HEPATITIS C:  NATURAL HISTORY, PATHOGENESIS, THERAPY AND PREVENTION

Release Date:  June 30, 1998

RFA:  DK-98-017

P.T.

National Institute of Diabetes and Digestive and Kidney Diseases
National Cancer Institute
National Institute of Allergy and Infectious Diseases
National Institute on Alcohol Abuse and Alcoholism
National Institute on Drug Abuse
Office of AIDS Research
Office of Research on Minority Health
American Digestive Health Foundation

Letter of Intent Receipt Date:  October 13, 1998
Application Receipt Date:  November 13, 1998

PURPOSE

The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK),
National Cancer Institute (NCI), National Institute of Allergy and Infectious
Diseases (NIAID), National Institute on Alcohol Abuse and Alcoholism (NIAAA),
National Institute on Drug Abuse (NIDA), Office of AIDS Research (OAR), and the
Office of Research on Minority Health (ORMH) in partnership with the American
Digestive Health Foundation invite grant applications for both basic and clinical
research in the areas of pathogenesis, natural history, therapy and prevention
of hepatitis C.  The hepatitis C virus is a major cause of acute and chronic
liver disease in the United States and now ranks second only to alcoholism as the
cause of cirrhosis and end-stage liver disease.  Acute hepatitis C leads to
chronic infection in approximately 75% of cases.  Chronic hepatitis C is often
asymptomatic and can be mild, but in a proportion of patients, the chronic
infection leads to progressive liver disease and ultimately cirrhosis and end
stage-liver disease, including cancer.  The determinants of outcome and
progression of liver disease in hepatitis C are unknown but may be related either
to viral, behavioral, environmental or genetic factors of the infected host. 
Alcohol use, other medical conditions, and co-infection with other viruses may
also affect the disease outcome of hepatitis C infection.  At present the therapy
of hepatitis C is unsatisfactory.  Only 20-25 percent of patients respond to
currently available therapies with long term remission of liver disease.  The
mechanism(s) by which alpha interferon and other anti-viral agents induce
clearance of virus and improvement of liver disease in only a subpopulation of
patients is not known.  In addition, its lack of response in a high proportion
of patients with hepatitis C is also unexplained.  Thus, the elucidation of the
mechanism(s) by which hepatitis C leads to liver injury and the factors
determining the course and outcome of chronic infection with and without therapy
are the focus of this RFA.  Noting that the most effective way to prevent the
liver disease of hepatitis C is through the generation of a preventative vaccine,
this RFA also supports the submission of applications with the aim of generating
a vaccine for hepatitis C.

In recognition of the importance of this research, the American Digestive Health
Foundation (a cooperative effort of the American Gastroenterological Association,
the American Society of Gastrointestinal Endoscopy, and the American Association
for the Study of Liver Disease) will be providing partial funding through the NIH
for direct costs of the portfolio of grants that receive support under this
initiative.

HEALTHY PEOPLE 2000

The Public Health Service (PHS) is committed to achieving the health promotion
and disease prevention objectives of "Healthy People 2000," a PHS-led national
activity for setting priority areas.  This RFA, Hepatitis C:  Natural History,
Pathogenesis, Therapy, and Prevention, is related to the priority area of chronic
disabling diseases.  Potential applicants may obtain a copy of "Healthy People
2000" (Full Report:  Stock No. 017-001-00474-0 or Summary Report:  Stock No. 017-
001-00473-1) through the Superintendent of Documents, Government Printing Office,
Washington, DC 20402-9325 (telephone 202-512-1800).

ELIGIBILITY REQUIREMENTS

Applications may be submitted by domestic and foreign for-profit and nonprofit
organizations, public and private, such as universities, colleges, hospitals,
laboratories, units of State and local governments, and eligible agencies of the
Federal Government.  Racial/ethnic minority individuals, women, and persons with
disabilities are encouraged to apply as Principal Investigators.

MECHANISM OF SUPPORT

Support of this program will be through the NIH grant-in-aid research project
grant (R01) award.  Responsibility for the planning, direction, and execution of
the proposed project will be solely that of the applicant.  Awards will be
administered under PHS grants policy as stated in the PHS Grants Policy
Statement.

Applicants from institutions that have a General Clinical Research Center (GCRC)
funded by the NIH National Center for Research Resources may wish to identify the
GCRC as a resource for conducting the proposed research.  If so, a letter of
agreement from either the GCRC program director or principal investigator should
be included with the application.

