RESEARCH

INVOLVING

HUMAN

BIOLOGICAL

MATERIALS:

ETHICAL

ISSUES

AND POLICY

GUIDANCE

VOLUME I

Report and 

Recommendations 

of the 

National Bioethics 

Advisory Commission

Rockville, Maryland

August 1999
The National Bioethics Advisory Commission (NBAC) was established by Executive Order 12975,

signed by President Clinton on October 3, 1995. NBAC’s functions are defined as follows: 

a) NBAC shall provide advice and make recommendations to the National Science and Technology

Council and to other appropriate government entities regarding the following matters: 

1) the appropriateness of departmental, agency, or other governmental programs, policies,

assignments, missions, guidelines, and regulations as they relate to bioethical issues arising

from research on human biology and behavior; and

2) applications, including the clinical applications, of that research.

b) NBAC shall identify broad principles to govern the ethical conduct of research, citing specific

projects only as illustrations for such principles. 

c) NBAC shall not be responsible for the review and approval of specific projects. 

d) In addition to responding to requests for advice and recommendations from the National Science

and Technology Council, NBAC also may accept suggestions of issues for consideration from

both the Congress and the public. NBAC also may identify other bioethical issues for the

purpose of providing advice and recommendations, subject to the approval of the National

Science and Technology Council.

National Bioethics Advisory Commission

6100 Executive Boulevard, Suite 5B01, Rockville, Maryland 20892-7508

Telephone: 301-402-4242 • Fax: 301-480-6900 • Website: www.bioethics.gov
RESEARCH

INVOLVING

HUMAN

BIOLOGICAL

MATERIALS:

ETHICAL

ISSUES

AND POLICY

GUIDANCE

VOLUME I

Report and 

Recommendations 

of the 

National Bioethics 

Advisory Commission

Rockville, Maryland

August 1999

Letter of Transmittal to the President

National Bioethics Advisory Commission

National Bioethics Advisory Commission Staff 

and Consultants

Executive Summary i

Chapter 1: Overview and Introduction 1

The Use of Human Biological Materials in Research 1

The Research Value of Human Biological Materials 1

Is Genetic Information Different from Other 

Medical Information? 3

Increasing Discussion About the Appropriate Research Use 

of Human Biological Materials 4

About This Report 9

Notes 10

References 11

Chapter 2: Collection, Storage, and Use of Human 

Biological Materials in the United States 13

Collections of Human Biological Materials 13

Identifiability of Human Biological Materials 15

The Value of Human Biological Materials to Current Research 19

Summary 23

Notes 24

References 24

Chapter 3: Current Guidance on the Use of Human

Biological Materials in Research 27

Introduction 27

Scope of the Current Federal Regulations 27

Medical and Scientific Organization Standards and Guidance 32

International Perspectives on the Use of 

Human Biological Materials in Research 33

Publication Guidelines 34

Medical Record Protection 35

Summary 38

Notes 39

References 40

Chapter 4: Ethical Perspectives on the Research 

Use of Human Biological Materials 41

Introduction 41

Promoting Benefits and Minimizing Harms and Wrongs 42

Potential Harms from Breaches of Privacy and Confidentiality 43

Group-Related Harms 46

Respecting Persons Who Are Sources of Biological Materials 47

Just Institutions, Policies, and Practices 49

Commodification of the Body and Its Parts:

Issues of Justice and Respect for Persons 50

Summary 51

Notes 52

References 52

Chapter 5: Conclusions and Recommendations 55

Introduction 55

Research Governed by the Federal Regulations:

Activities Beyond Clinical Care 56

Interpretation of the Existing Federal Policy for the 

Protection of Human Subjects 57

Expedited Review 60

Special Concerns About the Use of Unlinked Samples 60

Requirements for Investigators Using Coded or 

Identified Samples 62

Using Previously Obtained Informed Consent and Reconsent 62

Obtaining New Consent 63

Criteria for Waiver of Consent 66

Rendering Existing Identifiable Samples Unidentifiable

to Avoid the Need for Consent 70

Reporting Research Results to Subjects 71

Considerations of Potential Harms to Others 72

Publication and Dissemination of Research Results 73

Professional Education and Responsibilities 74

Use of Medical Records in Research on 

Human Biological Materials 74

Summary 75

Notes 75

References 76

Appendices

Appendix A: Beliefs About the Research Use of 

Human Biological Materials 77

Appendix B: Code of Federal Regulations, Title 45, Part 46 81

Appendix C: Comparison Table of Professional Statements 99

Appendix D: Guidance for Institutional Review Boards

Reviewing Research Using Human 

Biological Materials 105

Appendix E: Public Comments on NBAC’s 

February 22, 1999, Draft 111

Appendix F: Public and Expert Testimony 113

Appendix G: Commissioned Papers 115



y 

Patricia Backlar

Research Associate Professor of Bioethics

Department of Philosophy

Portland State University

Assistant Director

Center for Ethics in Health Care

Oregon Health Sciences University

Portland, Oregon

Arturo Brito, M.D.

Assistant Professor of Clinical Pediatrics

University of Miami School of Medicine

Miami, Florida

Alexander Morgan Capron, LL.B.

Henry W. Bruce Professor of Law

University Professor of Law and Medicine

Co-Director, Pacific Center for Health Policy and Ethics

University of Southern California 

Los Angeles, California

Eric J. Cassell, M.D., M.A.C.P.

Clinical Professor of Public Health

Cornell University Medical College

New York, New York

R. Alta Charo, J.D.

Professor of Law and Medical Ethics

Schools of Law and Medicine

The University of Wisconsin

Madison, Wisconsin

James F. Childress, Ph.D.

Kyle Professor of Religious Studies

Professor of Medical Education

Co-Director, Virginia Health Policy Center

Department of Religious Studies

The University of Virginia

Charlottesville, Virginia

David R. Cox, M.D., Ph.D.

Professor of Genetics and Pediatrics

Stanford University School of Medicine

Stanford, California

Rhetaugh Graves Dumas, Ph.D., R.N.

Vice Provost Emerita and Dean Emerita

The University of Michigan

Ann Arbor, Michigan

Laurie M. Flynn

Executive Director

National Alliance for the Mentally Ill

Arlington, Virginia

Carol W. Greider, Ph.D.

Professor of Molecular Biology and Genetics

Department of Molecular Biology and Genetics

The Johns Hopkins University School of Medicine

Baltimore, Maryland 

Steven H. Holtzman

Chief Business Officer

Millennium Pharmaceuticals Inc.

Cambridge, Massachusetts

Bette O. Kramer

Founding President

Richmond Bioethics Consortium

Richmond, Virginia

Bernard Lo, M.D.

Director

Program in Medical Ethics

The University of California, San Francisco

San Francisco, California

Lawrence H. Miike, M.D., J.D.

Kaneohe, Hawaii

Thomas H. Murray, Ph.D.

President

The Hastings Center

Garrison, New York

Diane Scott-Jones, Ph.D.

Professor

Department of Psychology

Temple University

Philadelphia, Pennsylvania

Harold T. Shapiro, Ph.D., Chair

President

Princeton University

Princeton, New Jersey

Executive Director

Eric M. Meslin, Ph.D.

Research Staff 

Kathi E. Hanna, M.S., Ph.D., Research Director

Emily C. Feinstein, Research Analyst*

Melissa Goldstein, J.D., Research Analyst*

E. Randolph Hull, Jr., Research Analyst*

Stu K. Kim, M.S., J.D., Intern

J. Kyle Kinner, J.D., M.P.A., Presidential Management Intern

Debra McCurry, M.S., Information Specialist

Daniel J. Powell, Intern

Andrew Siegel, Ph.D., J.D., Staff Philosopher

Sean A. Simon, Research Analyst*

Robert Tanner, J.D., Research Analyst

Consultants

Burness Communications, Communications Consultant

Sara Davidson, M.A., Editor

Elisa Eiseman, Ph.D., Science Consultant

Tamara Lee, Graphic Designer

Administrative Staff

Jody Crank, Secretary to the Executive Director

Evadne Hammett, Administrative Officer

Patricia Norris, Public Affairs Officer

Lisa Price, Secretary

Margaret C. Quinlan, Office Manager

Sherrie Senior, Secretary

*Until May 1999

Executive Summary

Introduction

Biomedical researchers have long studied human biological materials—such as cells collected in research

projects, biopsy specimens obtained for diagnostic purposes, and organs and tissues removed during surgery—

to increase knowledge about human diseases and to

develop better means of preventing, diagnosing, and treating these diseases. Today, new technologies and advances

in biology provide even more effective tools for using such

resources to improve medicine’s diagnostic and therapeutic potential. Yet, the very power of these new technologies

raises a number of important ethical issues.

Is it appropriate to use stored biological materials in

ways that originally were not contemplated either by the

people from whom the materials came or by those who

collected the materials? Does such use harm anyone’s

interest? Does it matter whether the material is identified,

or identifiable, as to its source, or is linked, or linkable,

to other medical or personal data regarding the source?

The extent to which a research sample can be linked with

the identity of its source is a significant determination in

assessing the risks and potential benefits that might occur

to human subjects. For this reason, the National Bioethics

Advisory Commission (NBAC) has developed a schema to

describe the character of the personal information associated with particular samples of human biological materials as they exist in clinical facilities or other repositories

and in the hands of researchers. (See Table 1.)

Ethical researchers must pursue their scientific aims

without compromising the rights and welfare of human

subjects. However, achieving such a balance is a particular challenge in rapidly advancing fields, such as human

genetics, in which the tantalizing potential for major

advances can make research activities seem especially

important and compelling. At the same time, the novelty

of many of these fields can mean that potential harms to

individuals who are the subjects of such research are poorly

understood and hence can be over- or underestimated.

This is particularly true of nonphysical harms, which can

occur in research conducted on previously collected

i

Table 1: Categories of Human Biological

Materials

Repository Collections

Unidentified specimens: For these specimens, identifiable 

personal information was not collected or, if collected, was 

not maintained and cannot be retrieved by the repository.

Identified specimens: These specimens are linked to 

personal information in such a way that the person from

whom the material was obtained could be identified by name,

patient number, or clear pedigree location (i.e., his or her 

relationship to a family member whose identity is known).

Research Samples

Unidentified samples: Sometimes termed “anonymous,”

these samples are supplied by repositories to investigators

from a collection of unidentified human biological specimens.

Unlinked samples: Sometimes termed “anonymized,” these

samples lack identifiers or codes that can link a particular

sample to an identified specimen or a particular human being. 

Coded samples: Sometimes termed “linked” or “identifiable,”

these samples are supplied by repositories to investigators

from identified specimens with a code rather than with personally identifying information, such as a name or Social

Security number. 

Identified samples: These samples are supplied by 

repositories from identified specimens with a personal 

identifier (such as a name or patient number) that would 

allow the researcher to link the biological information derived

from the research directly to the individual from whom the

material was obtained.
ii

human biological materials when investigators do not

directly interact with the persons whose tissues, cells, or

DNA they are studying.

Increasing concerns about the use of genetic and

other medical information have fueled the current debate

about medical privacy and discrimination. Because medical research can reveal clinically relevant information

about individuals, scientists must ensure that those who

participate in research are adequately protected from

unwarranted harms resulting from the inadvertent release

of such information. Although protection of human subjects in research is of primary concern in the U.S. biomedical research system, research that uses biological

materials—materials that often are distanced in time and

space from the persons from whom they were obtained—

raises unique challenges regarding the appropriate

protection of research subjects.

Research sponsors, investigators, and Institutional

Review Boards (IRBs) thus must exercise great care and

sensitivity in applying professional guidelines and government regulations to protect subjects whose biological

materials are used in research. Properly interpreted and

modestly modified, present federal regulations can protect subjects’ rights and interests and at the same time

permit well-designed research to go forward using

materials already in storage as well as those newly collected by investigators and others. Fundamentally, the

interests of subjects and those of researchers are not in

conflict. Rather, appropriate protection of subjects provides

the reassurance needed if individuals are to continue to

make their tissue, blood, or DNA available for research.

Indeed, public confidence in the ethics and integrity of

the research process translates into popular support for

research in general.

Policies and guidelines governing human subjects

research should permit investigators—under certain circumstances and with the informed, voluntary consent of

sample sources—to have access to identifying information sufficient to enable them to gather necessary data

regarding the subjects. Provided that adequate protections exist (which usually, but not always, include

informed consent), such information gathering could

include ongoing collection of medical records data and

even requests for individuals to undergo tests to provide

additional research information. In some cases, it even

will be acceptable for investigators to convey information

about research results to the persons whose samples have

been studied. Where identifying information exists, however, a well-developed system of protections must be

implemented to ensure that risks are minimized and that

the interests of sample sources are protected.

Finally, any system of regulation is most likely to

achieve its goals if it is as clear and as simple as possible.

This is especially true in the research use of human

biological materials, because the federal protections for

research subjects require investigators to outline the

involvement of human subjects in their studies and to

undergo institutional review of their protocols. Thus, one

reason to modify regulations is to clarify which protocols

are subject to what sorts of prior review; likewise, illustrations and explanations may be useful in clarifying how

the regulations apply to novel or complicated fields that

use human biological materials.

How well does the existing Federal Policy for the

Protection of Human Subjects (the so-called Common

Rule, codified at 45 CFR Part 46) meet these objectives?

Specifically, does it provide clear direction to research

sponsors, investigators, IRBs, and others regarding the

conduct of research using human biological materials in

an ethical manner? NBAC finds that it does not adequately do so. In some cases, present regulatory language

provides ambiguous guidance for research using human

biological materials. For example, confusion about the

intended meaning of terms such as “human subject,”

“publicly available,” and “minimal risk” has stymied

investigators and IRB members. Beyond these ambiguities, certain parts of current regulations are inadequate to

ensure the ethical use of human biological materials in

research and require some modification.

In this report, NBAC offers a series of recommendations that have been developed to address perceived

difficulties in the interpretation of federal regulations and

in the language of position statements of some professional organizations; ensure that research involving

human biological materials will continue to benefit from

appropriate oversight and IRB review, the additional burdens of which are kept to a minimum; provide investigators and IRBs with clear guidance regarding the use of

human biological materials in research, particularly with

regard to informed consent; provide a coherent public

policy for research in this area that will endure for many

years and be responsive to new developments in science;
iii

and provide the public (including potential research subjects) with increased confidence in research that makes

use of human biological materials. In particular, this

report provides interpretations of several important concepts and terms in the Common Rule and recommends

ways both to strengthen and clarify the regulations and to

make their implementation more consistent.

Recommendations

Interpretation of the Existing 

Federal Regulations

NBAC offers the following recommendations to improve

the interpretation and implementation of the existing

federal regulations as they apply to research using human

biological materials.

Recommendation 1:

Federal regulations governing human subjects

research (45 CFR 46) that apply to research

involving human biological materials should be

interpreted by the Office for Protection from

Research Risks (OPRR), other federal agencies

that are signatories to the Common Rule, IRBs,

investigators, and others, in the following specific

ways:

a) Research conducted with unidentified samples

is not human subjects research and is not regulated by the Common Rule.

b) Research conducted with unlinked samples is

research on human subjects and is regulated by

the Common Rule, but is eligible for exemption from IRB review pursuant to 45 CFR

46.101(b)(4).

c) Research conducted with coded or identified

samples is research on human subjects and regulated by the Common Rule. It is not eligible

for exemption unless the specimens or the

samples are publicly available as defined by 45

CFR 46.101 (b)(4). Few collections of human

biological materials are publicly available,

although many are available to qualified

researchers at reasonable cost. Therefore,

OPRR should make clear in its guidance that in

most cases this exemption does not apply to

research using human biological materials.

The current federal regulations appear to make eligible

for expedited review research on materials that will be

collected for clinical purposes or those that will be collected in noninvasive or minimally invasive ways for

research purposes. NBAC finds that there is no need to

distinguish between collections originally created for

clinical purposes and those created for research purposes. In both cases, research on the collected materials

should be eligible for expedited review if the research

presents no more than a minimal risk to the study subjects. (See the discussion of minimal risk below.)

Recommendation 2:

OPRR should revise its guidance to make clear

that all minimal-risk research involving human

biological materials—regardless of how they were

collected—should be eligible for expedited IRB

review. 

Special Concerns About the Use of 

Unlinked Samples

Given the importance of society’s interest in treating

disease and developing new therapies, a policy that

severely restricts research access to unidentified and

unlinked samples would severely hamper research and

could waste a valuable research resource. As noted in

Recommendation 1, research using unlinked samples

may be exempt from review. However, if coded or identified samples are rendered unlinked by the investigator,

special precautions are in order.

Recommendation 3:

When an investigator proposes to create unlinked

samples from coded or identified materials

already under his or her control, an IRB (or other

designated officials at the investigator’s institution) may exempt the research from IRB review if

it determines that

a) the process used to unlink the samples will be

effective, and

b) the unlinking of the samples will not unnecessarily reduce the value of the research.

Requirements for Investigators Using Coded or

Identified Samples

Repositories and IRBs share responsibility with

investigators to ensure that research is designed and
iv

conducted in a manner that appropriately protects human

subjects from unwarranted harms.

Recommendation 4:

Before releasing coded and/or identified samples

from its collection, a repository should require

that the investigator requesting the samples either

provide documentation from the investigator’s IRB

that the research will be conducted in compliance

with applicable federal regulations or explain in

writing why the research is not subject to those

regulations. 

Recommendation 5:

When reviewing and approving a protocol for

research on human biological materials, IRBs

should require the investigator to set forth

a) a thorough justification of the research design,

including a description of procedures used to

minimize risk to subjects,

b) a full description of the process by which samples will be obtained,

c) any plans to obtain access to the medical

records of the subjects, and

d) a full description of the mechanisms that will

be used to maximize the protection against

inadvertent release of confidential information.

When an investigator obtains access to a patient’s

medical records, either to identify sample sources or to

gather additional medical information, human subjects

research is being conducted. IRBs should adopt policies

to govern such research, consistent with existing OPRR

guidance related to medical records research.

Obtaining Informed Consent

Research using coded or identified samples requires

the consent of the source, unless the criteria for a consent

waiver have been satisfied. Unfortunately, the consent

obtained at the time the specimen was obtained may not

always be adequate to satisfy this requirement. When

research is contemplated using existing samples, the

expressed wishes of the individuals who provided the

materials must be respected. Where informed consent

documents exist, they may indicate whether individuals

wanted their sample to be used in future research and in

some instances may specify the type of research.

When human biological materials are collected,

whether in a research or clinical setting, it is appropriate

to ask subjects for their consent to future use of their

samples, even in cases where such uses are at the time

unknown. In this latter case, however, particular considerations are needed to determine whether to honor

prospective wishes.

Whether obtaining consent to the research use of

human biological materials in a research or clinical setting, and whether the consent is new or renewed, efforts

should be made to be as explicit as possible about the

uses to which the material might be put and whether it is

possible that the research might be conducted in such a

way that the individual could be identified. Obviously,

different conditions will exist for different research protocols, in different settings, and among individuals.

NBAC notes that the current debate about the appropriate use of millions of stored specimens endures because

of the uncertain nature of past consents. Investigators

and others who collected and stored human biological

materials now have the opportunity to correct past

inadequacies by obtaining more specific and clearly

understood informed consent.

Recommendation 6:

When informed consent to the research use of

human biological materials is required, it should

be obtained separately from informed consent to

clinical procedures. 

Recommendation 7:

The person who obtains informed consent in clinical settings should make clear to potential subjects that their refusal to consent to the research

use of biological materials will in no way affect the

quality of their clinical care.

Recommendation 8:

When an investigator is conducting research on

coded or identified samples obtained prior to the

implementation of NBAC’s recommendations, general releases for research given in conjunction

with a clinical or surgical procedure must not be

presumed to cover all types of research over an

indefinite period of time. Investigators and IRBs

should review existing consent documents to

determine whether the subjects anticipated and

agreed to participate in the type of research proposed. If the existing documents are inadequate
v

and consent cannot be waived, the investigator

must obtain informed consent from the subjects

for the current research or in appropriate circumstances have the identifiers stripped so that samples are unlinked.

Recommendation 9:

To facilitate collection, storage, and appropriate

use of human biological materials in the future,

consent forms should be developed to provide

potential subjects with a sufficient number of

options to help them understand clearly the

nature of the decision they are about to make.

Such options might include, for example:

a) refusing use of their biological materials in

research,

b) permitting only unidentified or unlinked use of

their biological materials in research,

c) permitting coded or identified use of their biological materials for one particular study only,

with no further contact permitted to ask for

permission to do further studies,

d) permitting coded or identified use of their 

biological materials for one particular study

only, with further contact permitted to ask for

permission to do further studies, 

e) permitting coded or identified use of their 

biological materials for any study relating to

the condition for which the sample was originally collected, with further contact allowed to

seek permission for other types of studies, or

f) permitting coded use of their biological materials for any kind of future study.*

Criteria for Waiver of Consent

When an investigator proposes to conduct research

with coded or identified samples, it is considered

research with human subjects. Ordinarily the potential

research subject is asked whether he or she agrees to participate. Seeking this consent demonstrates respect for

the person’s right to choose whether to cooperate with

the scientific enterprise, and it permits individuals to

protect themselves against unwanted or risky invasions

of privacy. But informed consent is merely one aspect of

human subjects protection. It is an adjunct to—rather

than a substitute for—IRB review to determine if the

risks of a study are minimized and acceptable in relation

to its benefits.

When a study is of minimal risk, informed consent is

no longer needed by a subject as a form of self-protection

against research harms. However, it is still appropriate to

seek consent in order to show respect for the subject,

unless it is impracticable to locate him or her in order to

obtain it. Thus, when important research poses little or

no risk to subjects whose consent would be difficult or

impossible to obtain, it is appropriate to waive the

consent requirement.

Recommendation 10:

IRBs should operate on the presumption that

research on coded samples is of minimal risk to

the human subject if 

a) the study adequately protects the confidentiality of personally identifiable information

obtained in the course of research, 

b) the study does not involve the inappropriate

release of information to third parties, and 

c) the study design incorporates an appropriate

plan for whether and how to reveal findings to

the sources or their physicians should the findings merit such disclosure.

Failure to obtain informed consent may adversely

affect the rights and welfare of subjects in two basic ways.

First, the subject may be improperly denied the opportunity to choose whether to assume the risks that the

research presents, and second, the subject may be

harmed or wronged as a result of his or her involvement

in research to which he or she has not consented.

Further, when state or federal law, or customary

practice, gives subjects a right to refuse to have their biological materials used in research, then a consent waiver

would affect their rights adversely. Medical records privacy statutes currently in place or under consideration

generally allow for unconsented research use and could

be interpreted to suggest a similar standard for research

using human biological materials. But as new statutes are

enacted, it is possible that subjects will be given explicit

rights to limit access to their biological materials.

Recommendation 11:

In determining whether a waiver of consent would

adversely affect subjects’ rights and welfare, IRBs

should be certain to consider

* Commissioners Capron, Miike, and Shapiro wrote statements

regarding their concerns about various aspects of this recommendation. (See page 65 of the full report.)
vi

a) whether the waiver would violate any state or

federal statute or customary practice regarding

entitlement to privacy or confidentiality,

b) whether the study will examine traits commonly considered to have political, cultural, or

economic significance to the study subjects,

and 

c) whether the study’s results might adversely

affect the welfare of the subject’s community.

Even when research poses no more than minimal risk

and a consent waiver would not affect the rights and welfare of subjects, respect for subjects requires that their

consent be sought. However, on some occasions, demonstrating this respect through consent requirements could

completely halt important research. An investigator who

requests a waiver of the informed consent requirement

for research use of human biological materials under the

current federal regulations must provide to the IRB

evidence that it is not practicable to obtain consent.

Unfortunately, neither the regulations nor OPRR offers

any guidance on what defines practicability. 

Recommendation 12:

If research using existing coded or identified

human biological materials is determined to present minimal risk, IRBs may presume that it

would be impracticable to meet the consent

requirement (45 CFR 46.116(d)(3)). This interpretation of the regulations applies only to the use

of human biological materials collected before the

adoption of the recommendations contained in

this report (specifically Recommendations 6

through 9 regarding informed consent). Materials

collected after that point must be obtained according to the recommended informed consent process

and, therefore, IRBs should apply their usual standards for the practicability requirement.

NBAC recognizes that if its recommendation that

coded samples be treated as though they are identifiable

is adopted, there may be an increase in the number of

research protocols that will require IRB review. If, however, such protocols are then determined by an IRB to

present minimal risk to a subject’s rights and welfare, the

requirement for consent may be waived if the practicability requirement is revised for this category of research.

However, it must be noted that by dropping the requirement that consent must be obtained if practicable, NBAC

does so with the expectation that the process and content

of informed consent for the collection of new specimens

will be explicit regarding the intentions of the subjects

and the research use of their materials. (See Recommendations 6 through 9 concerning informed consent.)

According to current regulations, the fourth condition for the waiver of consent stipulates that “whenever

appropriate, the subjects will be provided with additional

pertinent information after participation” (45 CFR

46.116(d)(4)). Thus, according to the regulations, an

IRB, while waiving consent (by finding and documenting

the first three required conditions), could require that

subjects be informed that they were subjects of research

and that they be provided details of the study—a 

so-called debriefing requirement. In general, NBAC 

concludes that this fourth criterion for waiver of consent

is not relevant to research using human biological materials and, in fact, might be harmful if it forced investigators to recontact individuals who might not have been

aware that their materials were being used in research.

Recommendation 13:

OPRR should make clear to investigators and

IRBs that the fourth criterion for waiver, that

“whenever appropriate, the subjects will be provided with additional pertinent information after

participation” (45CFR 46.116(d)(4)), usually does

not apply to research using human biological

materials.

Reporting Research Results to Subjects

Experts disagree about whether findings from

research should be communicated to subjects.

However, most do believe that such findings should not

be conveyed to subjects unless they are confirmed and

reliable and constitute clinically significant or scientifically relevant information.

Recommendation 14:

IRBs should develop general guidelines for the

disclosure of the results of research to subjects

and require investigators to address these issues

explicitly in their research plans. In general, these

guidelines should reflect the presumption that the

disclosure of research results to subjects represents an exceptional circumstance. Such disclosure should occur only when all of the following

apply:
vii

a) the findings are scientifically valid and confirmed,

b) the findings have significant implications for

the subject’s health concerns, and

c) a course of action to ameliorate or treat these

concerns is readily available.

Recommendation 15:

The investigator in his or her research protocol

should describe anticipated research findings and

circumstances that might lead to a decision to disclose the findings to a subject, as well as a plan for

how to manage such a disclosure.

Recommendation 16:

When research results are disclosed to a subject,

appropriate medical advice or referral should be

provided.

Considerations of Potential Harms to Others

The federal regulations governing the protection of

research subjects extend only to individuals who can be

identified as the sources of the biological samples. The

exclusive focus of the regulations on the individual

research subject is arbitrary from an ethical standpoint,

because persons other than the subject can benefit or be

harmed as a consequence of the research.

Recommendation 17:

Research using stored human biological materials,

even when not potentially harmful to individuals

from whom the samples are taken, may be potentially harmful to groups associated with the individual. To the extent such potential harms can be

anticipated, investigators should to the extent

possible plan their research so as to minimize

such harm and should consult, when appropriate,

representatives of the relevant groups regarding

study design. In addition, when research on

unlinked samples that poses a significant risk of

group harms is otherwise eligible for exemption

from IRB review, the exemption should not be

granted if IRB review might help the investigator

to design the study in such a way as to avoid those

harms.

Recommendation 18:

If it is anticipated that a specific research protocol

poses a risk to a specific group, this risk should be

disclosed during any required informed consent

process.

Publication and Dissemination 

of Research Results

Publishing research results with identifiable information in scientific or medical journals and elsewhere may

pose a risk to the privacy and confidentiality of research

subjects. Public disclosure of such information through

written descriptions or pedigrees may cause subjects to

experience adverse psychosocial effects. In addition,

without the informed consent of the individual, such disclosure infringes on the rights of the subject or patient.

Because of the familial nature of information in pedigrees, their publication poses particularly difficult questions regarding consent. Investigators and journal editors

should be aware that the ways in which research results

are publicized or disseminated could affect the privacy of

human subjects. NBAC believes that the source of funding, i.e., public or private, should not be an important

consideration in determining the ethical acceptability of

the research.

Recommendation 19:

Investigators’ plans for disseminating results of

research on human biological materials should

include, when appropriate, provisions to minimize

the potential harms to individuals or associated

groups. 

Recommendation 20:

Journals should adopt the policy that the published results of research studies involving human

subjects must specify whether the research was

conducted in compliance with the requirements of

the Common Rule. This policy should extend to

all human subjects research, including studies

that are privately funded or are otherwise exempt

from these requirements.

Professional Education and Responsibilities

Public and professional education plays an essential

role in developing and implementing effective public policy regarding use of human biological materials for

research. By education, NBAC is referring not simply to

the provision of information with the aim of adding to

the net store of knowledge by any one person or group;

rather, education refers to the ongoing effort to inform,

challenge, and engage. Widespread and continuing

deliberation on the subject of this report must occur to
viii

inform and educate the public about developments in 

the field of genetics and other areas in the biomedical 

sciences, especially when they affect important cultural

practices, values, and beliefs.

Recommendation 21:

The National Institutes of Health, professional

societies, and health care organizations should

continue and expand their efforts to train investigators about the ethical issues and regulations

regarding research on human biological materials

and to develop exemplary practices for resolving

such issues. 

Recommendation 22:

Compliance with the recommendations set forth

in this report will require additional resources. All

research sponsors (government, private sector

enterprises, and academic institutions) should

work together to make these resources available.

Use of Medical Records in Research on Human

Biological Materials

In recent years, attention increasingly has been paid

by policymakers to the need to protect the health information of the individual. Extensive efforts at the state and

federal levels to enact such protections have resulted in

the setting of a variety of limitations on access to patient

medical records. NBAC notes that debates about medical

privacy are relevant to researchers using human biological materials in two ways. First, these researchers often

need access to patient medical records, either to identify

research sample sources or to gather accompanying clinical information. Such activities constitute human subjects research and should be treated accordingly. Second,

the development of statutes and regulations to protect

patient medical records could have the unintended consequence of creating a dual system of protections, one for

the medical record and one for human biological materials. Moreover, restrictions on access to the medical record

could impede legitimate and appropriate access on the

part of investigators whose protocols have undergone

proper review.

Recommendation 23:

Because many of the same issues arise in the context of research on both medical records and

human biological materials, when drafting medical records privacy laws, state and federal legislators should seek to harmonize rules governing 

both types of research. Such legislation, while

seeking to protect patient confidentiality and

autonomy, should also ensure that appropriate access for legitimate research purposes is

maintained.

Summary

To advance human health, it is critical that human biological materials continue to be available to the biomedical research community. Increasingly, it will be essential

for investigators to collect human biological materials

from individuals who are willing to share important clinical information about themselves. In addition, it is crucial that the more than 282 million specimens already in

storage remain accessible under appropriate conditions

and with appropriate protections for the individuals who

supplied this material.

The growing availability to third parties of genetic and

other medical information about individuals has fueled

the current debate about medical privacy and discrimination, and NBAC is sensitive to the possibility that the

use of information obtained from human biological samples can lead to harms as well as benefits. These concerns

require that those who agree to provide their DNA, cells,

tissues, or organs for research purposes not be placed at

risk. Measures to provide appropriate protections for

individual privacy and for the confidentiality of clinical

and research data are important if significant research is

to continue. The recommendations provided in this

report are intended to promote the goals of improving

health through biomedical research while protecting the

rights and welfare of those individuals who contribute to

human knowledge through the gift of their biological

materials.
Overview and Introduction

Chapter One 1

The Use of Human Biological 

Materials in Research

Biomedical researchers have long studied humanbiological materials—such as cells collected in

research projects, biopsy specimens obtained for diagnostic purposes, and organs and tissues removed during

surgery—to increase knowledge about human diseases

and to develop better means of preventing, diagnosing,

and treating these diseases. Today, new technologies and

advances in biology provide even more effective tools for

using such resources to improve medicine’s diagnostic and

therapeutic potential. Human biological materials also

constitute an invaluable source of information for public

health planning and programming, through disease surveillance and studies of disease incidence and prevalence.

Yet, the very power of these new technologies raises a

number of important ethical issues. Is it appropriate to

use stored biological materials in ways that originally

were not contemplated either by the people from whom

the materials were collected or by those who collected

the materials? Does such use harm anyone’s interest?

Does it matter whether the material is identified, or identifiable, as to its source, or is linked, or linkable, to other

medical or personal data regarding the source?

Based on the many successes of past research that has

used human biological materials, it seems highly likely

that future studies also will benefit millions of people.

How should this prospect be weighed against the chance

that the studies could harm or wrong the individuals

whose material is being studied, their families, or other

groups of which they are members? Under what circumstances should researchers seek informed consent from

people whose biological materials (either existing or to be

collected) they propose to study? How should consent

requirements be adjusted if the sources of the existing

biological materials would be difficult or impossible to

locate, or if they have died?

The Research Value of Human

Biological Materials

The medical and scientific practice of storing human biological materials is more than 100 years old. Human biological collections—which include DNA banks, tissue

banks, and repositories—vary considerably, ranging from

large collections formally designated as repositories to

blood or tissue informally stored in a researcher’s laboratory freezer. Large collections include archived pathology

materials and stored cards containing blood spots from

newborn screening tests (Guthrie cards).1 Tissue specimens are stored at military facilities, forensic DNA banks,

government laboratories, diagnostic pathology and cytology laboratories, university- and hospital-based research

laboratories, commercial enterprises, and nonprofit

organizations.2 Archives of human biological materials

range in size from fewer than 200 specimens to more

than 92 million. Conservatively estimated, at least 282

million specimens (from more than 176 million individual cases) are stored in the United States, and the collections are growing at a rate of over 20 million cases per

year. (See Chapter 2.)

In this report, the term “human biological materials”

is defined to encompass the full range of specimens, from

subcellular structures such as DNA, to cells, tissues (e.g.,

blood, bone, muscle, connective tissue, and skin), organs

(e.g., liver, bladder, heart, kidney, and placenta), gametes

(i.e., sperm and ova), embryos, fetal tissues, and waste

1
2

(e.g., hair, nail clippings, urine, feces, and sweat, which

often contains shed skin cells). At the present time,

research using human embryos is not eligible for federal

funding, and, therefore, current federal regulations governing research with human subjects do not apply. The

use of human embryos in research does, however, raise

special ethical concerns, which are addressed in part in 

a separate National Bioethics Advisory Commission

(NBAC) report.3 Should the congressional ban on embryo

research be lifted or partially rescinded, however, many 

of the issues addressed in this report would be relevant to embryo research, although additional ethical 

considerations would apply.

The most common sources of human biological materials are diagnostic or therapeutic interventions in which

diseased tissue is removed or tissue or other material is

obtained to determine the nature and extent of a disease.

Even after the diagnosis or treatment is complete, a portion of the specimen routinely is retained for future clinical, research, or legal purposes. Specimens also are

obtained during autopsies. In addition, volunteers

donate organs, blood, or other tissue for transplantation

or research, and some donate their bodies after death for

transplantation of organs or anatomical studies. Each

specimen may be stored in multiple forms, including

slides, paraffin blocks, formalin-fixed, tissue culture, or

extracted DNA. Repositories provide qualified commercial and noncommercial laboratories with access to specimens for both clinical and research purposes. 

In addition to its future clinical use, a specimen of

human biological material can be used to study basic

biology or disease. (See Chapter 2.) It can be examined

to determine its normal and abnormal attributes, or it 

can be manipulated to develop a research tool or a potentially marketable product. Just as a clinician chooses biological materials appropriate to the clinical situation at

hand, a researcher’s choice of such materials depends on

the goals of the research project. The selected tissue can

be used only once, or it can be used to generate a renewable source of material, such as by developing a cell line,

a cloned gene, or a gene marker. In addition, proteins can

be extracted, or DNA isolated, from particular specimens.

