As director of the National Institutes of Health, Elias Zerhouni oversees the activities of the world's leading medical research organization. He spoke with NIH MedlinePlus' Christopher Klose about the value of medical research and clinical trials.
What does medical research mean to the average person?
Dr. Zerhouni: Medical research is the search for cures to illness and disease. It has been one of the most important human activities throughout history. But it is important to note that modern medical science, based on molecular biology, only began in earnest with the discovery of the structure of DNA in 1953.
What was so important about the discovery of DNA?
Dr. Zerhouni: Until then, diseases were understood to be caused by external factors, such as germs. DNA told us we had to go in a completely different direction and understand the structure and function of biological molecules and the information they conveyed; to deal with the intrinsic biologic pathways of human disease.
Could you give an example of disease that is caused by internal factors?
Dr. Zerhouni: For more than a century, there was the theory that viruses cause cancer. Some, such as cervical cancer, are triggered or aggravated by viruses. But a great many others do not seem to be. What is clear is that "cancer" is a disease that expresses itself, always, by a tumor that grows and invades. With more than 200 types and subtypes known today, the research challenge is to understand and block all the pathways to cancer so that people don't end up in its irretrievable late stages.
Where does medical research stand today?
Dr. Zerhouni: We are in the infancy of medical research. After 50 years of molecular biology and genetic research, we realize that you don't get to a disease through just one cause or abnormality. There may be multiple, interacting ones.
For example, when I became NIH Director (in 2002), I would receive a few reports each year that a certain gene or protein was involved in a particular disease. That happens every week now. The Cancer Genome Project just reported three new DNA abnormalities in glioblastoma, the brain cancer Senator Kennedy is fighting.
Discoveries like these are very important clues. Medical research is like a detective story, always searching for new leads to follow. It is very important to sustain medical research.
"Without scientific knowledge, it is hard to have a public health policy that makes sense."
Most of us have heard about "clinical trials," but don't really understand them and where they fit into the research picture. Could you explain, please?
Dr. Zerhouni: Clinical trials involve the testing of new ideas with people. There are essentially two kinds, observational and interventional. Observational trials are designed to teach us something about why people get sick, especially to uncover the biomarkers of illness. The best example of this is the Framingham Heart Study, which has tracked four generations of families since 1948. It established the correlation between cholesterol—from a high-fat diet of milk, cheese, and meat (thought to be good for you)—and heart disease.
Back in the lab, to understand and try to prevent damage from cholesterol, researchers discovered an enzyme that is critical to its formation. They developed drugs to block the enzyme. Then they tested the drugs in interventional trials, which are meant to determine whether an experimental drug, treatment, or procedure works.
How trustworthy are clinical trials?
Dr. Zerhouni: The trials have to be very rigorous, very objective. That is why in the 1940s and 1950s, NIH implemented the double-blind, randomized, prospective trial. It remains the gold standard today. When you can demonstrate, in a statistically valid way, through a randomized trial, that the mortality rate from heart disease for X thousand people (treated with an experimental drug, for example) is Y percent lower than that of X thousand people who have not been treated with the drug, but with a placebo, you have conclusive medical proof.
As a public health institution, we want things to be based on strong scientific evidence. That is why we sometimes retest the validity of existing treatments, as we did with estrogen replacement therapy in post-menopausal women. It was believed to be a sort of cure-all to reduce heart disease, promote bone health, and keep women young. People weren't happy with NIH for questioning such a long-held practice, but the results proved it was detrimental and has changed medical practice!
That is why we believe that when something is recommended to millions of people, it must be based on solid evidence.
Where does science enter into the debate over health care?
Dr. Zerhouni: Without scientific knowledge, it is hard to have a public health policy that makes sense. Fortunately, there is solid backing in Congress for science-based policy. It is a real tribute to Senator Specter and other champions in the House and Senate that they strongly support medical research, despite the fact there is no immediate political reward for doing so.
What's been the payoff for the American taxpayer?
Dr. Zerhouni: With cardiovascular disease, the results have been extraordinary. Since 1970, we have reduced the mortality rate from cardiovascular disease by 70 percent, at an average cost of $4 per person a year for cardiovascular research.
That's quite a buy …
Dr. Zerhouni: It's a huge buy!
Have you ever participated in a research trial?
Dr. Zerhouni: I am part of an observational study with the NIH blood bank. They're testing the metabolism of iron in both men and women, over time.
What is it like?
Dr. Zerhouni: There is something very altruistic about clinical trials. We tell people not to expect anything and that the trials could be risky, but the hope is that the results will be beneficial. And you know what? The great majority of people participate anyway. They say, "Even if it doesn't help me, maybe it will benefit my children or grandchildren."
A new law is about to require that the results of clinical trials be posted on the Internet. What impact will releasing this kind of information have?
Dr. Zerhouni: What you're talking about is an information bank that's going to be wider and more public in a way, but be more effective for researchers and the public. And there is a sacred trust here—the trust between scientists, patients and their doctors, industry, the public, and lawmakers—everyone involved. I think it's important to have a very open, transparent world where that happens, to build the evidence that supports the trust.
So NIH is really a good place to come for results, isn't it?
Dr. Zerhouni: I don't know of any better. Thousands of years ago, people had sorcerers and witchcraft. Today, you have this marvelous institution.