This RFA is a one-time solicitation.  Future unsolicited competing continuation
applications will compete with all investigator-initiated applications and be
reviewed according to the customary peer review procedures.  The total requested
project period for an application submitted in response to this RFA may not
exceed five years.  A maximum of five years can be requested for foreign awards. 
The anticipated award date is July 1, 1999.

Applications comprising multicenter clinical trials for the treatment of
hepatitis C will not be considered responsive to this RFA.  Such applications can
respond to the Program Announcement PAR-98-071 entitled "Small Grants in
Digestive and Nutritional Disorders".

FUNDS AVAILABLE

For FY 1999, $5.15 million will be committed to fund applications submitted in
response to this RFA.  It is anticipated that 17 to 22 awards will be made,
however, this funding level is dependent upon the receipt of a sufficient number
of applications of high scientific merit.  The American Digestive Health
Foundation will provide additional funds for across the board support this
initiative, but funding decisions will be the sole prerogative of the NIH. 
Although this program is provided for in the financial plans of the NIDDK, NCI,
NIDA, NIAAA, NIAID, ORMH, OAR, and the American Digestive Health Foundation, the
award of grants pursuant to this RFA is also contingent upon the availability of
funds for this purpose.

RESEARCH OBJECTIVES

Background

The hepatitis C virus (HCV) is a major cause of acute and chronic liver disease. 
In the United States, hepatitis C accounts for approximately 20 percent of acute
viral hepatitis and 60-70 percent of chronic viral hepatitis.  In 1995, chronic
hepatitis C infection accounted for 30 percent of all transplants making it the
single major indication for liver transplantation in adults.  Approximately 75
percent of persons infected with this virus develop chronic infection.  Chronic
hepatitis C is typically insidious and asymptomatic, but leads to cirrhosis and
end-stage liver disease in 20-30 percent of persons, usually over the course of
2 to 3 decades.  Nearly 4 million Americans are infected with hepatitis C and the
infection is more common in minority populations than in non-Hispanic whites.

Chronic hepatitis C is responsible for an estimated 8,000 to 10,000 deaths
annually.  At present there are no means of prevention of hepatitis C, and
treatments are unsatisfactory.  A recent NIH Consensus Development Conference
summarized the current knowledge about hepatitis C and made recommendations
regarding management and therapy.  The Conference also provided key
recommendations of areas for future research studies.  Those areas related to
this RFA were:

o  Monitoring of the epidemiology of acute and chronic hepatitis C with
additional focus on the specific mode of transmission in minority groups,
institutionalized individuals, and injection and intranasal drug users as well
as studies on sexual, household, occupational, nosocomial and perinatal
transmission,

o  Long term studies defining the natural history of hepatitis C in all infected
persons, as well as among specific cohorts such as minorities, children, the
aged, persons with hemophilia, and individuals co-infected with HIV, with an
emphasis on identifying factors associated with disease progression to cirrhosis
as well as studies on establishing the best means of monitoring for the early
detection of hepatocellular carcinoma using alpha fetoprotein testing and
ultrasonography and other detection modalities still to be established,

o  Studies on the pathogenesis and mechanisms of liver cell injury by HCV,
elucidation of cytopathic effects of the virus, mechanism(s) of liver fibrosis
and liver cell necrosis particularly through the generation of new animal and
cell culture models. One of the significant impediments to progress against
hepatitis C is the absence of suitable animal and cell culture models.  This
issue was described by the consensus conference as "a major bottleneck" and the
development of such model systems as a "high priority. Also, studies to define
the bases for persistence of or recovery from viral hepatitis and on detailing
the mechanism(s) of development of hepatocellular carcinoma in patients with
hepatitis.

o  The generation of effective new anti-viral therapies that inhibit virus
replication and prevent or delay the progression of liver disease concomitant
with a full understanding of the molecular virology of the virus,

o  Studies of alcohol ingestion and the course of disease as well as the
interaction between HCV and diabetes mellitus, obesity, iron metabolism and
medications,

o  Development of a safe and effective vaccine

Research Areas of Focus for this RFA

The current RFA addresses the areas of research recommended by the NIH Consensus
Development Conference through the specific request for basic and clinical
research grant applications related to Transmission, Clinical Manifestations,
Natural History of Acute and Chronic Hepatitis C, Transfusion-related Hepatitis
C, Liver Cell Injury, Fibrosis and Cirrhosis, Hepatocellular Carcinoma, Treatment
of Hepatitis C and Vaccine Development.

