COMPARATIVE BIOLOGY:  MECHANISMS OF AGING
 
RELEASE DATE:  October 30, 2002
 
RFA:  AG-03-003

National Institute on Aging (NIA)
 (http://www.nih.gov/nia/)

LETTER OF INTENT RECEIPT DATE:  December 23, 2002

APPLICATION RECEIPT DATE:  January 23, 2003  
 
THIS RFA CONTAINS THE FOLLOWING INFORMATION

o Purpose of this RFA
o Research Objectives
o Mechanism of Support 
o Funds Available
o Eligible Institutions
o Individuals Eligible to Become Principal Investigators
o Where to Send Inquiries
o Letter of Intent
o Submitting an Application
o Peer Review Process
o Review Criteria
o Receipt and Review Schedule
o Award Criteria
o Required Federal Citations

PURPOSE OF THIS RFA 

The NIA is soliciting applications that use comparative biology 
approaches to understand the biological mechanisms that lead to changes 
in human and other animal cells and tissues with age.  The major 
questions to be addressed under this RFA are:  How does increasing age 
lead to biological changes, especially decrements in cell, tissue and 
organ function; and what sets the rate of aging such that different 
organisms have different life expectancies?  Studies that take 
advantage of the differences in aging and life expectancy between 
species and within species to investigate hypotheses on the mechanisms 
of aging are encouraged.
 
RESEARCH OBJECTIVES

Background 

This RFA follows on a workshop held by the NIA in February, 2002 on 
Comparative Biology of Aging.  A publication from that meeting can be 
accessed on the Science of Aging Knowledge Environment (SAGE KE) at 
http://sageke.sciencemag.org/cgi/content/full/sageke;2002/17/pe5?&view=print

We do not yet know why the function of many human tissues and organs 
increasingly declines with age.  Senescence takes place in most 
organisms, resulting in increasing mortality with age.  Humans are 
among some of the longest-lived organisms but some organisms, such as 
tortoises, live longer and some, such as the bristle cone pine tree 
live for thousands of years.  At the other end of the spectrum, many 
organisms have very short life expectancy.

Hypotheses of aging have been advanced and provide a framework for 
study of the causes of biological changes seen with aging.  

The free radical damage theory of aging implies that accumulation of 
free radicals, such as reactive oxygen species(ROS) that result from 
respiration, results in damage to lipids, proteins and/or nucleic 
acids.  This damage accumulates and, eventually, function of tissue is 
impaired.  It has long been assumed that the more oxygen that is 
metabolized by mitochondria, the more reactive oxygen species (ROS) 
will be produced.  Not yet clear is how mitochondria from some species 
might metabolize oxygen more efficiently than mitochondria from other 
species, and thus produce ROS at a lower rate.  Comparative approaches 
should be useful for elucidating the molecular basis for differences in 
mitochondrial efficiency among species and for testing whether 
production of ROS and repair of resulting damage are key to determining 
longevity.  Such information might also be useful in understanding 
differences in oxygen utilization and oxidative stress in different 
tissues and organs within a species.

The telomeres that protect the functional ends of chromosomes have been 
implicated in the process of cell senescence, the limited replication 
potential of non-stem cell populations in the body.  However, the role 
of telomeres in determining how long cells can continue to replicate 
and function before senescing, or how long an organism lives, is far 
from clear.

In some model organisms, single gene changes can result in extended or 
shortened life expectancy.  Thus, there appears to be a genetic 
component to longevity determination within a species.  Although 
considerable progress has been made identifying genes involved in 
longevity regulation within species, e.g. fruit flies, nematodes and 
mice, and similar genes are found across species, relatively little is 
known about the genes that account for the striking differences in 
longevity between species.  Comparative approaches should prove useful 
in identifying these genes.

