The five-year research plan called for collaboration between NICHD and other agencies of the Public Health Service to develop and implement epidemiologic studies of SIDS. NICHD is working with CDC and the Indian Health Service to investigate infant deaths among the American Indians of the Aberdeen Reservation. They have an annual SIDS rate three times that of the remaining population in North and South Dakota, making it the highest in the nation. It is important to gain more information on these deaths to (1) determine whether some are not SIDS, and may be preventable through public health efforts, and (2) to learn more about causes of SIDS. The joint project will establish a surveillance network for infant deaths on the Aberdeen reservation, and a pilot protocol to investigate the causes. We plan to fund these efforts through interagency agreements in FY 1991.

NICHD defines research priorities for future years of the fiveyear research plan by convening workshops. On March 25, 1991, NICHD brought together all the researchers that are studying fetal hemoglobin to critically examine the available scientific information, and determine the potential of fetal hemoglobin kinetics to identify infants at risk for SIDS. In the fourth year, we will be conducting a study to evaluate biochemical and metabolic screening technologies for SIDS risk. One of the biochemical markers that may be worth pursuing is fetal hemoglobin. During the first two months of life, infants stop producing the oxygen carrying blood protein they used in utero, called fetal hemoglobin, and produce the adult type of hemoglobin. There is controversy in the scientific literature whether elevated fetal hemoglobin levels in a proportion of SIDS victims discriminate them from other infants. Since there are no defined prognostic tests for SIDS risk at this time, it is important to pursue this biochemical finding for infant screening.

Question. How much does the Institute estimate will be spent on SIDS specific research in FY 1991? How much on SIDS related research?

Answer. The NICHD revised estimate for funding SIDS specific research in FY 1991 is $5,500,000; the amount for SIDS related research, $33,000,000.

Question. How much is provided in the President's budget request for SIDS research in fiscal year 1992? Is this sufficient to fully implement the 3rd year of the five-year plan? If not, how much more is necessary to fully implement the 3rd year?

Answer. The FY 1992 President's budget request includes a total of $41,500,000 for SIDS research. Of that amount, $6,100,000 is for activities that relate to the third year of the five-year plan. Full cost for the third year would require an additional $4,400,000 over the budget request, for a total of $10,500,000.

SUBCOMMITTEE RECESS

Senator HARKIN. Thank you very much. The subcommittee will stand in recess to reconvene at 1:35 p.m. to hear the rest of the Institutes.

[Whereupon, at 12:34 p.m., Thursday, March 14, the subcommittee was recessed, to reconvene at 1:35 p.m. the same day.]

(AFTERNOON SESSION, 1:43 P.M., THURSDAY, MARCH 14, 1991)

The subcommittee met at 1:43 p.m., in room SD-192, Dirksen Senate Office Building, Hon. Tom Harkin (chairman) presiding. Present: Senators Harkin, Hatfield, and Specter.

DEPARTMENT OF HEALTH AND HUMAN SERVICES

NATIONAL INSTITUTES OF HEALTH

NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

STATEMENT OF DR. DAVID HOEL, ACTING DIRECTOR

OPENING STATEMENT OF SENATOR HARKIN

Senator HARKIN. Thank you very much. The subcommittee will resume its sitting.

Dr. Hoel, I want to welcome you before the committee in your first appearance representing the National Institute of Environmental Health Sciences.

We have your budget that totals $254.4 million, which is about 5.6 percent more than last year.

I know the Institute has been interested for a number of years in getting underway on the construction of a new building in Research Triangle Park, NC, where the Institute is located. We will have a chance to talk about that and other issues.

At this time, I would be pleased if you would proceed with any opening statement that you care to make.

Dr. HOEL. Thank you very much, Mr. Chairman. It is, indeed, a pleasure to be here.

Before beginning, I would like to acknowledge Dr. David Rall, who retired last fall after 20 years as the director of NIEHS. During his tenure, he built both the Institute and the National Toxicology Program for which everyone in the environmental health area is indeed indebted.

METAL TOXICITY

This afternoon I would like to briefly describe two areas of the many things that NIEHS is involved in, and the first is-and it has already been mentioned-the problems with metal toxicity. I believe that NIEHS has been a leader in the research on metal toxicity and understanding the human health aspects of these toxicants.

In particular, we are thinking these days about lead, mercury, and manganese. There are programs now with regard to lead abatement that a number of the areas of the government are involved with. Our research is continuing with Dr. Needleman of the University of Pittsburgh who is looking at the possible apparent

permanent effects of low-level lead exposure on intellectual and psychobehavioral functions.

Also, clinical studies are being carried out to find better drugs to treat lead poisoned children. We are also quite interested, through the contracts mechanism, in the lead transfer from the mother to the fetus, whether this is from bone or diet or just what. We are developing that work.

We finished a major conference on the health effects of lead and, in fact, I have the new publication in Environmental Health Perspectives that came out last November.

