New NIH director says research will change face of U.S. medicine

Published: July 10, 2005  |  Source: fortwayne.com
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DETROIT – (KRT) – Dr. Elias Zerhouni has begun his third year as director of the National Institutes of Health, the country’s leading medical research agency. He oversees 27 separate institutes, 17,000 employees and a $28 billion budget.

His tenure comes at a critical time in medicine.

The entire human genetic map has been completed. Molecular advances enable researchers to study diseases at the cellular level. And stem cells, a unique structure capable of taking on a variety of jobs, depending on where they are placed, hold the promise of becoming the body’s best tool to fix parts harmed by disease or injury.

Zerhouni, a radiologist, came to the NIH’s Bethesda, Md., campus from the Johns Hopkins University School of Medicine, where he led the radiology department before going on to become vice dean for research and executive vice dean at the medical school.

Recently, Zerhouni talked with the Detroit Free Press.

Q: Tell me a little about yourself first. How old are you? Where do you live?

A: I was 54 (in April). I live in Baltimore. I’m married with three kids, two boys and one girl. I commute during the week to the NIH. I have a small apartment there. I drive back to Baltimore on the weekends.

Q: You are from Algeria, an Arab country. What was it like growing up there?

A: Algeria is on the Mediterranean, so I grew up by the sea. I’m still very attached to the sea. I love to swim. Algeria is a bilingual country, French and Arabic, a country that’s the intersection with Africa, Europe and the Middle East. We had a tremendous ability as a country to attract multiple cultures.

Q: What influence did that have on you?

A: It gave me an ability to deal with people from diverse backgrounds. I’m curious about people from other cultures. You create bonds with them.

Q: And your religion?

A: I’m a Muslim.

Q: Sunni?

A: Yes. I think most of the Mediterranean Arab countries are Sunni.

Q: Recently, you told Congress that Americans pay $96 a year for NIH research. How do you envision that $96 will pay off in health gains?

A: Think about it this way. Every five years of research we’ve done has lengthened life expectancy by one year over the past 30 years. Heart disease once was the No. 1 killer, and over 30 years we’ve reduced mortality from heart disease by 50 percent. Deaths from heart disease today are almost equal to cancer. So for every five years of investment, in current dollars, we lengthen healthy lives by one year.

(EDITORS, BEGIN OPTIONAL TRIM)

People are living longer and healthier. Disability in our senior population has dropped by 30 percent in 20 years. People are surviving cancer. We have 9 to 10 million cancer survivors. We are finding more cancer early, and people are surviving it. Survival has doubled over the past 20 years. If you look at Osteoporosis, it used to make people completely disabled. Now we know how to prevent it and how to stop it. So if you look at our seniors and predict how many would be disabled, it would be about 10 million. Research shows it’s actually less than 7 million. That’s a 30 percent improvement. That’s where we stand.

Here’s where we’re going now. We just completed the Human Genome in 2003. Interestingly, that’s probably the landmark for medical research. The reason is because now we are identifying the genes involved in complex diseases at a rapid rate. People become blind at an increasing rate as they age. Blindness is going to be a major cause of disability. Same with hearing.

With age-related macular degeneration, 3 to 5 million people will lose their eyesight if we don’t find a way to prevent that. So NIH has found that some supplements can reduce the incidence by 25 percent. Last month, three groups identified one gene that relates to a blood factor called factor H. It has to do with the Immune Response of the blood, and it seems to be involved in 30 percent-50 percent of all these cases. But clearly, at least we now understand it better. Maybe we can find a way to prevent this abnormal factor H from damaging the eye.

Same with Alzheimer’s disease. Fifteen years ago, we had no clue what the disease was. Ten years ago, we finally understood that it was due to plaques and degeneration of neurons. Five years ago, we identified some of the lipoproteins involved in cholesterol metabolism. Today we are putting trials together that show we could delay the onset of Alzheimer’s disease. If we could do that by delaying the onset by five years, we can reduce the burden of the disease by 50 percent.

Let me make it simple. In the 20th century, and for as long as we’ve known medicine, we used to intervene when a disease struck you, when you lost some function.

With the Human Genome and our understanding of the molecular basis of disease, we’re going to go from curing to preempting disease over the next 20 to 25 years. That’s going to be a complete change.

I think the picture that’s emerging is, there is no magic bullet. Disease is a complex, interlocking system of molecules that act with each other. If you could intervene, with molecular interventions, maybe you could prevent the onset of diabetes or heart disease or Alzheimer’s. We will find biomarkers that will determine who is at risk for a disease and who is not at risk.