A variety of correlations with long life have been noted in several 
different species; factors such as body size, protective lifestyle 
(flying as opposed to terrestrial or high vs. low predation 
environments, for instance), and social lifestyle may all be involved.  
However, none of the hypothesized influences on aging rate and 
longevity has been adequately tested and proven to be a cause of 
changes with age.  In addition, the molecular and genetic bases for 
longer life expectancy that results from environmental influences are 
not characterized.

Comparison between organisms with different life expectancies, or with 
characteristics that, according to hypotheses on aging, should be 
predictive of life expectancy, is very likely to be a productive 
approach to testing hypotheses and advancing new ones that explain 
aging.  However, this productive approach has not been widely used. 

For example, animals may be phylogenetically closely related, such as 
the mouse and naked mole rat, but have considerably varying life 
expectancies, in this case about two years compared to over 20 years, 
respectively.  Alternatively, comparisons between humans and other 
primates, or between primate species with widely varying life 
expectancies would also be valuable.  Understanding the biological 
differences between these closely related species at the molecular, 
cell and tissue levels may help to understand the causes of senescence.  
Such studies would also help determine whether relationships between 
biological mechanisms of aging and life expectancy or aging rates 
observed among non-primate phylogenies also apply to humans and closely 
related species.  

It is also unclear that the mechanisms that make a difference in life 
expectancy among relatively shorter-lived species are the same ones 
that account for the life expectancies of very long-lived species, 
e.g., long-lived primates, including humans, as well as long-lived 
species in other phylogenies.  Studies to extend comparisons involving 
mechanisms of aging to primates would be useful in answering this 
question.

Variation of life expectancies within species can be quite large, and 
the causes of this variation are likely to be informative.  Thus, the 
honeybee can produce a worker or a queen from the same egg, depending 
on early feeding of the larva, and possibly other factors.  Yet the 
queen bee lives 5-8 years, while the worker lives less than a year.  

Some organisms have properties that, according to some aging 
hypotheses, would seem predictive of short or long life expectancy.  
The budgerigar is approximately the same body size as a mouse but has 
much higher lifetime energy consumption.  This would seem to predict 
greater production of reactive oxygen species and, thus, shorter life 
expectancy.  Yet, the budgerigar lives almost ten times as long as a 
mouse.  

Finally, within an organism, some cells have a shorter life relative to 
other cells (for example, a columnar absorptive cell from the 
intestinal epithelium as opposed to a cardiac myocyte).  It is unclear 
how longer lived cells maintain tissue homeostasis in spite of 
predicted accumulation of damage with greater age. In each of the above 
examples, and many others, careful studies that use comparisons to test 
hypotheses of aging would be valuable to understanding aging 
mechanisms.  

Objectives and Scope

This RFA is intended to encourage mechanistic, basic research using 
comparative biology approaches to investigate aging.  Research that 
takes maximal advantage of unique properties of species available for 
laboratory study is particularly encouraged.  Studies should be focused 
on well-described hypotheses for why functional changes and mortality 
increase with age, and why rates of change and life expectancy vary 
among species or strains.  Studies may be at the molecular, cellular, 
tissue, organ, or organism level.  Studies comparing humans with other 
species, including other primate species, are encouraged.  Such studies 
may include physiologic measures and collection of body fluids, 
tissues, or cells for in vitro use.  Studies under this RFA may not 
include clinical interventions or therapeutic evaluations.  Studies 
focused on models for a particular disease process, as opposed to a 
general mechanism of aging and altered life expectancy, are not 
appropriate under this announcement.  The examples below illustrate 
some potential areas of interest but are intended as examples only and 
are not exclusive.

o  Studies to identify genes that explain differing life expectancies 
between species, including species with exceptionally long life 
expectancies.

o  Studies on mechanisms of senescence or protection from senescence in 
stem cells and how stem cell lifespan influences organism lifespan

o  Studies in multiple species to determine if genes whose expression 
results in increased longevity in one species also increase longevity 
in other species.  For example, do the mutations in genes that result 
in longer life span for worms, flies and mice also result in longer 
life span in other organisms.