o  Transmission.  Studies are requested to elucidate the modes of non-parenteral
transmission of hepatitis C, particularly within specific cohorts such as
minority populations, lower socioeconomic groups, alcohol users, immunosuppressed
persons, the young and the aged.  Investigations of nonspecific means of
decreasing transmission in high risk groups such as substance abusers, medical
care personnel, dialysis and transplant patients are also sought.  Mechanisms of
enhanced transmission possibly associated with host genetic susceptibility or
viral types are also of interest.

o  Clinical manifestations.  Elucidation of the basis for differing clinical
presentations-icteric hepatitis, anicteric hepatitis, cholestatic hepatitis,
fulminant hepatitis and determination of the basis for such clinical symptoms as
fatigue, myalgia, arthritis and pruritus is needed.  The determination of the
biological mechanisms and clinical implications of extrahepatic HCV-related
manifestations such as cryoglobulinemia, glomerulonephritis, arthritis, porphyria
cutanea tarda and neuropathies is also needed, as well as the investigation of
the association and etiology of HCV-related B cell lymphomas.

o  Natural history of acute and chronic hepatitis C infection and disease
outcome.  Studies are needed to elucidate the immunological and virologic basis
of recovery from acute hepatitis C as opposed to persistence of viral infection
after acute infection.  The role of host genetic background in outcome of
infection should be explored.  In addition, investigations are needed of viral
and host factors responsible for and mechanisms of continued persistence of
infection with and without hepatocellular injury in chronic hepatitis C as well
as the determination of factors responsible for disease progression including:
alcohol and smoking, diet and nutrition, environmental factors, geographic
location, the role of concomitantly administered medications and nutritional
supplements and other viral co-infections.  Also, studies on alcohol"s effects
on levels of viremia in HCV-infected individuals, and whether alcohol enhances
expression of HCV proteins in the liver or skews the cellular immune response to
HCV (e.g., by preferentially affecting specific cell types such as TH1 vs. TH2)
are sought.

o  Transfusion-related hepatitis C.  Longþterm studies should define the natural
history of hepatitis C infection in specific populations that have received and
continue to receive frequent transfusions of blood components and pooled plasma
derivatives.  Persons with hematologic disorders, such as hemophilia,
thalassemia, sickle cell disease, and persons that have been and may be further
exposed to different genotypes of HCV should be included.  Genetic interactions
could facilitate escape from initially established immune mechanisms.  Studies
should focus on the long-term morbidity and mortality of chronically infected
individuals, including factors contributing to cirrhosis and hepatocellular
carcinoma and to amelioration by therapies directed against HCV itself.  Factors
to be considered are viral characteristics (genotypic variations, viral load),
host characteristics (gender, age, genetic susceptibility, and contributions of
the underlying disease), antecedent and superimposed co-infections (HBV, HIV and
other agents affecting hepatic and immunologic functions), and allogeneic
exposure to variant proteins in infused materials.  Potential contributing
factors to variations in the course of HCV infection include geographic location,
diet, alcohol, smoking, environmental contaminants and medications.

o  Liver cell injury.  Basic research studies are sought to define the biologic
mechanisms by which hepatitis C virus induces cell injury, be it directly or
indirectly, including interaction of apoptotic cell pathways, intracellular
signaling pathways and possible contributions of oxidants and oxidant factors,
iron and cytoprotection factors.  Applications are also sought that develop in
vitro viral propagation for the study of mechanisms of liver cell infectivity and
cellular injury.  The goal of this research could also be the development of a
readily available cell culture system that is fully permissive for viral
replication thus promoting the identification of infectious molecular clones,
pathways of infection and liver cell injury.

o  Model Systems.  Applications are sought that develop in vitro viral
propagation for the study of mechanisms of cell infectivity.  A goal of this
research might be to identify antiviral strategies and neutralizing antibodies
and epitopes.  Another goal could be the development of a readily available cell
culture system that is fully permissive for viral replication thus promoting the
identification of infectious molecular clones in the support of the analysis of
the viral structure.  Studies are also requested that develop small animal models
of acute and chronic infection for the characterization of replicative cycle of
the virus, the hosts" immune response to the virus, mechanisms of recovery and
persistence, and viral mechanisms of liver pathogenesis including oncogenesis.