There is substantial research value both in unidentified material (i.e., material that is not linked to an

individual) and in material linked to an identifiable person

and his or her continuing medical record. In the former,

the value to the researcher of the human biological material is in the tissue itself and often in the associated clinical information about that individual, without the need to

know the identity of the person from whom it came. For

example, investigators may be interested in identifying a

biological marker in a specific type of tissue, such as cells

from individuals with Alzheimer’s disease or specific

tumors from a cancer patient. In such cases, beyond

knowing the diagnosis of the individual from whom the

specimen was obtained, researchers may not require

more detailed medical records, either past or ongoing.

Sometimes, however, it is necessary to identify the

source of the research sample, because the research value

of the material depends upon linking findings regarding

the biology of the sample with updated information

from medical or other records pertaining to its source.

For example, in a longitudinal study to determine the

validity of a genetic marker as a predictor of certain diseases, the researchers would need to be able to link each

sample with the medical record of its source in order to

ascertain whether those diseases developed. In one case,

a recent study of late-onset Alzheimer’s disease linked

the presence of the disease with the apolipoprotein-E

allele by studying the stored tissues of 58 families with a

history of Alzheimer’s disease and then examining

autopsy records for evidence of the disease in those individuals whose tissue revealed the presence of that allele

(Payami et al. 1996).

Already, research using biological materials has produced tests to diagnose a predisposition to conditions such

as cancer and heart disease and to a variety of genetic 

diseases that affect millions of individuals. In some cases,

prevention or treatment is available once a diagnosis is

made; in those cases, knowing the identity of the specimen source would permit communication of relevant

medical information to the source that may be of importance to his or her health. In other cases, when medical

interventions are unavailable, having one’s specimen

linked with a disease predictor is likely to be of less clinical value to the individual and might even be troubling.

Human biological materials also may be used for

quality control in health care delivery, particularly in

diagnostic and pathology laboratories. In addition, these
3

materials are used to identify an individual, such as in

paternity testing and in cases of abduction or soldiers

missing in action, as well as in other forensic matters for

which biological evidence is available for comparison.

The advent of technologies that can extract a wide array

of information from these materials generally has

increased the potential uses—in research and otherwise—of human biological materials that are unrelated to

individual patient care.

By using the power of new DNA technologies and

other molecular techniques, scientists potentially can

turn to millions of stored human biological materials as

sources of valuable scientific, medical, anthropological,

and sociological information. Indeed, these technologies

are so powerful—even revolutionary—that they also

hold the ability to uncover knowledge about individuals

no longer alive. Three interesting cases, reported in

recent years, serve as examples:

■ In 1997, scientists at the University of Oxford

announced that they had compared DNA extracted

from the molar cavity of a 9,000-year-old skeleton

(known as Cheddar Man) to DNA collected from 

20 individuals currently residing in the village of

Cheddar; this resulted in the establishment of a

genetic tie between the skeleton and a schoolteacher

who lived just half a mile from the cave where the

bones were found (DiChristina 1997).

■ Scientists used enzyme-linked assays to analyze tissues more than 5,000 years old and to track the historic spread of diseases such as malaria and

schistosomiasis, obtaining knowledge that can

enlighten current efforts to control infectious disease.4

■ In early 1999, a U.S. pathologist and a group of

European molecular biologists announced that they

had found DNA sequences in the Y chromosome of

the descendants of Thomas Jefferson that matched

DNA from the descendants of Sally Hemings, a slave

at Monticello. The data establish only that Thomas

Jefferson was the most likely of several candidates

who might be the father of Eston Hemings, Hemings’

fifth child, but also have raised a storm of controversy

(Foster et al. 1998).

The demonstrated use of these technical capabilities

suggests that human tissue and DNA specimens that have

been sitting in storage banks for years—even a century—

could be plumbed for new information to reveal something not only about the individual from whom the tissue

was obtained, but possibly about entire groups of people

who share genes, environmental exposures, and ethnic or

even geographic characteristics. Clearly, the same is true

for materials that may be collected in the future. DNA,

whether already stored or yet to be collected, can be used

to study genetic variation among people, to establish

relationships between genes and characteristics (such as

single gene disorders), or, more generally, to conduct

basic studies of the cause and progression of disease, all

with the long-term goal of improving human health. One

of the many initiatives that is providing information that

may help us achieve this goal is the federally funded

Human Genome Project, which expects to map and

sequence the entire human genome by the year 2003

(Collins et al. 1998).

Is Genetic Information Different from

Other Medical Information?

In the past few decades, concern about the misuse of

genetic information often has spurred debate about the

misapplication of medical information in general. Public

discourse and concern about the potential availability of

personal genetic information has been intense in recent

years for a number of reasons, including 1) the lack of

any protection from the misuse of this information outside the research context (e.g., employment discrimination), 2) the role of genetic information in early and often

contentious public policy debates about reproductive

medicine and family planning, 3) a difficult history of

and continuing concerns with relation to eugenics and

genetic discrimination, and 4) the rapid pace of the

Human Genome Project and other developments in

human biology.

Genetic information is one form of biological or medical information. Like certain other types of medical

information, genetic analyses can reveal sensitive information about an individual. Some aspects of genetic

information, however, seem to many to distinguish it

from other types of medical information. For example,

genetic information concerning an individual sometimes

can reveal similar information regarding a person’s

relatives or entire groups of people (ASHG 1998). In
4

addition, the detailed information contained in a person’s

genes is largely unknown to that person. Moreover,

because DNA is stable, stored specimens may become the

source of increasing amounts of information as new

genes are mapped (Annas, Glantz, and Roche 1995). In

the words of Francis Collins, Director of the National

Human Genome Research Institute, “We are hurtling

towards a time where individual susceptibilities will be

determinable on the basis of technologies that allow your

DNA sequence to be sampled and statistical predictions

to be made about your future risk of illness.”5

Some claim that the major distinguishing characteristics of genetic information are its predictive capabilities

and its implications for individuals other than the person

from whom the information was derived (IOM 1994).

Gostin, for example, has suggested that “genomic” data

are qualitatively different from other health data

because they are inherently linked to one person; in

other words, one’s DNA is unique except in the case of

identical twins (1995). In addition, genetic information

does not change over time. Although other pieces of

medical information about an individual might change

over the course of his or her lifetime, except in the case

of mutations, DNA does not.

Others argue, however, that genetic information is not

inherently distinct from other types of medical information (Murray 1997). Other types of medical information

may be strongly correlated with particular diseases.

Moreover, infection with a virus has implications for

people other than the person actually infected. Likewise,

the health status of a person living in a toxic environment, such as near the Chernobyl nuclear accident site,

has implications for others living in that same environment. Clearly, many of the concerns that pertain to the

misuse of personal genetic information apply equally to

certain other types of personal medical information.

Increasing Discussion About the

Appropriate Research Use of Human

Biological Materials

Increasing concerns about the use of medical information

have fueled general debate about medical privacy and

discrimination. Because medical research can reveal clinically relevant information about individuals, scientists

must ensure that those who participate in research are

protected adequately from unnecessary harms resulting

from the inadvertent release of such information.

Although protection of human subjects in research is of

primary concern in the U.S. biomedical research system,

research that uses biological materials—which are often

distanced in time and space from the persons from whom

they were obtained—raises unique challenges regarding

the appropriate protection of research subjects. Although

medical research generally is considered a public good

and is supported vigorously by the American public, the

power of technology to find an extraordinary amount of

detailed information in a single cell raises the specter that

information about individuals will be discovered and

used without their consent and possibly to their detriment. Although this type of information also might be

obtained through a variety of other means, DNA analysis

currently is the most powerful means and increasingly is

the method of choice.

In recent years, these varied concerns have resulted in

consumer, scientific, and professional groups beginning

to address the issues surrounding the collection and use

of human biological materials (AAMC 1997; ACMG

1995; ASHG 1988; Clayton et al. 1995; Grizzle et al.

1997; HUGO 1998). In addition, media focus on highly

contentious cases involving biological samples—such as

the storage and research use of stored neonatal blood

spots for anonymous studies of HIV prevalence in a given

population and the military’s establishment of a DNA

bank—has made the issue of research use of human

biological materials a matter of increasing public concern.

In the course of its deliberations, NBAC has identified

several trends that contribute to the need for a comprehensive public policy concerning the use of these biological materials for research purposes: 

■ increasing public perceptions that personal genetic

and other medical information could be used to discriminate against individuals in employment or by

denying them access to benefits such as health or life

insurance, or could be stigmatizing in some way,

■ growing public concern about privacy of medical

records,

■ the emergence of new considerations regarding both

the nature of consent to participate in research protocols and the disclosure of results, and
5

■ disagreement among scientific and medical groups

regarding conditions that need to be satisfied to

ensure that appropriate ethical standards are incorporated into all research protocols using human biological materials, primarily as related to the requirements

for review and to the nature of the required consent

process.

One particular area of concern centers upon the question of whether the information that may be obtained

from the research use of human biological materials

places those who are the sources of the samples at unacceptable risk. For example, such data might reveal information about an individual’s disease susceptibility (e.g.,

carrying a gene that is associated with an increased risk

of colon cancer or breast cancer). When an intervention

exists that can be pursued to counteract the increased

health risk—such as regular mammograms, dietary modification, or drug treatment—some might judge the

information worth receiving and worth the psychological

and financial risks associated with it. If, however, the

analysis reveals information about a condition for which

no intervention is currently available (e.g., susceptibility

to Huntington’s disease or Alzheimer’s disease), many

individuals might perceive the risks of uncovering such

information as outweighing the benefits. In any case,

concern may arise when an individual did not consent in

advance or show any interest in receiving such information. Some would argue that learning about an adverse

health status should be intentional, since it can provoke

anxiety and disrupt families, particularly if nothing can

be done about it and the finding has potential implications for other family members (Wilcke 1998).

Potential for Discrimination and Stigmatization

There is growing recognition that human biological

materials can be analyzed to ascertain significant amounts

of genetic and other medical information about the person from whom a specimen was obtained. In particular,

there is increasing concern among some policymakers

and patient groups that this information could be used to

discriminate against individuals in insurance and

employment or could be stigmatizing for individuals and

families (ASHG 1995; Hudson et al. 1995; NCHGR 1993;

Rothenberg et al. 1997). In January 1998, the White

House released a report entitled Genetic Information and

the Workplace6 that was prepared by the U.S. Departments

of Labor and Health and Human Services (DHHS) and

the Equal Employment Opportunity Commission. This

report predicted that by the year 2000, 15 percent of

employers plan to check the genetic status of prospective

employees and cited a 1995 Harris poll that revealed that

more than 85 percent of Americans are concerned that

insurers and employers may have access to their genetic

information (Taylor 1995).

Concern about insurers and employers having access

to genetic information has a basis in fact. In the 1970s,

several insurance companies and employers discriminated

against sickle cell carriers, even though their carrier

status did not and would not affect their health

(Holtzman 1989). In the absence of universal access to

health care or laws that prevent discrimination on the

basis of health status, there is a history of concern that

medical information may be used to deny individuals

insurance or employment (Gostin 1991; NCHGR 1993;

U.S. Congress OTA 1992). In addition to these possible

financial harms, research findings about one’s future

medical status can, in some cases, inflict psychological or

social harms (Davison, Macintyre, and Smith 1994). It

should be noted, however, that to date there is little

empirical evidence documenting extensive employment

or insurance discrimination based on genetic status

(Wertz 1997).

Concerns About Privacy of Medical Records

Health care systems increasingly rely on information

technology such as electronic records to manage and

facilitate the flow of sensitive and clinically relevant

health information. This new reliance has had positive

effects in clinical practice, but these trends also magnify

concerns about privacy of certain genetic and other medical information. Recent commentary about privacy of

medical records and attempts to protect privacy through

legislation are evidence of the growing public concern

about these issues. Currently, Congress and DHHS have

been discussing legislative and regulatory approaches to

protect patient privacy (U.S. Congress GAO 1999).

An ongoing concern in medical care and in the protection of research subjects is the potential invasion of

privacy or the compromise of confidentiality. Measures to
6

provide appropriate protections, both of individual privacy and of the confidentiality of clinical and research

data, are important if research using this information is to

enjoy broad support. When research samples are identifiable (i.e., linked or linkable to the person who provided

them), specific steps must be taken to ensure protections

in the collection, storage, and use of the data. However,

computerized medical records and databases raise concerns about who has access to data (i.e., the security of

these databases) and about whether or not these data are

linked to individual patient records. It is widely believed

that current confidentiality practices are insufficient to

safeguard medical information. In addition, different

cultural and religious groups may have differing definitions of privacy or confidentiality (Medical Research

Council 1998).

Privacy concerns may arise within the context of “secondary use” of the specimens collected. “Secondary use”

means that the samples and the information derived from

them are being used or analyzed for purposes that extend

beyond the purpose for which the specimens were originally collected.7 For example, when materials are collected during surgical procedures and are used solely for

clinical purposes, the clinical use of these specimens 

raises few privacy concerns beyond those about the 

confidentiality of the medical record itself. This is

because the materials are being used for the direct diagnostic or therapeutic benefit of an individual and because

the custodian of the biological specimen does not allow

others access to it. Only when the use of such materials

extends beyond the original clinical use do privacy issues

arise. For example, if a sample is used as part of a

research study into familial linkage of a specific disease

and the family pedigree is published as a result of the

study, an individual might be easily identifiable even

without any names attached (Botkin et al. 1998).

Body Parts, Bodies, and Self-Identity

The medical and scientific communities have become

increasingly aware of a spectrum of beliefs about the relationship between a person and his or her body or body

parts (Andrews and Nelkin 1998). The use of human

biological materials in research can raise ethical, cultural,

and religious issues about the relationships among body

parts, bodies, and self-identity. However, ethical and religious traditions do not always provide clear guidance

about the ways in which human tissues should be

obtained or used. Although there are variations among

them, selected Western religious traditions offer some

insight about the significance of the human body, and

they generally favor the transfer of human biological

materials as “gifts.” As such, human tissues would warrant some measure of respect, which is the basis often

expressed for restricting sales of human tissues and

organs. But cultural differences can be significant because

of the different symbolic nature or status cultures attach

to specific body parts or tissues.8

Nature of Consent to Research Participation

When Human Biological Materials Are Used

Informed consent is a key component of the ethical

use of persons as subjects in medical experiments. It is

widely accepted and explicit in federal regulations that

the informed consent of potential subjects must be

obtained before enrolling them in particular research

protocols. For research involving human biological materials, the role of informed consent has been much less

clear, and new considerations have emerged regarding

both the nature of the required consent in these cases and

the guidelines that should apply regarding the disclosure

of results. In particular, the use of new genetic and other

technologies to study human biological materials presents several challenges to the consent process—particularly if the material is linked to a specific individual. First,

because the use of the material does not pose a physical

harm to the subject, potential harms become more speculative. Second, the complete research uses of the material may have been unknown and unanticipated at the

time of collection. Third, the analyses might provide

information that could lead to stigmatization, discrimination, or psychosocial problems for groups of individuals

who share certain characteristics (Foster, Eisenbraun,

and Carter 1997). Finally, there is greater awareness that

the study may generate ambiguous results, tempting for

clinical use but not really ready for reliable application

(Reilly 1980; Reilly, Boshar, and Holtzman 1997).

In addition, physicians and hospitals customarily

have not sought a patient’s explicit, informed consent to

permit the use of pathology specimens for specific
7

research purposes; instead, permission to use stored

material for other than clinical purposes has been general

(i.e., granted with the understanding that such use is

merely a possibility). In a recent study of hospital consent

forms, for example, it was found that 17 percent of large

hospitals disclose potential research uses of records, and

15 percent mentioned research use of tissue samples

(Merz, Sankar, and Yoo 1998). Once stored, human biological materials have been available for research, usually

without the knowledge or consent of the sources, particularly if the materials are unidentifiable.

Federal regulations govern research with human subjects, including research with human biological materials. (See Appendix B, Subpart A, Part 46, Title 45 of the

Code of Federal Regulations [CFR].)9 This system of federal protections involves review of the proposed research

by an Institutional Review Board (IRB) and a determination of the need for the informed consent of the research

subject. In situations for which informed consent is

required, the identifiability of the source of the material

and the risks posed by the research are central to determining the breadth and depth of the consent requirement.

(See Chapter 3 for further discussion.)

The use of human biological materials raises subtle

but significant distinctions in the applicability of federal

regulations, the review of research protocols, and the

obtaining of consent, as the sources of materials may be

patients, volunteer research subjects, or cadavers.

Contention continues to surround a number of issues

regarding the conditions for informed consent and/or IRB

review. First, there is the question of who defines and

determines what constitutes “minimal risk,” an important

concept in the language of the federal regulations (Merz

1996). Others believe that certain genetic research (e.g.,

on a stigmatizing genetic predisposition to a disease, such

as alcoholism or schizophrenia) is greater than minimal

risk and should, therefore, always receive a thorough IRB

review. Because of these ongoing concerns, many

observers, including some health advocacy and scientific

groups, have called for increased attention to the consent

process pertaining to the research use of stored and yet to

be collected human DNA and tissues (Clayton et al. 1995).

Informed consent is a process, the effectiveness of

which has been debated widely and which many agree

can be improved. Discussions about its relative value in

clinical and research settings are by no means unique to

genetics or the issue of human biological materials. What

people are told, what they understand, and what they

remember when consent is sought is likely to vary as

much when providing DNA or tissue as when consenting

to medical interventions. When human biological material is stored, people may not understand, for example,

that it might be used for research unrelated to their own

disease status. When told a specimen is being kept “for

research,” a patient may believe the material will be used

only for research related to his or her own condition.

Patients may not realize that federal and state regulations

require that specimens be stored for a certain length of

time. In most cases, the repositories in which specimens

are stored were designed for a particular purpose, and

the protocols and procedures that are followed in collecting and disseminating samples might not have addressed

issues regarding access, destruction, or future uses of the

materials, such as for research (Merz 1996).

Other familiar issues arise with respect to informed

consent. How specific, for example, must consent documents be for materials collected in a clinical context? How

detailed should disclosure be regarding the intended

purposes of subsequent research studies with stored

materials? How much information should be provided to

patients in clinical settings regarding the possibility of

postdiagnostic research on stored materials? These questions are likely to have different answers depending upon

whether the specimen already has been collected or will

be collected in the future and upon whether the material

was initially obtained as part of medical treatment or for

a research protocol. It stands to reason that a person’s

rights and interests are better protected if that person has

some form of control over his or her removed biological

material, especially if it remains identifiable. 

Group Concerns

Information obtained through research may have

implications for families, groups, and others (Foster,

Eisenbraun, and Carter 1997). Recently, the concept of

community consultation in research with human subjects has received increasing attention. For example,

NBAC heard testimony from the National Institute of
8

Allergy and Infectious Diseases (NIAID) regarding the

essential nature of community involvement in NIAID’s

AIDS clinical trials.10 Representatives of the community

of participants in those research studies worked together

with investigators in the research process, from the formulation of clinical questions to be addressed, through

the design of the studies, recruitment at a community

level, and the execution and analysis of the research itself.

It was concluded that such participation provided invaluable benefits to the research.

The Centers for Disease Control and Prevention also

has recognized the growing role of community involvement in public health initiatives, establishing a

Workgroup for Community Engagement to consider a

growing body of literature reflecting the experiences of

those involved in engaging individuals and organizations

in communities across the country (CDC 1997). While

community engagement increasingly has become a basic

element of health promotion, health protection, and disease prevention, few formalized procedures for seeking

community involvement in research with human subjects exist.

To date, two sets of federal regulations governing

informed consent procedures require a form of community consultation. The first involves research in which

subjects are enrolled in studies under emergency circumstances. These regulations pertain to research subject to

regulations codified by the Food and Drug

Administration (FDA) and carried out under an FDA

investigational new drug application or investigational

device exemption (see Title 21 CFR Part 50) and research

for which the Secretary of Health and Human Services

has waived the general requirements for informed consent (45 CFR 46.116(a), (b), and 46.408). The regulations provide for consultation (including, when

appropriate, consultation carried out by the IRB) with

representatives of the communities in which the research

(or clinical investigation, in the case of the FDA regulations) will be conducted and from which the subjects will

be drawn. Moreover, public disclosure of plans for the

research and the risks and expected benefits is required

of investigators prior to initiation of the research. Finally,

public disclosure of the results of the study is required

following its completion. The second set of requirements

has been in effect since the 1970s, and today the Indian

Health Service has a policy of requiring prior to the initiation of human subjects research the approval of the

Tribal Government that has legal jurisdiction (Indian

Health Service 1987). 

Differing Opinions Regarding the Ethical

Research Use of Human Biological Materials

Recent scientific developments have increased the 

scientific value and importance of human biological

materials. Therefore, increased demand for the use of

such materials can be expected. This generates a greater

level of responsibility for scientists and policymakers.

From available public statements, however, it seems that

the scientific community often disagrees about how to

ensure the appropriate respect for persons, as well as

their biological materials, while at the same time they

facilitate important health and medical research. Within

the past few years, many professional groups have issued

policy statements describing their views on these issues.

(See Appendix C.) The sheer variety of thoughtful

approaches is an indication that consensus on the resolution of challenges to the use of human biological materials has been difficult to achieve, particularly with respect

to requirements for IRB review and the nature of the

consent process.

A stable consensus must strike the right balance

between the desire to increase knowledge and the necessity of appropriately protecting individual interests. On

the one hand, there are those who think that emphasis

should be placed on the distinctive nature of personal

and familial medical information, the right of personal

choice regarding the continual use of one’s body or its

parts (and, therefore, the information inherent in the

materials taken from it), and the necessity of being able

to exercise a measure of control over the research that can

be conducted with one’s DNA and tissues. On the other

hand, others believe that in an era of increasing professional and legal regulations as well as an increasing

emphasis on individual autonomy, renewed consideration

must be given to the more extensive use of this invaluable

and often irreplaceable research resource; the inestimable

societal and individual benefits that have been gained

and that will continue to be gained through the research
9

use of these materials; the responsibility, explicit or

implicit, of individuals to contribute to this common

good, especially if risks are minimal; and the serious

threat posed to the continuation of these critical research

efforts by unnecessarily restrictive policies.

About This Report

In response to its original charge to consider “issues in

the management and use of genetic information, including but not limited to human gene patenting,” NBAC

chose to first consider the research use of human biological materials, because the issue is relatively well defined,

clearly important, and the focus of a great deal of current

interest. There are four basic premises underlying the

framework of analysis used by NBAC in the development

of its recommendations:

■ First, research use of human biological materials is

essential to the advancement of science and human

health; therefore, it is crucial that there be permissible

and clearly defined conditions under which such

materials can be used.

■ Second, the people who provide human biological

materials for research should be protected and

respected.

■ Third, the rapidly advancing Human Genome Project

and associated technologies, as well as the application

of a molecular-based approach to understanding

human disease, have raised issues of autonomy and

medical privacy. These issues are relevant to all areas

of medical research using human biological materials,

not merely genetic research.

■ Fourth, there is disagreement within the scientific

community about the nature of risks to individuals

and about the levels and types of protections that are

needed to ensure that biological samples can be used

in research with minimal risks to those whose materials are used.

NBAC organized its assessment of the conditions

under which research using human biological materials

should be permitted around five considerations: 

■ whether the materials were already collected and

stored, or are to be collected in the future,

■ the conditions under which the materials were/are

collected (e.g., clinical versus research setting),

■ whether the research sample used can be linked by

anyone (or any combination of people) to the source, 

■ whether the risks posed by the research affect individuals, communities, or both, and

■ the types of protections that might be employed to

protect against harms (specifically, measures to protect against invasions of privacy or discrimination,

such as coding schemes, individual informed consent, community consultation, and prior review and

approval by an IRB).

In reviewing these issues, NBAC relied on the existing

regulatory framework governing federally sponsored

research involving human subjects, 45 CFR 46 (Subpart A),

or the “Common Rule.” It was believed that because the

large and diverse community of biomedical scientists

already is familiar with these regulations and because

NBAC also is charged more generally with the task of

reviewing the adequacy of the federal system of protections

for research involving human subjects, the Common Rule

would serve as a useful framework for analysis.

Organization of This Report

To assist it in its deliberations, NBAC reviewed relevant scientific, ethical, religious, legal, and policy literature, commissioned scholarly papers on several topics

relevant to its tasks, and invited members of the public

and representatives of professional and consumer organizations to provide written and verbal testimony. (See

Appendices E, F, and G.) In addition, NBAC posted drafts

of this report on its Website (www.bioethics.gov) and

solicited public comments.

To date, there has been a paucity of information concerning the acquisition, use, and storage of human biological materials. For example, no central database exists

to capture information about stored materials. Thus, to

assist in its review, NBAC commissioned a study to assess

the magnitude and characteristics of the existing collections of human biological materials. Chapter 2 summarizes what is known about storage and use of such

materials, including where they are stored, the size of

collections, and the sources and uses of the materials. It

also provides background on the various research uses of

human biological materials and a schema for classifying

the status of human biological materials according to

their linkage to the sample source.
10

Chapter 3 summarizes the existing federal regulations

governing the use of human biological samples in

research. (The regulations are also presented in their

entirety in Appendix B.) When NBAC began its review of

the use of human biological materials in research, it was

aware that a number of scientific and medical organizations had done thoughtful work on the issue. Several of

these organizations have developed position statements

and recommendations reflecting their efforts to work

through the many ethical and policy issues that the topic

raises. To gain an understanding of the range of positions

that exist among organizations that have considered this

subject carefully, NBAC conducted a comparative analysis of these statements as they applied to the issue of protections for the appropriate use of human biological

materials in research. This analysis is found in Chapter 3,

as is a description of efforts to address these issues in

other countries. 

NBAC believes that any set of recommendations in

this area must be informed by ethical considerations.

Chapter 4 reviews the central considerations for policy

on the research use of biological materials. It aims to

articulate in a systematic way the moral considerations

that should be taken into account when developing policies about the collection, storage, and use of human biological materials. Chapter 5 synthesizes the various

policy issues that emerge from the preceding chapters

and offers recommendations for the future.

Finally, the Commission valued the input from members of the American public (those individuals who are

not clinicians, medical researchers, or ethical experts)

regarding the use of human biological materials. In addition to hearing public testimony at each of its meetings

on this topic, NBAC convened seven discussion forums

held across the country to obtain a sense of what

Americans believe and feel about uses of such materials,

about the ethical obligations of those who may learn significant health risk information from the research use of

such samples, and about privacy protections. Input from

all of these sources assisted the Commission as it deliberated, and findings from the forums are summarized in

Appendix A.

Notes

1 Guthrie cards consist of special filter paper that contains dried

blood spots from newborn babies and identifying information,

such as the mother’s name and address, the hospital of birth, the

baby’s medical record number, and the baby’s doctor’s name and

address. The cards are used to test newborns for a variety of 

diseases.

2 For the purposes of this report, the term “specimen” refers to 

the human biological material as it is stored in the repository. 

The term “sample” is used to refer to the material as it is used in

research. NBAC believes that this distinction becomes important

when considering the applicability and adequacy of the existing

federal protections for human subjects.

3 NBAC addresses issues relevant to human embryo research in 

a separate report, forthcoming, 1999.

4 Information on the Egyptian Mummy Tissue Bank can be found

at www.mcc.ac.uk/Museum/general/mummy.htm.

5 Collins, F.S. “Perspectives.” Testimony before NBAC. October 4,

1996. Bethesda, MD.

6 The report is available at www.dol.gov/dol/_sec/public/media/

reports/genetics.htm.

7 See Alpert, S., 1997, “Privacy and the Analysis of Stored Tissues.”

This background paper was prepared for NBAC and is available in

Volume II of this report.

8 See Campbell, C., 1997, “Research on Human Tissues: Religious

Perspectives.” This background paper was prepared for NBAC and

is available in Volume II of this report.

9 The Federal Policy for the Protection of Human Subjects (or

“Common Rule” as it is sometimes called) was promulgated by 

17 federal agencies that conduct, support, or otherwise regulate

human subjects research; the Food and Drug Administration also

adopted certain provisions of the Common Rule. The Federal

Policy is designed to make uniform the human subjects protection

system in all relevant federal departments and agencies. The

Common Rule and other human subjects regulations are codified

at Title 45 Part 46 of the Code of Federal Regulations, and it is the

National Institutes of Health Office for Protection from Research

Risks that has taken the lead within the federal government in the

task of harmonizing human subjects protections across agencies. 

10 Presentation by John Y. Killen, M.D., Director of the National

Institute of Allergy and Infectious Diseases, Division of AIDS, to

NBAC on December 9, 1997.
11

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Annas, G.J., L.H. Glantz, and P.A. Roche. 1995. “Drafting the

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317:744–747.
Collection, Storage, and 

Use of Human Biological

Materials in the United States

Chapter Two 2

Collections of 

Human Biological Materials 

As part of its analysis, the National Bioethics Advisory

Commission (NBAC) has sought to understand and

describe the magnitude, diversity, and use of collections

of human biological materials in the United States. To

this end, NBAC commissioned a study to assess the size

and characteristics of existing collections of these materials.1 In addition, a study was prepared that reviewed the

historical contribution of collections of human biological

materials to biomedical research and to the subsequent

development of new clinical studies.2 Based largely on

these studies, this chapter provides information about

several characteristics of collections of human biological

materials; presents a schema by which NBAC classifies

human biological materials (i.e., the extent to which specimens are identifiable as they exist in the repository and

as research samples in a scientific study); and describes

some of the important purposes for which collections of

human biological materials have been used in the past

and may be used in the future.

In this report, the term “human biological materials”

is defined to encompass the full range of specimens, 

from subcellular structures such as DNA, to cells, tissues

(e.g., blood, bone, muscle, connective tissue, and skin),

organs (e.g., liver, bladder, heart, kidney, and placenta),

gametes (i.e., sperm and ova), embryos, fetal tissues, and

waste (e.g., hair, nail clippings, urine, feces, and sweat,

which often contains shed skin cells). NBAC addresses

the research use of human embryos and fetal tissue in a

separate report.3

NBAC estimates that as of 1998, more than 282 million specimens of human biological materials were stored

in the United States, accumulating at a rate of more than

20 million cases per year (the term “specimen” refers to an

individual quantity of material; several specimens can be

obtained from one case, or individual, and several specimens can be obtained from one tissue biopsy or blood

drawing).4 (See Table 2-1.) Each specimen of human 

tissue may be stored in multiple forms, such as slides,

paraffin blocks, formalin-fixed, frozen, tissue culture, or

extracted DNA. The size and detail of collections vary

considerably, ranging from formal, highly organized

repositories to the storage of materials in a researcher’s

laboratory freezer. Individual collections of human 

biological materials range from fewer than 200 to more

than 92 million individual quantities of material and

generally fall into the following categories:

■ large tissue banks, repositories, and core facilities,

■ materials collected as part of longitudinal studies,

■ tailored collections for research studies requiring

unique tissue collections,

■ pathology specimens, initially collected for clinical

purposes,

■ newborn screening tests accumulating in various 

laboratory sites,

■ forensic DNA banks,5

■ umbilical cord blood banks,

■ organ banks,

■ blood banks,

■ sperm, ovum, and embryo banks, and

■ individual investigators’ collections.

Large collections of human biological materials

include archived pathology specimens obtained over

many years during diagnostic and surgical procedures or

13
14

at autopsy and stored cards containing blood spots from

newborn screening tests (Guthrie cards) that have accumulated for a number of years. These specimens are

stored at military facilities, forensic and other DNA

banks,6 government laboratories, diagnostic pathology

and cytology laboratories, university- and hospital-based

research laboratories, commercial enterprises, and

nonprofit organizations.

Two of the largest tissue repositories in the world, the

National Pathology Repository and the DNA Specimen

Repository for Remains Identification, are housed within

a single institution, the Armed Forces Institute of

Pathology (AFIP), and together they store more than 

94 million specimens. (Although the repositories supported by the National Institutes of Health [NIH] are not

as large as are those of AFIP, NIH is one of the largest

financial supporters of repositories, providing more than

$53 million in funding in Fiscal Year 1996.) Collectively,

the pathology departments at Graduate Medical Education

(GME) teaching institutions constitute the largest and oldest stores of tissue specimens in the United States, with

some more than 100 years old.7 In addition, state newborn

screening laboratories collectively have archives that total

more than 13 million individual specimens. 

Together, the AFIP National Pathology Repository,

GME teaching institution pathology departments, and

newborn screening laboratories contain more than

265.5 million diagnostic and therapeutic specimens from

more than 170 million individuals. Overall, only a small

percentage of these specimens currently are used for

research, educational, or quality control purposes. The

vast majority of them are stored for clinical and legal

reasons (e.g., confirmatory diagnoses, malpractice

actions). Most of the specimens included in these collections generally are referred to as “pathology specimens”

and have been the primary source of human biological

materials used in research to date. In fact, the vast majority of materials currently stored in the United States originally were collected for diagnostic or therapeutic reasons

(e.g., transplantation or transfusion), with varying levels

of specificity regarding future uses indicated during the

informed consent process. 

Blood banks, for example, collect approximately

12 million units of blood a year, but only about

20,000 to 40,000 units of blood are stored at any one

time, and most of the blood collected is used for transfusions, with little used for other purposes, such as

research and quality control. Organ banks do not collect

the same volume of tissue as do blood banks, but they are

similar in that most of the organs and tissues collected are

used for transplants, with little available for research.

Forensic DNA banks collect and store tissues for use in

Table 2-1. Stored Human Biological Materials in the United States

Type of Repository Number of Cases* Number of Specimens** New Cases/Year

Large Tissue Banks, Repositories, >2,600,000 >96,000,000 364,825

and Core Facilities

Longitudinal Studies >263,500 >263,500 unknown

Pathology Specimens >160,000,000 >160,000,000 >8,000,000

Newborn Screening Laboratories >13,500,000 >13,500,000 <10,000 to >50,000

Forensic DNA Banks 380,000 380,000 unknown

Umbilical Cord Blood Banks 18,300 18,300 unknown

Organ Banks unknown >75,500 >75,500

Blood Banks unknown ~12,000,000 ~12,000,000

Total >>176,500,000 >>282,000,000 >20,000,000

*A case refers to an individual.

**Specimens refers to number of units of material derived from cases. Thus, there might be several specimens obtained from a single case (or individual).
15

criminal investigations, while the Department of Defense

DNA Specimen Repository and some commercial DNA

banks store DNA specimens for remains identification.

Sperm, ovum, and embryo banks store specimens for

anonymous donation or for later use by the individual

source. Umbilical cord blood banks also store blood for

anonymous donation and later use by families who may

someday need their newborns’ cord blood for medical

reasons.

However, as biomedical research requires more precisely categorized samples with associated clinical data,

biological materials collected specifically for research

purposes increasingly are in demand. In these cases,

materials are more likely to have been collected with

explicit consent given to their use in research. As a result

of these research needs, special repositories have been

established, sometimes involving multiple partners 

from private industry and academia. (See Exhibit 2-A.)

Furthermore, a fair number of current research efforts are

engaged simultaneously in creating special collections

and contributing to existing banks of human biological

materials, with investigators who are conducting large,

longitudinal studies collecting and banking materials

from study participants over considerable periods of

time. Together, these special research collections now

contain more than 2.3 million samples.

Identifiability of 

Human Biological Materials

A key consideration in deciding whether the federal regulations apply and whether Institutional Review Board

review and informed consent is required for the research

use of human biological materials is the determination of

whether, as defined in federal regulations, a human subject is involved in the research. This determination may

be affected by the extent to which biological material can

be linked to the person from whom it was obtained. The

debate about research use of human biological materials

has been at times complicated by the fact that the language that is used varies and often is at odds with the categories used in the applicable federal regulations. For

example, previous guidelines and reports frequently

categorize specimens by the identifying conditions

under which they are stored in repositories (with or

Exhibit 2-A: Collaboration Between

Universities and Private Industry in

Creating Genetics Databases

Recent advances in computer technology and the

growth of the Internet have made access to biological and medical information contained in databases

increasingly more manageable for researchers. In

fact, computational biology—the umbrella term for

bioinformatics and medical informatics—rapidly is

becoming an essential skill for biochemists, epidemiologists, molecular biologists, and physicians

(Smaglik 1998). One result is that collaboration

between universities and private industry has

become more commonplace.