o  Studies on strategies different organisms use to deal with oxidative 
stress through reduced production of ROS, or through repair, 
replacement, or prevention of damaged molecules (for example, DNA) and 
cells and how this strategy results in different life expectancies.  

o  Studies to identify key molecular and genetic changes that dominate 
as a result of selection for longer lived animals within a species.

o  Studies of telomere biology between species to determine how 
telomere and telomerase function correlate with life expectancy of the 
organism (or specific cell types within an organisms?).

o  Studies of environmental influences that substantially change the 
rate of aging or life expectancy within and between species, especially 
the resulting changes in gene expression and physiology that contribute 
to this effect.

o  Studies to define periods of development and adulthood where aging 
and longevity factors exert their effect.

o  Studies to understand the cellular and molecular basis of the 
changes in tissue or organ function with age by comparisons between 
organisms with different tissue-aging properties

o  Mechanistic studies that make use of organisms not currently broadly 
used for aging research but that have special interest to study of 
aging in light of mechanisms proposed for aging.

MECHANISM OF SUPPORT
 
This RFA will use the NIH R01 award mechanism.  As an applicant you 
will be solely responsible for planning, directing, and executing the 
proposed project.  This RFA is a one-time solicitation.  Future 
unsolicited, competing-continuation applications based on this project 
will compete with all investigator-initiated applications and will be 
reviewed according to the customary peer review procedures. The 
anticipated award date is September 2003. 

This RFA uses just-in-time concepts.  It also uses the modular 
budgeting format. (see 
http://grants.nih.gov/grants/funding/modular/modular.htm).   

FUNDS AVAILABLE

The NIA anticipates that a total of $1.5 million will be available in 
FY 2003 to fund new grants in response to this RFA.  An applicant may 
request a project period up to five years and a budget for direct costs 
up to $200,000 a year.  Because the nature and scope of the proposed 
research will vary from application to application NIA anticipates that 
the size and duration of awards will also vary. It is anticipated that 
5-7 grants will be supported.  Awards are contingent upon availability 
of funds and the receipt of a sufficient number of applications of 
outstanding scientific and technical merit.  At this time it is not 
known whether this RFA will be reissued.  

ELIGIBLE INSTITUTIONS
 
You may submit (an) application(s) if your institution has any of the 
following characteristics:
	
o For-profit or non-profit organizations 
o Public or private institutions, such as universities, colleges, 
hospitals, and laboratories 
o Units of State and local governments
o Eligible agencies of the Federal government  
o Domestic or foreign
 
INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS   

Any individual with the skills, knowledge, and resources necessary to 
carry out the proposed research is invited to work with their 
institution to develop an application for support.  Individuals from 
underrepresented racial and ethnic groups as well as individuals with 
disabilities are always encouraged to apply for NIH programs.   

WHERE TO SEND INQUIRIES

We encourage inquiries concerning this RFA and welcome the opportunity 
to answer questions from potential applicants.  Inquiries may fall into 
three areas:  scientific/research, peer review, and financial or grants 
management issues:

o Direct your questions about general scientific/research issues and 
regarding projects focused on non-neural tissues to:

Jill L. Carrington, Ph.D.
Biology of Aging Program 
National Institute on Aging 
Gateway Building, Suite 2C231
7201 Wisconsin Avenue
Bethesda, MD  20892-9205
Telephone:  (301) 496-6402
Email: carringtonj@nia.nih.gov

For questions about involvement of humans in studies under this RFA, 
contact:

Evan C. Hadley, M.D.  
Geriatrics and Clinical Gerontology Program                                         
National Institute on Aging, NIH 					 
Gateway Building, Suite 3E327 
7201 Wisconsin Avenue
Bethesda MD 20892-9205
Telephone: (301) 435-3044 
Email: ehadley@nih.gov 

For questions on studies focused on the nervous system under this RFA, 
contact:

Bradley C. Wise, Ph.D.
Neuroscience and Neuropsychology of Aging Program
National Institute on Aging
Gateway Building, Suite 3C307
7201 Wisconsin Avenue
Bethesda, MD   20892-9205
Telephone:  (301) 496-9350
FAX:  (301) 496-1494
Email:  wiseb@nia.nih.gov

o Direct your questions about peer review issues to: 

Mary Nekola, Ph.D.
Scientific Review Office
National Institute on Aging 
Gateway Building, Room 2C212
Bethesda, MD  20892-9205
Telephone:  (301) 496-9666
Email: nekolam@nia.nih.gov

o Direct your questions about financial or grants management matters 
to:

Linda Whipp
Grants and Contracts Management Office
National Institute on Aging 
Gateway Building, Room 2N212
Bethesda, MD  20892-9205
Telephone:  (301) 496-1472
Email: whippl@nia.nih.gov

LETTER OF INTENT

Prospective applicants are asked to submit a letter of intent that 
includes the following information:

o Descriptive title of the proposed research
o Name, address, and telephone number of the Principal Investigator
o Names of other key personnel 
o Participating institutions
o Number and title of this RFA 

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 IC staff to estimate the potential review 
workload and plan the review.
 
The letter of intent is to be sent by the date listed at the beginning 
of this document. The letter of intent should be sent to:

Chief of Review
Scientific Review Office
National Institute on Aging
7201 Wisconsin Avenue, Suite 2C212, MSC 9205
Bethesda, MD 20892-9205
Telephone:  (301) 496-9666
FAX:  301-402-0066
Email: NekolaM@nia.nih.gov

SUBMITTING AN APPLICATION

Applications must be prepared using the PHS 398 research grant 
application instructions and forms (rev. 5/2001).  The PHS 398 is 
available at http://grants.nih.gov/grants/funding/phs398/phs398.html in 
an interactive format.  For further assistance contact GrantsInfo, 
Telephone (301) 435-0714, Email: GrantsInfo@nih.gov.

SPECIFIC INSTRUCTIONS FOR MODULAR GRANT APPLICATIONS: Applications must 
be submitted in a modular grant format.  The modular grant format 
simplifies the preparation of the budget in these applications by 
limiting the level of budgetary detail.  Applicants request direct 
costs in $25,000 modules.  Section C of the research grant application 
instructions for the PHS 398 (rev. 5/2001) at 
http://grants.nih.gov/grants/funding/phs398/phs398.html includes step-
by-step guidance for preparing modular grants.  Additional information 
on modular grants is available at 
http://grants.nih.gov/grants/funding/modular/modular.htm.

USING THE RFA LABEL: The RFA label available in the PHS 398 (rev. 
5/2001) application form must be affixed to the bottom of the face page 
of the application.  Type the RFA number on the label.  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. The RFA 
label is also available at: 
http://grants.nih.gov/grants/funding/phs398/label-bk.pdf.
 
SENDING AN APPLICATION TO THE NIH: Submit a signed, typewritten 
original of the application, including the Checklist, and 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 the time of submission, two additional copies of the application 
must be sent to:

Chief of Review
Scientific Review Office
National Institute on Aging
7201 Wisconsin Avenue, Suite 2C212, MSC 9205
Bethesda, MD 20892-9205
 
APPLICATION PROCESSING: Applications must be received by the 
application receipt date listed in the heading of this RFA.  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 already 
reviewed, but such applications must include an Introduction addressing 
the previous critique.

PEER REVIEW PROCESS

Upon receipt, applications will be reviewed for completeness by the CSR 
and responsiveness by the NIA.  Incomplete applications will be 
returned to the applicant without further consideration.  And, if the 
application is not responsive to the RFA, CSR staff may contact the 
applicant to determine whether to return the application to the 
applicant or submit it for review in competition with unsolicited 
applications at the next appropriate NIH review cycle.