In the area of mercury, Dr. Löe has already mentioned the dental amalgams issue aired on the "60 Minutes" TV program. We have begun through one of our research centers-Tom Clarkson at Rochester-a very interesting epidemiological study in the Seychelles Islands where individuals there are exposed to low-level mercury through consumption of fish. We hope to develop a better understanding of the low end of the dose response curve with regard to human exposures.

In the area of manganese, we had a conference earlier this week. This is quite important to the EPA because it is being proposed that manganese be used as a gasoline octane booster in this country. We have to discover what are possible information gaps on health effects. We do not want to create another situation as we had with lead.

So, I think in this area we need both the epidemiological clinical work, exposure understandings, and, in particular, basic work in mechanism so that we can concentrate on the effects of

neurobiology and fetal exposure.

INTERPRETATION OF TOXICOLOGICAL TEST DATA

The second area of interest is in interpretation of toxicological test data. Through the National Toxicology Program, NIEHS is involved with generating this for the Federal Government. And what we want to do is to improve the methods for estimating the lowdose effects to man based on the findings in high-dose toxicological studies. And here we are concentrating on generating supplemental information on oncogene activation, pharmacokinetics, receptor binding, cell proliferation, and so forth. The regulatory agencies will be able to incorporate this data with our toxicological findings so that they could do a better job in terms of estimating human health risk from these studies.

We are also quite interested in research in biomarkers for measuring both environmental exposures and molecular effects in people. We see also an important future research area in terms of genetic susceptibility to toxicants.

In these areas, a couple of examples would be the issue of dioxin and the effects at low levels and the idea that it is a receptor mediated effect and what effect this might have with regard to risk assessments in setting low-dose levels. I think we will see some of this during this year. There is quite a concentrated research effort here.

And also with asbestos and the controversies about abatement of asbestos in buildings. Here the argument is concerning the toxi

cological effects of fiber type and size and so on. And this depends upon basic research.

PREPARED STATEMENT

So, my message here is that we need the basic research that ties with the applied toxicological findings so that we can do a better job in terms of handling health-risk assessments.

I thank you and would be happy to answer any questions. [The statement follows:]

STATEMENT OF DR. DAVID HOEL

The National Institute of Environmental Health Sciences (NIEHS) is unique among the research institutes of the National Institutes of Health because its focus centers on environmental health effects. Because these exposures occur throughout life, NIEHS research touches on all aspects of human development, from conception and birth throughout life.

The NIEHS is committed to developing the necessary scientific base the world community requires to deal effectively with environmental health problems. Through its efforts to seek the causes of environmentally related diseases and disorders, and to identify ways to prevent them, the Institute is the primary center for environmental health research in the world. Its long-term goals are to develop the extensive research base, advanced scientific methodology, and carefully trained manpower essential to understand, and ultimately prevent, adverse effects of exposure to environmental agents.

NIEHS supports research and training programs conducted in universities and studies in private research laboratories throughout the U.S. This work is of the highest quality and productivity. Non-federal scientists supported by NIEHS make an unique contribution to the field of environmental health sciences but I would like to stress our intramural program and the current and planned efforts of NIEHS scientists.

Much of NIEHS's research involves study of fundamental biologic processes and how environmental agents interfere with these processes at the cellular and molecular levels. Basic research seeks to understand the underlying mechanisms of environmental diseases and to develop effective interventions. Basic research is vital to public health officials in designing disease intervention strategies and in developing public policy. NIEHS research into the mechanisms of asbestos-caused illnesses illustrates these points.

Toxicological and epidemiological studies of asbestos-exposed populations have contributed to our understanding, yet more precise managements of risks from low-level exposures to predominantly short fibers require an understanding of the biological mechanisms involved. NIEHS Scientists are conducting the basic research needed to understand the mechanisms of biological action of asbestos and to better define the significance of certain key parameters such as fiber type, fiber size and lung clearance mechanisms. We have shown that chrysotile asbestos particles inhaled into the lung attract lung "scavenger" cells, known as macrophages, to where the particles are lodged. These macrophages secrete proteins which appear to initiate a defensive fibrogenic response. An understanding of the basic mechanisms involved in asbestos-induced diseases will allow more precise and meaningful risk assessments and may even provide the basis for developing new approaches to disease intervention and prevention. Such assessments are vital for developing and implementing public health protection and disease prevention programs. Knowledge of the mechanisms of action for asbestos fibers also may allow meaningful risk assessments for other fibers such as fiber glass, mineral wool and ceramic fibers which are being developed and used in place of asbestos. NIEHS Scientists and those supported by NIEHS are conducting this basic research.

Basic research at NIEHS serves another important function. It provides the foundation by which scientists can explain the relevance to humans of health effects found in long-term toxicological studies conducted in animals or identified in epidemiological studies. This information is vital to public