Three recent examples illustrate this trend. In

April 1997, the Whitehead Institute/Massachusetts

Institute of Technology Center for Genome

Research formed the first “functional genomics

consortium” with one pharmaceutical company,

Bristol-Myers Squibb, and two biotechnology firms,

Affymetrix and Millennium Pharmaceuticals, in order

to discover innovative ways to gather and compare

genetic data (Durso 1997). The industry participants agreed to contribute a total of $8 million per

year in money and equipment to the Whitehead

Institute for five years in exchange for commercial

rights to any technology developed under this program (Roush 1997). Two years later, ten members of

the pharmaceutical industry (Bayer, Bristol-Myers

Squibb, Glaxo Wellcome, Hoechst Marion Roussel,

Roche Holding, Novartis, Pfizer, Searle, SmithKline

Beecham, and the Zeneca Group) and the

Wellcome Trust of London announced that they have

formed a consortium “to create an archive of human

genetic variation” that would be available free via the

Internet (Marshall 1999). The participants have

agreed to spend a total of $45 million to support the

mapping work of the genome centers at Washington

University, the Whitehead Institute, and the Sanger

Centre in England. These single nucleotide polymorphisms or SNPs (pronounced snips) are map points

along the DNA sequence that it is hoped will help

researchers identify variant genes that contribute to

the manifestation of a particular disease (Wade

1999). Most recently, representatives from SmithKline

Beecham proposed an initiative to build population

genetics resources using the U.K. National Health

Service, which provides comprehensive health care

to 59 million people as well as valuable medical

information contained in detailed patient records and

archived tissue samples (Fears and Poste 1999).
16

without identifiers), although current federal regulations permit investigators to access stored specimens,

make them anonymous by removing identifiers, and

then use them in research without seeking the consent

of the source. (See Chapter 3 for further discussion.)

Part of the confusion surrounding the term “identifiable,” therefore, arises from the fact that people sometimes refer to the state of the information attached to the

biological material in the repository (i.e., the specimen)

and sometimes refer to the biological material and the

accompanying information that is provided to the

researcher (i.e., the sample). For example, a specimen

might be identified in the repository, but no identifying

information is forwarded with the research sample that is

sent to the scientist. This distinction is of considerable

importance because the potential for both benefit and

harm is greater when the sample is directly or easily

linked to the donor, placing the burden of protection in

different places depending on who has access to the

information (i.e., the researcher, the pathologist, or

both). If samples are identifiable, the potential exists for

the investigator or a third party to contact the source or

act in some way that might negatively affect him or her.

NBAC has adopted the following definitions of

human biological materials, depending on whether they

are being stored in a repository or whether some of the

material from a repository has been selected for research

purposes. (See below and Table 2-2.)

Repository collections include human biological materials (i.e., specimens) of two types:

1. Unidentified specimens are those for which identifiable personal information was not collected or, if 

collected, was not maintained and cannot be retrieved

by the repository.

2. Identified specimens are those that are linked to personal information in such a way that the person from

whom the material was obtained could be identified

by name, patient number, or other information (e.g.,

his or her relationship to a family member whose

identity is known).

Most repositories contain identified specimens,

because the vast majority of human biological materials

in storage originally were collected for diagnostic or therapeutic purposes and thus included identifying information. Examples of repositories that contain identified

materials include pathology laboratories and newborn

screening laboratories, where specimens are collected

and stored with identifying information, such as the

patient’s name, hospital identification number, and/or

Social Security number. In addition to identifying information, clinical and demographic information often is

available with these specimens. In contrast, relatively few

collections of human biological materials contain

unidentified specimens. Consider the following examples

of repositories that store unidentified specimens:

A repository that collects specific blood of types such as 

O-positive (O+

) or AB-negative (AB-). Donors who have

these blood types are asked to contribute to the bank

because they have these specific types, but the only

information that is recorded about the donor when the

specimen is collected is the blood type.

A repository that collects human biological materials, such

as brain, pancreas, or kidney tissues that originally were

collected by a hospital, but are submitted to the repository

with no identifying information. These specimens may be

accompanied with some corresponding clinical and demographic information, but any information provided with

the specimen is insufficient, either directly or indirectly, 

to identify the individual from whom the specimen

originally was collected.

Research samples are the collections of human biological

materials provided to investigators by repositories. Such

materials can be categorized into at least four types,

which are differentiated by the amount of information

that is conveyed to the investigator about the person

from whom the sample material was obtained. NBAC

defines the different types as follows:

1. Unidentified samples—sometimes termed “anonymous”—are those supplied by repositories to investigators from a collection of unidentified human

biological specimens.

2. Unlinked samples—sometimes termed “anonymized”—are those that lack identifiers or codes that

can link samples to identified specimens or particular

individuals. Typically, repositories send unlinked

samples from identified human biological specimens

to investigators without identifiers or codes so that

identifying particular individuals through the clinical

or demographic information that is supplied with the

sample or biological information derived from the
17

research would be extremely difficult for the investigator, the repository, or a third party. Unlinked

samples also include those samples that are already

in an investigator’s possession and whose identifiers

have been removed by a disinterested party.

3. Coded samples—sometimes termed “linked” or

“identifiable” samples—are those supplied from identified specimens by repositories to investigators.

However, these samples do not include any identifying information, such as patients’ names or Social

Security numbers. Rather, they are accompanied with

codes. In such cases, although the repository (or its

agent) retains the ability to link the research findings

derived from a sample with the individual source by

using the code, the investigator (or one reading a

description of the research findings) would not be

able to do so.

4. Identified samples are those supplied by repositories

from identified specimens with personal identifiers

(such as names or patient numbers) that are sufficient

to allow the researcher to link directly the biological

information derived from the research with the individual from whom the material was obtained.

By definition, unidentified samples can be obtained only

from collections of unidentified materials. Because of the

scarcity of truly anonymously collected human biological

materials, few research samples are unidentifiable. An

example of a researcher’s collection of unidentified samples follows:

A researcher studying malaria needs O+ blood to grow

the malaria parasite. The researcher requests from a

repository blood that is O+

. When the blood originally

was collected, the repository labeled each vial with a

number but kept no record of which unit of blood came

from which donor.

On the other hand, repository collections of identified

materials may be provided to researchers as unlinked,

coded, or identified samples. The use of unlinked samples

in research is common. Unlinked samples are used when

a one-time need for tissue and clinical/demographic information arises. Because no link is maintained between the

sample and the individual from whom it came, neither

the researcher nor the repository knows which sample

came from which source. Therefore, the only way to

obtain additional information about or another sample

from a particular source would be to request additional

materials from the entire group. The following is an

example of such a scenario: 

A researcher at a university is studying a mutation of a

gene that may be associated with prostate cancer. The

researcher needs 100 samples of prostate tumors with

accompanying clinical information, such as the size of the

tumor, and does not need any other information about the

individuals from whom the tumors were removed. The

researcher contacts the pathology department at the university and requests the samples. The pathologist pulls

100 specimens from the pathology archives, records in a

separate file the medical records numbers of the selected

specimens, removes any identifying information, gives

each specimen a new unique identifier, and provides the

samples to the researcher. No link is maintained between

the samples and the individuals from whom they were

obtained. This means that neither the researcher nor the

pathologist knows which sample came from which patient,

although the pathologist may retain a record of the group

of 100 samples used.

Another common category of samples used in

research is coded samples. Coded samples may be used

when a researcher anticipates the need to obtain additional medical information about the source, to provide

information to the source, or to obtain additional samples over time. For coded samples, the identification of

the individual is not provided. Instead, each sample

receives a unique identifier, and the repository, for quality

control or other purposes, maintains a link between the

unique identifier and the identity of the individual. This

link also provides the potential for one-way flow of information from the repository to the researcher and, at

times, for a reverse flow of information from the

researcher to the repository. Thus, coded samples could

allow researchers to obtain follow-up data on treatment,

recurrence, and survival and may allow researchers to

communicate research findings to subjects or to their

physicians. An example of the use of coded samples in

research follows:

A researcher studying systemic lupus erythematosis (SLE)

wants to know if there is a way to predict whether a

patient will eventually require a kidney transplant. The

researcher uses frozen serum from patients with SLE that

has been coded for research purposes. During the course

of this research, a unique serological marker is found that

may be predictive of rapidly progressive kidney disease.
18

The researcher wants to determine if there is a connection

between the newly discovered marker and patients requiring a kidney transplant. Therefore, the researcher wants

to receive follow-up information about each patient, particularly information relating to time until renal failure

and need for dialysis and/or kidney transplant.

Identified samples are used when the research involves

continual sample collection and/or clinical follow-up or

when the researcher has direct contact with the research

subject. With identified research samples, the investigator can go back directly to the source of the sample and

request additional information. An example follows:

A researcher who is investigating the genetic causes of 

psoriasis identifies patients with psoriasis or psoriatic

arthritis through medical records and requests samples of

skin biopsies from the pathology laboratory. After the

researcher completes the experiments on the skin biopsy

samples, the patients and their families are contacted to

further participate in the research by providing blood

samples. This allows the researcher to perform linkage

analysis to try to localize genes that may play a role in the

development of psoriasis.

The Need to Identify the Sample Source for

Research or Clinical Purposes

For research samples that are identified or coded,

there are several possible reasons that an investigator may

wish to go back to the source to gather additional clinical or biological information or to provide potentially

valuable therapeutic information to the individual.

Increasingly, genetic research requires that sufficient phenotypic (i.e., clinical) information accompany the genotypic (i.e., DNA-based) information obtained from the

biological material. Thus, investigators identify those

individuals of interest according to the requirements of

their research protocol and then intensively investigate a

smaller subset of that group. As smaller subpopulations

of interest are identified, clinical investigators are likely to

require more clinical information about the population

being studied, which will entail the use of a mechanism

for ongoing information retrieval. With coded research

samples, the “trustee” of the sample retains the ability to

gather more data for the investigator. With identified

research samples, the investigator can request additional

information directly. The possibility that the investigator,

or an agent of the investigator, will contact the source (or

the source’s physician) for additional information should

be discussed during the consent process.

Circumstances also may exist in which an investigator

wants to provide information to the sample source,

whether directly or indirectly. An example is an investigator who discovers new information that leads to an earlier

diagnosis of a clinical condition, an effect of a previously

administered therapy, or a misdiagnosis that might have

important implications for the health of an individual

source. Another example is the discovery of an infectious

agent and its public health implications. In both cases,

compelling arguments have been made supporting the

investigator’s duty to contact the source. In cases in

which the implications of a finding are not clear (i.e., in

which findings are preliminary or in which no effective

Table 2-2: Categories of Human Biological

Materials

Repository Collections

Unidentified specimens: For these specimens, identifiable

personal information was not collected or, if collected, was 

not maintained and cannot be retrieved by the repository.

Identified specimens: These specimens are linked to personal information in such a way that the person from whom

the material was obtained could be identified by name, patient

number, or clear pedigree location (i.e., his or her relationship

to a family member whose identity is known).

Research Samples

Unidentified samples: Sometimes termed “anonymous,”

these samples are supplied by repositories to investigators

from a collection of unidentified human biological specimens.

Unlinked samples: Sometimes termed “anonymized,” these

samples lack identifiers or codes that can link a particular

sample to an identified specimen or a particular human being. 

Coded samples: Sometimes termed “linked” or “identifiable,”

these samples are supplied by repositories to investigators

from identified specimens with a code rather than with personally identifying information, such as a name or Social

Security number. 

Identified samples: These samples are supplied by repositories from identified specimens with a personal identifier (such

as a name or patient number) that would allow the researcher

to link the biological information derived from the research

directly to the individual from whom the material was

obtained.
19

intervention is available), such contact is less desirable

and more controversial. This is because the possibility

exists that individuals could act on these findings, however tentative and conditional, in ways that might result

in harm.

The Value of Human Biological

Materials to Current Research

Historically, the science of pathology has led the way in

the investigation of the mechanisms of disease causation

by proceeding progressively from whole organs and tissues to cells, and then from the subcellular to the

supramolecular and molecular manifestations of disease

expression (Rosai 1997). The range of medical benefits

already obtained through the use of stored biological

samples is impressive. (See Exhibit 2-B.)

Biomedical research routinely relies on the availability

of stored human biological materials as well as the willingness of individuals to participate in research protocols

by donating blood, tissue, or DNA samples to research.

Research in cancer, infectious diseases, and mental disorders is advanced by access to such materials. In addition,

large, longitudinal studies that aim to study the causes of

diseases in certain populations over time depend on a

continuous source of biological materials for study. Some

examples of the many areas of research that rely on the

availability of stored human biological materials are

provided below.

Cancer Research

Part of the reason that pathology specimens have

served as invaluable resources for an enormous amount

of cancer research is that the availability of large archives

of carefully documented and clinically correlated specimens has permitted researchers to apply directly new

detection technologies to existing biological materials.

This is a far more rapid and less expensive approach than

initiating new prospective studies for each new promising candidate gene for many of the varieties of human

cancer. Conducting such studies not only would be

extraordinarily costly in terms of dollars and human

effort, but would require study periods of many years, or

even decades. 

Recent progress in elucidating the initiation and progression of cancer has been most dramatic and gratifying

Exhibit 2-B: Past Research Use of

Human Biological Materials

■ In 1953, autopsies of American soldiers killed in

the Korean conflict revealed that atherosclerosis

begins at a much earlier age than was previously

thought and that blockage of arteries can be far

advanced in the absence of symptoms; this

research contributed to findings concerning diet

and exercise that have had a major public health

impact in this country, evidenced by a significant

reduction in coronary artery disease (Enos,

Holmes, and Beyer 1953; Enos, Beyer, and

Holmes 1955; Solberg and Strong 1983; Strong

1986).

■ In the late 1960s, the study of tissue samples

from an unusual tumor of the vagina led to the discovery that a nonsteroidal estrogen hormone

diethylstilbestrol (DES), then commonly given to

women during pregnancy, is carcinogenic (Herbst

and Scully 1970; Herbst, Ulfelder, and Poskanzer

1971; Herbst et al. 1974; Herbst 1981). 

■ Thirty years ago, a series of studies on tissue

samples of precancerous lesions of the uterine

cervix led to the routine use of Pap smears, which

have played an important role in the early diagnosis and more successful treatment of cervical cancer (Herbst and Scully 1970; Herbst, Ulfelder, and

Poskanzer 1971; Herbst et al. 1974; Herbst 1981;

Younge, Hertig, and Armstrong 1949). 

■ Analysis of tissue from autopsies of persons in

certain occupations, such as chemical manufacturing and uranium mining, has established

causal links between exposure to environmental

substances and certain diseases, including a cancer of the liver known as hepatic angiosarcoma

and cancer of the bronchial epithelium (Creech

and Johnson 1974; Dannaher, Tamburro, and

Yam 1981; Falk et al. 1981; Popper et al.

1978; Regelson et al. 1968; Roth 1957).

■ The analysis of autopsied lung tissue obtained

from smokers played a major role in establishing

that smoking causes lung cancer, that the risk of

cancer increases with the duration of exposure to

the chemicals contained in cigarette smoke, and

that precancerous changes in the bronchial

epithelium can be reversed by cessation of

smoking (Auerbach et al. 1962; Auerbach,

Hammond, and Garfinkel 1979; Flehinger et al.

1984; Frost et al. 1984).
20

in the area of colorectal cancer (Lengauer, Kinzler, and

Vogelstein 1997). During the past decade, at least five

specific genetic changes have been identified that seem to

constitute a progressive pathway from normal to neoplastic colon tissues. Some of these revelations have been

derived in subsets of patients with known hereditary

forms of colorectal cancer, while others appear more generally to be present in those without known patterns of

familial inheritance. At least one of these genetic changes,

the inactivation of the p53 gene, is known to occur, at

least at times, in the germline, while the others appear to

be exclusively of somatic origin (Kinzler et al. 1991a;

Kinzler et al. 1991b; Kinzler and Vogelstein 1996).

Research on the role of the p53 gene was facilitated by

the availability of a large human tissue repository containing various forms and stages of colorectal cancers, as

well as blood specimens from the same patients. The tissue archive consisted largely of typically fixed and

embedded specimens, but in addition, the scientists benefited immensely from a large collection of frozen samples

(Fearon, Hamilton, and Vogelstein 1987; Fearon and

Vogelstein 1990; Goelz et al. 1985; Vogelstein et al. 1988;

Vogelstein et al. 1989).

Screening Human Biological Materials

Archives to Track Viruses

Stored biological specimens can be valuable resources

during public health emergencies, when investigators are

trying to identify or track an emerging virus. For example,

in 1993, healthy young people in the Four Corners area

of the American Southwest began mysteriously dying

from a form of pneumonia. Within months, the hantavirus

was identified as the culprit. The rapid solution of this

public health mystery can be attributed to many sources,

including a suspicious clinician, an epidemiologist,

observant Navajo elders, and two human tissue archives.

One archive was that of the Centers for Disease Control

and Prevention (CDC), which contained vast libraries of

viruses, viral proteins, and serum specimens from around

the world. The second archive held pulmonary tissues

from the autopsied victims of this strange new disease.

The availability of the CDC archive permitted initial

serological screening tests, from which arose the first

suggestion that a hantavirus might be involved. The

initial screens were followed by tests of autopsy tissue

specimens with specific hantavirus monoclonal antibodies,

and, ultimately, the tissue samples were exposed to

hantavirus genetic probes that revealed the presence

and tissue distribution of viral genetic material. These

molecular tools permitted identification of the local

deer mouse as the host of the pathogenic hantavirus.

Studies of older human autopsy tissue established that

the virus was, in fact, not a new variant but a fairly old

virus with a well-established symbiotic relationship

with the mice in the region. To initiate human infections, this relationship must have been disturbed in

some way (Wrobel 1995).

Human Tissue as a Singular Resource 

in Brain Research

Sometimes the use of biological materials is the only

way to study certain human diseases and aspects of

human disease, such as some diseases of the brain and

the central nervous system. Currently, no accurate animal

or tissue culture models exist for many common diseases

of the human brain, including brain tumors and most of

the primary neurodegenerative diseases (e.g., Alzheimer’s

disease, Parkinson’s disease, Amyotrophic Lateral

Sclerosis [ALS], or multiple sclerosis). Moreover, neurological specimens, particularly of the brain, often are

inaccessible.

Until relatively recently, most brain tumor research

was conducted with animal models or with cultured

immortalized brain cell lines. Over the last five years,

however, several studies correlating genetic alterations in

human brain tumors with the degree of malignancy and

prognosis have been conducted that relied on the availability of frozen samples and specially fixed samples of

human brain cancers in order to assess gene amplification, gene deletions, gene mutations, and cell cycle

parameters. Many insights into the pathobiology of brain

tumors are emerging from these studies (Blessed,

Tomlinson, and Roth 1968; Masliah et al. 1991; Raine

1997; Will et al. 1996).

Longitudinal Studies

Longitudinal studies, in which the same group of

individuals is studied at intervals over a period of time,

often collect large numbers of specimens that can be used

for retrospective, current, or future research. Several
21

well-known longitudinal studies have been conducted

over the years, including the Physicians’ Health Study,

the Nurses’ Health Study, and the Framingham Heart

Study. 

As an example, the NIH Women’s Health Initiative

(WHI) is a 15-year research program, concluding in the

year 2005, that focuses on the major causes of death, disability, and impaired quality of life in postmenopausal

women. WHI’s overall goal is to reduce coronary heart

disease, breast and colorectal cancer, and osteoporosis in

postmenopausal women through prevention, intervention, and risk factor identification. The study will involve

more than 164,500 women of all races and socioeconomic backgrounds ages 50 to 79. The women will be

enrolled in either a clinical trial or an observational study

and will be followed for 8 to 12 years, during which time

they will provide multiple blood samples. Participants

sign a consent form that states that the collection of blood

samples is for use in future research, which may include

genetic research, and that participants will not be

informed of any test results. Participants may refuse to

have their samples used for genetic research. Participants’

charts contain identifying information, including name,

Social Security numbers, addresses, and telephone numbers, and they are barcoded. Blood samples are labeled

with matching barcodes to link them back to the charts.

All study records are kept indefinitely for analysis and

follow-up.

Relying on Stored Materials for Locating Genes 

The human genome has been identified as the complete set of genetic instructions that initiates the development of an individual. Although the DNA of any two

individuals is roughly 99.9 percent identical, the last

tenth of a percent of the DNA that is not identical is the

source of considerable genetic variation. Inherited susceptibility to various diseases—which occurs when a

gene fails to provide the correct instructions for a trait or

function—is one small part of this diversity. Researchers

look for genes by constructing finer and finer maps of

known gene locations or by comparing the DNA of individuals (or, more commonly, of families) with a given 

disease or trait to the DNA of those who do not have that

disease or trait.

The first phase of identifying a disease-related gene 

is the collection of diagnostic information and blood

samples from an appropriate set of affected individuals

and their relatives. Typically, blood samples are drawn

from family members, and the blood cells are

immortalized so that they can be grown continuously

in the laboratory. These immortalized cells, called cell

lines, then can be used to make DNA in unlimited quantities, allowing many different researchers access to

this resource. The art of this collection phase lies in

identifying the appropriate families.

Linkage studies are used widely to detect and locate

genes that determine susceptibility to certain disorders.

These studies often are based on the identification of

large, densely affected families to compare the inheritance

patterns of known sections of DNA (called markers) to

the family’s transmission of the disorder. If a known

marker can be correlated with the presence or absence of

the disorder, the location of the suspect gene is narrowed.

Great strides in linkage analysis, including laboratory and

statistical methods, are increasing the power of this

method and decreasing its cost.

Linkage-disequilibrium studies in isolated populations capitalize upon the likelihood that the susceptibility

genes for a particular disorder probably came from one or

a few founding members. Whether the isolation of the

population is geographic or cultural, there are fewer individuals in the community’s original founding genealogies

and therefore fewer variations of the disease genes

within the population. This limited variation makes easier

the search for genetic association with a disease, and the

fact that the groups of markers that surround each of

these susceptibility genes are likely to have the same

limited variation further simplifies gene identification.

(See Exhibit 2-C for a description of such a research

study under way in Iceland.)

Pinpointing the likely genetic anomaly in linkage and

linkage-disequilibrium studies can occur only when an

investigator has narrowed the search to a fairly small

region in the genome. That “small” region, however, still

may be large enough to contain DNA that codes for

dozens of traits, and the investigator must then choose

which parts of the region to study further. Because the

Human Genome Project is well on the way to identifying

the location of all genes, the identification of possible

susceptibility genes will become increasingly facile. Once

the genes in a narrow DNA region are cataloged, each

may be tested and the susceptibility gene identified.

An example of the use of DNA repositories in linkage

studies is the National Institute of Mental Health’s
22

Exhibit 2-C: Iceland’s Health Records Database

A plan to construct a central database of health records in Iceland has garnered recent international attention both

for its promise for human genetics research and for the ethical questions that it raises. The database, which will contain “nonpersonally identifiable health data” from the medical records of Icelandic citizens, was authorized by recent

legislation passed in Iceland’s Parliament (Act 1998). Like collections of human biological materials stored in the

United States, the centralized bank of health records is regarded as a potentially valuable research resource. It also

raises familiar ethical questions, including “What constitutes personally identifiable information?” “How can privacy

be protected in the course of research?” and “How should research involving patient data be conducted in an ethically acceptable manner” (Act 1998)?8

The information to be included in this central database will come from a variety of sources, including health

records, genealogical records, and genetic information from biological samples collected with informed consent

from volunteers. The new legislation grants Decode Genetics a 12-year license to construct, operate, and receive

a substantial share of the profit from the database. During that time, Decode will use the vast amounts of patient

information to conduct research into the origin and nature of various diseases (Lyall 1999).

Several factors make Iceland a unique location for genetics research and its health records database a particularly valuable tool for researchers. First, Iceland’s relatively homogeneous gene pool facilitates research into disease-causing mutations. In addition, Iceland’s state-financed health care system maintains thorough health records,

and various public and private sources maintain extensive genealogical records. When these records are combined

with the data from biological samples, the database becomes a valuable tool in tracing the genetic factors of various diseases (Enserink 1998; Specter 1999). As an official of Iceland’s Ministry of Health and Social Security comments, “This situation imposes on us an ethical obligation and gives us a unique opportunity to promote medical

sciences” (Haraldsdottir 1999a).9

However, some observers believe that this database raises serious ethical questions. Discussion has centered

on three issues: consent, privacy, and the commercialization of the database (Enserink 1999; Lewontin 1999; Lyall

1999). First, Iceland’s new law allows information to be submitted without patient consent. All that is required is the

consent of the health institutions that hold the medical records. Patients may “opt out” of participation by informing

the Director General of Public Health of their wishes. Some have questioned whether this plan is appropriate in light

of the potentially sensitive nature of the information (Lewontin 1999; Lyall 1999; Schwartz 1999). Approximately 

10 percent of citizens are estimated to have opted out or plan to opt out of participation in the database. 

Privacy is another concern. The very factors that make the database scientifically useful also might create a situation in which personal identification can be deduced from “nonpersonally identifiable data.” For example, the new

legislation permits Decode to process data on the health database and connect it with genealogical and “genetic

data” (Act 1998).10 Although the law stipulates that linking databases is allowed “provided that data are processed

and connected in such a way that they cannot be linked to identifiable individuals,” some experts have questioned

how such requirements will work in practice (Act 1998). At least one privacy expert who evaluated the database

says that identification would be easy to deduce (Berger 1999; Schwartz 1999). Still, it is difficult to know how to

weigh the impact of such invasions of privacy in a country with a national system of medical insurance and in which

most genealogical data is exempt from basic privacy laws (Specter 1999).

Finally, observers have questioned whether the plan to allow one company to own and operate the database is in

the best interests of either science or of the people of Iceland. Although the law permits Iceland’s Ministry of Health

free access to the database, it permits access by others only so long as such access does not affect Decode’s 

commercial interests. It remains unclear what the scope of access to the data will be in practice (Haraldsdottir 

1999b). The new law, however, will not alter the current level of access to Iceland's health information. Subject to

laws pertaining to the handling of personal data, others may continue to use health records for research.

A number of issues regarding the construction and operation of the database are still unresolved. These include

how the existing European laws and standards regarding confidentiality of data will apply to information obtained from

the database, and how much cooperation realistically can be expected from health practitioners (Duncan 1999).

The plan to construct this database comes at a time when a great deal of excitement is apparent regarding the

prospects of clinical breakthroughs stemming from genetic epidemiology. Tissue banks represent valuable

resources in this endeavor. As large-scale projects are proposed to create or utilize databases, and as many of the

same questions about consent, privacy, and commercialization arise, it becomes even more critical to develop an

ethical approach to the development of this promising research strategy.
23

Genetics Initiative, begun in 1989.11 The goal of this special, large-scale initiative in molecular genetics is to collect data from a sufficient number of families to identify

the genes that influence the onset of selected mental disorders. This initiative enabled the establishment of a

national repository of demographic, clinical, diagnostic,

and genetic data from individuals with bipolar disorder,

schizophrenia, or Alzheimer’s disease in order to aid

researchers in identifying factors responsible for these

disorders. 

In association studies, the investigator hypothesizes

that a specific gene or genes may influence the disorder

and examines whether individuals with the disorder have

a different version of the gene than individuals without it.

Unlike linkage studies, which usually focus on large

groups of related family members, association studies can

be conducted using unrelated individuals.

Research Requiring Unique Tissue Collections

Most researchers using human biological materials

have relied on specimens from pathology laboratories or

existing tissue banks. However, some research studies

require specialized samples—that is, samples with specific biological, clinical, or demographic characteristics.

In such cases, a unique collection of materials must be

created. Although these collections might have limited

appeal to the broad research community, they are of great

value to a small group of investigators.

Examples of the need for specialized samples are the

health examination surveys conducted by CDC. Since

1960, CDC’s National Center for Health Statistics has

conducted seven health examination surveys of the 

population of the United States: the National Health

Examination Surveys Cycles 1, 2, and 3; the National

Health and Nutrition Examination Surveys (NHANES) I,

II, and III; and the Hispanic Health and Nutrition

Examination Survey (HHANES). These surveys are

designed to assess periodically through interviews and

direct physical examinations the health and nutritional

status of children and adults in the United States. The

surveys employ interviews to answer questions regarding

demographics, socioeconomic status, dietary habits, and

other health-related issues. Physical and dental examinations also are conducted, and these include physiologic

assessments and laboratory tests. Blood samples are

collected as part of the physiologic assessments and are

placed in storage banks after the laboratory tests are

completed.

Cumulatively, all of CDC’s health examination surveys

have analyzed and banked samples from more than 85,000

participants. The most recent survey, NHANES III,12

conducted between 1988 and 1994, performed laboratory

tests on approximately 29,314 people of all races, 

1 year and older, from 81 counties in 26 states. Some of

the 30 topics investigated in NHANES III included high

blood pressure, high cholesterol, obesity, lung disease,

osteoporosis, HIV/AIDS, hepatitis, diabetes, allergies,

anemia, the effects of second-hand smoking, Helicobacter

pylori, immunization status, growth and development,

dietary intake, antioxidants, and nutritional blood measures. NHANES I analyzed blood and urine samples from

23,808 study participants, and NHANES II analyzed

20,322 samples. HHANES was a one-time survey conducted from 1982 to 1984 that provided data on 11,653

people of Hispanic origin.

Summary

This chapter provides examples of how human biological

materials have been and continue to be invaluable

resources for a wide variety of studies aimed at understanding the etiology and progression of disease and the

effects of viral and environmental impacts on health, as

well as for identifying genes that might be responsible for

the underlying mechanisms of disease. Tremendous variability exists in the identifiability of the samples used,

depending upon the source of the material and the purpose of the research. In some cases, such as the study of

the hantavirus, identifying the individuals who served as

the sources of the samples was not necessary. For other

types of research, however, such as the studies of families

with a high prevalence of mental illness in which extensive information on demographics, diagnosis, and family

history is crucial, the ability to identify the source of the

sample may be necessary.

Most of the specimens that are stored in repositories

never will be used in research. And among those research

studies that do use stored human biological materials,

many will rely upon large numbers of unidentified or
24

unlinked research samples to investigate the basic mechanisms of health and disease or to screen samples for evidence of disease, environmental insult, or responsiveness

to potential therapeutic agents. However, other studies

will rely on coded or identifiable samples. In other

words, an investigator might initially request samples

with no linking data and later request that additional

clinical data be linked to the sample. In still other cases,

the research might require the investigator to be able to

identify the sample source, or the sample source might

even be a patient as well as a research subject of the

investigator. How human biological materials are used in

research and the extent to which samples can be linked

to their sources are critical considerations in attempting

to determine the risks to and necessary protections of the

persons who serve as the sources of the materials.

Notes

1 Elisa Eiseman collected these data. Her report, “Stored Tissue

Samples: An Inventory of Sources in the United States,” 1997

(available in Volume II of this report) is not meant to be a 

comprehensive inventory; however, it does identify the major

repositories or archives of stored human biological materials.

2 See Korn, D., 1998, “Contribution of the Human Tissue Archive

to the Advancement of Medical Knowledge and the Public Health,”

a paper prepared for NBAC and available in Volume II of this

report. 

3 NBAC addresses certain issues relevant to human embryo and

fetal tissue research in a separate report, forthcoming, 1999.

4 This estimate attempts to count both the numbers of individuals

from whom stored human biological materials are derived as well

as the number of specimens. For example, when a patient enters

the hospital for a biopsy, the resulting tissue is accessioned in the

pathology department as a single specimen. However, that single

biopsy may generate several samples, including a number of slides,

a paraffin block, and a frozen sample.

5 Only forensic DNA banks established according to state and 

federal regulations and laws are discussed in this report. The use 

of human biological materials in other repositories for forensic 

purposes also raises several ethical issues and is not addressed in

this report.

6 The term “DNA bank” refers to a facility that stores extracted

DNA, transformed cell lines, frozen blood or other tissue, or 

biological materials for future DNA analysis. Such materials are

usually stored with some form of individual identification for later

retrieval. DNA databanks are repositories of genetic information

obtained from the analysis of DNA, sometimes referred to as “DNA

profiles.” The genetic information is usually stored in computerized

form with individual identifiers.

7 Graduate Medical Education (GME) programs are the primary

means of medical education beyond the four-year medical school

training received by all physicians. Usually called residency programs, they are based in hospitals or other health care institutions,

some of which do and some of which do not have formal relationships with medical schools. GME teaching institutions include

medical schools; the Armed Forces hospitals; Veterans Affairs 

medical centers; the Public Health Service; state, county and 

city hospitals; nonprofit institutions; and health maintenance

organizations.

8 “Personal data: all data on a personally identified or personally

identifiable individual. An individual shall be counted as 

personally identifiable if he can be identified, directly or indirectly,

especially by reference to an identity number, or one or more 

factors specific to his physical, physiological, mental, economic,

cultural or social identity” (Act 1998).

9 According to a poll of 600 people conducted for an Icelandic

daily paper, Dagur, 11.6 percent of Icelandic citizens have already

opted out or plan to opt out of the database (www.mannvernd.is).

10 “The licensee shall be authorised to process data on the health

sector database from the health data recorded there, provided that

data are processed and connected in such a way that they cannot

be linked to identifiable individuals. The licensee shall develop

methods and protocols that meet the requirements of the Data

Protection Commission in order to ensure confidentiality in 

connecting data from the health-sector database, from a database 

of genealogical data, and from a database of genetic data. With

regard to linking the data on the health-sector database with 

other databases than those specified here, the Act on recording 

and handling of personal data shall apply” (Act 1998). 

11 See the National Institute of Mental Health at www.nimh.gov/.

12 NHANES, www.cdc.gov/nchswww/about/major/nhanes/nhanes.htm.

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Current Guidance on the Use 

of Human Biological Materials 

in Research

Chapter Three 3

Introduction

Currently, in the United States, the infrastructure that

oversees the use of human biological materials in

research includes federal regulations, state statutes governing the privacy of and research use of medical records,

policies developed by domestic scientific and professional

societies, and guidelines developed by other countries

and international organizations. When the National

Bioethics Advisory Commission (NBAC) began its review

of the use of human biological materials in research, it

found that the work of a number of other organizations

provided useful information regarding the range of positions that exist among those who have considered this

subject carefully. This chapter summarizes the current

existing federal regulations1 and how the practice of

Institutional Review Board (IRB) review and informed

consent might be viewed when considering the ethical

research use of human biological materials. (The federal

regulations are reproduced in Appendix B of this report.)

The chapter also provides a synopsis of the status of the

debate over privacy of medical information and outlines

existing policies regarding the research use of human biological materials that have been developed by scientific

and medical organizations, both in the United States and

internationally.

Scope of the Current Federal

Regulations

The Federal Policy for the Protection of Human Subjects

(45 CFR 46 or the “Common Rule,” as it is sometimes

called) is a set of regulations that was adopted 

independently by 17 federal agencies that conduct,

support, or otherwise regulate human subjects research;

the Food and Drug Administration (FDA) also adopted

certain provisions of the Common Rule and is governed

by additional regulations that apply to research on products in its regulatory purview.2 As implied by its title, the

Common Rule is designed to make uniform the human

subjects protection system in all relevant federal departments and agencies. The National Institutes of Health

Office for Protection from Research Risks (OPRR) has

taken the lead within the federal government in working

to make human subjects protections across agencies

consistent.3

When the federal regulations are applied to research

using human biological materials, a series of initial

inquiries is needed to determine whether the regulations

apply at all. This series of questions follows.

Does the Activity Constitute Research?

The federal regulations do not apply to exclusively

clinical interventions, even if they are experimental procedures. Rather, they apply to research, defined as “a systematic investigation designed to develop or contribute

to generalizable knowledge” (46.102(d)). Therefore, if

the use of the materials occurs solely as a part of a clinical intervention, as might be the case in a pathology laboratory, then the federal regulations do not apply. If the

use of materials has both clinical and research components, however, it might be subject to the federal regulations (see below). Thus, if a pathology laboratory saves

tissue that was left over from a clinical intervention in

order to conduct further, research-oriented testing, that

research would be subject to the federal regulations.

27
28

Is the Research Subject to Federal Regulation?