o  Fibrosis and cirrhosis.  Studies are needed to investigate mechanisms of
augmented liver matrix formation and hepatic fibrosis formation induced by
hepatitis C.  Studies are also needed to better define means of staging of
fibrosis in chronic hepatitis C using liver biopsy tissue as well as noninvasive
means such blood tests or imaging procedures.  Studies are also requested that
develop small animal models of acute and chronic infection for the
characterization of viral mechanisms of liver pathogenesis including oncogenesis. 
Also studies are needed to determine the mechanism(s) by which alcohol enhances
virus-induced cytopathology in hepatocytes, and whether chronic alcohol
consumption sensitizes hepatocytes to the fibrogenic effects of cytokines,
especially in the presence of HCV infection.  Also, alcohol"s effects on
hepatocellular pathology need to be investigated in transgenic animals that
express HCV structural and non-structural proteins.

o  Hepatocellular carcinoma (HCC).  Studies are needed to elucidate the
mechanism(s) of development of hepatocellular carcinomas in HCV-infected
patients.  Epidemiologic studies are needed to determine the contribution of HCV
to the development of HCC, with an emphasis on studies of etiologic co-factors
that might interact with HCV to promote the development of liver cancer. 
Examples of such co-factors include concurrent infection with other tumor viruses
such as hepatitis B and the human immunodeficiency virus (HIV), aflatoxin, iron
stores, hormones/growth factors and cirrhotic changes. Also, studies are needed
to elucidate why alcohol increases the progression rate of HCC in HCV infection. 
Studies are sought to investigate the role of genetic susceptibility to HCV-
related HCC, as well as the relationship of HCC to specific HCV genotypes.  Of
particular importance are studies to develop techniques for the early detection
of HCC, such as inexpensive and specific blood tests and/or new imaging
techniques.

o  Treatment.  Research applications designed to identify and develop new
therapeutic modalities based upon HCV"s replication cycle and protein
structures/activities as well as the host response to the virus are encouraged. 
Liver cancer therapies are needed.  Model system development as outlined above
would help in these research efforts.  In addition, studies are needed to improve
current treatment modalities of HCV-related liver disease.  These include studies
to better define the determinants of response to therapy, the mechanisms by which
alpha interferon treatment leads to decreases in viral load and virus eradication
as well as the mechanisms of resistance to interferon treatment whether viral or
host, immunological or related to intracellular signaling pathways of alpha
interferon effects. Application are sought to develop better and practical means
of predicting a response to alpha interferon and other treatments including
mathematical models using predictive factors, develop means of defining whether
and when viral eradication versus viral suppression has occurred during therapy,
and elucidate the mechanisms of toxicities and side effects of interferon
treatment and means of their management and amelioration especially in regard to
the use of long term therapy. Studies on why alcoholics are resistant to
interferon treatment are needed to develop the optimum treatment for this large
sub-group of patients

o  Vaccine Development.  Applications are sought to: 1) develop fully permissive
tissue culture systems that support viral replication, since no in vitro systems
currently exist, either to serve as a source of virus or as a method of screening
possible anti-viral strategies, including vaccines, 2) develop well
characterized, representative small animal models to determine immune response
to HCV-induced disease and malignant sequelae and to test the safety and efficacy
of proposed vaccines, 3) emphasize basic and applied studies on the
identification of HCV viral or viral-induced antigens that elicit protective
immunity and that form the basis for vaccine preparation, 4) elucidate the
mechanism(s) of development of hepatocellular carcinomas in HCV-infected
patients, 5) enhance understanding of the molecular determinants of both cellular
and humoral immunity to HCV, the nature of antigenic variation as related to
quasi-species diversity, and the mechanism(s) by which HCV regularly eludes the
host immune system and established persistent infections

INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS

It is the policy of the NIH that women and members of minority groups and their
sub-populations must be included in all NIH supported biomedical and behavioral
research projects involving human subjects, unless a clear and compelling
rationale and justification is provided that inclusion is inappropriate with
respect to the health of the subjects or the purpose of the research.  This
policy results from the NIH Revitalization Act of 1993 (Section 492B of Public
Law 103-43).

All investigators proposing research involving human subjects should read the
"NIH Guidelines For Inclusion of Women and Minorities as Subjects in Clinical
Research," which have been published in the Federal Register of March 28, 1994
(FR 59 14508-14513), and in the NIH Guide For Grants and Contracts, Volume 23,
Number 11, March 18, 1994.

Investigators may also obtain copies from these sources or from the program staff
or contact person listed under INQUIRIES.  Program staff may also provide
additional relevant information concerning the policy.

