem. For example, in 1998, the FDA approved the drug Abacavir as part of a promising approach to treat HIV infection. Unfortunately, the drug caused a severe, potentially fatal hypersensitivity reaction in some patients. Follow-up research uncovered a particular genetic sequence associated with the bad reaction. In 2008, the FDA added recommendations to test the DNA of patients before prescribing to the drug’s label, reducing hypersensitivity reactions almost to zero. The move also generated cost savings because patients can now be prescribed the safest and most effective drug. This new field of using DNA testing to choose the right drug at the right dose for the right patient at the right time is called pharmacogenomics.
In the past, women diagnosed with breast cancer and negative lymph nodes have faced a difficult decision about whether to undergo chemotherapy. While NIH studies have shown that most women are cured after lumpectomy and radiation, the small additional increase in cure rate by following up with chemo motivates most women to go through this grueling experience. Tools developed through the Human Genome Project are now helping to make this decision much more personalized. Molecular testing of breast cancer cells, using a diagnostic test called Oncotype DX.0, makes it possible to see which genes are active in an individual tumor. That pattern enables doctors to predict the chance of cancer recurrence with a high degree of accuracy. This genomic test is now being used by approximately 50,000 women annually. A large fraction of these women will be found not to need chemo, sparing them needless suffering and saving our health care system $100 million.
Every year, influenza kills more than 36,000 Americans and hospitalizes 200,000 more. NIH researchers are closing in on a universal flu vaccine that would protect against multiple strains of influenza for extended periods of time and do away with the costly, time-consuming process of making, distributing, and administering millions of seasonal flu vaccines. A two-step vaccination strategy was able to protect animals against multiple strains of influenza. Ongoing clinical trials are assessing the safety and efficacy of this vaccine approach and will allow scientists to identify vaccine candidates to move forward into large-scale trials.
In the past, most drugs have been developed through trial and error. Now, with growing information about the molecular basis of disease stemming from the Human Genome Project, it is possible to design drugs that go right to the vulnerable target of the disorder. A recent example is the development of a new drug, called PLX4032 or vemurafenib, for the most deadly form of skin cancer, malignant melanoma. The drug was specifically designed to block the effects of a gene called BRAF, which was shown by DNA sequencing to be dangerously overactive in most cases of melanoma, thereby driving the malignant process. The drug has caused melanoma tumors to shrink significantly in nearly half of patients and reduced their chance of dying by nearly two-thirds. Interestingly, a form of leukemia not previously connected to melanoma also has been found to have the same flaw in the BRAF gene, raising the possibility that it too may respond to the experimental drug.
Each year, approximately 56,000 Americans become infected with HIV; globally, the annual number of new infections is roughly 2.6 million. NIH sponsored landmark clinical trials that successfully demonstrated that treatment of HIV-infected pregnant women could significantly reduce transmission of HIV from mother to child, thereby decreasing the global infection rate, alleviating human suffering, and reducing mortality and costs associated with life-time treatment. The findings revolutionized approaches to controlling the epidemic by fostering early treatment as a primary strategy to prevent further infections. The “treatment as prevention” strategy has been tested and proven successful in other contexts and populations, including couples for which one partner is HIV-positive.
Lung cancer is the most common cause of cancer deaths in the United States and the world. In most cases, however, lung cancer is not detected until symptoms appear—usually after the disease has spread beyond the lungs, making treatment much more difficult. Data from the NIH-funded National Lung Screening Trial demonstrated that screening with low-dose, helical computerized tomography (CT) results in 20% fewer lung cancer deaths among current and former heavy smokers than screening with simple X-ray technology. This development marks the first time that a screening test has been found to reduce mortality from lung cancer.
Public Health Emergencies
Foodborne bacterial infections, such as the Escherichia coli (E. coli) outbreak in Germany that killed dozens of people and sickened more than 2,000 others in 2011, and the emergence of dangerous human viruses, such as the one that caused the Severe Acute Respiratory Syndrome (SARS) epidemic in 2003, are biological puzzles that can have devastating implications for public health and the economy. Using genomic technologies that arose from the Human Genome Project, investigators can now quickly sequence bacterial and viral pathogens, enabling the development of diagnostic kits to confirm the source of such incidents and inform intervention strategies.
About 7,000 rare diseases are known to affect humans. Taken together, such rare disorders constrain or shorten the lives of more than 25 million Americans. Tools provided by the Human Genome Project have led to the discovery of the precise cause of more than 4,500 of these conditions in just the last few years. Even more importantly, for an increasing number of those disorders, knowledge of the basic DNA defect has led to entirely new approaches to treatment. Consider the example of children who suffer from progeria, a rare disease that causes dramatic, premature aging. These children age at seven times the normal rate, dying of heart attacks and strokes at an average age of 13. Discovery of the molecular cause of progeria has led to a clinical trial of a drug, originally developed for cancer, that is showing promise of slowing or stopping the course of the disease.