The federal regulations apply only to research that is

supported by funding from one of the federal agencies

that subscribes to the Common Rule or to research that

is conducted at an institution that has executed an

Assurance with the federal government that research,

including research not otherwise covered by the regulations, will nonetheless be governed by them. FDA regulations also apply to research on an investigational new

drug, device, or biologic deemed to be involved in interstate commerce (21 CFR 130.2(a)(12) and (13) and 36

CFR 5037). For example, an investigator conducting privately funded research at a large university that has executed a Multiple Project Assurance with the federal

government usually will be required to abide by the federal regulations.4 Multiple Project Assurance agreements

also include a provision that prevents researchers at an

institution from bypassing federal regulations often by

conducting the research off-site or with a private, unregulated company. Instead, these Assurances typically

promise that researchers affiliated with the institution will

abide by the federal regulations no matter where or with

whom they work. Thus, research on human biological

materials that is conducted using private funds and that

involves investigators who are free of affiliations with

institutions that have executed a Multiple Project Assurance

and who are not conducting research on products subject to

FDA regulation may not be subject to the federal human

subjects regulations.

Does the Research Involve a “Human

Subject?” 

Currently, the federal regulations apply only to

research involving a “human subject,” defined as “a living

individual about whom an investigator conducting

research obtains: (a) data through intervention or interaction with the individual, or (b) identifiable private

information.” Specifically, 

Intervention includes both physical procedures by

which data are gathered (for example, venipuncture)

and manipulations of the subject or the subject’s environment that are performed for research purposes.

Interaction includes communication or interpersonal

contact between investigator and subject. Private

information includes information about behavior that

occurs in a context in which an individual can reasonably expect that no observation or recording is

taking place, and information which has been provided for specific purposes by an individual and

which the individual can reasonably expect will not

be made public (for example, a medical record).

Private information must be individually identifiable

(i.e., the identity of the subject is or may readily be

ascertained by the investigator or associated with the

information) in order for obtaining the information to

constitute research involving human subjects

(46.102(f)(1) and (2)).

Based on this definition, it is apparent that an investigator who interacts with a person to obtain a new blood

or saliva sample is conducting human subjects research,

regardless of whether the investigator records any personal information about the subject.

When working with existing stores of biological

materials, an investigator is defined as conducting

research on a human subject when he or she obtains

“identifiable private information.” Section 46.102(f)(2)

defines “identifiable” to mean “the identity of the subject

is or may readily be ascertained by the investigator or...

associated with the information.” OPRR interprets “identifiable” to include samples with codes that, with the

cooperation of others, could be broken in order to reveal

the name of the sample source.5 On the other hand,

according to the regulations, research on samples provided to the investigator with no personal identifiers

and without codes linked to personal identifiers would

not be covered by the regulations, because no human

subjects would be involved. This provision has been the

cause of some confusion in the research community.

According to the regulations, research on samples that

are linked, even through a code, to personal information about the tissue source constitutes research on

human subjects and is subject to the federal regulations.

For example, a researcher may be interested in performing basic work toward the development of the mapping and sequencing of the human genome. He or she

might request tissue samples from a repository that has

stored specimens from an entire kindred. The samples

are identified by position within the kindred (e.g.,

“father,” “daughter,” “maternal aunt”), but the identity of
29

the family was not recorded at the time the materials

were collected. Thus, even if the investigator and the

repository were to attempt to recontact the tissue sources,

it would not be possible, because their identities are

unknown. In this scenario, according to the regulations,

there would be no human subjects involved, no IRB

review would be necessary, and consent from the tissue

sources for new and unanticipated forms of research

would not be required. If, however, means were developed to link this material to particular individuals, the

use of these samples would, under federal regulations,

become human subjects research.

Finally, under current federal regulations, only living

individuals may be human subjects. Research involving

tissues from individuals who are deceased at the time of

the research is not subject to the Common Rule, regardless of whether prior informed consent was obtained.

Such research, however, may be subject to the requirements of applicable state law. Of course, ethical concerns

may pertain to the use of such tissues that are beyond the

scope of current laws or regulations. In addition, in cases

in which research using samples from deceased individuals involves identifiable private information about their

living relatives, those relatives may themselves be human

subjects under the federal regulations and must be

afforded all of the required protections. Indeed, certain

types of genetic research or research on families could

pose risks for living relatives of the deceased (DeRenzo,

Biesecker, and Meltzer 1997).

For example, if research were to be conducted on the

autopsy material of a 30-year-old woman who died in a

traffic accident, and it was inadvertently discovered and

disclosed that she possessed the gene for Huntington’s

disease (which might not become manifest until age 50),

then that woman’s children automatically fall into a highrisk category for Huntington’s disease. Were they to be

informed of this finding, they would face the prospect of

being tested for the gene as well as of coping with the

psychosocial aspects of being at risk. It also is possible

that they would face health insurance and employment

discrimination.

Is the Research Eligible for an Exemption?

In some cases, research on human subjects is eligible

to be exempted from IRB review and other regulatory

requirements, such as subject consent. Work with

“unlinked” samples is probably eligible for such an

exemption. For example, one scenario might be that an

institution called HBM Collection of America has in its

collection a number of tissue specimens from kindreds.

An investigator requests from the company samples from

a family with achondroplasia (dwarfism). The company

takes samples from Family Jones, strips all references to

the family name “Jones,” and supplies the samples to the

investigator marked only by position within the family

group, such as “father,” “mother,” “maternal aunt,” or

“son.” The investigator has no way of knowing that the

samples come from the Family Jones and thinks of them

as unidentifiable. If the company has not maintained a

record linking the samples to Family Jones, then, according to the regulations, no human subject is involved in

the investigator’s research on the samples and no IRB

review or informed consent is required. However, if the

company has maintained a record that it sent samples

from Family Jones—and only Family Jones—to the

investigator, then, in fact, the identity of each tissue

source can be nearly or completely reconstructed by

combining what the investigator knows (family position)

with what the company knows (the name of the family).

The federal regulations are somewhat ambiguous regarding whether this meets the regulatory definition of identifiability, although it appears that it would. Keeping in

mind that one of the reasons for concern about the identifiability of the family is the possibility that research

information could flow back to the sample source, this

scenario appears to describe a situation in which information could be linked between the investigator and a

particular member of the family (with some added difficulty if there is more than one maternal aunt or son).

Even more complex would be a scenario in which

HBM Collection of America provides samples from several family groups, e.g., Family Jones, Family Smith, and

Family Williams. In this situation, no individual tissue

source can be determined with precision, but each individual can be identified as a member of the small group

that makes up these three families. If the investigator

were to discover provisionally that samples from one of

the families provided by the company indicated that its
30

sources were at some risk of significant illness, he or she

could be tempted to send this ambiguous but possibly

useful information to the sources via the company’s

record of which families’ samples are being studied. With

respect to current federal regulations, however, it is not

clear whether such a research protocol would be considered human subjects research. Even if it were, it probably

would be eligible for an exemption.

For Research Requiring Review, 

What Are the IRB Requirements?

For research in which individuals who provide biological materials are identifiable and that, therefore, is

subject to the federal regulations, two basic protections

for human subjects generally come into play: 1) informed

consent usually is required, and 2) IRB review is required

to ensure an acceptable balance between risks and benefits. (See Appendix B for a description of IRBs.) There are,

however, exceptions and variations that are pertinent to

research using human biological materials.

The twin protections of informed consent and IRB

review might not apply if the research is found to be

exempt from the federal regulations. The positions of the

persons who have the authority to determine if an

exemption applies will vary among institutions, depending upon the particular terms of the Assurance negotiated

with the government. In many cases, this individual will

be the chair of the research or clinical department in

which the investigator works. In others, it will be the

chair or the administrator of the IRB.

The regulations state that such an exemption may be

applied, for example, to “research involving the collection or study of existing specimens if the information is

recorded by the investigator in such a manner that subjects cannot be identified, directly or through identifiers

linked to the subjects” (46.101(4)). As noted, OPRR currently interprets this regulation to mean that investigators

who conduct research with coded samples are not eligible for the exemption if there is a ready means by which

the codes could be broken (including by cooperation

with other individuals and institutions) and if specific

research results could be linked to specific subjects.

Expedited IRB Review

For research that is not exempt from IRB review and

informed consent by the subjects, opportunities

nonetheless exist for streamlining the review process.

Research activities that 1) present no more than minimal

risk to human subjects and 2) involve only procedures

listed in certain categories6 may be reviewed by the IRB

through the expedited review procedure (authorized by

45 CFR 46.110 and 21 CFR 56.110).

Federal regulations already make many forms of

human biological materials collection (e.g., fingernail

clippings, saliva samples, and small blood draws) eligible

for expedited review (63 Fed Reg 60364, November 9,

1998). They also make research use of existing samples

eligible for expedited review under some circumstances

(63 Fed Reg 60364, Sec (f)(5)). However, the phrasing of

the federal regulations is ambiguous with regard to existing collections that were developed in a research context.

For research on human biological materials, a key

question concerning eligibility for expedited review will

be whether the research poses more than a minimal risk

to subjects. This assessment will depend upon the kind

of information sought, the psychosocial and clinical significance of the research to the subjects, and the likelihood that the findings will be transmitted to the subjects

or to anyone else who could associate the findings with

the subjects.

Informed Consent Requirements

If the research is not otherwise exempt from federal

regulations, all human subjects research generally

requires informed consent of subjects. However, this

requirement can be altered or waived if certain criteria,

set forth at 45 CFR 46.116(d), are met:

1) The research involves no more than minimal risk to

the subjects,

2) The waiver or alteration will not affect adversely the

rights and welfare of the subjects,

3) The research could not be practicably carried out

without the waiver or alteration, and 

4) Whenever appropriate, the subjects will be provided

with additional pertinent information following their

participation.

The meaning of “minimal risk,” therefore, is central to

determining if a nonexempt protocol is eligible for a

waiver of the consent requirements. It also is a key con-
31

sideration in determining whether a protocol is eligible

for expedited review. In addition, the practicability of

obtaining consent is an important consideration in

reviewing research using human biological materials, as

there may be a temporal and spatial distance between the

time the material was obtained and the point at which it

is used for research.

IRB Concern for Third-Party Interests

As mentioned earlier, the federal regulations are

focused on living individuals, especially identifiable individuals. If identifiable, individuals almost always are entitled to be asked whether they wish to be human subjects

of research. In addition, the IRB process is available to

review a protocol to assess its risks and benefits to subjects. However, nowhere in this process are the concerns

of third parties explicitly taken into account.

And yet, research on one individual may reveal

important, even sensitive, information about others.

Genetic testing on the deceased, as noted above, can

yield information about living relatives. And testing on a

number of otherwise unrelated individuals may yield

information pertinent to many unrelated people who

share salient characteristics, such as race, ethnicity, or the

presence of a predisposing condition. This, in turn, could

result in members of the group facing, among other

things, stigmatization and discrimination in insurance

and employment. 

In the view of some, the strict focus of the federal regulations on the interests of the individual research subject

may be problematic in the context of research with

human biological materials. Ways in which third-party

interests can be identified and protected where appropriate should be considered and are discussed further in

Chapters 4 and 5.

Applying the Regulations to a Research Protocol:

Issues for IRBs to Consider

Imagine a gene for a form of prostate cancer.

Researchers may wish to screen large numbers of samples

of prostate tissue currently stored in academic and commercial repositories to identify those who have markers

for this hypothetical gene. Having identified this subset,

investigators then may wish to examine the medical

records of those men who appear to have the gene in

order to identify correlations in areas such as medical

history, symptomology, characteristics of the tumor, treatment choices, and outcomes. This work, in turn, may

result in identifying further subsets for more refined

study designed to correlate the gene with a particular

type of tumor or treatment response.

Under current regulations, any link between the samples

that are used by the researcher and the men from

whom the materials were obtained would render the

activity human subjects research. This identifiability,

even if mediated by coding systems, would trigger the

requirement for IRB review (at applicable institutions).

The review might be eligible for expedited procedures,

however, if the protocol were deemed to be of minimal

risk to the subjects and fulfilled the other requirements

for expedited review.

If the initial screen of all of the samples, conducted

solely for the purpose of identifying which men have the

gene, were conducted with unlinked samples, according

to the regulations, the research could be exempt from IRB

review. However, this would allow the researcher to

receive only a limited amount of clinical and demographic information when the sample is sent from the

repository. If the researcher chooses to use coded samples

in order to obtain follow-up information or to communicate information back to the sample source, the research

would be subject to IRB review, either full review or expedited review. In either case, it will be up to the IRB to

determine whether the researcher would need to get

consent from the source. This will depend upon whether

the subject gave consent for such research at some time

in the past. If not, the IRB will require consent unless it

finds that consent can be waived because the research is

of minimal risk and it is impracticable to go back to the

source for that consent. 

Research conducted using coded samples would

allow for a second screen in which the subset of men

whose tissues showed a marker for the gene would have

their medical records examined. The same issues regarding minimal risk would apply to this screen, but a seemingly greater risk would exist that findings would

develop in the course of research that might prompt

investigators to consider communicating them to the

sources or to their physicians. For example, if the data
32

strongly indicate that those with the markers respond

dramatically better to one treatment than to another,

investigators might wonder whether it would be best to

communicate this information to a patient and/or to his

physician so that the treatment can be pursued before the

patient’s health declines irreversibly.

At the same time, in the view of many, the tentative

nature of such findings may make their communication

problematic. For example, because some prostate treatments may have significant side effects, such as impotence and incontinence, and because the clinical data on

the need to detect and treat slow-growing prostate cancers in older men are ambiguous, disclosure of such tentative findings may cause patients to experience great

uncertainty and anxiety without the assurance of clinical

benefit. It is the difficulty of understanding the meaning

of minimal risk with regard to psychosocial harm (as

opposed to physical harm) that makes this issue so complex and, in turn, makes the decision about eligibility for

consent waivers so difficult. It is important to note, however, that disclosure of medical information also can be

beneficial to the subject. 

Medical and Scientific Organization

Standards and Guidance

When NBAC began its review of the use of human biological materials in research, the thoughtful work on the

issue done by a number of scientific and medical organizations was considered. Many such organizations have

developed position statements and recommendations

that reflect their efforts to work through the many ethical

and policy issues that the topic raises. These position

statements, although lacking the force of the federal regulations, can be influential in shaping the behavior and

practices of the scientific community. NBAC conducted a

comparative analysis of 14 statements as they applied to

the issue of protections for the appropriate use of human

biological materials in research. (See Appendix C.) In

general, considerable disagreement was apparent among

the statements regarding what constitutes an identifiable

human subject, when informed consent should be

required, and what constitutes proper consent.

Confusion in the definitions, combined with vague regulatory language, has contributed to the considerable

challenge that IRBs face in reviewing this type of

research. For example, some groups call unidentified and

unlinked samples anonymous materials, that is, materials

that were originally collected without identifiers or are

otherwise impossible to link to their sources. Others use

the phrase “anonymous use” to indicate that although the

materials may retain identifiers in the repository, the

investigator does not have access to that information.

Many groups recommend different protections

according to the degree to which samples used in a

research protocol can be linked to a subject. Therefore,

how a group defines identifiable information is important

when considering the protections that it recommends.

Some groups define “identifiable” samples as exclusively

“coded” materials; others use the term “identifiable” to

encompass both “coded” and “directly identified” materials (Clayton et al. 1995). The Pathologists Consensus

Statement, for example, recommends that different protections be applied to research that uses archived, coded

samples than to research that uses directly identified

samples. The statement emphasizes the importance and

feasibility of “maintaining patient identity and clinical

information separate from research data through the use

of coding” (Grizzle et al. 1997). 

Many organizations have provided guidelines on how

to address some of the difficult decisions that arise in the

course of research using stored materials. These decisions

include when and how to recontact individuals regarding

consent for new research uses of their samples; how to

judge the adequacy of previously given consent; and how

to assess protocols that propose to remove identifying

information from samples before using them in research7

(ACMG 1995). In addition, a number of organizations

have discussed extensively how to design a manageable

informed consent process that would address the individual’s concerns about the present and future uses of his

or her sample and that would be comprehensible to

patients and research subjects. The types of consent proposed range from general consent (consent to future,

unspecified research uses of the material), to layered consent (which offers the subject the option to consent to a

variety of classes of research), to specific consent for a

unique designated protocol.

In some cases, the statements offer insightful discus-
33

sion regarding what level of consent is appropriate for the

use of materials. Regarding general consent, the

American Society of Human Genetics points out that in

certain instances, general consent may be inappropriate,

noting that “[i]t is inappropriate to ask a subject to grant

blanket consent for all future unspecified genetic

research projects on any disease or in any area if the

samples are identifiable in those subsequent studies”

(ASHG 1988). On the other hand, the Pathologists

Consensus Statement notes that there may be value in

requiring general consent, stating that “[t]o give a

description of each and every research protocol which

might be performed in the (sometimes distant) future on

a patient’s tissue is an unreasonable burden for the

patient and the researcher” (Grizzle et al. 1997).

Several statements advocate a form of layered consent

for collecting all samples in the future. The National

Heart, Lung, and Blood Institute (NHLBI) provides

thoughtful discussion on the content of a proposed threetiered consent in which, as NHLBI describes it, an individual is offered the option of consenting to the current

study (first level), a study with goals broadly related to

the area of the original study (second level), and a study

with goals unrelated to the area of the original study

(third level) (NHLBI 1997).

International Perspectives on the Use of

Human Biological Materials in Research

Statements addressing the ethical use of human tissues in

research were issued in 1998 by the European Group of

Ethics (EGE), advising the European Commission, the

Human Genome Organisation (HUGO), the three major

funding organizations in Canada, and the World Health

Organization (WHO).8 The EGE—a group of national ethics

commissions—issued its Opinion on Human Tissue Banking

(1998), which covers a wide variety of human tissues used for

diagnostic, therapeutic, and research purposes. In contrast to

the statements issued in the United States, the EGE opinion

focuses primarily on regulating therapeutic uses of tissue (e.g.,

transplants) and stresses safety as an ethical imperative, calling

for strict control of human tissue banks. It recommends a system that would protect the identity of the source while permitting the source to be traced if necessary in order to

address matters regarding the safety of the donated tissue. The EGE also provides an overview of the status of

legislation and ethical guidelines with regard to human

tissue banking in the Member States of the European

Union.

The HUGO Ethics Committee issued its Statement on

DNA Sampling: Control and Access, which addresses several

ethical issues pertinent to sample collection and sharing

in genetic research (1998). Of primary importance in this

statement is the source of the material, “that is, whether

it was collected during routine medical care or during a

specific research protocol since this affects the ambit and

the choices available in the consent process.” HUGO’s

Ethics Committee bases its specific recommendations

concerning the use of stored materials in research on two

factors: “1) the source of the sample, and 2) whether

there was, at the time the sample was collected, ‘general

notification’ of the institution’s policy concerning future

uses of samples.” Of the categories of materials it defines,

the Committee recommends the most stringent protection for the research use of “routine samples, obtained

during medical care and stored...before notification of

such a policy” (HUGO 1998).

Addressing research conducted in the future, the

HUGO Ethics Committee provides recommendations

regarding the choices that should be offered in the consent process. It lists the potential uses of the sample and

the data that may be obtained from it as important information to include in the process and recommends that

the consent process also should indicate “whether the

sample and its information will: identify the person, code

the identity, or anonymize the identity so that the person

cannot be traced although some demographic and clinical data may be provided.”

The statement from HUGO is notable for its focus on

protecting the rights of family members in addition to

those of individual sources. It notes as ethical prerequisites “respect for individual values, familial needs and

cultural differences as well as the possibility of withdrawal of consent to participate.” Reflecting this focus, it

recommends that special considerations be made for

access by “immediate relatives” in situations in which

“there is a high risk of having or transmitting a serious

disorder and prevention or treatment is available.”
34

Finally, its call for international standardization of “ethical requirements for the control and access of DNA samples and information” is a recommendation echoed by

other international groups.

In 1998, the three major funding organizations in

Canada issued standards and procedures for governing

research involving human subjects (Medical Research

Council 1998). In a section devoted to the use of human

tissue in research, the Canadian statement addresses

issues of privacy and confidentiality, free and informed

consent, and the use of previously collected tissues.

Elsewhere in this document, other concerns raised by

human genetic research, such as protecting families and

biological relatives and the banking of genetic material,

are discussed.

The Canadian statement distinguishes four categories

of tissue: identifiable (immediately linkable to a specific

individual), traceable (potentially traceable provided

there is access to further information such as a patient

record or a database), anonymous, and anonymized. It

states that the investigator does not need to seek consent

unless applicable law so requires “when collected tissue

has been provided by persons who are not individually

identifiable (anonymous and anonymized tissue), and

where there are no potential harms to them.” The statement notes that even when it is not possible to identify

an individual, the “interests of biological relatives and distinct cultural groups may be adversely affected through

research uses of their anonymous tissue.” It requires that

researchers involving families and groups in genetic

research reveal potential harms to the ethics board and

outlines how researchers will deal with those harms.

The WHO Human Genetics Programme in 1998

issued its Proposed International Guidelines on Ethical Issues

in Medical Genetics and Genetic Services, which devotes a

section to “Banked DNA.” According to the document,

the purpose of these proposed guidelines is “to assist policy-makers, officials, practitioners and other health workers in the Member States of WHO in ensuring that

genetic information and genetic services are introduced

into the broader medical practice of the nations in ethically acceptable ways.” The WHO proposes that existing

stored specimens “should not be subject to new rules for

consent or recontact that may be established in the

future,” and states that, in the future, “a blanket informed

consent that would allow use of a sample for genetic

research in general, including future, as yet unspecified

projects, appears to be the most efficient and economical

approach, avoiding costly recontact before each new

research project.”

The WHO, in addressing the issue of samples to be

collected in the future, recommends a list of issues to

consider when policies are developed. These include the

protection of individuals from possible discrimination,

possible benefits to the individual from research findings,

the possibility of multiple uses of the same sample in different and unforeseen research projects, possible sharing

of biological materials among collaborators, and the

advantages and disadvantages for individuals and

researchers of removing all identifiers from a sample. In

addition, the WHO’s proposal, like that issued by

HUGO, discusses the interests that biological relatives

have in the control of DNA specimens. The document

states that “control of DNA may be familial, not only individual” and recommends that “blood relatives may have

access to stored DNA for purposes of learning their own

genetic status, but not for purposes of learning the

donor’s status.”

To summarize, these statements reveal that many of

the guidelines are based on common ethical considerations, such as respect for privacy and confidentiality,

respect for autonomy operationalized by a requirement

of informed consent, and the noncommercialization of

human biological materials. A common position seems to

be emerging that a person’s rights and interests are best

protected if that person has some form of control over his

or her removed biological material. Nonetheless, a rich

diversity of positions exists on how to control access to

and use of human biological materials and the data

obtained from them. A greater standardization of policies

with regard to the use of DNA samples certainly would

facilitate future international cooperation in biomedical

research.

Publication Guidelines

Publishing research findings in the peer-reviewed

literature is a principal method of sharing research
35

information (Fienberg, Martin, and Straf 1985) and is an

important goal of many researchers. As such, it represents

a common gateway to information in the research process.

Indeed, dissemination of new scientific knowledge has

been described as an important ethical obligation (Meslin

1994). As gatekeepers in the process, journal editors set

standards for the work that is accepted for publication and

sometimes require compliance with ethical standards

(Botkin et al. 1998). Ethical requirements are described in

the Uniform Requirements for Manuscripts Submitted to

Biomedical Journals published by the International

Committee of Medical Journal Editors (1999) and

have been adopted by more than 500 journals and the

OPRR Guidebook (OPRR 1993). In light of the incentive to publish within the scientific community, publication requirements represent a potentially effective

means of influencing research practices (Amdur and

Biddle 1997). 

Nonetheless, the question of whether publication

requirements should include ethical standards is controversial (Caelleigh 1993; Snider 1997). The convenience

or effectiveness of using publication as an ethical checkpoint may not be a sufficient reason for involving ethical

standards as part of the publication process. However,

one could argue that a responsibility on the part of journal editors to set ethical standards for publication stems

from the harms that may arise from the act of publishing.

In Chapter 4, NBAC argues that specific risks are associated with publishing pedigrees and other research information. These risks might be dramatically reduced if all

journals adopted the Uniform Requirements. 

Medical Record Protection

Many protocols that call for the research use of human

biological materials also will require that information

from relevant medical records accompany the tissue.

Such information would, as noted, allow investigators to

correlate characteristics of the tissue with characteristics

of the etiology and the course of the patient’s disease and

the patient’s response to various treatments.

The federal regulations that govern human subjects

research apply to the use of medical records. Efforts to

link one record with another or to link a record with an

interview of the patient can be considered research under

the federal definitions. If the records have any personal

identifiers, then this constitutes human subjects research

and requires IRB review and patient/subject consent,

subject, of course, to the exceptions outlined above.

Indeed, the regulations governing tissue use and medical

record use basically are the same, and on a practical level,

they treat tissue as simply another form of a medical

record.

Currently, no federal law protects the privacy of medical records, unless the records are held by the government. Recent legislative movements, however, have

sought to address this issue. The passage of the Health

Insurance Portability and Accountability Act of 1996

(HIPAA) effectively set a deadline for Congress to act to

protect personal privacy. HIPAA required the Secretary of

Health and Human Services, in consultation with the

National Committee on Vital and Health Statistics, to

make recommendations to Congress on ways to protect

“individually identifiable” information and to establish

penalties for wrongful disclosure of personal health information. The Secretary presented those recommendations

in September 1997; Congress now has until August 1999

to enact a privacy law. If Congress fails to act, the

Secretary is directed to promulgate regulations within 42

months of HIPAA enactment (i.e., by February 21, 2000)

relating to the privacy of health information transmitted

in connection with specified electronic transactions. On

August 11, 1998, the Department of Health and Human

Services (DHHS) proposed such regulations, designed to

protect the electronic flow of medical data between

health care providers, insurers, and clearinghouses from

improper access or alteration. The proposed regulations

and accompanying technical guidance require all parties

that deal with electronic health information to establish

responsible and appropriate safeguards, to develop security plans, to provide training for employees, to secure

physical access to records, and to implement a digital signature procedure in order to verify the identities of the

persons accessing medical records.

Although the 105th Congress considered several

proposals regarding medical privacy, no law was passed

during the 1998 session. The major patient protection

bills that were considered all contained confidentiality
36

provisions and gave individuals the right to inspect and

copy their medical records, except in special circumstances.9 In addition, several legislative proposals focused

exclusively on medical records confidentiality.10 These

bills differed in their treatment of certain issues, such as

the appropriate uses of personally identifiable information, whether federal regulations should be applied to

both federally and nonfederally funded researchers who

use personally identifiable data, and how broad federal

preemption of state laws pertaining to confidentiality

should be.

With respect to research, the bills differed in both

their treatment of federally and privately funded research

and in their reliance on the current IRB system. Many of

the bills required approval by an IRB for federally funded

and nonfederally funded research.11 One bill permitted

disclosure to health researchers if such disclosure was

“reviewed by a committee, board, or informal organization in accordance with confidentiality standards specifying permissible and impermissible uses of the

information.”12

Finally, the legislative initiatives generally differed on

whether to establish a floor or a ceiling for federal standards. Many of these initiatives would have preempted

most state laws, except those pertaining to mental health

and public health activities.13 Others would not have preempted any state laws that provide a greater level of protection for personally identifiable health information.14

The latter position is generally consistent with the recommendations presented to Congress by DHHS.

State Laws

General statutory and common law rules lay the

groundwork in many states for a claim of a violation of

privacy against nonconsensual use of medical records.

Indeed, nearly every state has laws or regulations that

provide varying degrees of protection for information

contained within medical records. Recently, states have

adopted these statutes most often in the context of protecting the confidentiality of records regarding certain

diseases, such as HIV, AIDS, and various mental illnesses.

In most instances, these acts are aimed at preventing the

use of such personal medical information by insurance

companies and employers, thereby protecting the

individual from discrimination and/or stigmatization.

However, the variability of state law protections has been

cited as a problem in and of itself.

Where statutes exist, they specifically may contemplate access to medical records for research use.

California’s medical records confidentiality law, for

example, states that “information may be disclosed to

public agencies, clinical investigators, health care

research organizations, and accredited public or private

nonprofit educational or health care institutions for bona

fide research purposes. However, no information so disclosed shall be further disclosed by the recipient in any

way which would permit identification of the patient.”15

This section exempts releases of unidentifiable medical

information for bona fide research purposes from the

law’s general requirement of patient authorization for any

release.

The California law defines medical information as

“any individually identifiable information in possession

of or derived from a provider of health care regarding a

patient’s medical history, mental or physical condition, or

treatment,”16 language that is similar to that of the

Common Rule. Finally, it is interesting to note that

California separately addresses disclosure of genetic test

results contained in an “applicant or enrollee’s medical

records” by a health care service plan. The law forbids

disclosure by a health care service plan of “results of a test

for a genetic characteristic to any third party in a manner

that identifies or provides identifying characteristics of

the person to whom the test results apply, except pursuant to a written authorization.”17

Florida and Minnesota laws also address specifically

the use of medical records in research. Florida’s general

medical record confidentiality statute states that records

“may not be furnished to, and the medical condition of a

patient may not be discussed with, any person other than

the patient or the patient’s legal representative or other

health care practitioners and providers involved in the

care or treatment of the patient, except upon written

authorization of the patient.”18 However, as in California,

such records may be furnished without written authorization “[f]or statistical and scientific research, provided

the information is abstracted in such a way as to protect

the identity of the patient or provided written permission
37

is received from the patient or the patient’s legal

representative.”19

In Minnesota, 

[a] provider, or a person who receives health

records from a provider, may not release a patient’s

health records to a person without a signed and

dated consent from the patient or the patient’s

legally authorized representative authorizing the

release, unless the release is specifically authorized

by law....[A] consent is valid for one year or for a

lesser period specified in the consent or for a 

different period provided by law.20

An exception to Minnesota’s general rule is that health

records “may be released to an external researcher solely

for purposes of medical or scientific research.” The state

allows the release of health records generated before

January 1, 1997, if the patient has not objected or does

not elect to object after that date; in contrast, the state

requires that, for health records generated on or after

January 1, 1997, the provider must

■ disclose in writing to patients currently being treated

by the provider that health records, regardless of

when generated, may be released and that the patient

may object, in which case the records will not be

released; and 

■ use reasonable efforts to obtain the patient’s written

general authorization that describes the release of

records in item (i), which does not expire but may be

revoked or limited in writing at any time by the

patient or the patient’s authorized representative.

Furthermore, in making a release for research purposes, the provider must make a reasonable effort to

determine that

■ the use or disclosure does not violate any limitations

under which the record was collected;

■ the use or disclosure in individually identifiable form

is necessary to accomplish the research or statistical

purpose for which the use or disclosure is to be made;

■ the recipient has established and maintains adequate

safeguards to protect the records from unauthorized

disclosure, including a procedure for removal or

destruction of information that identifies the patient;

and

■ further use or release of the records in individually

identifiable form to a person other than the patient

without the patient’s consent is prohibited.

In addition to existing statutes, there has been a

recent proliferation of state legislative initiatives addressing the use of medical information.21 Many of these initiatives attempt to protect an individual’s privacy interest

by preventing the dissemination of personal information

and do so by restricting the ability of those who hold

medical records, such as hospital pathology laboratories,

to give out information from the records and by restricting the ability of investigators to conduct such research

except in certain circumstances.

According to many of the pending initiatives, when a

researcher who uses human biological material requests

additional information about the source of a sample, the

record holder may have a legal obligation not to disclose

that information. Primarily, information from medical

records can be disclosed only if one of two conditions is

fulfilled: either the patient (or the patient’s legally authorized representative) provides a specific, written consent

that information from his or her medical record can be

released in the circumstances at hand, or the information

that is requested and released will not permit identification of the individual. Exactly what constitutes identifying information often is not defined by the legislative

initiatives, and it varies from state to state. Several proposed bills provide a civil action for negligent release of

personal information without consent or for violation of

the bills’ confidentiality requirements.

Finally, many legislative initiatives prohibit research

facilities from obtaining or retaining samples for genetic

testing unless the source has given consent or the sample

is used in anonymous research. A few states are considering bills that provide the sample source with greater

control over the sample’s uses by giving the source a legal

property right to the sample and to the information that

is derived from it.22 To date, however, only one state has

passed such a provision into law, and the property right

it grants does not address the source’s ability to profit

monetarily from the sample.23 What appears clear from

the state legislative initiatives is that a perceived need

exists to protect medical information, especially information that can be linked to an individual, from the
38

possible negative consequences of research conducted on

human biological materials and personal information

derived from such materials.

Courts themselves only recently have begun to recognize privacy rights with respect to individuals’ medical

records. Early cases viewed unauthorized disclosure as a

form of breach of statutory duty, libel, malpractice,

breach of trust, or breach of contract. The language in

one New York case strongly condemned what it deemed

a valid claim for unauthorized revelation of medical

secrets: “Despite the fact that in no New York case has

such a wrong been remedied, due most likely to the fact

that so few physicians violate this fundamental obligation, it is time that the obligation not only be recognized

but that the right of redress be recognized as well.”24

Similarly, the United States Court of Appeals for the

Third Circuit tentatively recognized a form of a privacy

right against the government’s request for access to medical records in order to investigate alleged health hazards.

The court balanced this right against seven factors: “the

type of record requested, the information it does or might

contain, the potential for harm in any subsequent nonconsensual disclosure, the injury from disclosure to the

relationship in which the record was generated, the adequacy of safeguards to prevent unauthorized disclosure,

the degree of need for access, and whether there is an

express statutory mandate, articulated public policy, or

other recognizable public interest militating toward

access.” In that case, the court held that “the public need

prevailed over the claim that medical records in general

were protected from discovery.”25 Of course, it is not necessarily true that all courts conducting this type of analysis would grant investigators access to medical records

despite asserted privacy rights.

More recently, the Second Circuit found that an individual has a constitutional right to privacy regarding HIV

status because a person’s medical condition is a matter

that an individual is normally entitled to keep private.26

Again, it is unclear how this would apply in a medical

research setting, but it is significant for its explicit

reliance on constitutional levels of protection for one’s

right to keep medical information private. Finally, some

state constitutions offer additional various types of

privacy protection.27

Summary

In its deliberations, NBAC has reviewed the applicability

of the existing federal regulations pertaining to research

with human biological materials and has identified some

notable ambiguities. First, the current regulations do not

make completely clear what is meant by “identifiability”

when determining whether in fact a human subject is

involved in research conducted using human biological

materials. Thus, confusion results regarding just how certain types of research relate to existing federal regulations

and requirements (based on how closely the samples are

linked to their sources and how easily those linkages can

be accomplished). The issue of identifiability is further

confounded by the researcher’s growing ability to identify

the source (even when ostensibly unidentified) because

of the unique nature of the clinical information that

accompanies the material when it is delivered from the

repository. The confusion about identifiability has implications for the harms that may occur and the consent that

may be required.

In addition, scientific and medical groups vary in how

they define the identifiability of samples and the protections recommended for each category. Several of these

groups have developed guidelines for IRBs and investigators to use as they confront the questions that arise when

research using existing human biological materials is proposed. These guidelines contain discussion, although not

explicit, regarding the mechanisms for ensuring that

human biological materials are stored and/or used in

such a way that the confidentiality of the source of the

material is protected. Moreover, current federal regulations are silent on the topic of group or community

harm. Thus, protocols that pose insignificant risks to

individuals but that may implicate strong group interests

do not receive special IRB attention. This has implications for groups such as kindreds or ethnic and racial

subpopulations as well as collectivities of individuals

who share a common trait, such as a genetic condition or

disease status.

In addition, existing regulations offer insufficient

guidance on the meaning of minimal risk or the nature of

the subjects’ rights and welfare to be protected, and they

do not make clear the status of living relatives of
39

deceased individuals whose stored samples are used in

research. This issue is addressed in Chapter 5; however,

NBAC makes no new recommendations in this area.

Although OPRR has indicated that these individuals may

in fact be considered human subjects by virtue of their

genetic relationship to the sample source, the regulations

do not specify how this consideration is to be handled by

IRBs. Finally, major unresolved issues remain that pertain

to the ongoing access to medical records. These issues

have significant implications for research using human

biological materials.

Despite the fact that the current regulations appear to

apply in most cases, other issues pertaining to adequate

protections arise. For example, provision of informed

consent is a required but insufficient protection of both

the interests of the research subject and the investigator.