NIH POLICY AND GUIDELINES ON THE INCLUSION OF CHILDREN AS PARTICIPANTS IN
RESEARCH INVOLVING HUMAN SUBJECTS

It is the policy of NIH that children (i.e., individuals under the age of 21)
must be included in all human subjects research, conducted or supported by the
NIH, unless there are scientific and ethical reasons not to include them.  This
policy applies to all initial (Type 1) applications submitted for receipt dates
after October 1, 1998.

All investigators proposing research involving human subjects should read the
"NIH Policy and Guidelines on the Inclusion of Children as Participants in
Research Involving Human Subjects" that was published in the NIH Guide for Grants
and Contracts, March 6, 1998, and is available at the following URL address:
http://grants.nih.gov/grants/guide/notice-files/not98-024.html

LETTER OF INTENT

Prospective applicants are asked to submit, by October 13, 1998, a letter of
intent that includes a descriptive title of the proposed research, the name,
address, and telephone number of the Principal Investigator, the identities of
other key personnel and participating institutions, and the number and title of
the RFA in response to which the application may be submitted.

Although a letter of intent is not required, is not binding, and does not enter
into the review of a subsequent application, the information that it contains
allows NIDDK staff to estimate the potential review workload and avoid conflict
of interest in the review.

The letter of intent is to be sent to:

Chief, Review Branch
Division of Extramural Activities
National Institute of Diabetes and Digestive and Kidney Diseases
45 Center Drive, Room 6AS-37F, MSC 6600
Bethesda, MD  20892-6600
Telephone:  (301) 594-8885
FAX:  (301) 480-3505

APPLICATION PROCEDURES

Applications are to be submitted on the grant application form PHS 398 (rev.
5/95).  Application kits are available at most institutional offices of sponsored
research and may be obtained from the Division of Extramural Outreach and
Information Resources, National Institutes of Health, 6701 Rockledge Drive, MSC
7910, Bethesda, MD 20892-7910, telephone (301) 435-0714, Email
GrantsInfo@nih.gov.

The RFA label available in the PHS 398 (rev. 5/95) application form must be
affixed to the bottom of the face page of the application.  Failure to use this
label could result in delayed processing of the application such that it may not
reach the review committee in time for review.  In addition, the RFA title and
number must be typed on line 2 of the face page of the application form and the
YES box must be marked.

Submit a signed, typewritten original of the application, including the
Checklist, plus three signed photocopies, in one package to:

CENTER FOR SCIENTIFIC REVIEW
NATIONAL INSTITUTES OF HEALTH
6701 ROCKLEDGE DRIVE, ROOM 1040 - MSC 7710
BETHESDA, MD 20892-7710
BETHESDA, MD 20817 (for express/courier service)

At time of submission, two additional copies of the application must be sent to:

Chief, Review Branch
Division of Extramural Activities
National Institute of Diabetes and Digestive and Kidney Diseases
45 Center Drive, Room 6AS-37F, MSC 6600
Bethesda, MD  20892-6600

Applications must be received by November 13, 1998.  If an application is
received after that date, it will be returned to the applicant without review. 
The Center for Scientific Review (CSR) will not accept any application in
response to this RFA that is essentially the same as one currently pending
initial review, unless the applicant withdraws the pending application.  The CSR
will not accept any application that is essentially the same as one already
reviewed.  This does not preclude the submission of substantial revisions of
applications previously reviewed, but such applications must include an
introduction addressing the previous critique.

REVIEW CONSIDERATIONS

Applications that are complete and responsive to the RFA will be evaluated for
scientific and technical merit by an appropriate peer review group(s) convened
by the NIDDK in accordance with NIH peer review procedures.  As part of the
initial merit review, all applications will receive a written critique and
undergo a process in which only those applications deemed to have the highest
scientific merit will be discussed, assigned a priority score, and receive a
second level review by the National Diabetes and Digestive and Kidney Diseases
Advisory Council or other Institute Advisory Council as assigned.