Applications that are complete and responsive to the RFA will be 
evaluated for scientific and technical merit by an appropriate peer 
review group convened by the NIA in accordance with the review criteria 
stated below.  As part of the initial merit review, all applications 
will:

o Receive a written critique
o May undergo a process in which only those applications deemed to have 
the highest scientific merit, generally the top half of the 
applications under review, will be discussed and assigned a priority 
score
o Receive a second level review by the National Advisory Council on 
Aging

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 comments, reviewers will be asked to discuss the 
following aspects of your application in order to judge the likelihood 
that the proposed research will have a substantial impact on the 
pursuit of these goals: 

o Significance 
o Approach 
o Innovation
o Investigator
o Environment
  
The scientific review group will address and consider each of these 
criteria in assigning your application's overall score, weighting them 
as appropriate for each application.  Your application does not need to 
be strong in all categories to be judged likely to have major 
scientific impact and thus deserve a high priority score.  For example, 
you may propose to carry out important work that by its nature is not 
innovative but is essential to move a field forward.

(1) SIGNIFICANCE:  Does your study address an important problem? If the 
aims of your application are achieved, how do they advance scientific 
knowledge?  What will be the effect of these studies on the concepts or 
methods that drive this field?

(2) APPROACH:  Are the conceptual framework, design, methods, and 
analyses adequately developed, well integrated, and appropriate to the 
aims of the project?  Do you acknowledge potential problem areas and 
consider alternative tactics?

(3) INNOVATION:  Does your project employ novel concepts, approaches or 
methods? Are the aims original and innovative?  Does your project 
challenge existing paradigms or develop new methodologies or 
technologies?

(4) INVESTIGATOR: Are you appropriately trained and well suited to 
carry out this work?  Is the work proposed appropriate to your 
experience level as the principal investigator and to that of other 
researchers (if any)?

(5) ENVIRONMENT:  Does the scientific environment in which your 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?

ADDITIONAL REVIEW CRITERIA: In addition to the above criteria, your 
application will also be reviewed with respect to the following:

o PROTECTIONS:  The adequacy of the proposed protection for humans, 
animals, or the environment, to the extent they may be adversely 
affected by the project proposed in the application.

o INCLUSION:  The adequacy of plans to include subjects from both 
genders, all racial and ethnic groups (and subgroups), and children as 
appropriate for the scientific goals of the research.  Plans for the 
recruitment and retention of subjects will also be evaluated. (See 
Inclusion Criteria included in the section on Federal Citations, below)

o BUDGET:  The reasonableness of the proposed budget and the requested 
period of support in relation to the proposed research.

RECEIPT AND REVIEW SCHEDULE

Letter of Intent Receipt Date: December 23, 2002
Application Receipt Date:  January 23, 2003
Peer Review Date:  May, 2003
Council Review:  August, 2003
Earliest Anticipated Start Date:  September, 2003

AWARD CRITERIA

Award criteria that will be used to make award decisions include:

o Scientific merit (as determined by peer review)
o Availability of funds
o Programmatic priorities.

REQUIRED FEDERAL CITATIONS 

INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH: 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 clinical research 
projects unless a clear and compelling justification is provided 
indicating 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 clinical research should read the AMENDMENT 
"NIH Guidelines for Inclusion of Women and Minorities as Subjects in 
Clinical Research - Amended, October, 2001," published in the NIH Guide 
for Grants and Contracts on October 9, 2001 
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); a 
complete copy of the updated Guidelines are available at 
http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_20
01.htm.   The amended policy incorporates: the use of an NIH 
definition of clinical research; updated racial and ethnic categories 
in compliance with the new OMB standards; clarification of language 
governing NIH-defined Phase III clinical trials consistent with the new 
PHS Form 398; and updated roles and responsibilities of NIH staff and 
the extramural community.  The policy continues to require for all NIH-
defined Phase III clinical trials that: a) all applications or 
proposals and/or protocols must provide a description of plans to 
conduct analyses, as appropriate, to address differences by sex/gender 
and/or racial/ethnic groups, including subgroups if applicable; and b) 
investigators must report annual accrual and progress in conducting 
analyses, as appropriate, by sex/gender and/or racial/ethnic group 
differences.

INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN 
SUBJECTS: The NIH maintains a policy 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 is available at 
http://grants.nih.gov/grants/funding/children/children.htm.

REQUIRED EDUCATION ON THE PROTECTION OF HUMAN SUBJECT PARTICIPANTS: NIH 
policy requires education on the protection of human subject 
participants for all investigators submitting NIH proposals for 
research involving human subjects.  You will find this policy 
announcement in the NIH Guide for Grants and Contracts Announcement, 
dated June 5, 2000, at http://grants.nih.gov/grants/guide/notice-
files/NOT-OD-00-039.html.

HUMAN EMBRYONIC STEM CELLS (hESC): Criteria for federal funding of 
research on hESCs can be found at 
http://grants.nih.gov/grants/stem_cells.htm and at 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html.  
Only research using hESC lines that are registered in the NIH Human 
Embryonic Stem Cell Registry will be eligible for Federal funding (see 
http://escr.nih.gov).   It is the responsibility of the applicant to 
provide the official NIH identifier(s)for the hESC line(s)to be used in 
the proposed research.  Applications that do not provide this 
information will be returned without review. 

PUBLIC ACCESS TO RESEARCH DATA THROUGH THE FREEDOM OF INFORMATION ACT: 
The Office of Management and Budget (OMB) Circular A-110 has been 
revised to provide public access to research data through the Freedom 
of Information Act (FOIA) under some circumstances.  Data that are (1) 
first produced in a project that is supported in whole or in part with 
Federal funds and (2) cited publicly and officially by a Federal agency 
in support of an action that has the force and effect of law (i.e., a 
regulation) may be accessed through FOIA.  It is important for 
applicants to understand the basic scope of this amendment.  NIH has 
provided guidance at 
http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm.

Applicants may wish to place data collected under this RFA in a public 
archive, which can provide protections for the data and manage the 
distribution for an indefinite period of time.  If so, the application 
should include a description of the archiving plan in the study design 
and include information about this in the budget justification section 
of the application. In addition, applicants should think about how to 
structure informed consent statements and other human subjects 
procedures given the potential for wider use of data collected under 
this award.

URLs IN NIH GRANT APPLICATIONS OR APPENDICES: All applications and 
proposals for NIH funding must be self-contained within specified page 
limitations. Unless otherwise specified in an NIH solicitation, 
Internet addresses (URLs) should not be used to provide information 
necessary to the review because reviewers are under no obligation to 
view the Internet sites.   Furthermore, we caution reviewers that their 
anonymity may be compromised when they directly access an Internet 
site.

HEALTHY PEOPLE 2010: The Public Health Service (PHS) is committed to 
achieving the health promotion and disease prevention objectives of 
"Healthy People 2010," a PHS-led national activity for setting priority 
areas. This RFA is related to one or more of the priority areas. 
Potential applicants may obtain a copy of "Healthy People 2010" at 
http://www.health.gov/healthypeople/.

AUTHORITY AND REGULATIONS: This program is described in the Catalog of 
Federal Domestic Assistance No. 93.866, and is not subject to the 
intergovernmental review requirements of Executive Order 12372 or 
Health Systems Agency review.  Awards are made under authorization of 
Sections 301 and 405 of the Public Health Service Act as amended (42 
USC 241 and 284) and administered under NIH grants policies described 
at http://grants.nih.gov/grants/policy/policy.htm and under Federal 
Regulations 42 CFR 52 and 45 CFR Parts 74 and 92.

The PHS strongly encourages all grant recipients to provide a smoke-
free workplace and to discourage the 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.

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