TOPICS > Science

Stimulating Science

February 16, 2004 at 12:00 AM EDT



WOMAN IN COMMERCIAL: Lipitor did it. My cholesterol numbers are way down.

SUSAN DENTZER: Cholesterol- lowering drugs like Lipitor are a key weapon in the war on heart disease, the leading cause of death among Americans. But this advance in medical care was a long time in coming.

In 1973, two scientists at the University of Texas Southwestern Medical Center, Drs. David Brown and Joseph Goldstein, first unlocked the secret of how cells obtain and use cholesterol. 12 years later, they won the Nobel Prize for their work. But it wasn’t until 1987 that the first cholesterol-lowering drug came on the market. And it took 14 more years before government guidelines recommended that as many as 36 million Americans should be taking these drugs. That’s too long, says Dr. Elias Zerhouni, director of the National Institutes of Health.

DR. ELIAS ZERHOUNI: We have to have accelerated strategies and find ways where the benefits of the laboratory research get translated much more quickly from the laboratory to our patients.

SUSAN DENTZER: So Zerhouni has spearheaded an effort to speed up the process, starting at NIH

DR. ELIAS ZERHOUNI: I thought it was very important for us to be open and be completely willing to self- examine NIH and say, “what is it that we should do better?”

SUSAN DENTZER: Under Zerhouni’s leadership, NIH officials recently consulted with more than 300 of the nation’s top researchers in academia, government and the private sector. The result of their deliberations is a new NIH plan called “The Roadmap.” It’s a proposal to reengineer the way much science is done, not just at NIH, but also at thousands of university and other labs across the United States.

The NIH, based here in Bethesda, Maryland, is a division of the federal Department of Health and Human Services. It’s the nation’s and the world’s largest biomedical research agency, with a mission to protect and improve human health. In reality, the NIH isn’t one entity, but rather a collection of 27 institutes and centers.

DR. ELIAS ZERHOUNI: Some of them are dedicated to fight cancer, heart disease, and some are dedicated to find out about different life stages of life, like aging. We have a national institute for aging, we have a national institute for child health and human development, and some are dedicated to basic research.

SUSAN DENTZER: NIH’s budget comes entirely from the government, and will total $28 billion this fiscal year. A small slice pays for research within the institutes themselves. The vast majority is given out in grants and contracts to roughly 220,000 scientists working at universities or other labs in the U.S. Zerhouni says it’s time for NIH to help propel the entire scientific establishment into seizing new research opportunities. Many of those opportunities stem from the sequencing of the human genome, a largely NIH-funded project that was completed this year.

DR. ELIAS ZERHOUNI: We know now that there are 33,000 genes in the human genome. Those 33,000 genes code for a million different molecules, different proteins. In each cell of our body we have over a million different proteins interacting with each other.

SUSAN DENTZER: And that means potentially billions of gene or protein malfunctions may be found to cause or contribute to disease. So Zerhouni says scientists need new tools to help them understand these processes and devise potential treatments. One example is a proposed new “molecular library” at NIH; at a cost of $125 million, it’s designed to aid scientists who are experimenting with drug treatments.

SCIENTIST: Each of these plates at…

SUSAN DENTZER: Dr. Chris Austin of NIH is overseeing efforts to build the library. He says it will be a database of information about how more than a half million different chemical compounds interact with human proteins and diseased cells.

DR. CHRIS AUSTIN: So if we’re interested in cancer, for instance, we’ll go to a library and we’ll pull all those… all those books down one at a time, all those compounds, 500,000, and we’ll test them for activity in a certain kind of cancer. And we’ll learn that there are maybe five or ten which work for that application, for that particular disease.

SUSAN DENTZER: Information about how all these compounds interact with different proteins and cell types will be gathered with the help of high-tech robots. Zerhouni says both the data and the chemical compounds themselves will be available for free to scientists around the world.

DR. ELIAS ZERHOUNI: What we want is a library that every scientist could have access to easily so they don’t have to spend years trying to do the research and accelerate the cure that way.

SUSAN DENTZER: Ideally, scientists will then be able to isolate more promising new candidates for drugs; those can then be developed by private pharmaceutical companies. Once new drugs are identified, they must be tested on thousands of patients in so-called clinical trials. So another part of NIH’s roadmap would dramatically accelerate the pace and scope of these tests. Dr. John Gallin heads NIH’s clinical center.

DR. JOHN GALLIN: We can do better, and that’s what the roadmap is all about, is to make it go faster, enable us to do studies in large numbers of patients, and to translate that quickly into something that can be used as a drug.

SUSAN DENTZER: Gallin says a major problem facing biomedical research is that too few patients are willing to participate in clinical trials. So NIH’s new roadmap calls for an unprecedented effort to recruit thousands of community physicians and their patients into clinical research.

DR. JOHN GALLIN: That means that doctors out in the field will get some special training on how to do clinical research. And yes, they will become part of the team that will enable us to broaden our access to the patient populations in the country. My goal is that 90 percent of all the patients who have diseases will be participating in clinical research as part of their care.

SUSAN DENTZER: The last major thrust of the roadmap is designed to change the way much scientific research is carried out. The old model is that of solitary scientists working alone in their labs. The new model is this research team working in the magnetic resonance imaging lab at NIH.

SCIENTIST: So here we’re looking at pictures of our patient’s heart, and you can see all four heart chambers.

SUSAN DENTZER: The team is attempting to better understand the heart’s mechanics. It’s a multidisciplinary one, composed of a cardiologist, a physiologist, a computer scientist and an engineer. On the day we visited, Zerhouni, a radiologist by training, joined in as well. The team has demonstrated that these advanced MRI techniques work better than traditional methods in diagnosing heart attacks quickly. They say those results have only been possible because they work together.

DR. ROBERT BALABAN: You live together, you live the problem together, and you bring the different approaches, the engineering approaches, the mathematical approaches, the clinical problem, which may be the focus of a lot of our attention. And having those people living and working together, I think, is really the key to solving the problems.

SUSAN DENTZER: Zerhouni says the roadmap will now pave the way for much more team science like this in the future.

DR. ELIAS ZERHOUNI: What we want to do is stimulate scientists from different fields to come together in different ways. So we’re going to fund interdisciplinary research centers and ask every university out there and every scientific group to come up with new ways of exploring science.

SUSAN DENTZER: So far NIH’S roadmap has received generally good reviews from scientists, federal policymakers and members of Congress. But a recent report from the National Academy of Sciences warns that the roadmap initiatives will need far more funding in 2005 and beyond. And the warning comes at a time when President Bush has proposed a slim 2.6 percent increase in NIH’s budget for fiscal 2005. Zerhouni acknowledges the challenges, but says drawing up the roadmap was the crucial first step. He says it’s now time to test whether it can help spark dazzling new findings in science, and then translate them into new treatments for patients.