The confusion comes in the area of exactly what to do about your cholesterol level and how to bring it down. What is required, perhaps even in the nonmedical area?

When you go to the grocery store, you go up and down the aisles now and see all these things, about reduced cholesterol. You wonder: Does it really work or not?

People need some better information on what kind of diet is best to keep their cholesterol levels at the lowest possible.

Dr. LENFANT. I would agree with you. We are greatly concerned with the fact that, for instance, the food industry advertises and emphasizes products with low cholesterol, but quite often, with complete disregard of the amount of saturated fats that are in these food products. Of course, as we all know, it is the saturated fat which is the most important element.

We are trying to correct this situation. We work with the FDA. Unfortunately, at this point in time, there are no food labeling regulations which are established, although I understand they are being developed.

Senator HARKIN. We will work on that this year, and hopefully we will have something through this year on a standard labeling for the FDA. That comes through another committee, but any advice you could give us on that would be a great help to us.

Dr. LENFANT. I should tell you that 1 week from today, at the next meeting of the National Cholesterol Education Program, we expect that a report which addresses a population-based strategy for the control of cholesterol and coronary heart disease will be released. You may recall, Mr. Chairman, that a couple of years ago we did release a report which was directed to high-risk subjects. The one that is going to appear in a week is population based, that is, it will provide some advice which can be used by nearly all people.

If you wish, I would be pleased to send you a copy of this report when it is published.

Senator HARKIN. When is that, a week from today?

Dr. LENFANT. Yes; and I should say, that this report will be endorsed by approximately 35 or 36 professional societies of this country.

Senator HARKIN. I certainly hope we get some publicity out on it,

too.

Dr. LENFANT. It will. We have a press conference which is scheduled to announce the release of this report.

Senator HARKIN. I look forward to that and if you have more indepth information, I would like to see that also.

FLUORIDE SAFETY

Dr. Löe, I grew up in a rural area drinking well water that was not fluoridated. I did not see a dentist until I was in high school. So much for health care in rural areas. By that time I needed a lot of dental work like everybody did in that area.

My kids, one about to enter high school and one still in grade school, have been drinking fluoridated water ever since they were old enough to drink water. They have never had any dental prob

lems. They go to see a dentist and they have never had any cavities or anything.

Now, clinical trials on the health effects of fluoride have raised some new issues on the safety of fluoride. I will not go through all the studies and the groups of rats and how much they were administered. What can you tell us about the health effects of fluoride in drinking water?

Should we be concerned or do the health benefits far outweigh any of the

Dr. LÖE. I think what you have said so far is recounting the dramatic story of the effect of fluoridation in this country, and I have reported on that several times in these hearings. It is a fact that we have accomplished in the United States what has not been accomplished in any other country-reduction in tooth decay to very low levels in the young population.

The discussion of the side effects of fluorides has been going on since the beginning of fluoridation; you probably remember the discussion, both in the press and in these chambers, when fluoridation was initiated in the 1940's and 1950's.

Senator HARKIN. It was a Communist plot.

Dr. LÖE. It was a Communist plot and a few other things that were mentioned for good measure.

However, in the 1970's Congress mandated a new study of the side effects of fluorides. The National Toxicology Program has now produced a preliminary set of data that would appear to indicate that in rats, with high dosage levels, you will find some very rare bone cancers that we call osteosarcomas.

This has occurred in five rats out of about 540 male rats. Nothing in the female rats but only in the male rats; one at midlevel doses of fluoride and four at the highest dosage, which is approximately 80 times the level that is recommended by the Public Health Service for water fluoridation.

Well, the short story here is, of course, that these are preliminary data. The data will be going through a process of peer review and interpretation before a conclusion is reached on the matter. In the meantime, at both the Department, through the Secretary and Assistant Secretary for Health, as well as at the NIH level, a process has been established through which we will analyze the data and provide the public with information.

We do not think there is any reason for panic at this point. The ultimate evidence would have to come from human studies and the National Cancer Institute has already studied the relationship between cancer and naturally and artificially fluoridated waters.

That occurred back in the 1970's. From that comprehensive study there was no indication that there was a relationship or any correlation between the amount of fluoride in some of the communities that had natural fluoridation or in other counties that had optimal fluoride in the waters, and the prevalence and incidence of

cancer.

The Cancer Institute is already involved in a new study to refine their methodology and to bring about an analysis of the various levels of fluoride intake in some communities, and the prevalence of these special bone cancers that have been reported.

One of the problems with this is that osteosarcoma is a very rare cancer. No more than 700 or 800 cases occur per year, and it could be a very difficult to prove either way, because of the low levels of this cancer.

But the "C" word has been spoken, and it is going to be a difficult thing to continue to talk about fluoridation out there if we do not provide the correct information to the public.

FLUORIDATION

Senator HARKIN. Dr. Broder, you were quoted I think in the paper as saying that there was no evidence in the past to link these two and you did not see any evidence in these studies that would basically link them.

I guess it did not occur in mice, it did not occur in femalesDr. LÖE. That is correct.

Dr. BRODER. Sir, the thing I would like to say is that in the mid1970's we examined this issue very carefully, with our Division of Cancer Etiology, and in effect, they did what amounted to, a county-by-county analyses of cancer statistics, both with natural fluoridation and also before and after studies of counties after fluoridation occurred.

In those studies in the mid-1970's there was no documented association between any increase of incidence or death rate of cancer, specifically bone cancers and cancers of the mouth were examined.

In addition, there are a number of other studies from other countries, including Great Britain, New Zealand, Australia and so on, which support this particular concept. There are many countries that have examined this issue and found that there was no association.