Moreover, there may be overriding state laws that apply

regarding the research use of medical records, thereby

limiting the ability of researchers to gather unlimited

information from individuals whose names are linked to

the biological material. Chapter 4 addresses the ethical

issues that should be considered when devising a strategy

for the review and conduct of research using human

biological materials.

Notes

1 As used in this report, the term “federal regulations” refers to the

Department of Health and Human Services (DHHS) regulations

contained in Part 46 of Title 45 of the Code of Federal Regulations,

except where noted.

2 In addition, on February 28, 1997, the Food and Drug

Administration announced a Proposed Approach to Regulation 

of Cellular and Tissue-Based Products [Docket Number 

97N-0068], which encompasses an array of medical products

derived from the human body and used for replacement, 

reproductive, or therapeutic purposes. The document is 

available at www.fda.gov/cber/gdlns/celltissue.txt.

3 The Office for Protection from Research Risks (OPRR) fulfills

responsibilities set forth in the Public Health Service Act. These

include: (1) Developing and monitoring, as well as exercising 

compliance oversight relative to: (a) HHS Regulations for the 

protection of human subjects in research conducted or supported

by any component of the Department of Health and Human

Services; and (b) PHS Policy on Humane Care and Use of

Laboratory Animals involved in research conducted or supported

by any component of the Public Health Service; (2) coordinating

appropriate HHS regulations, policies, and procedures both 

within HHS and in coordination with other Departments and

Agencies in the Federal Government; and establishing criteria for

and negotiation of Assurances of Compliance with institutions

engaged in HHS-conducted or supported research involving

human subjects and those engaged in PHS-conducted or supported

research using animals; (3) conducting programs of clarification

and guidance for both the Federal and non-Federal sectors with

respect to the involvement of humans and the use of animals in

research; and directing the development and implementation of

educational and instructional programs and generating educational

resource materials; 4) evaluating the effectiveness of HHS policies

and programs for the protection of human subjects and the

humane care and use of laboratory animals; and (5) serving as 

liaison to Presidential, Departmental, Congressional, interagency,

and non-governmental Commissions and Boards established to

examine ethical issues in medicine and research and exercises 

leadership in identifying and addressing such ethical issues.

4 The regulations require that each covered institution engaged 

in the conduct of research involving human subjects provide a

written assurance of compliance stating that it will comply with 

the requirements set forth in these regulations. The document is

referred to as an Assurance. Each Assurance sets forth the commitment of the institution to employ the basic ethical principles of the

Belmont Report and to comply with the regulations. There are several kinds of Assurance documents. If an independent investigator

provides an assurance of compliance to OPRR, the document is

called an Agreement. 

5 Personal communication from Dr. Gary B. Ellis, Director, OPRR,

April 8, 1998.

6 See 63 FR 60364-60367, November 9, 1998, for categories.

7 For example, the statement from the American College of

Medical Genetics (ACMG) lists factors to be considered “in deciding whether it is appropriate to use previously collected samples

without contacting the individual”: “[A]re or will the samples be

made anonymous?; the degree to which the burden of contacting

individuals may make it impracticable to conduct research; existence and content of prior consent; and risks and benefits” (1995).

8 For a more in-depth analysis of ethical and legal policy statements on the use of DNA samples in human genetic research 

from governmental, nongovernmental, and professional bodies 

at the international, regional, and national levels see Knoppers, 

B., M. Hirtle, S. Lormeau, C.M. Laberge, and M. Laflamme, 1997,

“Control of DNA Samples and Information.” This background

paper was prepared for NBAC and is available in Volume II of 

this report.

9 For example, S. 2330, S. 1890/H.R. 3605, S. 2416, H.R. 4250.

10 See “Health Care Personal Information Nondisclosure Act of

1998,” S. 1921; “Medical Information Privacy and Security Act,” 

S. 1368; “Consumer Protection and Medical Record Confidentiality

Act of 1998,” H.R. 3900; “Medical Privacy in the Age of New

Technologies Act of 1997,” H.R. 1815; “Fair Health Information

Practices Act of 1997,” H.R. 52, H.R. 1815.
40

11 See S. 1368, H.R. 1815.

12 H.R. 3900.

13 See S. 1921, H.R. 52, H.R. 3900.

14 S. 1368, H.R. 1815.

15 Cal. Civ. Code Ann. § 56.10(c)(7) (West 1982 and Supp. 1998).

16 Ibid. § 56.05(b).

17 Ibid. § 56.17.

18 Fla. Stat. § 455.667(5) (1997). 

19 Ibid. § 455.667(5)(d).

20 Minn. Stat. § 144.335 subdivision 3a (1997).

21 See, for example, 1997 MA H.B. 2668; 1998 UT H.B. 271;

1997 NY S.B. 3286; 1997 MI H.B. 5459; 1997 FL S.B. 1850; 1997

DE S.B. 153.

22 See, for example, 1998 UT H.B. 271; 1997 MI H.B. 5459.

23 See Oregon’s statute addressing an individual’s rights in genetic

information, ORS @ 659.715 (1997).

24 93 Misc. 2d 201 (N.Y. Sup. Ct. 1977).

25 United States v. Westinghouse Electric Corp., 638 F.2d 570 

(3d Cir. 1980).

26 Doe v. City of New York, 15 F.3d 264, 267 (2d Cir. 1994).

27 See, for example, Alaska Const. Art. I, Section 22; Ariz. Const.

Art. II, Section 8; Cal. Const. Art. 1, Section 1; Fla. Const. Art. 1,

Sections 12, 23; Haw. Const. Art. 1, Section 6; Ill. Const. Art. I,

Section 6; La. Const. Art. I, Section 5; Mont. Const. Art. II, Section

10; S.C. Const. Art. I, Section 10; Wash. Const. Art. I, Section 7.

Generally, these state constitutional provisions require that state

action must have caused the violation for protections to apply

(IOM 1994). California’s constitutional privacy right is more

explicit; it can be applied to privacy infringements by private 

parties. See Cal. Const. Art. 1, Section 1: Heda v. Superior Court,

225 Cal. app. 3d 525 (Cal. Dist. Ct. app. 1990); Soroka v. Dayton

Hudson Corp. 1 Cal. Rptr. 2 d 77 (Cal. Ct. app. 1991).

References

Amdur, R.J., and C. Biddle. 1997. “Institutional Review Board

Approval and Publication of Human Research Results.” Journal of

the American Medical Association 277:909–914.

American College of Medical Genetics (ACMG). Storage of

Genetics Materials Committee. 1995. “Statement on Storage and

Use of Genetic Materials.” American Journal of Human Genetics

57(6):1499–1500.

American Society of Human Genetics (ASHG). Ad Hoc Committee

on DNA Technology. 1988. “DNA Banking and DNA Analysis:

Points to Consider.” American Journal of Human Genetics

32(5):781–783. 

Botkin, J.R., W.M. McMahon, K.R. Smith, and J.E. Nash. 1998.

“Privacy and Confidentiality in the Publication of Pedigrees.”

Journal of the American Medical Association 279:1808–1812.

Caelleigh, A.S. 1993. “Role of the Journal Editor in Sustaining

Integrity in Research.” Academic Medicine 68(9):S23–S29. 

Clayton, E.W., K.K. Steinberg, M.J. Khoury, E. Thomson, 

L. Andrews, M.J.E. Kahn, L.M. Kopelman, and J.O. Weiss. 

1995. “Informed Consent for Genetic Research on Stored 

Tissue Samples.” Journal of the American Medical Association

274:1786–1792.

DeRenzo, E.G., L.G. Biesecker, and N. Meltzer. 1997. “Genetics

and the Dead: Implications for Genetics Research with Samples

from Deceased Persons.” American Journal of Medical Genetics

69:332–334.

Fienberg, S.E., M.E. Martin, and M.L. Straf, eds. 1985. Sharing

Research Data. Washington, DC: National Academy Press.

Grizzle, W., W.W. Grody, W.W. Noll, M.E. Sobel, S.A. Stass, 

T. Trainer, H. Travers, V. Weedn, and K. Woodruff. 1997. Ad Hoc

Committee on Stored Tissues. College of American Pathologists.

“Recommended Policies for Uses of Human Tissue in Research,

Education, and Quality Control.” Archives of Pathological Laboratory

Medicine 123(4):296–300. 

Human Genome Organization Ethics Committee (HUGO). 1998.

Statement on DNA Sampling: Control and Access. London: HUGO.

International Committee of Medical Journal Editors. 1999.

“Uniform Requirements for Manuscripts Submitted to Biomedical

Journals.” Medical Education 33(1):66–78. 

Institute of Medicine (IOM). 1994. Committee on Regional Health

Data Networks. In Health Data in the Information Age, eds. M.S.

Donaldson and K.N. Lohr. Washington, DC: National Academy

Press.

Medical Research Council, Natural Science and Engineering

Research Council, Social Sciences and Humanities Research

Council. 1998. Tri-Council Policy Statement: Ethical Conduct for

Research Involving Humans. Ottawa: Public Works and Government

Services.

Meslin, E.M. 1994. “Toward an Ethic in Dissemination of 

New Knowledge in Primary Care Research.” In Disseminating

Research/Changing Practice: Research Methods for Primary Care,

Vol. 6, eds. E.V. Dunn, P.G. Norton, M. Stewart, F. Tudiver, and

M.J. Bass, 32–44. Thousand Oaks, CA: Sage Publications. 

National Heart, Lung, and Blood Institute (NHLBI), NIH. 1997.

Report of the Special Emphasis Panel, Opportunities and Obstacles to

Genetic Research in NHLBI Clinical Studies. Bethesda, MD: National

Institutes of Health. 

Office for Protection from Research Risks (OPRR). 1993. 

Protecting Human Research Subjects: Institutional Review Board

Guidebook. Washington, DC: U.S. Government Printing Office.

Snider, D.E. 1997. “Patient Consent for Publication and the 

Health of the Public.” Journal of the American Medical Association

278:624–626.

World Health Organization (WHO). 1998. “Proposed International

Guidelines on Ethical Issues in Medical Genetics and Genetic

Services.” Law and the Human Genome Review 9:239–251.
Ethical Perspectives 

on the Research Use of 

Human Biological Materials

Chapter Four 4

Introduction

For centuries, the scientific study of the human body

has generated important medical information.

Although current uses of human biological materials for

diagnostic, therapeutic, research, and educational purposes contribute to this ongoing process of discovery, at

the same time they raise a number of ethical issues for

research subjects and their families, investigators,

Institutional Review Boards (IRBs), and society in general

(Merz 1996; Merz, Leonard, and Miller 1999). This

chapter examines several of these ethical issues—many of

which have surfaced in preceding chapters—and it provides the background for the National Bioethics Advisory

Commission’s (NBAC’s) recommendations, which follow

in Chapter 5.

As noted in Chapter 2, some human biological materials have been stored for decades, millions more specimens will be gathered and stored in the next year, and

tens of millions more will be gathered and stored over the

next decade. The individuals who are the sources of

existing specimens are identifiable in some cases but not

in others. Some of these specimens were gathered during

clinical procedures for which informed consent was

obtained, while others were not. However, even when

informed consent was given for the medical procedures

that produced the specimens, the individuals may not

have consented to possible future research uses of the

material. In many—perhaps most—cases, individuals

were not aware that their specimens were being stored or

had no knowledge that they might be used for various

research purposes by a number of investigators.

Obtaining information by taking a medical history or

by interpreting the tracings on an electrocardiogram may

not have the same significance for many individuals and

their family members as would biopsying a piece of tissue or drawing blood. Perhaps this is because the latter

involves an element of fear of the unknown and the unfamiliar. However, many of the interests of the sources of

biological materials may depend upon the additional

(and yet to be determined) information that the materials

could yield, such as information that would predict an

individual’s health. In addition, because the nucleated

somatic cell contains the complete genetic code of the

person from whom the specimen was taken, any cell

from any part of the body could be subjected to genetic

analysis (with the potential for providing vast amounts of

information); thus, true anonymity does not ultimately

exist. And some types of medical research, particularly

genetic research, reveal information not only about the

individual sources of the biological materials but also

about members of their families or of groups with which

they share certain characteristics. For all of these reasons,

and because of deep concerns about possible misuses of

genetic information (e.g., in employment and insurance

discrimination) and particularly in light of past abuses of

such information in the United States (Kevles and Hood

1992), widespread interest exists in ensuring that appropriate ethical constraints on the practices of gathering

and storing human biological tissues that may be used for

research are in place.

This chapter discusses the three principles—

beneficence, respect for persons, and justice—that, since

their formulation by the National Commission for the

Protection of Human Subjects of Biomedical and

Behavioral Research in its influential Belmont Report

(1979), have provided a broad ethical framework for

assessing and directing research involving human

41
42

subjects. The Belmont Report was intended “to provide an

analytical framework [to] guide the resolution of ethical

problems arising from research involving human subjects.” This chapter also draws upon the ethical guidance

provided by federal regulations designed to protect

human research subjects, as well as upon laws, policies,

and professional codes that bear on this subject.

Particularly important are rules pertaining to privacy and

confidentiality, which are now the subject of considerable

societal debate in relation to computerized medical

records and genetic research. In addition, this chapter

refers to perspectives offered by bioethicists and others

on the research use of human biological materials.1

Several bioethicists have argued, for example, that excessively individualistic interpretations of the ethical principles and rules governing research involving human

subjects fail to address the needs of relevant groups and

communities (Emanuel and Weijer 1999).

Although NBAC in this report considers all of these

sources of ethical guidance, it does not assume that they

are equally authoritative or insightful. Rather, NBAC provides its own analysis of the major ethical issues and

argues for specific ways in which to address the relevant

moral concerns. Part of this analysis considers the extent

to which research using human biological materials falls

under the ethical principles and rules that ordinarily govern research with human subjects and the extent to

which it is distinctive. 

In making ethical judgments about the research use of

human biological materials, it is not always necessary to

pit the interests of future beneficiaries of current research

against the interests of those who have provided the

human biological materials. First, scientists share the

moral (and often legal) obligation to design their experiments in such a way as to minimize possible harms and

wrongs to subjects. Second, individuals often participate

eagerly in research studies because they are altruistic or

socially benevolent. Third, some patients may participate

in research because they hope to benefit—now or in the

future—from the resulting scientific and medical developments. Thus, virtually all parties to the discussion

acknowledge both the value of biomedical research and

the need to minimize harms and wrongs to subjects.

Indeed, the challenge is not to trade off the potential

health benefits from research against the protection of

sources and others, but rather to find ways in which to

maximize the opportunities for developing new knowledge and new treatments while, at the same time, ensuring appropriate protections from harms and wrongs.

Only then will the public have the degree of trust in

researchers and confidence in scientific research that is

needed to facilitate important scientific breakthroughs.

Promoting Benefits and Minimizing

Harms and Wrongs

According to the National Commission, “[b]eneficence...

requires that we protect against risk of harm to subjects

and also that we be concerned about the loss of the substantial benefits that might be gained from research”

(National Commission 1979). The principle of beneficence thus encompasses not only research efforts to produce generalizable knowledge that can benefit society,

but also efforts to avoid harming persons, to minimize

possible harms, and to assess possible harms in relation

to possible benefits. Researchers, IRBs, and others have

an obligation to minimize harms and the risks of harm to

research subjects.

All harms may be viewed as setbacks to interests

(Feinberg 1987). But it is also necessary to identify and,

whenever possible, assign weights to various interests of

both individuals and groups. Rather than simply trying

to present those interests in the abstract, this chapter

considers them in relation to the principles, regulations,

and guidelines that already identify many of the relevant

harms and assigns them some weights relative to each

other, sometimes by establishing certain presumptions

and indicating the conditions under which those

presumptions can be rebutted.

In addition to harms, at least as narrowly construed,

wrongs can occur to individuals and to groups. That is,

although a right, such as a right to privacy, can be violated,

not every wrong, such as an unjustified breach of privacy, is in itself a harm or even causes a harm. For

example, if someone enters our house and rummages

through our possessions, but takes nothing and leaves

everything exactly as it was so that we are not aware of

what happened, it is appropriate to say that even though
43

no harm occurred, we were wronged because our right to

privacy was violated. Thus, we may be wronged without

being harmed, just as we may be harmed without being

wronged. In short, an ethical framework that seeks to

clarify policy in the area of human subjects research rests

upon the concept of wrongs as well as the concept of

harms.

NBAC’s analysis begins with the assumption that the

potential harms and wrongs to individuals and groups

through research on human biological materials usually

will not be physical harms or wrongs. Instead, they arise

not from “touching” an individual (as would be the case

in most clinical research interventions), but from the

acquisition, use, or dissemination of information obtained

from the research sample itself (i.e., the individuals who

provide those materials). Such uses present a risk that a

nonphysical harm or wrong may occur. Obviously, the

easier it is to connect the sources of biological materials

with the materials themselves and the more widely available the information linking sources and samples, the

greater the concern about risks to the individuals

involved. Hence, different ethical judgments may be

appropriate for unidentified, unlinked, coded, and identified samples. However, it is not always ethically justifiable to use unidentified or unlinked samples rather than

coded or identified samples, because some potentially

beneficial research may require more information than

can be provided by unidentified or unlinked samples.

Furthermore, investigators sometimes may be tempted to

choose unidentified or unlinked samples in order to avoid

the more stringent standards and procedures required for

coded or identified samples—for example, the requirement for measures to protect privacy and confidentiality.

Rules protecting privacy and confidentiality—

concepts that are closely connected, although distinct—

often protect individuals from unwanted and potentially

harmful disclosures of information about themselves.

Such rules reflect not only efforts to respect persons by

authorizing them to determine the degree of access to this

information that they will grant to others, but also by protecting persons from the potential harms that may result

from the unauthorized disclosure of that information.

Potential Harms from Breaches of

Privacy and Confidentiality

In Chapter 1, NBAC described some of the factors that

may contribute to the potential for discrimination and

stigmatization, in particular relating to privacy and confidentiality. Here, NBAC discusses some of the ethical

foundations for addressing these concerns.

Privacy and Confidentiality

Privacy refers to a state or condition of limited access

to an individual and to information about that individual.

Rules of or rights to privacy enable individuals to maintain this state. Some definitions conflate the condition of

privacy with a right to privacy, which refers to the individual’s right to control access to him- or herself.

However, it is useful to distinguish privacy as a state or

condition from privacy as a right, because individuals can

experience privacy without having any control over others’ access to them (others may simply ignore them), and

they can have a right to privacy that is not sufficient to

guarantee their privacy (others may violate their right)

(Beauchamp and Childress 1994).

Privacy is a multilayered concept. Anita Allen, for

example, identifies four dimensions of genetic privacy:

informational, decisional, physical, and proprietary

(1997). She observes that while genetic privacy refers

principally to informational privacy (Westin 1994), each

of the other three dimensions also may be implicated in

genetics. Physical privacy focuses on persons and personal

spaces, decisional privacy on an individual’s decisionmaking, and proprietary privacy on appropriation and

ownership. All four dimensions may come into play in

concerns about privacy in relation to human biological

materials.

Individuals have an interest in avoiding the unnecessary exposure of their bodies to the view of others and in

not having intimate or embarrassing facts about themselves disclosed, even if such exposure or disclosure does

not threaten other of their interests. Concerns about privacy often are closely related to concerns about dignity,

because in most, if not all, cultures, some modes of

exposing the body in some contexts are considered

undignified and demeaning, and some intimate information is considered embarrassing and even shameful.
44

For the most part, once biological material is removed

from the body and analyzed, it is the interest in maintaining the confidentiality of any information derived

from the material, rather than the interest in maintaining

the privacy of the individual, that is the issue.

Nevertheless, disclosure of particular information may be

either a breach of informational privacy or a breach of

confidentiality, depending upon who makes the disclosure. Confidentiality emerges as an issue when one person makes information available, whether through verbal

communication, a physical examination, an analysis of

biological materials, or some other means, to another

person who pledges not to disclose it to others without

authorization. When individuals grant access to their

bodies for purposes of health care and research—for

example, through providing biological materials for

examination—they necessarily surrender some degree of

privacy; however, they often wish to restrict access to any

information that may emerge from that examination.

Rules of confidentiality and rights to confidentiality

expressed in professional codes, laws, and regulations

authorize individuals to maintain confidentiality within

certain limits.

In this report, confidentiality mainly concerns access

to and use of information physically contained in a database, such as a medical record. People often want information about themselves to be kept in confidence,

particularly when an agreement has been made or an

expectation set that further access to their biological

materials and to the information these materials contain

will be limited appropriately. Although such confidentiality protections are provided in federal research regulations (45 CFR 46.116(a)(5)), nothing in the regulations

will provide complete protection against the inadvertent

disclosure of such information. In addition, rules of confidentiality rarely are considered absolute, and various

exceptions are recognized. What counts as a justifiable

limitation or exception to confidentiality will depend

upon a complex weighing of conflicting legitimate

interests (Andrews et al. 1994).

NBAC also is aware that publishing identifiable information in scientific and medical journals can pose a risk

to privacy and confidentiality. Publishing personal

information, whether through direct descriptions of

individuals or through pedigrees, infringes upon the

rights of subjects or patients if they have not provided

informed consent for such publication (Botkin et al. 1998),

and it may result in adverse psychosocial effects. IRBs can

obtain further guidance on this issue (OPRR 1993). In

addition, as noted in Chapter 3, journal editors should

review the Uniform Requirements, a set of guidelines

published by the International Committee of Medical

Journal Editors for the acceptance and dissemination of

research (ICMJE 1991).

Discrimination in Health Insurance and

Employment

On July 14, 1997, President Clinton, upon releasing

the report “Health Insurance in the Age of Genetics” (U.S.

Department of Health and Human Services 1997),

expressed his hope that American citizens would not be

forced to “choose between saving their health insurance

and taking tests that would save their lives.” 2 The

President was referring to the concern of some that useful genetic information might be misused to discriminate

against them. In addition to concerns about misuse of

genetic tests, some believe that being listed in a tumor

registry or replying truthfully to questions about their

family medical histories may be just as risky as having a

positive test for a genetic disorder reported in their medical record. Given current social and institutional

arrangements, persons known to have health problems

or to have certain susceptibilities to diseases may in fact

be at risk of discrimination in obtaining and maintaining

health insurance and employment.

The actual extent of insurance and employment discrimination on genetic grounds remains a matter of speculation, because although some evidence is available on

this subject (Lapham, Kozma, and Weiss 1996), most of

it is derived from surveys in which individuals self-report

discrimination, with little or no independent verification

of the accuracy of their perceptions (Billings et al. 1992).

Moreover, the risk of health insurance discrimination

mainly involves policies, the issuance of which is subject

to individual medical underwriting. However, many

Americans who have private health insurance obtain it

through employment-based, large-group policies that are

not subject to such underwriting. Nevertheless, some
45

forms of individual underwriting may affect tens of

millions of Americans (Stone 1996). Furthermore, many

people obtain health insurance through self-insured

employers, and this conflation of roles—the employer

both pays for and administers the health insurance

plan—may tempt some employers to discriminate in

employment in order to reduce perceived health risks

that could increase the cost of providing insurance.

Wertz has reported data obtained from surveys of

1,084 geneticists, primary care physicians, and a sample

of patients receiving genetic counseling on a number of

topics, including genetic discrimination (1997). These

surveys revealed few instances of employment or insurance refusal. Still, the geneticists reported that approximately 550 individuals were refused employment, fired,

or denied life insurance based on their genetic constitutions. In a Harris poll, commissioned by Wertz and involving 1,000 adults, 3 percent of the general public reported

being refused employment or being fired, 3 percent

reported being denied health insurance, and 5 percent

reported being denied life insurance “because of an

inherited disease or condition.” Because employment discrimination can have such devastating consequences for

individuals and their families, these data should be taken

seriously, and follow-up studies in this area should be

conducted (Wertz 1997).

The policies that would be needed to reduce the risks

of discrimination in health insurance or employment

vary with the magnitude (both probability and severity)

of those risks, and hence with the institutional arrangements that either magnify or diminish them. For example, if blood were collected from identifiable individuals

for use in a study of the basic biological mechanisms of

platelet formation, one could argue that the disclosure of

that information poses little, if any, risk of discrimination

to the individuals who donated the blood. If, however,

the same specimens were later used to determine

whether trace amounts of alcohol could be found in the

blood, the potential for discrimination increases. And if

that blood were collected in the workplace, concerns

about the potential for discrimination would become

even more pronounced.

The risk of discrimination in health insurance is not

an inevitable effect of the existence of information about

illness or susceptibility; instead, it is a byproduct of the

current structure of the U.S. insurance market, in which

most health insurance is employer based, and some private insurers compete in part by attempting to avoid fully

insuring sick (and therefore costly) individuals. If this

particular set of institutional arrangements were modified

in certain ways or were abolished, the risk of discrimination in health insurance could decrease substantially. At

the same time, the case for restricting access to biological

sample information in order to reduce the risk of insurance discrimination also would decrease. Clearly, such

discrimination in life insurance and disability insurance

can arise in any country that depends on private insurance and individual underwriting.3 Furthermore, a lively

debate exists in the United States and elsewhere about

whether it is even possible to draw a line between genetic

and nongenetic information in the context of any type of

insurance system (Thomson 1998; Murray 1987).

It follows that in societies in which powerful institutions pose significant threats of discrimination on the

basis of genetic or other medical information, greater

restrictions on access to such information will be needed

than in societies in which such threats are absent. If federal and state laws prohibiting insurance and employment discrimination on the basis of genetic and other

medical information are passed and effectively implemented, the balance between interests that weigh in favor

of more restricted access to and greater source control

over biological samples, on the one hand, and those that

weigh in favor of freer access and more permissive

research uses of those samples, on the other hand, would

shift accordingly. Therefore, it is important to remember

that any policies developed now may require revision in

the future.

Stigmatization

When disclosure of genetic or medical information

occurs, an individual may suffer the harm of stigmatization, even if he or she is not denied insurance or employment. Stigmatization is closely related to discrimination;

like discrimination, stigmatization is a form of exclusion

by labeling, which often involves at least an intimation of

unwholesomeness, taint, or blame. Stigmatization usually

is imposed on individuals from without, through the
46

negative perceptions and judgments of others; however,

individuals often internalize those negative attitudes.

Although there is an unfortunate tendency to focus only

on the stigmatization that results from being identified as

having a genetic disorder, other types of illness can be

equally or even more stigmatizing (e.g., sexually transmitted diseases, disfiguring conditions, and, in some cultures, cancer).

The burden of stigmatization varies among individuals and depends significantly on cultural attitudes toward

disease. For example, some might find it stigmatizing to

learn, as the result of participating in a research study,

that they possess a genetic marker that predisposes them

to psoriasis, a condition that can be disfiguring. Others

might not consider this to be stigmatizing. Some consider

it to be stigmatizing to be a Tay-Sachs disease carrier,

because it has the potential to put their children’s health

at risk; however, others who have been found to be such

carriers do not view the condition as stigmatizing

(American Jewish Congress 1998). Stigmatization is not

limited to associations between persons or groups and

certain diseases; it also may occur when studies perpetuate certain stereotypes within ethnic or social groups.

Stigmatization is difficult to define and even harder to

measure. For example, although the Oxford English

Reference Dictionary defines stigma as “a mark or sign of

disgrace or discredit,” the reference to a physical characteristic does not capture adequately the type of moral

wrong inflicted or harm caused when a person is made to

feel ashamed, excluded, or blamed. Unfortunately, concern about stigmatization still exists in other areas of

research, as NBAC noted in its recent report on research

involving mental disorders (1998) and as others have

observed (Nuffield Council on Bioethics 1998). When, in

the future, science can provide more information about

the nature (and universal prevalence) of genetic susceptibility to disease and can share this information with the

public, the risk of stigmatization on genetic grounds may

diminish. But more information will be needed. Given

the difficulty in identifying and quantifying stigma,

researchers and IRBs must find ways in which to address

this issue in evaluating protocols that use human biological materials.

Familial Conflict and 

Other Psychosocial Harms

In some instances, biological information, like other

medical information, may create intra-familial conflict.

For example, genetic analysis of blood may reveal that a

husband is not the father of a child. Or if a daughter tests

positive for Huntington’s disease, she reveals the genetic

status of her parents and possibly her siblings, who may

not want to be aware of this devastating information. In

some cultures, a family learning that the prospective

spouse of one of its members has a genetic disorder or a

certain medical condition may attempt to prevent the

marriage from occurring. Even if the beliefs underlying

such actions reflect mistaken views about genetics or

indefensible assumptions about responsibility for disease, these conflicts and the harms and wrongs that they

can generate are quite real.

In addition, learning that a family member is, for

example, a carrier for a genetic condition can force families into difficult situations—emotionally, physically, and

economically. Information that an individual is at elevated

risk for a disease such as cancer or may have unwittingly

passed on a deleterious genetic trait to his or her offspring is sensitive. And in most cases, it should be provided to others only with the full knowledge and consent

of the individual from whom the sample was obtained.

Group-Related Harms

Closely related to discrimination and stigmatization is

another potential harm that individuals may suffer

because of perceived links between medical information

about them contained in a biological sample and what

may be called their ascriptive (or group-based) identity.

The harm of negative racial stereotyping, for example, is

one that befalls individuals because of their ascriptive

group identity. The term “ascriptive” indicates that the

identity in question is assigned by others, independent of

the choice of the individual thus identified. Individuals

who are vulnerable to ascriptive identity harms have a

special interest in avoiding situations in which information obtained from their biological samples contributes to

the reinforcement of harmful stereotypes. Thus, it is
47

arbitrary to limit consideration of potential harms to

those affecting the individual research subject, especially

given the power of new biomedical research technologies

to affect the lives of many.

The ascriptive identity harms that individual research

subjects may suffer are harms that other members of their

ascriptive group who have not contributed samples also

may suffer as a consequence of the research. Research

that is designed to study a group or that retrospectively

implicates a group may, for example, place the group at

risk of being perceived as unusually susceptible to disease. This, in turn, could result in members of the group

facing, among other things, stigmatization and discrimination in insurance and employment whether or not they

contributed samples to the study. At issue for both the

individual research subject and the group is that the

research might reveal information about them—namely,

the higher probability of the occurrence of certain diseases—that places them at risk of psychosocial and other

harms.

An individual whose identifiable sample reveals him

or her to be especially susceptible to a disease may be at

greater risk of harm than those individuals about whom

such specific information does not exist. This fact sometimes justifies the additional special protections afforded

the individual research subject. However, circumstances

may exist in which the individual research subject faces

less risk of harm than other members of a group to which

he or she belongs. For example, a socially and economically well-situated research subject likely will be at less

risk of suffering the effects of insurance and employment

discrimination than those lacking stable employment or

health insurance. Moreover, the stigmatization sometimes associated with a disease may be far more injurious

to a group than to a particular individual, especially

when the group is one that is already socially and politically marginalized. As research on human genetic variation increases, additional ethical concerns may arise

regarding research on identified groups; such concerns

are now the subject of research (Foster, Bernsten, and

Carter 1998) and are a new priority for the federally

funded Human Genome Project (Collins et al. 1998).

Respecting Persons Who Are Sources

of Biological Materials

Treating Persons as Moral Agents

Every person has an interest in being treated as a moral

agent—that is, as an individual capable of exercising

choices consistent with his or her own values, preferences, commitments, and conceptions of good. Part of

the moral justification for requiring informed consent in

research and treatment is to ensure that patients and

research subjects are treated respectfully as agents, not as

passive objects to be used merely for the ends of others.

More broadly, however, respecting persons is essential to

a relationship of trust between them and the researchers

who want to use their biological materials. Still more

broadly, the respect owed to individuals in using information about them raises general concerns about the dignity with which human beings are treated—a concern

recognized in the Universal Declaration on the Human

Genome and Human Rights, recently adopted by the

United Nations General Assembly (UNESCO 1998).

A case can be made that current practices concerning

human biological materials sometimes fail to treat persons with due respect, because researchers may unintentionally be misleading regarding why materials are being

gathered and the uses to which the materials will be put.

For example, the person who draws the blood may not

know that it will be stored indefinitely and may be used

in any number of ways in the future, and therefore, this

person may have no intention to mislead. Nevertheless,

the institutionalized practice of storing biological specimens for future uses is one for which those who control

the practice are responsible, and this practice, as we have

seen, apparently does not always adequately inform individuals about future uses of the materials.

Informed Consent

A number of fundamental ethical questions are raised

by the research use of human biological materials: What

kind of consent is needed for research use? Who should

provide this consent? For what purpose should the consent be provided? Informed consent is recognized to be

both a legal and moral requirement for medical interventions in general and for all experiments with human
48

subjects that involve more than minimal risk. In addition

to the review of research involving human subjects by an

IRB, informed consent has been a primary, albeit imperfect, means for protecting the interests, welfare, and

rights of individuals who are subjects of research.

As this chapter has indicated, risks encompass not

only potential physical harms from bodily invasions,

including the minimal harms that may result from procedures such as drawing blood or swabbing cells from the

inside of a cheek, but also psychosocial harms, especially

stigmatization and other assaults on an individual’s sense

of self-worth. In other words, when people allow others

access to their bodies, they become vulnerable to other

unwanted and potentially more serious harms. For this

reason, it is misleading to suggest that informed consent

protects a person who is undergoing a simple procedure

such as giving blood only from the remote possibility

of harm that may result from the needle stick (beyond

the unpleasant but momentary sensation of the needle

stick itself).

Five elements of informed consent can be distinguished: 1) disclosure (of relevant risks and benefits of

the procedure), 2) competence (on the part of the patient

or subject) to make a decision whether to accept the

treatment or to participate in the research, 3) comprehension (of the relevant risks and benefits), 4) choice (an

expressed decision to accept the treatment or participate

in the experimentation), and 5) voluntariness (of the

choice to accept treatment or to participate in research)

(Faden and Beauchamp 1986). Clearly, informed consent

plays a role in any ethically sound system for collecting

and using biological samples, at least to this extent: The

requirement of informed consent must be met for medical treatments in general and for most types of research.

The question is whether an ethically sound system for

collecting, storing, and using biological samples will

require additional or amplified applications of the

requirement of informed consent in order to express all

that the principle of respect for persons entails in this

context. In Chapter 5, NBAC offers several recommendations for specifying the requirements of the principle of

respect for persons, for specifying the rule of informed

consent for this specific context, and for reducing the

risks of various wrongs and harms that are discussed in

this chapter.

It is one thing to argue that the prevention of nonconsensual bodily invasion and disrespectful treatment

justifies restrictions on research, and quite another to

argue that the mere possibility of various wrongs and

harms—some of which may not be so serious and others

of which may be unlikely to occur—provides an equally

compelling reason to restrict research. Informed consent

clearly is required when risks are more than minimal in

order to allow the individual to decide whether the

potential harms are relevant and substantial. Yet, some of

the harms mentioned in this chapter are not certain, and

in many cases they are extremely unlikely. Therefore, in

such cases, consideration may be given to waiving the

requirement for informed consent.

Special issues arise in interpreting the requirements of

the principle of respect for persons and the rule of

informed consent in research in the context of using

existing biological materials for research purposes. As

noted earlier, hundreds of thousands and perhaps millions of individual specimens may have been collected as

part of clinical procedures, without patients’ providing

specific consent to their use in research. Thus, existing

collections present a special challenge, given the value

that federal (and, indeed, international) regulations,

guidelines, and codes place on informed consent. The

ethical question is whether biological materials that are

collected without consent—or without specific consent—to their use in research may be used for that purpose. In NBAC’s judgment, where the research uses

identified or coded samples from previously collected

specimens, such uses usually are not justified without the

source’s consent, because the risks to sources and others

may be more than minimal. However, the use of unidentified or unlinked samples for research could be justified

in some cases if other appropriate protections were in

place, despite the lack of informed consent.