Review Criteria

The goals of NIH-supported research are to advance our understanding of
biological systems, improve the control of disease, and enhance health.  In the
written review, comments on the following aspects of the application will be made
in order to judge the likelihood that the proposed research will have a
substantial impact on the pursuit of these goals.  Each of these criteria will
be addressed and considered in the assignment of the overall score.

o  Significance:  Does this study address an important problem?  If the aims of
the application are achieved, how will scientific knowledge be advanced?  What
will be the effect of these studies on the concepts or methods that drive this
field?

o  Approach:  Are the conceptual framework, design, methods, and analyses
adequately developed, well-integrated, and appropriate to the aims of the
project?  Does the applicant acknowledge potential problem areas and consider
alternative tactics?

o  Innovation:  Does the project employ novel concepts, approaches or method? Are
the aims original and innovative?  Does the project challenge existing paradigms
or develop new methodologies or technologies?

o  Investigator:  Is the investigator appropriately trained and well suited to
carry out this work?  Is the work proposed appropriate to the experience level
of the principal investigator and other researchers (if any)?

o  Environment:  Does the scientific environment in which the work will be done
contribute to the probability of success?  Do the proposed experiments take
advantage of unique features of the scientific environment or employ useful
collaborative arrangements?  Is there evidence of institutional support?

o  Appropriateness of the proposed budget and duration in relation to the
proposed research.

o  Adequacy of plans to include both genders, minorities and their subgroups, and
children as appropriate for the scientific goals of the research.  Plans for the
recruitment and retention of subjects will also be evaluated.

The initial review group will also examine the provisions for the protection of
human and animal subjects, and the safety of the research environment.

o  Availability of special opportunities for furthering research programs through
the use of unusual talent resources, populations, or environmental conditions in
other countries that are not readily available in the United States or that
provide augmentation of existing U.S. resources.

AWARD CRITERIA

The anticipated date of award is July 1, 1999.

Award criteria are: scientific merit as determined by peer review, availability
of funds, and programmatic priorities of participating Institutes.

INQUIRIES

Inquiries concerning this RFA are encouraged.  The opportunity to clarify any
issues or questions from potential applicants is welcome.

Direct inquiries regarding programmatic issues to:

Thomas F. Kresina, Ph.D.
Division of Digestive Diseases and Nutrition
National Institute of Diabetes and Digestive and Kidney Diseases
45 Center Drive, MSC 6600
Bethesda, MD  20892-6600
Telephone:  (301) 594-8871
FAX:  (301) 480-8300
Email:  tk13v@nih.gov

John S. Cole, III, Ph.D.
Division of Cancer Biology
National Cancer Institute
6130 Executive Boulevard, Room 540, MSC 7398
Bethesda, MD  20891-7398
Telephone:  (301) 496-1718
FAX:  (301) 496-2025
Email:  jcole3@helix.nih.gov

Sandra L. Melnick, Dr.P.H.
Division of Cancer Control and Population Sciences
National Cancer Institute
6130 Executive Boulevard, Room 535, MSC 7395
Bethesda, MD  20891-7395
Telephone:  (301) 435-4914
FAX:  (301) 402-4279
Email:  sm33k@nih.gov

Dr. Sam Zakhari
Biomedical Research Branch
National Institute on Alcohol Abuse and Alcoholism
6000 Executive Boulevard, Room 402
Bethesda, MD  20892-7003
Telephone:  (301) 443-0799
FAX:  (301) 594-0673
Email:  sz14w@nih.gov

Leslye D. Johnson, Ph.D.
Chief, Enteric and Hepatic Diseases Branch
National Institute of Allergy and Infectious Diseases
Solar Building, Room 3A22
Bethesda, MD  20892
Telephone:  (301) 496-7051
FAX:  (301) 402-1456
Email:  Lj7m@nih.gov

Direct inquiries regarding fiscal and administrative matters to:

Ms. Donna Huggins
Division of Extramural Activities
National Institute of Diabetes and Digestive and Kidney Diseases
45 Center Drive, MSC 6600
Bethesda, MD  20892-6600
Telephone:  (301) 594-8848
Email:  HugginsD@extra.niddk.nih.gov

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic Assistance No.
93.848.  Awards are made under authorization of the Public Health Service Act,
Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158, 42 USC 241
and 285) and administered under PHS grants policies and Federal Regulations 42
CFR 52 and 45 CFR Part 74.  This program is not subject to the intergovernmental
review requirements of Executive Order 12372 or Health Systems Agency review.

The PHS strongly encourages all grant and contract recipients to provide a smoke-
free workplace and promote the non-use of all tobacco products.  In addition,
Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain
facilities (or in some cases, any portion of a facility) in which regular or
routine education, library, day care, health care or early childhood development
services are provided to children.  This is consistent with the PHS mission to
protect and advance the physical and mental health of the American people.

Weekly TOC for this Announcement
NIH Funding Opportunities and Notices

	Office of Extramural Research (OER)			National Institutes of Health (NIH) 9000 Rockville Pike Bethesda, Maryland 20892			Department of Health and Human Services (HHS)
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