However, we do treat these results seriously, and we feel that the best way of dealing with this issue is with facts and informed opinions. We are re-evaluating the data collected from the mid-1970's, and I have directed the Division of Cancer Etiology to submit a progress report with their findings by the summer of this year, June if possible. We hope, at that point, to make those statistics and followup information available to the NIH community and to the committee.

Senator HARKIN. Thank you.

Dr. Raub?

Dr. RAUB. May I just make an addendum, to stress how carefully coordinated this overall effort is. As a scientific organization, we have an obligation not to prejudge information, to let the data tell us what it has to say.

On the other hand, we have an obligation to evaluate it thoroughly. As Dr. Löe indicated, the first step here is for the National Toxicology Program, which is part of the National Institute of Environmental Health Sciences, to complete its detailed analyses of the rat and mouse data. We hope to have that data before the end of April of this year.

As Dr. Broder indicated, the Cancer Institute will be updating its analyses from human epidemiology and have the latest information on that. Dr. Löe and his colleagues are updating the information with respect to public health impacts and consequences. All of

that will be synthesized in a multistep process through the Public Health Service to ensure that we make the most thorough and balanced set of public statements when this is completed.

PEDIATRIC AIDS

Senator HARKIN. I am glad to hear that. Dr. Fauci, I do not mean to go over all the AIDS questions that Senator Bumpers asked. I think he covered that quite well. I want to focus on one small area very briefly and that is pediatric AIDS.

I became interested in that this year while I was reading the findings that some children who have HIV infected mothers are born HIV positive and some are not. Some children who take their mother's milk get HIV; some do not. Some of the manifestations of the illness that are in adults do not occur in children and vice versa.

It seems to me to be a very fertile area for research trying to figure out why this is happening in some and not in others. I just wonder what you can tell us about the area of pediatric AIDS. Are we doing enough in that? Do we need to do more?

I have a specific question about testing drugs. You do adults; you have to go through the whole procedure again through FDA for children. Should we change that? What is happening in that area? So just address yourself to the full area of pediatric AIDS.

Dr. FAUCI. I will very briefly address those issues, Mr. Chairman. With regard to the work on pediatric AIDS, there are several areas, including the areas in fundamental research on the response of the developing human to HIV infection versus the adult.

There is absolutely no question that some of the manifestations of HIV infection in a child or an infant is significantly different than that in an adult. Particularly, for example, in the area of lung disease. The interstitial pneumonitis that children get that adults rarely get is unrelated to any other infections.

The profound effect of the virus on the developing nervous system is clearly seen in the infant. Even though you do get severe neuropsychiatric problems in an adult, the relative proportion and severity in infants is very clear. The susceptibility to bacterial infections because of problems with antibody responses in infants is another area which needs exploring. Those are just three examples of the important areas that need to be further investigated.

Over the past couple of years we have intensified our efforts in pediatric AIDS research in fiscal year 1991, we have $81 million, up from just a few years ago of $37 million in pediatric AIDS research. But there is still more that needs to be done.

With regard to clinical trials, right now out of the 47 clinical trial units in our AIDS clinical trial group, 15 now are devoted solely to pediatric AIDS, in addition to several of the adult trials which have a pediatric component. And over the past 2 years, we have intensified our collaborative effort with the Child Health Institute in which we are utilizing each other's expertise-they, in their pediatric centers and we with our AIDS clinical trials unit experience.

So there is a lot of activity, but I must say again that there is more which needs to be done because it is a problem if one looks at

the demography of HIV infection. Pediatric AIDS is going to intensify over the next few years because the rate of new cases of HIV infection. The rates are disproportionately rising now among IV drug users and their sexual partners, and women and children born of those unions.

So right now what we are going to be seeing are relatively higher rates of infection among these groups than among the classic groups that we have seen in the early and mid-1980's, namely the male homosexual populations.

So it is a problem that is not going to go away. It is going to get worse in the 1990's.

With regard to your question about drugs that are tested in children, the philosophy in the past is rapidly changing. Until recently, it has been standard practice in our clinical trials to never test a drug for a disease that affects both adults and children, in a child or an infant. Drugs were tested in children only after being thoroughly tested and proven effective and safe in adults.

And likewise, even after it had been proven to be safe and effective in an adult, it would not be unusual to go back and do the entire clinical trial over again in a child.

This philosophy has changed, because we do not have that long period of time with HIV infected infants and children.

What we have seen over the past couple of years now is essentially simultaneous studies of the same drug in adults as well as in children and in infants. This process reduced by at least a couple of years the delay that we initially experienced with the availability of AZT, for example, for infants and children, which just this past year has been granted a treatment IND for infants from over 3 months old to 12 years old.

NIAID CLINICAL TRIALS

Senator HARKIN. Of the 34 drugs that are in clinical trials, how many of those are being done simultaneously?

Dr. FAUCI. There are several. There are DDI studies, AZT studies, and intravenous immunoglobulin studies. The predominant being the DDI and the AZT studies in children.

It is more important and it has happened over these past few months that at least we have a drug that can be standard treatment for the children and that is what the treatment IND for AZT has allowed. Before, unless you were on a clinical trial and you were a child, you had access to absolutely no drug.

Senator HARKIN. Should we expand that? It sounds like you are just doing a few out of the 34.

Dr. FAUCI. Yes; right now, as new drugs come on, the philosophy has changed. As they go on to clinical trials, they will be given to both children and adults on a clinical trial.

Senator HARKIN. Are you doing this in other areas? Should we be doing it in other areas, doing it simultaneously, rather than doing one and then going to the other?

Dr. BRODER. The philosophy has emerged and has been heading toward the area of not having very long delays. There was an era in which a drug had to have every I dotted and every T crossed