A second challenge arises when individuals are asked

to provide samples for possible use in future research,

even though an approved research protocol does not yet

exist. Clearly, individuals cannot give specific, informed

consent today to the use of their materials some time in

the future, although some form of “prospective authorization” may still be possible. In a separate report, NBAC

considered whether persons while competent should be
49

permitted to give a “prospective authorization” to participation in research if they should lose their capacity to

consent (NBAC 1998). NBAC recognized that, within

limits and with other appropriate protections, individuals could give prospective authorization to a particular

class of research if its risks, potential direct and indirect

benefits, and other pertinent conditions have been

explained. Allowing individuals to express their preferences for future research is consistent with respecting

persons, and it may be less problematic when the

research will be conducted not on their bodies but on

biological materials they have provided, when the risks

are mainly psychosocial, when the risks are minimal or

can be minimized—for example, through unidentified or

unlinked use—and when the risks have been explained

to potential sources who then provide their biological

materials for this purpose.

Objectionable, Unacceptable, or 

Questionable Research

Individuals and groups also may have an interest in

the type of research in which a sample is to be used, and

some may find the intended use of the knowledge that

would be gained by the research to be objectionable. For

example, for religious or cultural reasons, some may

believe that their biological materials should not be used

in contraceptive research or in studies that are aimed at

identifying individuals who are prone to violence or

other socially unacceptable behaviors. Some individuals

may object to the possibility that researchers could sell

their samples to companies for profit. Still others may

have concerns if the materials were obtained in an

unusual or deceptive manner. Or, some individuals or

groups, such as some Native Americans, may have strong

beliefs about the integrity of the body, whether living or

dead.4

Postmortem Uses of Biological Materials

Many existing biological materials have been obtained

from individuals who are long dead, and the plain truth

is that any specimen stored long enough will outlast its

source. It might be thought that once the source is dead,

no interests remain that require protection, but for a

number of reasons, this is not the case. For example, the

decedant’s family or other loved ones may have an interest in how the material is used, or members of the

source’s ascriptive group may have an interest in what

happens to it. Furthermore, individuals may have interests that survive their deaths, such as the interest in what

happens to their children and grandchildren after they

themselves die. Similarly, persons may have an interest in

the uses to which their biological materials are put,

whether these uses occur before or after their deaths.

This may be true especially if they consider certain uses

impermissible per se, based on their deepest, life-long

religious or ethical values. In addition, new information

obtained about persons after they have died may affect

the memories, perspectives, and relationships of family

members and others.

Even if, strictly speaking, the dead do not have interests that require protection, the living may want to establish policies to ensure that some of these outcomes do not

occur (DeRenzo, Biesecker, and Meltzer 1997). Such

policies could be viewed as means of reducing the worries of the living about what might happen after their

deaths. Thus, a policy of unrestricted access to the stored

specimens of deceased persons cannot be justified on the

grounds that no ethical issues are at stake (Nelkin and

Andrews 1998). If people restrict use of their materials

when they are still alive, those restrictions also should

apply after their deaths. (Chapter 3 provides a discussion

of the current regulatory perspective on this issue.)

Just Institutions, Policies, and Practices

Although in the past the principle of justice has been

neglected relative to the other Belmont principles—

beneficence and respect for persons—in recent years it

has come to the forefront. Justice requires the fair and

equitable distribution of benefits and burdens in

research, in accord with both the formal criterion of treating similar cases in a similar way and various material criteria that specify relevant similarities and differences

among individuals and groups (Beauchamp and

Childress 1994). More broadly, justice in the context of

genetics concerns “the protection of individual persons

and cultural groups from unjust social prejudices and

arrangements that would burden individual choice or
50

degrade the worth of certain groups defined in invidious

ways” (Murphy and Lappe 1994). In addition, as previously noted, the risks of discrimination in health insurance and employment raise significant questions about

whether institutions and policies are just.

Some of the ethical concerns regarding the research

use of human biological materials fall under more than

one general principle. For example, justice may require

that certain procedures are in place that will ensure fair

participation on the part of a particular group in designing research protocols that may have a negative impact

on that group. Indeed, justice, along with the other two

Belmont principles, should be interpreted to include

communities as well as individuals. Just as beneficence

may require attending to group harms, and respect for

persons may necessitate attending to their communities,

so justice may mandate the provision of procedures for

group participation in the planning of research. 

Questions arise about just patterns of distribution of

both the burdens and the benefits of research involving

human biological materials. Insufficient attention has

been paid to justice in the selection of sources of specimens for research purposes. For example, specimens

may be collected from a given population because that

population is at risk for a certain genetic condition. Once

those specimens are collected in a repository, it may be

easier to conduct future, unrelated studies on the stored

tissue instead of collecting a new set of specimens from a

more representative spectrum of society. As a result, the

population that originally provided the specimens may

bear the burden of additional research, with the risk of

being stigmatized for disease susceptibility, largely

because its specimens were readily available for research.

Justice requires that further attention be paid to ways in

which the burdens and risks of research can be distributed more equitably.

The weight that should be accorded society’s interest

in the benefits of applied biomedical research also will

depend in part upon how widely these benefits are distributed and to whom. If the distribution of benefits is

grossly inequitable, it is misleading to speak of a common interest in medical progress. Consequently, the case

for tolerating increased risks to the interests of those who

provide specimens for the sake of society’s interest in

medical progress becomes weaker if some people—

including some who provide the biological materials—

lack access to important health care benefits because they

cannot afford them. Nevertheless, if significant benefits of

medical progress accrue to a large number of people or to

those suffering from rare, but debilitating or lethal diseases, a societal interest is relevant, even if not all benefit

or not all benefit equally. Furthermore, potential benefits

of that research may accrue to future generations, raising

issues of intergenerational justice.

Some of the possible policies that could be adopted to

protect the sources of biological materials and others

from wrongs and harms likely will require increased

expenditures for research. However, a just distribution of

the burdens of research requires this investment, when

needed and within appropriate limits, to reduce those

wrongs and harms. A just distribution also can help

ensure public trust in research and facilitate public contributions of biological materials to important research

endeavors. Elsewhere, NBAC has recommended that if

additional protections are required for human subjects in

research, all who support the research, from both the

public and the private sectors, should work together to

ensure that sufficient resources are made available

(1998).

Commodification of the Body and Its

Parts: Issues of Justice and Respect 

for Persons

The distribution of the financial gains that may be realized through various uses of human biological materials

raises a number of concerns. Some individuals and

groups have sought to share in the profits that are generated by patentable biologic inventions that were developed with the use of their biological materials. Perhaps

the most famous case is that of John Moore, who claimed

a financial interest in the cell line that was developed

from his spleen tissue.5 The California Supreme Court

rejected Moore’s claim and hence any claim to a portion

of the profits derived from uses of the cell line. However,

it did affirm that the physicians who used Moore’s spleen

tissue to develop the cell line had a duty to disclose this

fact to him in advance.
51

The two parts of the ruling mark an important distinction between the following questions: 1) Is the individual entitled to some or all of the profits that are

realized from a product in the development of which his

or her biological specimen played a role? and 2) Is the

individual entitled to disclosure of the fact that his or her

biological sample may be used to develop a profitable

item, and can that individual refuse to allow such uses?

These questions suggest that two distinct interests are

present: the financial interest in profiting from the use of

one’s sample and the interest in knowing whether one’s

physician or the researcher has an ancillary financial

interest that might change or even compromise his or her

professional conduct. The second interest, although less

tangible than the first, may be extremely important to

some individuals, who may want to be aware of and perhaps take steps to avoid health care relationships that are

characterized by significant conflicts of interest or to

decline to participate in such studies.

Apart from the legal ruling in this case, the generation

and distribution of profits from human biological materials may raise for some individuals and groups fundamental conceptions of distributive justice. From some

perspectives, it would be misleading to refer only to the

interest that individuals have in a share of the profits

derived from uses of their biological samples and

whether this interest should be recognized as a legal

property right. According to some commentators, individuals not only have an interest but also a property

right, because their tissues, blood, and DNA are their

property.

Some moral philosophers have assumed or argued

that a person’s body is his or her property, in the sense of

a moral property right (Locke 1963). The model of the

body as “property” stems from a claim of self-ownership

and seeks to authorize individuals to exercise control

over the use and disposition of their body and body parts

(Andrews 1986). This view tends to treat the body as

incidental rather than as intrinsic to personal identity,

and it allows the transfer of organs and tissues to others

by donation or sale without compromising the nature of

the self. However, as the Moore case demonstrates, conflict can arise when, for example, a patient and a

researcher assert competing claims or “property rights” to

excised body tissues. By contrast, some cultural and religious traditions in the United States hold that the body

and its parts are not reducible to property that can be

bought and sold, even though they may be donated for

research and other purposes (Murray 1987). The conflicting religious and philosophical traditions that inform

the discussion of the body as property render this a topic

that deserves fuller consideration in another context. For

the purposes of this report, however, it is sufficient to

note that these conflicting traditions form a background

against which the research use of human biological materials can be considered.

Summary

Any ethically sound policy for research uses of human

biological materials must reflect a defensible balance of

the ethical reasons that support greater control over the

use of human biological materials and stronger protections for subjects, on the one hand, and the ethical reasons that support greater access to samples for purposes

of conducting clinically beneficial research and/or clinical

interventions, on the other hand. These reasons will vary

in weight and impact depending on the identifiability of

the sample sources and on the probability and magnitude

of various wrongs and harms that may occur.

The major ethical reasons that support greater control

over the use of human biological materials by sources

and the institution of more rigorous safeguards against

harms and wrongs that may occur to sources include

avoiding discrimination in insurance and employment,

stigmatization, group harms, familial conflicts (including

those of the survivors of the deceased), and uses that are

objectionable to the source. As this chapter indicates, it

may be possible to avoid or at least greatly reduce the risk

of some of these harms and wrongs by developing, for

example, stronger protections of privacy and confidentiality. Rather than assuming that a necessary conflict

exists between promoting important research and protecting biological sample sources and others against various wrongs and harms, NBAC holds that policymakers

should seek—with the widest possible public and professional participation—to develop policies that avoid

tradeoffs, while recognizing and setting procedures to
52

deal with situations that sometimes necessitate such tradeoffs, especially those involving less weighty interests. The

recommendations that follow in the next chapter indicate

some possible directions for policies that can both promote important research and provide sufficient safeguards

for the rights and welfare of sources of biological materials

and their families, groups, and communities.

Notes

1 See Buchanan, A., 1998, “An Ethical Framework for Biological

Samples Policy” and Campbell, C., 1997, “Research on Human

Tissue: Religious Perspectives.” These background papers were prepared for NBAC and are available in Volume II of this report.

2 Remarks by President Clinton. The White House, July 14, 1997.

3 Knoppers, B., M. Hirtle, S. Lormeau, C.M. Laberge, and M.

Laflamme, 1997, “Control of DNA Samples and Information.” 

This background paper was prepared for NBAC and is available 

in Volume II of this report.

4 Dukepoo, F., “Sensitivities and Concerns of Research 

in Native American Communities.” Testimony before NBAC. 

July 14, 1998. Portland OR.

5 Moore v. Regents of California et al., 793 P.2d 479 (Cal. 1990).

References

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Values.” In Genetic Secrets. Protecting Privacy and Confidentiality in

the Genetic Era, ed. M.A. Rothstein, 31–59. New Haven: Yale

University Press. 

American Jewish Congress. 1998. “Genetic Disease and the Jewish

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Andrews, L. 1986. “My Body, My Property.” Hastings Center Report

16:28–38.

Andrews, L.B., J.E. Fullerton, N.A. Holtzman, and A.G. Motulsky.

1994. Assessing Genetic Risks: Implications for Health and Social

Policy. Washington, DC: National Academy Press.

Beauchamp, T.L., and J.F. Childress. 1994. Principles of Biomedical

Ethics, 4th ed. New York: Oxford University Press.

Billings, P.R., M.A. Kohn, M. deCuevas, J. Beckwith, J.S. Alper, 

and M.R. Natowicz. 1992. “Discrimination as a Consequence of

Genetic Testing.” American Journal of Human Genetics 50:476–482. 

Botkin, J.R., W.M. McMahon, K.R. Smith, and J.E. Nash. 1998.

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Journal of the American Medical Association 279:1808–1812. 

Collins, F.S., A. Patrinos, E. Jordan, A. Chakravarti, R. Gesteland,

and L. Walters. 1998. “New Goals for the U.S. Human Genome

Project: 1999–2003.” Science 282:682–689. 

DeRenzo, E.G., L.G. Biesecker, and N. Meltzer. 1997. “Genetics

and the Dead: Implications for Genetics Research with Samples

from Deceased Persons.” American Journal of Medical Genetics

69(3):332–334. 

Emanuel, E., and C. Weijer. 1999. “Protecting Communities in

Research: Putting Principle into Practice.” Paper presented at the

Belmont Revisited Conference, April 1999. University of Virginia.

Faden, R.R., and T.L. Beauchamp. 1986. A History and Theory of

Informed Consent. New York: Oxford University Press.

Feinberg, J. 1987. Harm to Others: The Moral Limits of the Criminal

Law. New York: Oxford University Press.

Foster, M.W., D. Bernsten, and T.H. Carter. 1998. “A Model

Agreement for Genetic Research in Socially Identifiable

Populations.” American Journal of Human Genetics 63:696–702.

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Biomedical Journals.” Journal of the American Medical Association

277:927–934. 

Kevles, D., and L. Hood, eds. 1992. The Code of Codes. Cambridge:

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Lapham, E.V., C. Kozma, and J.O. Weiss. 1996. “Genetic

Discrimination: Perspectives of Consumers.” Science 274:621–624. 

Locke, J. 1963. Two Treatises of Government. Introduction and notes

by P. Laslett. New York: New American Library.

Merz, J. 1996. “Psychosocial Risks of Storing and Using Human

Tissues in Research.” Risk: Health, Safety and Environment

8:235–248. 

Merz, J., D.G. Leonard, and E.R. Miller. 1999. “IRB Review and

Consent in Human Tissue Research.” Science 283:1647–1648.

Murphy, T.F., and M.A. Lappe, eds. 1994. Justice and the Human

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Murray, T.H. 1987. “Gifts of the Body and the Needs of Strangers.”

Hastings Center Report 17:30–38.

National Bioethics Advisory Commission (NBAC). 1998. 

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Nelkin, D., and L. Andrews. 1998. “Do the Dead Have Interests?

Policy Issues for Research After Life.” American Journal of Law and

Medicine 24 (2–3):261–291. 

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Stone, D.A. 1996. “The Implications of the Human Genome

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Murray, and T.H. Murray, 133–157. Bloomington, IN: Indiana

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Advancement of Science.

Conclusions and

Recommendations

Chapter Five

5

Introduction

Ethical researchers must pursue their scientific aims

without compromising the rights and welfare of

human subjects. Achieving such a balance is a particular

challenge in rapidly advancing fields, such as human

genetics, in which the tantalizing potential for major

advances can make research activities seem especially

important and compelling. At the same time, the novelty

of many of these fields can mean that potential harms to

individuals who are the subjects of such research are

poorly understood and hence could be over- or underestimated. This is particularly true of nonphysical harms,

which can occur in research conducted using previously

collected human biological materials when investigators

do not interact directly with the persons whose tissues,

cells, or DNA they are studying.

Research sponsors, investigators, and Institutional

Review Boards (IRBs) thus must exercise great care and

sensitivity in applying professional guidelines and government regulations to protect subjects whose biological

materials are used in research. Properly interpreted and

carefully modified, present federal regulations can protect subjects’ rights and interests and at the same time

permit well-designed research to proceed using materials

already in storage as well as those newly collected by

investigators and others. Fundamentally, the interests of

subjects and those of researchers are not in conflict.

Rather, appropriate protection of subjects provides the

reassurance that is needed if individuals are to continue

to make their tissue, blood, or DNA available for

research. Indeed, public confidence in the ethics and

integrity of the research process translates into popular

support for research in general.

For many, the central issue in research that involves

the use of human tissues and cells is the harm that may

occur when private information about the subject’s present or future health status—often previously unknown

even to the subject—is revealed. One simple protection

for subjects would be to render anonymous all human

biological materials used in research. That approach

would, however, curtail many valuable investigations.

Instead, the protection of human subjects should take

into account the great value for many studies that use

human biological materials of having access to a certain

amount of personal and clinical data regarding the persons from whom the specimens were obtained. In other

words, the policies and guidelines governing human subjects research should permit investigators—under certain

circumstances and with the informed, voluntary consent

of sample sources—to have access to identifying information sufficient to enable them to gather necessary data

regarding the sources. Provided that adequate protections

(which usually, but not always, include informed consent) exist, such information gathering could include

ongoing collection of medical record data and even

requests for individuals to undergo tests to provide additional research information. In some cases, it even will be

acceptable for investigators to convey information about

research results to the persons whose samples have been

studied. When identifying information exists, however, a

well-developed system of protections must be implemented to ensure that risks are minimized and that the

interests of sources are protected.

Finally, any system of regulation is most likely to

achieve its goals if it is as clear and as simple as possible.

This is especially true in the research use of human biological materials, because the federal protections for

55
56

research subjects require investigators to outline the

involvement of human subjects in their studies and to

undergo institutional review of their protocols. Thus, one

reason to modify regulations is to clarify which protocols

are subject to what sorts of prior review; likewise, illustrations and explanations may be useful in clarifying how

the regulations apply to novel or complicated fields that

use human biological materials.

How well does the existing Federal Policy for the

Protection of Human Subjects (the so-called Common

Rule, codified at 45 CFR Part 46) meet these objectives?

Specifically, does it provide clear direction to research

sponsors, investigators, IRBs, and others regarding the

conduct of research using human biological materials in

an ethical manner? The National Bioethics Advisory

Commission (NBAC) finds that it does not adequately do

so. In some cases, present regulatory language provides

ambiguous guidance for research using human biological

materials. For example, confusion about the intended

meanings of terms such as “human subject,” “publicly

available,” and “minimal risk” has stymied investigators

and IRB members.1 Beyond these ambiguities, certain

parts of current regulations are inadequate to ensure the

ethical use of human biological materials in research and

require some modification. This chapter provides interpretations of several important concepts and terms in the

Common Rule and recommends ways to strengthen and

clarify the regulations and to make their implementation

more consistent.

The goals of these recommendations are to address

perceived difficulties in the interpretation of federal regulations and in the language of the position statements of

some professional organizations; to ensure that research

involving human biological materials will continue to

benefit from appropriate oversight and IRB review, the

additional burdens of which are kept to a minimum; to

provide investigators and IRBs with clear guidance

regarding the use of human biological materials in

research, particularly with regard to informed consent; to

provide a coherent public policy for research in this area

that will endure for many years and that will be responsive to new developments in science; and to provide the

public (including potential research subjects) with

increased confidence in research that makes use of

human biological materials. To accomplish these goals,

NBAC makes 23 recommendations in the following

areas:

■ adequacy and interpretation of existing federal 

policies for the protection of human subjects,

■ informed consent,

■ waiver of consent,

■ reporting of research results to subjects,

■ consideration of potential harms to others,

■ publication and dissemination of study results,

■ professional education and responsibilities, and

■ federal and state legislation governing medical

record privacy.

(See Appendix D for flow charts that illustrate NBAC’s

recommendations and existing regulations regarding

research using human biological materials.)

Research Governed by the 

Federal Regulations: Activities 

Beyond Clinical Care

In order to come under the purview of the current federal

regulations, an activity must be considered research, as

opposed to being considered a clinical intervention. The

regulations do not apply to purely clinical uses of human

biological materials or to other activities such as quality

control procedures or teaching. Rather, they apply to

research defined as “a systematic investigation designed

to develop or contribute to generalizable knowledge” (45

CFR 46.102(d)). Examination of stored materials undertaken solely as part of a clinical intervention—as when a

pathologist assesses a biopsied specimen to confirm a

diagnosis—falls outside the purview of the regulations

and of this report. But any study conducted on materials

that remain from a clinical intervention is subject to the

federal research regulations if the investigator is subject

to those regulations, if the research is otherwise regulated

by the FDA, or if the institution has agreed not to supply

samples for research without following the federal regulations.2 As investigators make greater use of human biological materials in a wide range of research projects,

specimen repositories must understand and adhere to

federal regulations. 
57

Interpretation of the Existing 

Federal Policy for the Protection 

of Human Subjects

In the context of studies that use human biological materials, the lack of clarity regarding several key regulatory

terms means that they cannot provide the guidance

needed by investigators, IRBs, and others. These terms

include “human subject,” “existing and publicly available,” “identifiable,” “minimal risk,” “rights and welfare,”

and “practicable.” In addition, it is not always clear which

types of research are exempt from IRB review or consent

requirements.

Criteria for Exemption from Review 

Ordinarily, when an identifiable individual is the subject of research, the regulations require IRB approval of

the study. But circumstances do exist in which this protection is unnecessary. The regulations provide two conditions under which research with human biological

materials from living individuals may be exempt from

IRB review, consent requirements, and other protections.

These conditions are when the samples “exist and are

publicly available and when the samples exist and information is recorded by the investigator in such a manner

that sources cannot be identified either directly or

through identifiers linked to the sources” (45 CFR

46.101 (b)(4)). The determination that a study is eligible

for exemption is made by the IRB administrator or other

institutional official. Of course, there are times when eligible studies should not be granted an exemption,

because IRB review would be wise even if not required. 

Logically, however, the first determination to be made

when considering whether a research protocol is subject

to review is whether one or more human subjects (as

defined by federal regulations) are involved. If so, review

may be required, unless the samples are “existing and

publicly available.” Each criterion is discussed below.

What Is a Human Subject? The “Identifiability” of

Samples and the Applicability of the Common Rule

Although studying human blood or tissue at first does

not appear to be the same as studying a human subject,

the examination of blood or tissue can yield information

about the person from whom it was obtained. Thus, even

the study of discarded surgical waste can be a form of

human subjects research. The federal regulations define a

human subject as “a living individual about whom an

investigator conducting research obtains: (a) data through

intervention or interaction with the individual, or (b)

identifiable private information.”3 Section 46.102(f)(2)

defines identifiable to mean that “the identity of the subject is or may readily be ascertained by the investigator

or...associated with the information.” The Office for

Protection from Research Risks (OPRR) interprets “identifiable” to include specimens with codes that, with the

cooperation of others, could be broken in order to reveal

the identity of the tissue source (1993). 

The academic and professional literature on the

research use of human biological materials includes a

variety of terms to describe the identifiability of research

samples. Part of the confusion about the interpretation of

the term “identifiable” arises from the fact that people

sometimes refer to the state of the information attached to

the biological material in the repository (i.e., the specimen)

and sometimes refer to the material (i.e., the sample) and

the accompanying information that is provided to the

researcher. For example, the specimen might be identified in the repository, but no identifying information is

forwarded with the sample sent to the researcher. This

distinction is of considerable importance, because the

potential for both benefit and harm is greater when the

sample is directly or easily linked to the person who provided the specimen, placing the burden of protection in

different places depending on who has access to the

information (e.g., the researcher, the pathologist, or

both). If samples are identifiable, the potential exists for

the investigator or a third party (e.g., insurer, employer)

to contact the subject or to act in some way that might

affect the subject. For example, an investigator might

want to contact an individual to gather more medical

information, obtain consent for additional or different

uses of the sample, provide information about the results

of the study, or communicate findings that might be of

clinical significance to that individual. Furthermore,

because current federal regulations define a human subject as a “living individual,” research using stored specimens from people who have died would not come under

the regulatory protection for human subjects.4
58

As noted in Chapter 2, NBAC adopted the following

definitions regarding the diverse status of human biological materials, depending upon whether they are sitting

in storage in a repository or whether some of the material

from a repository has been selected for research purposes.

These definitions were developed to help clarify the

meaning of the term “identifiability” for the purposes of

interpreting the federal regulations.

Repository collections of human biological materials (i.e., specimens) consist of two types:

■ Unidentified specimens are those for which identifiable personal information has not been collected or,

if collected, was not maintained and cannot be

retrieved by the repository.

■ Identified specimens are those linked to personal

information in such a way that the person from whom

the material was obtained could be identified by

name, patient number, or other information (e.g., his

or her relationship to a family member whose identity is known).

Research samples are the collections of human biological materials provided to investigators by repositories

or collected by investigators in the process of conducting

research. Such materials can be categorized into at least

four types, which are differentiated by the amount of

information that is conveyed to the investigator about the

person from whom the sample was obtained. NBAC

defines the different types as follows:

■ Unidentified samples—sometimes termed “anonymous”—are those supplied by repositories to investigators from a collection of unidentified human

biological specimens.

■ Unlinked samples—sometimes termed “anonymized”— are those that lack identifiers or codes that

can link samples to identified specimens or particular

individuals. Typically, repositories send unlinked

samples from identified human biological specimens to investigators without identifiers or codes so

that identifying particular individuals through the

clinical or demographic information that is supplied with the sample or biological information

derived from the research would be extremely difficult for the investigator, the repository, or a third

party. Unlinked samples also include those that are

already in an investigator’s possession and whose

identifiers have been removed by a disinterested

party.

■ Coded samples—sometimes termed “linked” or

“identifiable”—are those supplied from identified

specimens by repositories to investigators. However,

these samples do not include any identifying information, such as patients’ names or Social Security

numbers. Rather, they are accompanied by codes. In

such cases, although the repository (or its agent)

retains the ability to link the research findings derived

from a sample with the individual source by using the

code, the investigator (or one reading a description of

the research findings) would not be able to do so.

■ Identified samples are those supplied by repositories

from identified specimens with personal identifiers

(such as names or patient numbers) that are sufficient

to allow the researcher to link directly the biological

information derived from the research with the individual from whom the material was obtained.

The second criterion for exemption from the

Common Rule (that the samples are existing and that the

information is recorded by the investigator in such a

manner that subjects cannot be identified, directly or

indirectly through identifiers) reflects an underlying

premise of the federal regulations, namely that protection

is needed when research results can be linked to specific

human subjects. Thus, it would be appropriate for

research on unlinked samples to be exempt from IRB

review under most circumstances.

“Existing and Publicly Available” Materials

Regarding the first exemption (that the materials are

existing and publicly available), OPRR interprets the

term “existing” to mean any materials that already have

been collected—that is, materials that are “on the

shelf”—at the time the research is initiated, whether collected for previous research or nonresearch purposes

(OPRR 1993). Existing samples are thus differentiated

from samples to be collected at a later date as a part of the

research protocol in question.

The second criterion in the first exemption—the

requirement that samples be “publicly available”—is

more problematic. The reasons for exempting publicly

available data from the purview of the Common Rule are
59

that individuals have no expectation of privacy regarding

information to which anyone can gain access and that any

harm that may be associated with the disclosure of such

information already has occurred and should be the

responsibility of those who collected the data and made

them public. Well-known examples of sources of publicly

available information include telephone books and land

title records; however, it is not clear what kinds of biological materials might be considered publicly available.

In response to a request for clarification, OPRR

defined publicly available to mean that “unrestricted

access on demand (i.e., unrestricted availability subject

only to limited quantities and/or related costs) may be

considered a reasonable basis for claiming that a material

is ‘publicly available.’”5 Yet, this interpretation provides

minimal guidance, because it is not clear which public is

the relevant one (e.g., the general public, the scientific

community) and whether available means the same

thing as accessible.

Large repositories, often cited as examples of public

collections, have in place “strict policies to ensure that

cultures are distributed only to qualified organizations

and researchers with legitimate and justifiable scientific

uses for these materials.”6 Thus, the biological materials

are available not to anyone, but in general are restricted

to those who have legitimate research interests in their

use and presumably possess the capability to perform

sophisticated scientific studies that can reveal biological

information about the samples or even health-related

information about the persons from whom they came.7

Although collections might be widely and appropriately available to the research community, it appears that

they are rarely available to any member of the public.

Thus, the fact that researchers can readily access the

specimens does not make them publicly available as that

term is commonly understood. Despite the fact that the

materials exist in collections and are accessible to

researchers, the sources may well have an expectation of

privacy, including an expectation that the use of their

specimens is subject to regulation and, at times, dependent upon their consent.

It should be noted that the current regulatory policy

made sense in the context for which it was first created—

for example, a social or behavioral scientist who is using

information about people that can be found in directories

or newspapers or observed in recordings made of their

conduct in public settings. However, the exemption

would contradict the purpose of human subjects protection were it applied to innovative biological analyses of

stored human tissues or cells. This is because the information that may emerge from such a process is not existing in any genuine sense, much less publicly available. 

Thus, NBAC concludes that publicly available materials are those that are available to members of the general

public, not merely to specialists, researchers, or other

“qualified” persons. Although the accessibility of specimens is an important consideration in specifying appropriate levels of protection, more important considerations

include 1) whether the specimens are stored with codes,

links, or identifiers, 2) whether identifiable samples

(coded or identified) are delivered to investigators for

study, and 3) whether the repositories or retainers of the

specimens require any assurance that the research will be

conducted in a manner that will protect the rights and

interests of the sources.8

NBAC offers the following recommendations to

improve the interpretation and implementation of the

existing federal regulations as they apply to research

using human biological materials.

Recommendation 1:

Federal regulations governing human subjects

research (45 CFR 46) that apply to research involving human biological materials should be interpreted by OPRR, other federal agencies that are

signatories to the Common Rule, IRBs, investigators, and others, in the following specific ways:

a) Research conducted with unidentified samples

is not human subjects research and is not regulated by the Common Rule.

b) Research conducted with unlinked samples is

research on human subjects and is regulated by

the Common Rule, but is eligible for exemption from IRB review pursuant to 45 CFR

46.101(b)(4).

c) Research conducted with coded or identified

samples is research on human subjects and is

regulated by the Common Rule. It is not eligible

for exemption unless the specimens or the
60

samples are publicly available as defined by 

45 CFR 46.101(b)(4). Few collections of human

biological materials are publicly available,

although many are available to qualified

researchers at reasonable cost. Therefore, OPRR

should make clear in its guidance that in most

cases this exemption does not apply to research

using human biological materials.

OPRR should issue appropriate guidance for investigators and IRBs regarding these definitions and interpretations or should, if necessary, modify the language of the

Common Rule. 

NBAC recognizes that costs may be associated with

these interpretations of what constitutes a human subject

and believes that costs incurred by the investigator to satisfy this requirement should be considered valid and

reimbursable expenses by the funding agency. However,

NBAC does not believe that these interpretations of the

criteria for exemption and review will impede research.

Rather, they will ensure that research conducted on

coded or identified samples, even if widely available, will

be subject to the federal policy of protections. 

Expedited Review

The current federal regulations appear to make eligible

for expedited review research on materials that will be

collected for clinical purposes or those that will be collected in noninvasive or minimally invasive ways for

research purposes. Ambiguity in the language, however,

appears to make research on existing collections eligible

for expedited review only when they were developed for

nonresearch purposes. NBAC finds that there is no need

to distinguish between collections originally created for

clinical purposes and those created for research purposes.

In both cases, research on the collected materials should

be eligible for expedited review if the research presents

no more than a minimal risk to the study subjects. (See

the discussion of minimal risk below.)

Recommendation 2:

OPRR should revise its guidance to make clear

that all minimal-risk research involving human

biological materials—regardless of how they were

collected—should be eligible for expedited IRB

review. 

Special Concerns About the 

Use of Unlinked Samples

Several repositories maintain a record of the persons from

whom specimens were derived so that the repository can

track which samples are sent to a clinician or researcher.

Such samples may be numbered in such a way that even

the repository cannot link the sample to its source. Or,

samples might be numbered in such a way that although

the repository could confirm that a sample was sent, if

the investigator were to ask the repository for additional

material or clinical information specific to that source,

the repository would not be able to match the request

with a specific specimen. The repository could send

the investigator a duplicate set of the initial “batch” of

samples, but again with no linking data. However, in

some rare cases the study sample size might be so small

and the findings so unique that it would be relatively easy

to identify individuals even if their samples were not

linked. Investigators and repositories should scrutinize

these situations carefully in order to reduce the risk that

sources could be identified. In such instances, it may be

more appropriate to use only unidentified (not merely

unlinked) samples, to increase the sample size, or even to

consider the samples to be identifiable rather than

unidentifiable.

When researchers use unidentified and unlinked

samples, it is extremely difficult if not impossible for

them to contact the source. According to the federal regulations, research using existing samples of this type is

eligible for exemption from IRB review. The justification

for these regulations appears to be that because it is not

possible to contact the sources to ask their permission or

gain their consent to any specific uses of their tissues, and

because the potential for harm effectively disappears

because of a lack of specific identifiability, no special

restrictions on the use of such samples should apply.

Although at first glance this seems reasonable, some

controversy continues in the case of samples that have

been unlinked before being sent to the investigator. Some

might consider it ethically problematic that by having the

identifiers stripped, the investigator loses the opportunity

to obtain consent, as further contact would be impossible. In addition, it is incorrect to assume that because

the sources cannot be identified they cannot be harmed

or wronged. Some interests of the sample sources may be
61

harmed even if they are not completely identifiable, and

interests of others also may be at risk. For example, there

may be group or family interests that could be revealed

or placed at risk because of research that is conducted on

a class of similar, albeit individually unidentifiable,

samples. Individuals have an interest in avoiding uses of

their tissues that they regard as morally impermissible or

objectionable. Thus, were their materials to be used in

research that they would consider objectionable, it is

possible that some individuals could be wronged, if not

harmed. NBAC recognizes that these concerns are valid,

but does not find that they are sufficiently substantial to

restrict further use of such samples.

Because the samples are not linkable to individuals,

some of the most important arguments that weigh in

favor of restricted access do not apply. If the individual

cannot be identified, there is little or no risk of insurance

or employment discrimination, stigma, adverse psychological reactions, or familial conflict. Thus, to that extent,

the case for not allowing use of unidentified and

unlinked stored samples is significantly weakened.

However, the possibility remains that research findings

might still result in potential harms to groups or classes

of individuals (e.g., loss of health insurance coverage for

individuals found to share a particular trait or characteristic). Although the current regulations do not require

investigators to consider such risks to groups, good practice might, in some cases, warrant an effort to minimize

risks to others through consultation with relevant

groups, alterations in research design, or greater care in

the manner in which research results are reported. (See

also Recommendations 11, 17, and 18.)

Previous guidelines and reports (see Chapter 3) have

categorized samples by the conditions under which they

are stored (with or without identifiers). Current federal

regulations permit researchers to take existing samples,

render them anonymous by removing identifiers, and

then use them in research without seeking consent. It is

apparent to NBAC that some investigators incorrectly

interpret the regulations to mean that so long as they do

not know the identity of the sample source, even if the

sample is coded (linked), the research is exempt from IRB

review.

Given the importance of society’s interest in treating

disease and developing new therapies, a policy that

unduly restricts research access to these unidentified and

unlinked samples would severely hamper research and

could waste a valuable research resource. As noted in

Recommendation 1, research using unlinked samples

may be exempt from review; however, if coded or identified samples are rendered unlinked by the investigator,

special precautions are in order. 

Recommendation 3:

When an investigator proposes to create unlinked

samples from coded or identified materials

already under his or her control, an IRB (or other

designated officials at the investigator’s institution) may exempt the research from IRB review if

it determines that

a) the process used to unlink the samples will be

effective, and

b) the unlinking of the samples will not unnecessarily reduce the value of the research.

The IRB or reviewing body should exercise particular

care when the process of unlinking is not carried out by

a third party (such as the independent repository that

supplied the samples) but rather by the investigator or

someone working with or for the investigator. What matters is the outcome—that results from analysis of the

samples cannot be linked to their sources—rather than

the unlinking method used. Institutions and organizations that participate in research conducted with

unlinked samples should establish policies and procedures (e.g., the use of independent third parties to unlink

samples) to ensure that the unlinking occurs.

Although unlinking reduces the risk of injury to the

specimen sources, it cannot eliminate such risk, which is

an especially serious consideration if the unlinking

reduces the scientific value of the research (thereby lowering the benefit-to-risk ratio). Generally, it is NBAC’s

view that when it is feasible to conduct human biological

materials research that is in accordance with the usual

protections for research subjects, it is preferable to do so,

rather than to unlink the samples in order to circumvent

those protections.

Exemption from review should not be granted when

IRB review would help investigators avoid inflicting

harms upon groups (see Recommendation 17) or when

the scientific merit of the research is compromised by the
62

failure to use coded or identified samples with appropriate human subjects protections.

