immunogenicity with NICHD pertussis toxoid vaccine are under way. Immunization is complete, with no adverse reactions, and serological studies are in progress. In addition, a contract is in place to support preliminary and logistic planning for the efficacy trial. Immunization should begin about October 1. The vaccine for this trial will be made under contract by AMVAX, an American vaccine manufacturer, under a license to use the U.S. Government patent for the vaccine. A large scale U.S. trial of the NICHD pertussis toxoid vaccine is currently being planned.

a

Regarding the NICHD H. influenzae type b conjugate vaccine, contract is in place for a three-year trial in Charlotte, North Carolina. It is anticipated that the trial will show that we can safely and effectively immunize infants under six months of age against infections with this organism.

CONTENT OF PRENATAL CARE

Question. The Public Health Service Expert Panel on the Content of Prenatal Care identified several gaps in our knowledge of this subject. What research should be undertaken to fill these gaps?

Answer. The panel found that studies were lacking in many aspects of prenatal care and recommended that research be initiated in the following six areas: (1) preconception care; (2) risk assessment activities and data collection systems; (3) health promotion activities--specifically, counseling to promote and support healthful behavior, general knowledge of pregnancy and parenting, and information on proposed care; (4) optimal schedule of visits to physician considering the differing needs of healthy women and women in a medical or psychosocial risk category; (5) interventions to reduce psychosocial risk--specifically, substance abuse counseling and referral to treatment, food assistance and referral, home visits, and social and financial resources; (6) interventions to reduce medical risk--specifically, preeclampsia, infection (especially gonorrhea and HIV), intrauterine growth retardation, genetic and congenital disorders, preterm and postterm birth, and diabetes.

AGRICULTURAL USE OF REPRODUCTION RESEARCH

Question. Are there any examples, Dr. Alexander, of research findings in reproduction, supported by your Institute, that have applicability in agriculture?

Answer. A number of the research projects supported by this Institute have led to improvements in agricultural technology. An important application of the discovery of methods to create transgenic animals, for example, has been the insertion of specific genes into animals to enhance breeding capability, increase disease resistance, and improve the production of milk and lean, tender meat. A related application makes it possible to insert engineered genes into domestic livestock to produce valuable pharmaceutical products. Where such products are secreted in milk, for example, they can be isolated in high purity and large amounts. Other applications of research on reproduction that have proved useful in agriculture are treatments to induce artificial breeding seasons, which increase reproduction; the use of superovulation, in vitro

fertilization, and the transfer of embryos from high-quality animals to other domestic livestock; and, most recently, the identification of molecules that can improve pregnancy rates and reduce miscarriages and stillborn births in domestic animals.

QUESTIONS SUBMITTED BY SENATOR ARLEN SPECTER

CHILD HEALTH RESEARCH CENTERS

Question. Dr. Alexander, I understand that the Institute has responded favorably to the Subcommittee's recommendation to consider establishing a center grant program for child health research. Would you explain briefly what action the Institute has taken concerning this matter?

Answer. The NICHD has developed guidelines for establishing and operating a program of child health research centers. To announce the availability of funds for this program, the Institute issued a request for applications (RFA) on January 5, 1990. Over 130 copies of the RFA have been distributed in response to inquiries, and at least 25 strong applications are anticipated. The deadline for receipt of applications is April 23, 1990, with review scheduled to begin in July. It is expected that final awards will be made in September 1990.

Question. How many centers does the NICHD anticipate funding in fiscal year 1990? Does the President's budget include funding for any additional centers in 1991?

Answer. The NICHD expects that six child health research centers will be funded in FY 1990. The FY 1991 President's budget does not include funds for any additional centers.

Question. I understand that a central purpose of this program was to expand capacity for pediatric research by using the funds as "seed money" to build a foundation of institutional support. How are you ensuring that emerging programs, particularly those at children's hospitals and clinical centers, have a competitive shot at these funds?

Answer. Child health research center awards will be made only to children's hospitals or departments of pediatrics at medical schools. The announcement of the availability of funds for these centers was published in the NIH Guide to Grants and Contracts, which is sent to research institutions throughout the United States. In addition, copies of the announcement were sent to all medical school chairpersons of pediatrics, and NICHD staff have provided telephone counsel on application preparation to about fifty institutions.

The review guidelines for the center grants competition establish scientific merit of the research program as a primary criterion. In addition, however, there are several criteria which could increase the competitiveness of institutions with emerging programs. These factors include relevance of the theme or area of emphasis of the center to programmatic needs of the NICHD, institutional commitment to the requirements of the program,

probable impact of the center on pediatric research at the grantee institution and in the local medical environment, and efforts to develop novel mechanisms for recruiting candidates for support from groups (such as women and minorities) under-represented in pediatric research.

Question. If this Subcommittee could fully fund the new centers program, how much would be required in FY '91, and how many centers would it fund?