Q: You are a radiologist, so I’d like to ask: Why aren’t our tests, mammograms and CT scans, for example, better at finding disease or the spread of it? Will biomarkers give us more accuracy?

A: CT scans and mammograms are far more accurate than they were 30 years ago. Imaging is exploding. I think we’ve only seen the beginning of what imaging can do. We’re not doing single molecule imaging at the cellular level. There’s a technique called double quantum imaging. It basically can track a molecule within a cell. You’re going to see multi-scale progress. At the human scale, at the tissue scale, the organ scale, the cell scale, the molecular scale. You’ll see progress across all those fronts.

The question is, how do you get from where you are to the next step? The problem we have is, we’re detecting things, but we don’t know what’s a false positive (a test that inaccurately suggests a disease is present when it isn’t) or a false negative (a test that doesn’t find disease when it is present).

You need more specificity. You’ll get it from molecular imaging. One thing we can do in Alzheimer’s disease, for example, is we can image the plaques themselves. That’s a breakthrough. In the past, we couldn’t. If we can find out first who has the disease, and whether or not treatments are effective, that’s a great role for molecular imaging.

Q: Recently, more than 700 scientists sent you a petition protesting a shift in federal funds to more obscure germs that might be used in a bioterrorist attack. (The signers include two Nobel Prize winners, Sidney Altman, a Yale University molecular biologist, and Arthur Kornberg, a Stanford University biochemist.) Is that a fair criticism?

A: I don’t think their factual analysis is right. I think they misunderstand that the bio-defense investment was something in addition to the current investment in microbiology.

And they looked at just one institute when this research is done across all institutes. I had a meeting with the microbiology community (in late April). It was extremely good because we were able to talk about facts, which is what scientists should do: evaluate the facts.

We need to identify exactly what their concerns are because I don’t like this number game. I don’t like this dollar game. I really would like a discussion that is scientific, first and foremost.

Q: I want to talk about adult and embryonic stem cells. There are a few places that hope to proceed in the next year with clinical trials using adult stem cells for things like spinal cord repair or after a heart attack. What is NIH doing to facilitate or make that happen? Right now, many surgeries are done abroad and patients are in a quandary. What is the NIH’s role in sorting out the science and making sure things happen safely in America?

A: Our responsibility is to look at the science and the factual basis for the science, and we do that. We spend almost a half-billion dollars on stem cell research in general. Most of that is on adult stem cells, by the way. About $200 million is for animal experiments, to validate what is it we understand about embryonic and adult stem cells. The rest of it is spent on human and embryonic stem cells research.

In terms on what you refer to, like the treatment for spinal cord repair in Portugal, this is an experimental approach, which has not been published or vetted, so we need to have more understanding of what is being proposed. In terms of clinical trials, the agency that has the responsibility for making sure trials are safe and effective is the FDA (Food and Drug Administration).

Our approach is to understand that this science is not as advanced, in terms of its clinical implications. We think we are at a very early stage of the science. We need to understand better what people are telling us and observing. There’s a tremendous amount of empirical talk, without experimental evidence. Bring the data and let’s analyze it, in the most rigorous way possible. That’s what we do.

Q: With embryonic stem cells, so much of the work is being done in the private sector – or in the future, in a state like California allocating its own money to fund its own initiative. Are you concerned that too much of this research is galloping along without the proper federal oversight?

A: We have no limits on funding our research. We’ve developed training and a workforce that needs to do all of this. The key issue is, what stage is this research? There are a lot of scientific hurdles that need to be overcome. This topic has been so polarized. This area is advancing to the point where people make exaggerated claims that I’m hearing. We have to walk before we run.

For example, we don’t know how to control the proliferation potential of these cells. Nobody knows how to turn them off or to make them do something they aren’t already programmed to do, whether they are adult or embryonic.

There are many questions: How does a cell get integrated or rejected by its host? Let’s take one example. Tomorrow, if I had the ability to create a stem cell that provided insulin or secreted insulin, that wouldn’t be enough to solve the problem of diabetes. It would have to be regulated to produce just the right amount of insulin. If it produces too much insulin, it might harm the patient. The same is true of dopamine neurons. If you want to produce dopamine (a chemical in the brain), it’s not enough to produce dopamine, which we don’t know how to do yet. NIH is investing aggressively in that, and we’ve made progress. We need to regulate the production of dopamine, or you’ll have people who suffer from excess dopamine.

BY PATRICIA ANSTETT
Knight Ridder Newspapers

For more information on the NIH, go to www.nih.gov.
© 2005, Detroit Free Press.