Requirements for Investigators 

Using Coded or Identified Samples

Within the “identifiable” category of samples are two subcategories: coded samples and identified samples (i.e.,

where the sample source is expressly identified to the

investigator). Within the first category, a distinction may

exist between the information provided to the investigator

and that held by the repository. For example, the samples

might be encoded in such a way that the investigator cannot identify the sample source, but the entity storing the

specimen from which the sample has been derived—

such as a pathologist or DNA bank—can link the specimen source to the sample that was sent to the

investigator. Thus, the code could be broken. Although

identifying the source may be more difficult in the latter

scenario, because the possibility of linkage remains and

elevates the potential for harm, NBAC considers these

samples to be identifiable. It is important to note, however, that the ease of identifying the source is part of the

calculus in determining the overall level of risk posed by

the research. 

Repositories and IRBs share responsibility with

investigators to ensure that research is designed and

conducted in a manner that appropriately protects

human subjects from unwarranted harms. 

Recommendation 4:

Before releasing coded and/or identified samples

from its collection, a repository should require

that the investigator requesting the samples either

provide documentation from the investigator’s IRB

that the research will be conducted in compliance

with applicable federal regulations or explain in

writing why the research is not subject to those

regulations. 

Recommendation 5:

When reviewing and approving a protocol for

research on human biological materials, IRBs

should require the investigator to set forth

a) a thorough justification of the research design,

including a description of procedures used to

minimize risk to subjects,

b) a full description of the process by which

samples will be obtained,

c) any plans to obtain access to the medical

records of the subjects, and

d) a full description of the mechanisms that will

be used to maximize the protection against

inadvertent release of confidential information.

When an investigator obtains access to a patient’s

medical records, either to identify sample sources or to

collect additional medical information, human subjects

research is being conducted. IRBs should adopt policies

to govern such research, consistent with existing OPRR

guidance related to medical records research.

Using Previously Obtained Informed

Consent and Reconsent

Research using coded or identified samples requires the

consent of the source, unless the criteria for a consent

waiver have been satisfied. Unfortunately, the consent

signed at the time the specimen was obtained may not

always be adequate to satisfy this requirement.

Specimens that exist in storage at the time the research is

proposed may have been collected under a variety of

conditions (e.g., in a clinical setting or as part of an

experimental protocol). In some instances, individuals

make informed choices about how their sample should

be used subsequent to its original research or clinical use.

In other cases, for a variety of reasons, individuals may

not understand fully or may not have been given the

opportunity to consider carefully how their specimens

may be used in the future. When research is contemplated

using existing materials, the expressed wishes of the individuals who provided the materials must be respected.

Where consent documents exist, they may indicate

whether individuals wanted their samples to be used in

future research, and in some instances they may specify

the type of research.

IRBs should use the following criteria to evaluate the

applicability of such documents to the proposed

research:

■ Does the language or context of the consent form

indicate that the source was interested in aiding the

type of research being proposed?
63

■ If the source consented to the sample being used in

unspecified future studies, is that consent adequate

for the type of research being planned, given the circumstances under which the sample was collected

(e.g., whether the sample was requested by a treating

physician or whether the consent form offered alternatives to allowing the sample to be used in future

studies)? 

In some cases, an IRB may determine that an existing

consent form permitting unspecified future uses is sufficient. For example, Clayton et al. argue that, “[e]ven in

the absence of specific language about DNA testing, it

may be appropriate to infer consent if the source wished

for the sample to be used to determine why his or her

family had a particular inherited disorder” (1995). In

such cases, investigators should consider informing subjects that research is occurring and in certain cases also

give subjects the opportunity to “opt out.” Rarely, however, does the language that is included in typical surgical and other hospital consent forms provide an adequate

basis for inferring consent to future research.

Although an opt-out policy provides significant protection for sources and recognizes that their biological

material may have been collected without adequate disclosure, it also provides sources with the opportunity to

participate in research. When the IRB determines existing

consent documents to be inadequate and when the existing sample is identifiable, the individual should be contacted, offered the option of consenting to the specific

proposed protocol, and further offered the option of

deciding how the sample may be used in the future. 

As in the case with research in which new samples are

obtained, individuals should be provided with relevant

information that will help them decide whether they

would like to participate in research. Federal human subjects regulations list the basic elements of informed consent that, of course, also apply when consent is requested

for the use of existing samples (45 CFR 46.116(a)). The

following points are especially relevant: 

■ the risks and benefits of participation in the proposed

study along with a discussion of the possible consequences of consenting to future identifiable uses of

their sample,

■ the extent, if any, to which confidentiality will be

maintained,

■ under what circumstances, if any, sources will be

recontacted, and

■ an indication that if sources choose to have their

samples rendered unidentifiable, they cannot be

provided specific information about findings related

to their samples.

The rationale for including the option of authorizing

future research use of existing samples (rather than mere

disclosure that the sample may be used for a wide range

of purposes) is that in most cases, existing specimens will

have been collected without disclosure. Allowing persons

(whose previously collected materials are coded or identified) to choose either to authorize future research use or

to have their samples rendered unidentifiable for future

use can be viewed as an effort to repair this deficiency.

Even if such authorization bears only a remote resemblance to genuine informed consent, it can serve as an

expression of respect for persons in the context of proposed uses for existing samples. It is not adequate simply

to disclose to persons now that the material already taken

from them may be used in the future for purposes of

which they were unaware at the time of collection.9

Appropriate criteria should be used to determine

whether recontacting an individual source is appropriate,

and additional concerns should be addressed when

developing a plan to recontact any individuals. For

example, if explicit consent to use a sample was never

obtained (because it met the requirements for waiver),

IRBs should consider potential harms that might arise

should a subject learn, after the fact, that his or her material had been used in an experiment. 

Obtaining New Consent

When human biological materials are collected, whether

in a research or clinical setting, it is appropriate to ask

subjects for their consent to future use of their samples,

even when such uses are at the time unknown. The elements of the consent process for new samples should be

the same as those discussed earlier for the use of existing

identifiable samples.

Both in the literature and in testimony given before

NBAC, discussion has occurred regarding the concerns

that arise when administering a consent process in a clinical setting.10 These concerns often involve the fact that
64

the stress level may be high in clinical settings, rendering

them not conducive to a consent process that involves

making complex choices regarding issues that are not

related directly to clinical care and that involve speculation

about the distant future. In this setting, individuals may be

anxious about the clinical procedure they are about to

undergo and may not be prepared to consider carefully the

factors that go into making informed decisions about the

hypothetical research use of their tissues. The fact that

individuals also will be faced with making a number of

other decisions and with completing paperwork related to

the clinical procedures compounds the problem of administering an informed consent process in this setting. A better approach might be to discuss the future research use of

an individual’s specimen at some point before or after

consent is obtained for the clinical procedure.

NBAC acknowledges the important contribution to

this discussion of groups such as the National Action

Plan for Breast Cancer that have done thoughtful work

and made helpful suggestions on ways in which to

improve the overall consent process, including its design

and timing. However, it is clear that additional studies are

needed to determine the best time to administer this consent in clinical settings. As investigators and IRBs consider

this issue, it may be useful to consult the work of these

groups. Using their guidance and collective experience,

the scientific community should develop a consensus

regarding a standard method for human biological materials collection in both therapeutic and research contexts—one that would minimize the need for complex

efforts to recontact the source. 

Whether obtaining consent to the research use of

human biological materials in a research or clinical setting, and whether the consent is new or renewed, efforts

should be made to be as explicit as possible regarding the

uses to which the material might be put and regarding

whether it is possible that the research might be conducted in such a way that the individual could be identified. Obviously, different conditions will exist for

different research protocols, in different settings, and

among individuals. NBAC notes that the current debate

about the appropriate use of millions of stored specimens

has endured because of the uncertain nature of past consents. NBAC also recognizes that investigators and others

who have collected and stored human biological materials

now have the opportunity to correct past inadequacies by

obtaining more specific and clearly understood informed

consent. By doing so, the need to render samples unidentifiable through unlinking may become less frequent, and

the need to obtain reconsent thus may be minimized. It

is with these considerations in mind that NBAC makes

the following recommendations about improving the

consent process for the use of human biological materials

in research.

Recommendation 6:

When informed consent to the research use of

human biological materials is required, it should

be obtained separately from informed consent to

clinical procedures. 

Recommendation 7:

The person who obtains informed consent in clinical settings should make clear to potential subjects that their refusal to consent to the research

use of biological materials will in no way affect the

quality of their clinical care.

Recommendation 8:

When an investigator is conducting research on

coded or identified samples obtained prior to the

implementation of NBAC’s recommendations, general releases for research given in conjunction

with a clinical or surgical procedure must not be

presumed to cover all types of research over an

indefinite period of time. Investigators and IRBs

should review existing consent documents to

determine whether the subjects anticipated and

agreed to participate in the type of research proposed. If the existing documents are inadequate

and consent cannot be waived, the investigator

must obtain informed consent from the subjects

for the current research or in appropriate circumstances have the identifiers stripped so that samples

are unlinked.

Recommendation 9:

To facilitate collection, storage, and appropriate

use of human biological materials in the future,

consent forms should be developed to provide

potential subjects with a sufficient number of

options to help them understand clearly the

nature of the decision they are about to make.

Such options might include, for example:
65

a) refusing use of their biological materials in

research,

b) permitting only unidentified or unlinked use of

their biological materials in research,

c) permitting coded or identified use of their biological materials for one particular study only,

with no further contact permitted to ask for

permission to do further studies,

d) permitting coded or identified use of their 

biological materials for one particular study

only, with further contact permitted to ask for

permission to do further studies,

e) permitting coded or identified use of their 

biological materials for any study relating to the

condition for which the sample was originally

collected, with further contact allowed to seek

permission for other types of studies, or

f) permitting coded use of their biological materials for any kind of future study.*

Obtaining consent to future research on stored biological materials is difficult because it is impossible to

foresee many studies that may be designed in the future.

Also, patients may agree to have their biological materials used in some types of studies, but not in others.

Consent to future research is meaningful only if patients

appreciate, as much as possible, the types of studies that

may be conducted. However, describing future research

in detail may be confusing rather than helpful, especially

in the clinical setting, and could be administratively

* Commissioner Capron does not believe that (e) or (f) should be included among the options offered to potential subjects. IRBs are supposed to ensure a favorable risk-benefit ratio in all approved research, and subjects are supposed to be given accurate and understandable

information prior to providing consent to participate in a study. Because options (e) and (f) encompass future studies with unknown risks

and benefit, neither adequate IRB review nor informed consent is possible at the time when subjects are asked to provide consent for the

future use of stored material. Commissioner Shapiro concurs with this view regarding option (f) only. In the case of option (e), the range 

of studies is limited to “any study relating to the condition for which the sample was originally collected,” but even this definition will not

remedy the problem, in Commissioner Capron’s view. As for option (f), the use is confined to “coded” samples rather than the “identified”

samples permitted in option (e), but one premise of this report is that “coded” samples should be grouped with identified samples because

information produced from analyzing them potentially can be linked to identifiable persons. 

Commissioner Miike offers the following statement: “Recommendation 9 identifies the range of prospective consents that the Commission

has determined are reasonable for patients and research participants to assess and either assent to or decline. While the report does not 

necessarily make this explicit, at least my interpretation is that these are not being offered as a package: i.e., future consent forms need not

necessarily include all of these choices, but research institutions and patient care facilities should view these as a kind of menu from which

they might revise their current consent forms. In this range of prospective consents, the most controversial is Recommendation 9(f): ‘To 

permit coded use of their biological materials for any kind of future study.’ This general consent recommendation would seem to contradict

the Commission’s overall report, with its focus on consent as truly being informed. [This] report, however, addresses human biological materials collected both in research and clinical care settings. In the research setting, an extensive prospective consent form that includes the

entire range identified in Recommendation 9 seems reasonable. Given the nature of current consent documents in the clinical care setting,

however, I believe it is unreasonable to expect patients to deal with such a complicated consent form for permissible future research. In the

clinical setting, I am primarily concerned with separating the consent to treatment from the consent for possible future use of any biopsied

or surgically removed tissues. Patients, whose primary concern is treatment or diagnosis, cannot be expected to reasonably evaluate the

diverse range of prospective consent choices as identified in Recommendation 9. Thus, for practical purposes, a general consent form must

be used. For those concerned over the use of such a general prospective consent, my response is as follows: For participants in research 

projects who are asked to consent or decline to give permission for use of their tissues in future research projects, the range of consents 

identified in Recommendation 9 can be provided. However, for patients in clinical settings, the primary problem currently is that the consent

for possible future use in research of any tissue collected is buried in the clinical care consent form. This separate consent should be made

explicit by requesting two signatures—one for the clinical care, the other for possible future research uses (see Recommendation 6). As for

the specific language of the prospective research use, a complicated document will raise unnecessary concerns and would, I predict, lead to 

a significant decrease in the availability of such materials. Moreover, this report makes other recommendations which strengthen the current

informed consent process. Any general consent would be reviewed when future research projects are undertaken: 1) to assess whether the

consent is appropriate in view of the particular research project to be undertaken; 2) the practicability of contacting the tissue donor for

updating that consent; and 3) designing the project to strengthen confidentiality and/or to ensure anonymity. Without a general consent

option, I am concerned that consent forms in the clinical setting will become too complicated and patients will be overly concerned and opt

not to sign. Even when the research will be minimal risk and not require informed consent, such biological materials will be forever lost to

research, because they would have been excluded at the time of biopsy or excision from any future research use.”
66

burdensome. The National Institutes of Health (NIH)

and advocacy groups such as the National Action Plan for

Breast Cancer have worked on designing multilayered

consent forms that are both informative and practical.

Such efforts should be encouraged and continued.

This policy for existing samples should be supplemented with special attention to areas of research that are

considered sensitive or potentially objectionable to some.

In other words, even if the source of an identifiable existing sample chooses to render the sample identifiable and

authorizes future identifiable research uses, he or she

should enjoy the additional protection afforded by the

requirement of specific consent to uses of the sample that

he or she might consider sensitive or objectionable. Such

a category may include, for example, certain behavioral

genetics protocols, studies differentiating traits among

ethnic or racial groups, or research on stigmatizing characteristics such as addictive behavior.

Criteria for Waiver of Consent 

When an investigator proposes to conduct research with

coded or identified samples, it is considered research with

human subjects. Ordinarily the potential research subject

is asked whether he or she agrees to participate. Seeking

this consent demonstrates respect for the person’s right to

choose whether to cooperate with the scientific enterprise, and it permits individuals to protect themselves

against unwanted or risky invasions of privacy. But

informed consent is merely one aspect of human subjects

protection. It is an adjunct to—rather than a substitute

for—IRB review to determine if the risks of a study are

minimized and acceptable in relation to its benefits.

When a study is of minimal risk, consent is no longer

needed by a subject as a form of self-protection against

research harms. It is still appropriate to seek consent,

however, in order to show respect for the subject, unless

it is impracticable to locate him or her in order to obtain

it. Thus, when important research poses little or no risk

to subjects whose consent would be difficult or impossible to obtain, it is appropriate to waive the consent

requirement.

As stated in the current federal regulations, human

subjects research is presumed to require consent, but this

requirement can be altered or waived if all four of the following criteria, set forth at 45 CFR 46.116(d), are met: 

■ The research involves no more than minimal risk to

the subjects, 

■ The waiver or alteration of consent will not adversely

affect the rights and welfare of the subjects,

■ The research could not practicably be carried out

without the waiver or alteration, and

■ Whenever appropriate, the subjects will be provided with additional pertinent information after 

participation.

Determining the risks of research and the effects that

waived consent might have on the rights and welfare of

the subject are bedrock considerations in deciding

whether a subject’s consent is an essential part of human

subjects protections. Four key terms are central to this

determination: “minimal risk,” “rights and welfare,”

“practicability,” and “after participation.”

Minimal Risk

The regulations state that “minimal risk means that the

probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves

than those ordinarily encountered in daily life or during

the performance of routine physical or psychological

exams or tests” (45 CFR 46.102(i)). Identifying minimal

research risks thus depends upon a comparison of

research risks with risks that persons “ordinarily” face

outside of the research context.

However, when considering the risks of research conducted on human biological materials, one may question

the applicability of the threshold that the regulations

establish for assessing minimal risk. The risks encountered “during the performance of routine physical or psychological exams or tests” have limited utility as a

baseline. Although these risks can be compared to the

physical risks faced in the collection of new samples, they

are not really comparable with the risks of social and psychological harm relevant to research on biological samples. The risks encountered during the performance of a

medical exam evidently relate to harms that the intervention itself may produce. The risks of psychosocial harm

associated with research on biological samples, on the

other hand, relate to future uses of information derived

from samples.

The risks of daily life seem a more promising threshold

for assessing the risks of research on biological materials.
67

In research on biological samples, the potential harms of

central concern (e.g., stigmatization, insurance and

employment discrimination, familial conflict, anxiety,

violations of privacy) are those that may result if certain

information from biological samples (e.g., the subject’s

susceptibility to disease) is disclosed to noninvestigators.

But such information also commonly is contained in

medical records. Persons (research subjects and nonresearch subjects alike) generally face the risk that diagnostic, predictive, and other forms of information about

them contained in their medical records will be obtained

and used in a harmful manner. Although insufficient data

are available to make a decisive statement about the relative probabilities of harm resulting from uses of biological samples vis-a-vis access to medical records, one might

hold that the level of risk is similar in both cases. Indeed,

research on biological samples arguably poses fewer

risks, because the sources of even coded and identified

samples may be more difficult to trace than the subjects

of explicitly labeled medical records. Thus, one might

conclude that the risk involved in the use of biological

samples is minimal.

NBAC does not find this analysis of minimal risk to

be persuasive. Fundamentally, the issue is not whether

the risk of harm that research poses to subjects is in itself

minor or substantial; rather, the issue is whether the risks

that the research presents are more severe than risks that

individuals ordinarily confront. According to this interpretation, research risks could be substantial but nevertheless be considered “minimal.” The problem is that the

purpose of assessing whether risk is minimal is to help

IRBs determine what types of protections should be

required. Although a strict reading of the regulations may

permit an interpretation that allows one to consider great

risks of harm to subjects minimal, such an interpretation

certainly violates the spirit of the regulations.

An alternative interpretation of the regulations avoids

this result. According to this interpretation, the concept

of “‘risks of everyday life,’ has normative as well as

descriptive force, reflecting a level of risk that is not

simply accepted but is deemed socially acceptable”

(Freedman, Fuks, and Weijer 1993). In addition, any risk

that is not socially acceptable cannot properly be characterized as a risk of daily life. There is a widespread view

that the present risks of harm from uses of sensitive medical information about individuals are not acceptable and

that stronger privacy laws are needed to remedy this situation. Thus, the risks of harm resulting from the

improper use of medical records are not, according to

this interpretation, risks of daily life. It follows that one

cannot employ the risks of harmful uses of medical

records as a baseline for determining whether research on

biological samples is of minimal risk. This, in turn,

makes it difficult to perform a minimal risk analysis for

research on biological samples, as there are no apparent

alternatives that can plausibly serve as a baseline.

Nonetheless, NBAC believes that most research using

human biological materials is likely to be considered of

minimal risk because much of it focuses on research that

is not clinically relevant to the sample source, as compared to research with medical records, for example,

which is likely to be filled with clinically relevant findings

that could harm the individual if misused or used inappropriately by third parties.

Although the regulatory definition of minimal risk

appears inadequate for research on human biological

materials, NBAC recommends that in the assessment of

risk, IRBs should consider the following questions when

determining the extent to which a source could be

harmed: 

■ How easily identifiable is the source?

■ What is the likelihood that the source will be traced?

■ If the source is traced, what is the likelihood that

persons other than the investigators will obtain

information about the source? (Privacy/confidentiality laws may be relevant here, as are the integrity of

investigators and their institutional confidentiality

protections.)

■ If noninvestigators obtain information regarding the

source, what is the likelihood that harms will result,

including adverse consequences arising from the

reporting of uncertain or ambiguous clinical results?

(State and federal discrimination laws may be relevant

with respect to uses of information by third parties.)

As noted in Chapter 4, the likelihood of psychosocial

harms resulting from research on biological samples is

somewhat speculative at present. There are, however,

reasons to think that the risks of harm are generally
68

minimal or can be easily rendered minimal. Given current scientific practices, many studies are being conducted in which it is not necessary that investigators know

the identity of sample sources. In these cases, investigators will not have a need to trace sample sources although

they might require additional clinical information without identifying the source. Even in instances when investigators need to identify a source, it is not necessary to

reveal information about sources to third parties.

Although it is possible that noninvestigators will access

information about a source, investigators can minimize

this risk through appropriate confidentiality mechanisms. For example, protocols that include provisions for

isolating the results of genetic or other research results

completely from the source’s medical record and that

incorporate a prohibition on returning uncertain or

ambiguous information to sources (which would forestall

the communication of premature and potentially upsetting information) should in most cases ensure that risks

will be minimal.

Recommendation 10:

IRBs should operate on the presumption that

research on coded samples is of minimal risk to

the human subject if 

a) the study adequately protects the confidentiality

of personally identifiable information obtained

in the course of research, 

b) the study does not involve the inappropriate

release of information to third parties, and 

c) the study design incorporates an appropriate

plan for whether and how to reveal findings 

to the sources or their physicians should the

findings merit such disclosure.

Rights and Welfare

Failure to obtain consent may adversely affect the

rights and welfare of subjects in two basic ways. First, the

subject may be improperly denied the opportunity to

choose whether to assume the risks that the research

presents, and second, the subject may be harmed or

wronged as a result of his or her involvement in research

to which he or she has not consented.

A waiver of consent in the collection of new biological samples violates subjects’ rights because it would

expose them to unwanted bodily invasions. The interest

in being free from unwanted bodily invasions is the primary interest the requirement of informed consent was

instituted to protect. In the case of consent for the use of

existing samples, the interests at stake are different. In

this context, it is principally the social and psychological

harms delineated in Chapter 4 that are at issue. Subjects’

interest in controlling information about themselves is

tied to their interest in, for example, not being stigmatized and not being discriminated against in employment

and insurance. 

Although the risks of psychosocial harms generally

may be minor in research on human biological materials,

some important and exceptional cases are worth noting.

For example, controversial studies such as those that

involve behavioral genetics or that make explicit comparisons between ethnic or racial groups are likely to

offend some research subjects and may threaten their

ascriptive identities. Moreover, there remains the possibility that the results of such studies will be used to stigmatize and discriminate against group members (subjects

and nonsubjects alike).

Further, when state or federal law, or customary practice, gives subjects a right to refuse to have their biological materials used in research, then a consent waiver

would affect their rights adversely. Medical records privacy

statutes currently in place or under consideration generally allow for unconsented research use and could be

interpreted to suggest a similar standard for research

using human biological materials. But as new statutes are

enacted, it is possible that subjects will be given explicit

rights to limit access to their biological materials.

Recommendation 11:

In determining whether a waiver of consent would

adversely affect subjects’ rights and welfare, IRBs

should be certain to consider 

a) whether the waiver would violate any state or

federal statute or customary practice regarding

entitlement to privacy or confidentiality,

b) whether the study will examine traits commonly considered to have political, cultural, or

economic significance to the study subjects,

and 

c) whether the study’s results might adversely

affect the welfare of the subject’s community.
69

Practicability

Even when research poses no more than minimal risk

and when a consent waiver would not affect the rights

and welfare of subjects, respect for subjects requires that

their consent be sought. However, on some occasions,

demonstrating this respect through consent requirements

could completely halt important research. An investigator

who requests a waiver of the informed consent requirement for research use of human biological materials

under the current federal regulations must provide to the

IRB evidence that it is not practicable to obtain consent.

Unfortunately, neither the regulations nor OPRR offers

any guidance regarding what defines practicability.11

According to the Oxford English Reference Dictionary,

the term “practicable” is defined, in the ordinary sense, as

that which “can be done or used” or is “possible in practice.” The issue for regulatory purposes and (NBAC

would suggest) for the purpose of assessing the ethical

acceptability of this provision, is whether the practicability requirement—alone or in combination with other criteria for obtaining a waiver—adds guidance to the

investigators and IRBs that will make these decisions.

Informed consent may not be “possible in practice” when

there are many more subjects than there are individuals

to seek their consent or when the amount of time it

would take to recontact a subject or subjects would be

longer than the time it would take to complete the study.

Similarly, obtaining consent might be considered impracticable if the financial or labor costs of either a direct or

indirect recontact effort (such as mailing consent forms

and information) far exceeded the researcher’s budget. For

many research protocols, it is likely to be exceedingly

difficult to locate people in order to obtain consent. One

might even suggest that in research that is designed to

provide a direct benefit to some of the subjects, it would

be impracticable to take the time to recontact potential

subjects, because the delay in completing the study could

be considered a more serious harm than would be the

failure to obtain express consent. Although these are

reasonable examples of impracticability and, NBAC

would suspect, might be regarded by some as good reasons for granting a waiver, the trouble with the practicability requirement is that it forces a comparison between

otherwise incommensurable harms: the wrong that could

be committed by not obtaining informed consent and the

prohibitively costly and perhaps even needlessly intrusive

harm of attempting recontact. As with many types of

incommensurability in IRB review, the task of assessing risk

and benefit becomes far more problematic.

Recommendation 12:

If research using existing coded or identified

human biological materials is determined to present minimal risk, IRBs may presume that it

would be impracticable to meet the consent

requirement (45 CFR 46.116(d)(3)). This interpretation of the regulations applies only to the use

of human biological materials collected before the

adoption of the recommendations contained in

this report (specifically Recommendations 6

through 9 regarding informed consent). Materials

collected after that point must be obtained according to the recommended informed consent process

and, therefore, IRBs should apply their usual standards for the practicability requirement.

Even in instances when it might be considered practicable to obtain consent for research use of stored

human biological materials, it may be burdensome for

investigators to do so. NBAC believes that in assessing

the appropriateness of waiving consent, consideration

should be given principally to the criteria of minimal

risks and rights and welfare and that practicability should

not be a compelling consideration. Thus, IRBs should be

permitted to presume that contacting individuals who were

the sources of tissues in the past will be impracticable

enough to satisfy the regulatory requirements. Of course,

IRBs are free to forego the presumption and require

consent to minimal risk research whenever they believe

that a demonstration of respect for the subjects is

important and that the process will not pose significant

burdens on investigators.

NBAC recognizes that if its recommendation that

coded samples be treated as though they are identifiable

is adopted, there may be an increase in the number of

research protocols that will require IRB review. If, however, such protocols are then determined by an IRB to

present minimal risk to a subject’s rights and welfare, the

requirement for consent may be waived if the practicability requirement is revised for this category of research. 
70

NBAC believes that these interpretations and recommended changes in the regulations will allow important

research to proceed while also considering potential

harms to subjects. However, it must be noted that by

dropping the requirement that consent must be obtained

if practicable, NBAC does so with the expectation that

the process and content of informed consent for the collection of new specimens will be explicit regarding the

intentions of the subjects and the research use of their

materials. (See Recommendations 6 through 9 concerning informed consent.)

Providing Additional Information as Required

at 45 CFR 46.116(d)(4)

According to the current regulations, the fourth

condition for the waiver of consent stipulates that

“whenever appropriate, the subjects will be provided

with additional pertinent information after participation”

(45 CFR 46.116(d)(4)). The historical context for this

condition is the use of “deception” studies (e.g., in the

behavioral sciences) in which it is deemed crucial to the

study design that the subjects be unaware of the details

of the study design or, on occasion, that they are the subjects of the study. Thus, according to the regulations, an

IRB, while waiving consent (by finding and documenting

the first three required conditions), could require that

subjects be informed that they are subjects of research

and that they be provided details of the study—a 

so-called debriefing requirement.

The applicability of this condition in the context of

stored samples could be interpreted in a variety of ways.

If the first three conditions of waiver of consent are met,

the IRB might require, as an additional measure of protection, that the investigator provide some information to

the subjects. Such a communication would describe the

status of the research project and inform them that their

samples will be used or were used in the research. Such

a requirement might be appropriate only if consent

already had been obtained and the IRB determines that

reconsent is not required for a specific or new protocol.

The IRB might well recognize that only those subjects

who could be found would be so informed.

Respect for subjects’ rights and welfare in such circumstances will usually dictate that they be informed

after-the-fact of the research in which they have been

involved as naive or unwitting subjects and perhaps

offered the opportunity to withdraw their information

from the investigator’s data. In general, however, NBAC

concludes that this fourth criterion for waiver of consent

is not relevant to research using human biological materials

and, in fact, might be harmful if it forced investigators to

recontact individuals who might not have been aware

that their materials were being used in research.

Recommendation 13:

OPRR should make clear to investigators and IRBs

that the fourth criterion for waiver, that “whenever

appropriate, the subjects will be provided with

additional pertinent information after participation” (45 CFR 46.116(d)(4)), usually does not

apply to research using human biological materials.

“Opt Out” as an Additional Measure of

Protection When the Consent Requirement 

Has Been Waived

“Opt out” refers to the choice given to sources to

exclude themselves from a study. Unless someone has

“opted out,” he or she is assumed to be enrolled. If, after

a waiver of the consent requirement is granted, an investigator or IRB has residual concerns regarding the nature

of the research or the possibility that some individuals

might find the research objectionable, then an additional

measure may be taken to allow subjects to opt out of the

research. In this scenario, subjects would, if possible, be

contacted and given the choice of opting out; if they did

not respond or could not be found, the sample still could

be used because the consent requirement already would

have been waived. This differs significantly from a scenario in which the consent requirement has not been

waived. In such a scenario, if a person did not respond

with explicit consent or could not be located, his or her

sample could not be used in the research protocol.

Rendering Existing Identifiable Samples

Unidentifiable to Avoid the Need for

Consent

A more practical solution to using existing samples for

which it is impracticable or problematic to gain express
71

informed consent for their specific uses is to render the

samples unidentifiable. The rationale for this apparently

simple proposal is that in many cases existing specimens

were collected without anything close to adequate disclosure that they would be used for a range of purposes

unrelated to the context in which they were collected. 

Several drawbacks to rendering existing materials

unidentifiable for every use that is not specifically consented to by the source should be noted. First, the

administrative cost of rendering such materials completely unidentifiable would be high. Second, if a sample

is not identifiable, opportunities may be lost to protect

the well-being of the source or of his or her relatives (e.g.,

in the case of genetic conditions) when later research discovers therapeutically significant links between various

diseases or between diseases and genotypes. Third, rendering a sample unidentifiable restricts the usefulness of

that sample to investigators, who may wish to obtain

additional samples or who may wish to gather additional

medical information from the patient or the medical

record. Thus, there could be a scientific or medical price

to pay for this action. A possible ethical objection to this

practice is based on the belief that rendering existing

samples unidentifiable without consent is problematic

because researchers once had the opportunity to seek

consent but did not do so. Fourth, some investigators

may choose to render identifiable samples unidentifiable

in order to avoid the time and cost of IRB review and the

possibility that the IRB might require informed consent.

NBAC believes that rendering existing samples

unidentifiable in order to expedite research protocols

may be avoided in many situations by designing the

research in such a way that risks to the subjects are minimized. If risks are minimal, then it is possible that the

requirement for informed consent might be waived or

altered according to the regulations, 45 CFR 46.116(d).

If the nature of the research changes in the future—so

that an investigator now selects specific samples for additional studies that might increase risks beyond the minimal level—further IRB review would be required.

Moreover, for future sample collection, a consent process

that explicitly spells out the subject’s wishes concerning

uses of tissue will help to alleviate the investigator’s need

to use unidentified or unlinked samples.

Nevertheless, NBAC recognizes that some situations

will occur in which it is scientifically sound or desirable

to render samples unidentifiable through unlinking and

that there is little or no scientific or medical cost to doing

so. In addition, NBAC understands that recontacting

sources to seek consent could be costly and time consuming in situations in which there is little possibility for

stigmatization or harm once the identifiers are removed.

Furthermore, sample sources may not want to be contacted, and the process may be disruptive to them. With

these considerations in mind, NBAC concludes that, in

those circumstances in which valuable samples could not

otherwise be used, in which consent would be difficult to

obtain, and in which there is little or no scientific cost to

losing the link, it is ethically acceptable to render samples

unidentifiable without the source’s consent. In arriving at

this conclusion, NBAC also considered input from the

public that was received during its deliberations. Most

citizens emphasized in their comments that they did not

view their donated biological materials as something that

belonged to them, but rather as a gift to be used by the

scientific community, one that would be subject to review

for quality and ethical acceptability and one that would

be made if they could be assured that the information

obtained would not be used to discriminate against them.

Reporting Research Results to Subjects

Experts disagree about whether findings from research

should be communicated to subjects, although most do

believe that findings should not be conveyed unless they

are confirmed and reliable and constitute clinically significant or scientifically relevant information. Those who

oppose revealing unconfirmed findings argue that the

harms that could result from revealing preliminary data are

serious, including anxiety or unnecessary (and possibly

harmful) medical interventions. They prefer to avoid

such harms by controlling the flow of information to subjects and by limiting communications to those that constitute reliable information. MacKay, writing about the

development of genetic tests, contends that preliminary

results do not yet constitute “information” since “until an

initial finding is confirmed, there is no reliable information” to communicate to subjects, and that “even...confirmed findings may have some unforeseen limitations”
72

(1984). Subjects should not be given information about

their individual test results until the findings have been

confirmed through the “development of a reliable, accurate, safe and valid presymptomatic test” (MacKay 1984;

Fost and Farrell 1989). Others have argued that the principle of autonomy dictates that subjects have a right to

know what has been learned about them, and that therefore, interim results should be shared with subjects

(Veatch 1981).

Reilly suggests that IRBs should develop general policies governing the disclosure of information to subjects

to help make these determinations. At the very least, the

following three factors should be considered: “1) the

magnitude of the threat posed to the subject; 2) the accuracy with which the data predict that the threat will be

realized; and 3) the possibility that action can be taken to

avoid or ameliorate the potential injury” (1980). IRBs

should require investigators to define three categories of

findings: 1) “findings that are of such potential importance to the subject that they must be disclosed immediately”; 2) “data that are of importance to subjects...but

about which [the investigator] should exercise judgment

about the decision to disclose...[i]n effect, these are data

that trigger a duty to consider the question of disclosure”;

and 3) “data that do not require special disclosure” (Reilly

1980).

Recommendation 14:

IRBs should develop general guidelines for the

disclosure of the results of research to subjects

and require investigators to address these issues

explicitly in their research plans. In general, these

guidelines should reflect the presumption that the

disclosure of research results to subjects represents an exceptional circumstance. Such disclosure should occur only when all of the following

apply:

a) the findings are scientifically valid and

confirmed,

b) the findings have significant implications for

the subject’s health concerns, and

c) a course of action to ameliorate or treat these

concerns is readily available.

Recommendation 15:

The investigator in his or her research protocol

should describe anticipated research findings and

circumstances that might lead to a decision to

disclose the findings to a subject, as well as a plan

for how to manage such a disclosure.

Recommendation 16:

When research results are disclosed to a subject,

appropriate medical advice or referral should be

provided.

Considerations of Potential 

Harms to Others

The federal regulations governing the protection of

research subjects extend only to individuals who can be

identified as the sources of the biological samples. The

exclusive focus of the regulations on the individual

research subject is arbitrary from an ethical standpoint,

because persons other than the subject can benefit or be

harmed as a consequence of the research.

Risks to Groups

Research on samples that implicates groups may place

group members at risk of harm. For example, research

revealing that a racial or ethnic group is prone to a particular disease could be used to stigmatize and discriminate against group members.

OPRR guidance to IRBs and investigators on how best

to identify and minimize risks to groups is required.

Consultation with group members before designing and

implementing research on groups, for example, often

may be an effective way to understand and reduce risks.

However, additional work is needed to identify appropriate mechanisms for group consultation.