Answer. The FY 1991 President's budget provides approximately $1,882,000 for the continuation of the six child health research centers established in FY 1990. Full funding of the program in FY 1991 would require an additional $4,118,000. This amount would eliminate the downward negotiations in awards for the six existing centers and allow for the establishment of 9 additional centers, bringing the total number of centers to 15.

INFANT MORTALITY

Question. Dr. Alexander, while I understand the United States is making progress on reducing the infant mortality rate, it still ranks poorly compared to other developed nations and continues to have a large disparity between infant mortality rates for blacks and whites. Does the fiscal year 1991 budget include funds to broaden the Institute's research activities on infant mortality?

Answer. The Institute's initiative on the prevention of low birth weight and infant mortality will continue to be the number one priority in FY 1991. The budget request includes approximately $61.4 million to continue the research effort in this area at essentially the same level of activity as in FY 1990.

Question. What was the Institute's original budget request to the Public Health Service and how much was assumed for infant mortality research? How does this compare to the budget before the Subcommittee today?

Answer. The Institute's original budget request was submitted to NIH and totalled $712.5 million. Of that amount, approximately $96 million was allocated to infant mortality research, compared with $61.4 million in the FY 1991 President's budget.

NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

STATEMENT OF DR. DAVID P. RALL, DIRECTOR

SUMMARY STATEMENT

Senator HARKIN. Dr. Rall? We have your budget request which is $235,790,000, an increase of $6.56 million.

One of the things I would like to discuss with you is the establishment of a research center for health effects of agricultural chemicals. We will discuss that later, but please proceed.

OPENING REMARKS

Dr. RALL. Thank you, Mr. Chairman. It is a pleasure to be here. NIEHS, by studying those factors in the environment that affect human health, provides information necessary to prevent diseases, either through education of the patient, the public, and the physician; or to permit intelligent and rational health regulations.

I would like to present four interesting new research findings and describe two or three ongoing efforts. First of all, in air pollution, which is a critical problem with the Clean Air Act about to be reauthorized, one of the primary criteria contaminants is ozone.

OZONE

Our grantees have shown in very elegant studies that ozone at currently permitted levels injures the lung and decreases pulmonary function in school children in summer camps, and this is perfectly documented with clear correlation between the decrease in pulmonary function and the increase in ambient ozone levels above the criteria.

Second, I have talked often about lead before this committee and the recent report by Dr. Needleman that lead exposure 10 or 15 years ago in young children at levels which are low to moderate. Of those children, he has now followed up a great number of them. They are six to seven times less likely to finish high school and to have reading disabilities, a very devastating outcome.

CHEMICAL TESTING PROGRAM

In our chemical testing program, we studied one of the primary explosives that is used extensively, not only by the Armed Forces but by civilian construction workers, tetranitromethane which is an incredibly potent carcinogen in mice and rats, and we have so informed the regulatory authorities.

KIDNEY DISEASE

The last new finding refers to kidney disease and I discussed this a little bit last year. End-stage renal disease costs the U.S. Govern

ment about $3.4 billion a year. We started out with the premise that there were certain environmental, occupational, and lifestyle factors that might be associated with the cause of renal disease.

We have not gotten to those factors yet, but we have turned up some very interesting and very important findings. First we looked at nonprescription analgesics which have long been suspected of causing kidney damage.

We found first that aspirin has no affect on kidney disease which is very good to know. Second, we found that acetaminophen which is a very common over-the-counter drug if taken daily by patients-now the package insert says only take daily for 2 weeksthis is daily for over a year, increases the chances of end-stage renal disease at least threefold.

And if patients would just take their Tylenol or those other overthe-counter drugs as the package label says, it could cut down a significant amount of end-stage renal disease.

We are currently looking at the nonsteroidal anti-inflammatory agents such as ibuprofen and the results are a little early but it looks, particularly in elderly males, that there is a striking increase in renal disease. And as I said, I hope next year we will be able to talk about lifestyle, diet, occupational, and environmental factors.

But if the findings with simply acetaminophen are translated and the public understands them, there can be a significant saving right now.

AIDS DRUGS

In terms of our ongoing studies, we do study many of the AIDS drugs for perinatalteratology and toxic effects in young animals as a supplement to the clinical experience, and we think it is important that this be done, and in as timely a fashion as possible.

RADON

Our study on the effects of radon in about 4,500 people are well underway and in 2 or 3 years we hope to have what is probably the best study on the effects of radon in the home.

AGRICULTURAL ENVIRONMENTAL HEALTH

We listened, we understood, and we followed up on our discussion at this meeting last year. We are holding a conference on environmental health and agriculture and farm communities in July, and we will explore many of these issues. We anticipate we will be able to establish a center in agricultural health late this summer. Thank you very much. I would be pleased to answer any questions.

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