It also seems appropriate to highlight how some of

these issues should be discussed among researchers and

their professional organizations. For example, what is the

appropriate role of public health policy in developing

new knowledge from genetic epidemiology? Will additional ethical considerations be needed to ensure that the

benefits of public health objectives do not come at the

cost of individual concerns? For many studies, the

answer to the latter question may be yes. The net gain to

a particular population that results from being informed

about its increased risk (especially when something can

be done with this knowledge at an individual level) often

will outweigh the harms that come from labeling the

group as high risk.
73

Risks and Potential Benefits to Relatives 

of the Sample Source

Others who may be at some risk are first-degree relatives or next-of-kin of the source. The need to consider

these individuals as at risk is particularly evident when

the disease or condition being studied is genetic or

involves infectious agents or toxins to which family

members also may have been exposed. In these

instances, investigators are likely to be aware that the

research they are conducting on a sample might have

implications for those closely related to the sample

source—individuals who are readily identifiable.12 NBAC

does not assume that because there might be risks to relatives of the sample source, those risks warrant considering the relatives to be human subjects who deserve the

protection of informed consent.13 In fact, NBAC finds that

the possibility that a relative of the source could terminate a research protocol on the basis that he or she also

must give consent is not only impractical but troublesome. If the source has consented to the research use of

his or her sample, that consent alone is sufficient for the

research to proceed. However, although the regulations

do not require that the concerns of first-degree relatives

be considered, NBAC recognizes that there might be 

circumstances in which an investigator finds it useful,

beneficial, appropriate, and feasible to consider potential

harms and benefits applicable to such individuals.

A different set of concerns arises when the source of

the sample is deceased. Under federal regulations, people

are human subjects only while they are living. Research

involving human biological materials from individuals

who are deceased at the time of the research is not subject to the requirements of the Common Rule, regardless

of whether or not prior informed consent was obtained.

In addition, the existing regulations do not make explicit

the status of living relatives of deceased individuals

whose stored samples are used in research.14 However, it

is possible that the living relatives of the deceased sample

source might have an interest in the research, particularly

if the investigation has focused on hereditary traits.

Recommendation 17:

Research using stored human biological materials,

even when not potentially harmful to individuals

from whom the samples are taken, may be potentially harmful to groups associated with the

individual. To the extent such potential harms can

be anticipated, investigators should to the extent

possible plan their research so as to minimize such

harm and should consult, when appropriate, representatives of the relevant groups regarding study

design. In addition, when research on unlinked

samples that poses a significant risk of group

harms is otherwise eligible for exemption from

IRB review, the exemption should not be granted if

IRB review might help the investigator to design

the study in such a way as to avoid those harms.

Recommendation 18:

If it is anticipated that a specific research protocol

poses a risk to a specific group, this risk should be

disclosed during any required informed consent

process.

Publication and Dissemination of

Research Results

Publishing research results with identifiable information

in scientific or medical journals and elsewhere may pose

a risk to the privacy and confidentiality of research subjects. Public disclosure of such information through written descriptions or pedigrees may cause subjects to

experience adverse psychosocial effects. In addition,

without the informed consent of the individual, such disclosure infringes on the rights of the subject or patient.

Because of the familial nature of information in pedigrees, their publication poses particularly difficult questions regarding consent. Investigators should be aware

that the ways in which research results are publicized or

disseminated can affect the privacy of human subjects.

NBAC believes that the source of funding, i.e., public or

private, should not be an important consideration in

determining the ethical acceptability of the research.

Recommendation 19:

Investigators’ plans for disseminating results of

research on human biological materials should

include, when appropriate, provisions to minimize

the potential harms to individuals or associated

groups. 

In addition, journal editors have an ethical obligation

to publish only human subjects research that they have

reason to believe was conducted according to ethical

standards set forth in the Common Rule, which includes
74

review by an IRB. Recent studies have reported that ethical standards communicated in journals’ instructions to

authors vary widely, as do authors’ adherence to such

standards.

Recommendation 20:

Journals should adopt the policy that the published results of research studies involving human

subjects must specify whether the research was

conducted in compliance with the requirements of

the Common Rule. This policy should extend to

all human subjects research, including studies

that are privately funded or are otherwise exempt

from these requirements. 

Professional Education and

Responsibilities

Public and professional education plays an essential role

in developing and implementing effective public policy

regarding the use of human biological materials for

research. By education, NBAC is referring not simply to

the provision of information with the aim of adding to

the net store of knowledge by any one person or group;

rather, education refers to the ongoing effort to inform,

challenge, and engage. Providing education regarding

ethical issues in research that involves human biological

materials would mean that a variety of individuals and

groups would gain new tools with which to assess these

important issues. Therefore, opportunities for such education must be made available to IRBs, researchers, other

members of the research and academic community, political decisionmakers at the state and federal levels, interest groups, possible human subjects, and the eventual

consumers of research on human biological materials. In

addition, widespread and continuing deliberation must

occur regarding informing and educating the public

about developments in the field of genetics and in other

areas in the biomedical sciences, especially when they

affect important cultural practices, values, and beliefs.

Recommendation 21:

NIH, professional societies, and health care organizations should continue and expand their efforts

to train investigators about the ethical issues and

regulations regarding research on human biological materials and to develop exemplary practices

for resolving such issues. 

NIH can promote these efforts through the use of

workshops, conferences, requirements for training grants

and center grants, and funding for research on pertinent

topics related to this report, and professional societies

can develop training materials on these issues and disseminate information about how research centers have

addressed ethical issues regarding research on human

biological materials successfully. In doing so, the development of consent processes that allow patients and

research volunteers to make meaningful choices about

how biological materials might be used in future research

should be emphasized. 

Continued collaborative efforts between scientists,

patient representatives, and advocacy groups are likely to

be particularly fruitful in strengthening the consent

process. Discussions regarding this subject should

encompass the types of ethical concerns raised by the

storage and use of human biological materials and the

importance of appropriate protection of human subjects

whose materials are used in such research. Moreover,

because it is the research community that seeks access to

these materials, for policy purposes the moral burden

should fall upon researchers to elicit from prospective

contributors, both individuals and groups, the values and

meaning that they attach to the requested samples.

Recommendation 22:

Compliance with the recommendations set forth in

this report will require additional resources. All

research sponsors (the government, private sector

enterprises, and academic institutions) should

work together to make these resources available.

Use of Medical Records in Research on

Human Biological Materials

In recent years, attention increasingly has been paid by

policymakers to the need to protect the health information of the individual. Extensive efforts at the state and

federal levels to enact such protections have resulted in

the setting of a variety of limitations on access to patients’

medical records. NBAC notes that debates about medical

privacy are relevant to researchers using human biological materials in two ways. First, these researchers often

need access to patient medical records, either to identify
75

research sample sources or to gather accompanying clinical information. Such activities constitute human subjects research and should be treated accordingly. The

recommendations contained in this report provide a

model framework for considering research in which the

human subject is defined through his or her biological

material. Many of these recommendations could apply

equally to research in which the human subject is defined

through access to his or her medical record. Thus, policymakers, investigators, and IRBs considering medical

records research could benefit from NBAC’s work in the

area of human biological materials research.

Second, the development of statutes and regulations

designed to protect the patient’s medical record could

have the unintended consequence of creating a dual system of protections—one for the medical record and one

for human biological materials. Moreover, restricting

access to the medical record could impede legitimate and

appropriate access on the part of investigators whose protocols have undergone proper review.

Recommendation 23:

Because many of the same issues arise in the context of research on both medical records and

human biological materials, when drafting medical

records privacy laws, state and federal legislators

should seek to harmonize rules governing both

types of research. Such legislation, while seeking

to protect patient confidentiality and autonomy,

should also ensure that appropriate access for

legitimate research purposes is maintained.

Differences in the rules governing research on medical records and human biological materials should be

adopted only when it is critical to consider the important

differences between the two types of research, including

the fact that the information that may be found by studying cells and tissues differs in significant respects from

the information that is found in medical records.

Summary

To advance human health, it is critical that human 

biological materials continue to be available to the biomedical research community. Increasingly, it will be

essential for investigators to collect human biological

materials from individuals who are willing to share

important clinical information about themselves. In addition, it is crucial that the more than 282 million specimens already in storage remain accessible under

appropriate conditions and with appropriate protections

for the individuals who supplied this material.

The growing availability to third parties of genetic and

other medical information about individuals has fueled

the current debate about medical privacy and discrimination, and NBAC is sensitive to the possibility that the

use of information obtained from human biological

samples can lead to harms as well as benefits. These concerns require that those who agree to provide their DNA,

cells, tissues, or organs for research purposes not be

placed at risk. Measures to provide appropriate protections for individual privacy and for the confidentiality of

clinical and research data are important if significant

research is to continue. The recommendations provided

in this report are intended to promote the goals of

improving health through biomedical research while protecting the rights and welfare of those individuals who

contribute to human knowledge through the gift of their

biological materials.

Notes

1 King, M., “Genetics Research in Individuals, Families, and

Communities.” Testimony before NBAC. July 15, 1998. 

Portland, OR. 

2 The protections provided by the Common Rule currently apply

only to 1) research conducted or funded by one of the 17 agencies

that have agreed to be subject to the Common Rule or by any

other federal agency that has promulgated its own set of human

subjects research rules, or 2) research conducted at an institution

that has provided in its “Assurance” with the federal government

that all research with human subjects conducted at the institution

will be governed by the federal regulations whether or not the

research is federally sponsored. In addition, the FDA regulates

human subjects research involving an investigational new drug,

device, or biologic.

3 45 CFR 46.102(f)(1) and (2).

4 See 45 CFR 46.102 (f). If the source of the sample is deceased,

then, according to the regulations, there is no human subject, and

the regulations do not apply. However, circumstances may exist in

which research on samples of deceased individuals has implications for living relatives; if the findings were attached in some way

to these relatives, they might be considered human subjects, which

could trigger the federal regulations.
76

5 Personal communication from OPRR Director, Dr. Gary Ellis,

August 25, 1998.

6 American Type Culture Collection, www.atcc.org/.

7 Moreover, some newer DNA databases (e.g., those associated

with the federally funded Human Genome Project) are organized

based on the assumption that such information should be available

to any scientist wanting to investigate the basic structure or function of DNA. For example, the National Human Genome Research

Institute implements a policy requiring that primary human

genomic sequence data be rapidly released (within 24 hours of

generation).

8 In reviewing the policies and procedures of several repositories,

the Commission found that some require that investigators provide

a statement of their research intent and an assurance of compliance

with the Common Rule, but it is not clear that this practice is widespread, especially among smaller, more informal tissue collections.

9 Elsewhere, NBAC has discussed the issue of prospective authorization and found that under some circumstances it is an important

method of respecting individual choices (NBAC 1998). NBAC does

not regard prospective authorization alone as sufficient for enrollment in research, but recognizes its moral value and its use to

communicate to appropriate decisionmakers the person’s prior attitude about research participation.

10 NBAC Meeting. December 9, 1997. Arlington, VA.

11 Personal Communication, Dr. Gary Ellis, Director, OPRR,

August 25, 1998.

12 This distinction is worth noting. In the case of membership in a

group, persons might not be individually identifiable although

identified as a member of that group. In the case of biological relatives, persons related to the sample source are likely to be individually identifiable (DeRenzo, Biesecker, and Meltzer 1997).

13 OPRR has indicated that the living relatives might in fact be

considered human subjects by virtue of their genetic relationship

to the sample source, but the regulations—specifically the OPRR

Institutional Review Board Guidebook section on human genetic

research (pp. 5–42 to 5–63)—do not clearly specify how this consideration is to be handled by IRBs.

14 45 CFR 46.102. “Definitions: (f) Human subject means a living

individual about whom an investigator (whether professional or

student) conducting research obtains (1) data through intervention or interaction with the individual, or (2) identifiable private

information....”

References

Clayton, E.W., K.K. Steinberg, M.J. Khoury, E. Thomson, L.

Andrews, M.J.E. Kahn, L.M. Kopelman, and J.O. Weiss. 1995.

“Informed Consent for Genetic Research on Stored Tissue

Samples.” Journal of the American Medical Association

274:1786–1792.

DeRenzo, E.G., L.G. Biesecker, and N. Meltzer. 1997. “Genetics

and the Dead: Implications for Genetics Research with Samples

from Deceased Persons.” American Journal of Medical Genetics

69:332–334.

Fost, N., and P.M. Farrell. 1989. “A Prospective Randomized Trial

of Early Diagnosis and Treatment of Cystic Fibrosis: A Unique

Ethical Dilemma.” Clinical Research 37:495–500.

Freedman, B., A. Fuks, and C. Weijer. 1993. “In Loco Parentis:

Minimal Risk as an Ethical Threshold for Research upon Children.”

Hastings Center Report 23:13–19.

MacKay, C.R. 1984. “Ethical Issues in Research Design and

Conduct: Developing a Test to Detect Carriers of Huntington’s

Disease.” IRB 6(4):1–5.

National Bioethics Advisory Commission (NBAC). 1998. 

Research Involving Persons with Mental Disorders That May Affect

Decisionmaking Capacity. 2 vols. Washington, DC: U.S. Government

Printing Office.

Office for Protection from Research Risks (OPRR). 1993. Protecting

Human Subjects: Institutional Review Board Guidebook. Washington,

DC: U.S. Government Printing Office.

Reilly, P. 1980. “When Should an Investigator Share Raw Data 

with the Subjects?” IRB 2(9):4–5, 12.

Reilly, P., M.F. Boshar, and S.H. Holtzman. 1997. “Ethical Issues 

in Genetic Research: Disclosure and Informed Consent.” Nature

Genetics 15:16–20.

Veatch, R.M. 1981. A Theory of Medical Ethics. New York: 

Basic Books.
Beliefs About the Research Use

of Human Biological Materials

Appendix A

Background

The National Bioethics Advisory Commission

(NBAC) believes that the opinions of members of

the American public—those individuals who are neither

medical researchers nor ethical experts—regarding the

uses of stored human biological materials in research

provide important additional information for consideration in its report and recommendations. Therefore,

NBAC contracted with the Center for Health Policy

Studies (CHPS) to gather a selection of members of the

public in order to explore their knowledge, beliefs, and

feelings about a variety of issues regarding human biological materials. This study is available in Volume II of

this report. While the information gathered in the process

of the study informed NBAC’s discussions, the information reported here understandably is limited in its

generalizability.

Study Purpose

This study was conducted in order to explore public

knowledge, beliefs, and feelings about issues regarding

human biological materials in six distinct areas of inquiry:

consent and ownership; privacy and confidentiality;

stigmatization of ethnic groups; third party concerns;

sponsorship of research; and safeguards. More generally,

CHPS conducted public discussion forums across the

United States in order to obtain a sense of what the

American public believes and feels about uses of human

biological materials, about the ethical obligations of those

who may learn significant health information from those

materials, and about privacy protections. Forum locations included San Francisco, California; Miami, Florida;

Honolulu, Hawaii; Mililani, Hawaii; Boston, Massachusetts;

Cleveland, Ohio; and Richmond, Virginia. 

Findings

Knowledge about Storage of Human Biological

Materials

At the beginning of each forum and before the discussion of specific issues began, participants were asked a

number of questions in order to assess their knowledge

regarding the storage of human biological materials.

Members of the discussion groups were asked to identify what body parts, organs, or tissues may be classified as

human biological materials and ways in which such

materials may be collected. Participants’ knowledge

regarding the use of these materials for research purposes also was assessed. 

Across groups, participants generally understood

what constitutes human biological materials and what

these materials can reveal about people. However, most

participants had never considered what happens to tissue specimens once they have been used for their initial

purposes. Many believed that these samples are

destroyed or discarded. One exception was a participant

in the Honolulu forum who understood that tissue can

be stored for later re-testing or comparison. Many participants stated that they had had tissue removed during

a medical or surgical procedure, although not all of them

recalled what issues were covered in the consent forms

they had signed or even whether they had signed consent forms at all. Most who had signed consent forms

were not sure whether the forms discussed the disposition of the tissue.

77
78

Beliefs and Attitudes about Storage of Human

Biological Materials

The following sections present findings from the

forums on public beliefs and attitudes regarding human

biological materials. These findings include participants’

responses to hypothetical scenarios regarding issues pertaining to ownership and consent; privacy and confidentiality; stigmatization of ethnic groups; third party

concerns; sponsorship of research; and safeguards for

research.

Ownership and Consent

Regarding ownership, many participants believed

that if consent was provided for a procedure during

which tissue was removed from a patient’s body, the hospital or provider would own the tissue. A few believed

that the individual from whom the material is taken

should own the material. Participants in one of the

Hawaii forums distinguished between ownership of the

tissue by the hospital or the provider and ownership of

the information that may be revealed by the material by

the patient. 

Participants also were asked whether specific consent

should be obtained from patients to use samples for

research and whether they would want to consent to each

potential study of their tissues. Opinions varied across

groups. Some participants stated that there is no need to

specifically consent to research on stored specimens,

especially if those specimens are anonymous. Other participants, particularly those in the Cleveland and Miami

groups, believed they should provide consent for each

potential study of their tissues. However, many felt that a

general, one-time consent (i.e., blanket consent) for

research was sufficient. 

Privacy and Confidentiality

Participants were asked to share their feelings about

privacy rights and the importance of confidentiality.

Issues concerning insurance companies’ access to

research results, linkages between identities and research,

and potential threats to confidentiality were discussed.

Most forum participants expressed the strong belief that

insurance companies should not have access to the

results of genetic research on stored tissue specimens. 

Across groups, participants varied in their consideration of how to balance the advantages of conducting

research on genetic diseases with the possible abuses of

privacy that may occur during such research. In general,

most participants expressed positive views about the

value of medical research. Participants in the Hawaii

forums and in the San Francisco forum were vocal about

the importance of medical research and did not express

concern about potential privacy abuses. Participants in

Cleveland and Miami, however, did express concern

about the protection of their privacy rights. Many participants across forum sites stated that they wanted to be

notified if researchers later discovered medically useful

information about them from stored specimens, although

some participants in Cleveland disagreed and commented

that their privacy was more important. Some participants

in Boston believed that it is important to define what

comprises “medically useful information,” because they

did not believe findings indicating a propensity to disease

or risk of a genetic condition or disease met their criteria

for notification. San Francisco participants felt strongly

that their physicians, not researchers, should relay the

results of research.

Most participants agreed that the use of anonymous

specimens for research is acceptable and even necessary

for the public good. Moreover, across groups, most participants were not concerned about the linkage of demographics (e.g., age, sex, ethnic group) with their stored

specimens, although participants in Miami wanted to

ensure that their privacy would be maintained. Opinions

varied regarding the issue of linking identifying information with stored specimens. Most participants in Hawaii,

San Francisco, and Miami felt that linked research is

acceptable and appropriate. On the other hand, many

participants in Cleveland and some in Boston did not

want any links maintained between their stored specimens and their identities.

Across localities, participants expressed skepticism

when asked to consider what would happen if the confidentiality of research findings was not maintained. They

believed that privacy and confidentiality could not be

ensured because of the sophistication and complexity of

computer information systems and the general commercial health care environment.

Stigmatization of Ethnic Groups

Forum participants were asked to discuss how they

felt about researchers studying specific groups of people,
79

such as particular ethnic or racial groups. Participants

considered specifically whether such research potentially

could stigmatize certain groups. Generally, participants

across forums did not express concern that research

could stigmatize specific groups; however, participants in

most groups did mention that this research could result

in negative effects, including the denial of insurance coverage for members of the groups being studied and the

potential for the dissemination of research findings that

might later be disproved. Participants in all groups

believed that the groups being studied generally tend to

benefit from such research, and they cited examples, such

as research on Tay-Sachs disease and sickle cell disease.

Third-Party Concerns

Forum participants responded to a number of questions regarding genetic research in which one person’s

stored specimen could reveal certain information about

his or her family members. Across forums, participants

expressed mixed feelings about how and under what circumstances family members should be informed of such

research. Many participants said that they would want to

be informed of genetic research that revealed information

about them. Some recognized, however, that many family members might not want to be privy to this information, and issues arose regarding who should inform

family members of research results (e.g., physicians,

researchers, or the individuals from whom the tissue was

taken). When asked whether family members should be

provided the opportunity to consent to a study of their

relatives’ tissue, most believed that this would be inappropriate and difficult to achieve. Across groups, most

participants did not feel that negative consequences

would result from studying diseases that tend to run in

families.

Participants also were asked who should make decisions about specimen storage for those who are unable

to make such decisions. Categorically, participants

expressed the belief that legal guardians or medical surrogates should make these decisions, and some participants were vocal in stating that individuals’

preferences should be considered whenever possible

(e.g., for children).

Sponsorship of Research

Participants discussed how they felt about researchers

accessing their stored specimens and whether the kind of

organization sponsoring the research matters (i.e., a forprofit company, a university, or the federal government).

Most participants believed that researchers in all of these

kinds of organizations should be able to gain access to

stored specimens, although a few stated that important

differences among various kinds of research organizations do exist. Some participants in Cleveland, Boston,

and Miami believed that the profit motives of biotechnology and pharmaceutical companies set the research

they conduct apart from that conducted by academic

institutions. However, most of the participants in

Richmond, Mililani, and San Francisco believed that the

various sponsors of research are not characterized by significant differences in this respect.

Across groups, many participants were not concerned

about whether firms could profit from research on stored

specimens. A few participants in the Boston and Miami

forums did, however, express some discomfort regarding

the profit motives of companies. Some participants in

Honolulu and Miami indicated that they would want to

share in any profits that might result from research on

their stored specimens. Overall, however, most participants did not believe this was an important or practical

concern.

Safeguards

Across localities, participants who were asked about

issues related to safeguards for research and medical information felt that before conducting research on stored tissue specimens, researchers should be required to receive

approval from a committee or other entity that oversees

the ethics of research. When asked who should review and

oversee this research, participants identified individuals

who would typically comprise Institutional Review

Boards. In addition, some stated that representatives of the

groups studied and people with high ethical standards

(regardless of profession) should be included. Participants

could not, however, categorically identify a group that

could be trusted to protect medical information.

Code of Federal Regulations,

Title 45, Part 46

Appendix B

Subpart A: Federal Policy for the

Protection of Human Subjects (Basic

DHHS Policy for Protection of Human

Research Subjects)

Source: 56 FR 28003, June 18, 1991.

§46.101 To what does this policy apply?

(a) Except as provided in paragraph (b) of this section,

this policy applies to all research involving human

subjects conducted, supported or otherwise subject

to regulation by any Federal Department or Agency

which takes appropriate administrative action to

make the policy applicable to such research. This

includes research conducted by Federal civilian

employees or military personnel, except that each

Department or Agency head may adopt such procedural modifications as may be appropriate from an

administrative standpoint. It also includes research

conducted, supported, or otherwise subject to regulation by the Federal Government outside the

United States.

(1) Research that is conducted or supported by a

Federal Department or Agency, whether or not it

is regulated as defined in §46.102(e), must comply with all sections of this policy.

(2) Research that is neither conducted nor supported

by a Federal Department or Agency but is subject

to regulation as defined in §46.102(e) must be

reviewed and approved, in compliance with

§46.101, §46.102, and §46.107 through

§46.117 of this policy, by an Institutional Review

Board (IRB) that operates in accordance with the

pertinent requirements of this policy.

(b) Unless otherwise required by Department or Agency

heads, research activities in which the only involvement of human subjects will be in one or more of

the following categories are exempt from this

policy:1

(1) Research conducted in established or commonly

accepted educational settings, involving normal

educational practices, such as (i) research on

regular and special education instructional

strategies, or (ii) research on the effectiveness of

or the comparison among instructional techniques, curricula, or classroom management

methods.

(2) Research involving the use of educational tests

(cognitive, diagnostic, aptitude, achievement),

survey procedures, interview procedures or

observation of public behavior, unless:

(i) information obtained is recorded in such a

manner that human subjects can be identified,

directly or through identifiers linked to the subjects; and (ii) any disclosure of the human subjects’ responses outside the research could

reasonably place the subjects at risk of criminal

or civil liability or be damaging to the subjects’

financial standing, employability, or reputation.

(3) Research involving the use of educational tests

(cognitive, diagnostic, aptitude, achievement),

survey procedures, interview procedures, or

observation of public behavior that is not exempt

under paragraph (b)(2) of this section, if:

(i) the human subjects are elected or appointed

public officials or candidates for public office; or

(ii) Federal statute(s) require(s) without exception that the confidentiality of the personally

identifiable information will be maintained

throughout the research and thereafter.

(4) Research involving the collection or study of

existing data, documents, records, pathological

81
82

specimens, or diagnostic specimens, if these

sources are publicly available or if the information is recorded by the investigator in such a

manner that subjects cannot be identified,

directly or through identifiers linked to the 

subjects.

(5) Research and demonstration projects which 

are conducted by or subject to the approval 

of Department or Agency heads, and which 

are designed to study, evaluate, or otherwise

examine:

(i) Public benefit or service programs; (ii) procedures for obtaining benefits or services under

those programs; (iii) possible changes in or 

alternatives to those programs or procedures; 

or (iv) possible changes in methods or levels of

payment for benefits or services under those

programs.

(6) Taste and food quality evaluation and consumer

acceptance studies, (i) if wholesome foods without additives are consumed or (ii) if a food is

consumed that contains a food ingredient at or

below the level and for a use found to be safe, or

agricultural chemical or environmental contaminant at or below the level found to be safe, by

the Food and Drug Administration or approved

by the Environmental Protection Agency or the

Food Safety and Inspection Service of the U.S.

Department of Agriculture.

(c) Department or Agency heads retain final judgment

as to whether a particular activity is covered by this

policy.

(d) Department or Agency heads may require that specific research activities or classes of research activities conducted, supported, or otherwise subject to

regulation by the Department or Agency but not

otherwise covered by this policy, comply with some

or all of the requirements of this policy.

(e) Compliance with this policy requires compliance

with pertinent Federal laws or regulations which

provide additional protections for human subjects.

(f) This policy does not affect any State or local laws or

regulations which may otherwise be applicable and

which provide additional protections for human

subjects.

(g) This policy does not affect any foreign laws or regulations which may otherwise be applicable and

which provide additional protections to human 

subjects of research.

(h) When research covered by this policy takes place 

in foreign countries, procedures normally followed

in the foreign countries to protect human subjects

may differ from those set forth in this policy. [An

example is a foreign institution which complies 

with guidelines consistent with the World Medical

Assembly Declaration (Declaration of Helsinki

amended 1989) issued either by sovereign states or

by an organization whose function for the protection

of human research subjects is internationally recognized.] In these circumstances, if a Department or

Agency head determines that the procedures prescribed by the institution afford protections that are

at least equivalent to those provided in this policy,

the Department or Agency head may approve the

substitution of the foreign procedures in lieu of the

procedural requirements provided in this policy.

Except when otherwise required by statute,

Executive Order, or the Department or Agency head,

notices of these actions as they occur will be published in the Federal Register or will be otherwise

published as provided in Department or Agency

procedures.

(i) Unless otherwise required by law, Department or

Agency heads may waive the applicability of some 

or all of the provisions of this policy to specific

research activities or classes or research activities

otherwise covered by this policy. Except when otherwise required by statute or Executive Order, the

Department or Agency head shall forward advance

notices of these actions to the Office for Protection

from Research Risks, National Institutes of Health,

Department of Health and Human Services (DHHS),

and shall also publish them in the Federal Register

or in such other manner as provided in Department

or Agency procedures.1

1 Institutions with DHHS-approved assurances on file will abide 

by provisions of Title 45 CFR Part 46 Subparts A-D. Some of the

other departments and agencies have incorporated all provisions 

of Title 45 CFR Part 46 into their policies and procedures as well.

However, the exemptions at 45 CFR 46.101(b) do not apply to

research involving prisoners, fetuses, pregnant women, or human 

in vitro fertilization, Subparts B and C. The exemption at 45 CFR

46.101(b)(2), for research involving survey or interview procedures

or observation of public behavior, does not apply to research with

children, Subpart D, except for research involving observations of

public behavior when the investigator(s) do not participate in the

activities being observed.
83

§46.102 Definitions.

(a) Department or Agency head means the head of any

Federal Department or Agency and any other officer

or employee of any Department or Agency to whom

authority has been delegated.

(b) Institution means any public or private entity or

Agency (including Federal, State, and other 

agencies).

(c) Legally authorized representative means an individual

or judicial or other body authorized under applicable law to consent on behalf of a prospective subject

to the subject’s participation in the procedure(s)

involved in the research.

(d) Research means a systematic investigation, including

research development, testing and evaluation,

designed to develop or contribute to generalizable

knowledge. Activities which meet this definition 

constitute research for purposes of this policy,

whether or not they are conducted or supported

under a program which is considered research for

other purposes. For example, some demonstration

and service programs may include research activities.

(e) Research subject to regulation, and similar terms are

intended to encompass those research activities for

which a Federal Department or Agency has specific

responsibility for regulating as a research activity, 

(for example, Investigational New Drug requirements

administered by the Food and Drug Administration).

It does not include research activities which are incidentally regulated by a Federal Department or

Agency solely as part of the Department’s or Agency’s

broader responsibility to regulate certain types of

activities whether research or non-research in nature

(for example, Wage and Hour requirements administered by the Department of Labor).

(f) Human subject means a living individual about

whom an investigator (whether professional or 

student) conducting research obtains

(1) data through intervention or interaction with 

the individual, or

(2) identifiable private information.

Intervention includes both physical procedures by 

which data are gathered (for example, venipuncture)

and manipulations of the subject or the subject’s environment that are performed for research purposes.

Interaction includes communication or interpersonal

contact between investigator and subject. Private information includes information about behavior that occurs

in a context in which an individual can reasonably

expect that no observation or recording is taking place,

and information which has been provided for specific

purposes by an individual and which the individual can

reasonably expect will not be made public (for example,

a medical record). Private information must be individually identifiable (i.e., the identity of the subject is or

may readily be ascertained by the investigator or associated with the information) in order for obtaining the

information to constitute research involving human

subjects.

(g) IRB means an Institutional Review Board established

in accord with and for the purposes expressed in

this policy.

(h) IRB approval means the determination of the IRB

that the research has been reviewed and may be

conducted at an institution within the constraints 

set forth by the IRB and by other institutional and

Federal requirements.

(i) Minimal risk means that the probability and magnitude of harm or discomfort anticipated in the

research are not greater in and of themselves than

those ordinarily encountered in daily life or during

the performance of routine physical or psychological

examinations or tests.

(j) Certification means the official notification by the

institution to the supporting Department or Agency,

in accordance with the requirements of this policy,

that a research project or activity involving human

subjects has been reviewed and approved by an IRB

in accordance with an approved assurance.

§46.103 Assuring compliance with this policy

—research conducted or supported by any

Federal Department or Agency.

(a) Each institution engaged in research which is 

covered by this policy and which is conducted 

or supported by a Federal Department or Agency

shall provide written assurance satisfactory to the

Department or Agency head that it will comply with

the requirements set forth in this policy. In lieu of

requiring submission of an assurance, individual

Department or Agency heads shall accept the 
84

existence of a current assurance, appropriate for 

the research in question, on file with the Office for

Protection from Research Risks, National Institutes

Health, DHHS, and approved for Federal wide use

by that office. When the existence of a DHHSapproved assurance is accepted in lieu of requiring

submission of an assurance, reports (except certification) required by this policy to be made to

Department and Agency heads shall also be made 

to the Office for Protection from Research Risks,

National Institutes of Health, DHHS.

(b) Departments and agencies will conduct or support

research covered by this policy only if the institution

has an assurance approved as provided in this section, and only if the institution has certified to the

Department or Agency head that the research has

been reviewed and approved by an IRB provided for

in the assurance, and will be subject to continuing

review by the IRB. Assurances applicable to federally

supported or conducted research shall at a minimum include:

(1) A statement of principles governing the institution in the discharge of its responsibilities for

protecting the rights and welfare of human 

subjects of research conducted at or sponsored

by the institution, regardless of whether the

research is subject to Federal regulation. This

may include an appropriate existing code, declaration, or statement of ethical principles, or a

statement formulated by the institution itself.

This requirement does not preempt provisions of

this policy applicable to Department- or Agencysupported or regulated research and need not be

applicable to any research exempted or waived

under §46.101 (b) or (i).

(2) Designation of one or more IRBs established in

accordance with the requirements of this policy,

and for which provisions are made for meeting

space and sufficient staff to support the IRB’s

review and recordkeeping duties.

(3) A list of IRB members identified by name;

earned degrees; representative capacity; indications of experience such as board certifications,

licenses, etc., sufficient to describe each member’s chief anticipated contributions to IRB 

deliberations; and any employment or other

relationship between each member and the 

institution; for example: full-time employee,

part-time employee, member of governing panel

or board, stockholder, paid or unpaid consultant. Changes in IRB membership shall be reported to the Department or Agency head, unless in

accord with §46.103(a) of this policy, the existence of a DHHS-approved assurance is accepted. In this case, change in IRB membership shall

be reported to the Office for Protection from

Research Risks, National Institutes of Health,

DHHS.

(4) Written procedures which the IRB will follow 

(i) for conducting its initial and continuing

review of research and for reporting its findings

and actions to the investigator and the institution; (ii) for determining which projects require

review more often than annually and which

projects need verification from sources other

than the investigators that no material changes

have occurred since previous IRB review; and

(iii) for ensuring prompt reporting to the IRB 

of proposed changes in a research activity, and

for ensuring that such changes in approved

research, during the period for which IRB

approval has already been given, may not be 

initiated without IRB review and approval except

when necessary to eliminate apparent immediate

hazards to the subject.

(5) Written procedures for ensuring prompt reporting to the IRB, appropriate institutional officials,

and the Department or Agency head of (i) any

unanticipated problems involving risks to subjects or others or any serious or continuing noncompliance with this policy or the requirements

or determinations of the IRB; and (ii) any suspension or termination of IRB approval.

(c) The assurance shall be executed by an individual

authorized to act for the institution and to assume

on behalf of the institution the obligations imposed

by this policy and shall be filed in such form 

and manner as the Department or Agency head

prescribes.

(d) The Department or Agency head will evaluate all

assurances submitted in accordance with this 

policy through such officers and employees of the

Department or Agency and such experts or consultants engaged for this purpose as the Department or
85

Agency head determines to be appropriate. The

Department or Agency head’s evaluation will take

into consideration the adequacy of the proposed IRB

in light of the anticipated scope of the institution’s

research activities and the types of subject populations likely to be involved, the appropriateness of

the proposed initial and continuing review procedures in light of the probable risks, and the size and

complexity of the institution.

(e) On the basis of this evaluation, the Department 

or Agency head may approve or disapprove the

assurance, or enter into negotiations to develop an

approvable one. The Department or Agency head

may limit the period during which any particular

approved assurance or class of approved assurances

shall remain effective or otherwise condition or

restrict approval.

(f) Certification is required when the research is supported by a Federal Department or Agency and not

otherwise exempted or waived under §46.101 (b) or

(i). An institution with an approved assurance shall

certify that each application or proposal for research

covered by the assurance and by §46.103 of this

policy has been reviewed and approved by the IRB.

Such certification must be submitted with the application or proposal or by such later date as may be

prescribed by the Department or Agency to which

the application or proposal is submitted. Under 

no condition shall research covered by §46.103

of the policy be supported prior to receipt of the

certification that the research has been reviewed 

and approved by the IRB. Institutions without an

approved assurance covering the research shall 

certify within 30 days after receipt of a request for

such a certification from the Department or Agency,

that the application or proposal has been approved

by the IRB. If the certification is not submitted 

within these time limits, the application or proposal

may be returned to the institution.

(Approved by the Office of Management and Budget

under Control Number 9999-0020.)

§§46.104—46.106 [Reserved]

§46.107 IRB membership.

(a) Each IRB shall have at least five members, with varying backgrounds to promote complete and adequate

review of research activities commonly conducted by

the institution. The IRB shall be sufficiently qualified

through the experience and expertise of its members, and the diversity of the members, including

consideration of race, gender, and cultural backgrounds and sensitivity to such issues as community

attitudes, to promote respect for its advice and

counsel in safeguarding the rights and welfare of

human subjects. In addition to possessing the professional competence necessary to review specific

research activities, the IRB shall be able to ascertain

the acceptability of proposed research in terms of

institutional commitments and regulations, applicable law, and standards of professional conduct and

practice. The IRB shall therefore include persons

knowledgeable in these areas. If an IRB regularly

reviews research that involves a vulnerable category

of subjects, such as children, prisoners, pregnant

women, or handicapped or mentally disabled persons, consideration shall be given to the inclusion 

of one or more individuals who are knowledgeable

about and experienced in working with these 

subjects.

(b) Every nondiscriminatory effort will be made to

ensure that no IRB consists entirely of men or 

entirely of women, including the institution’s 

consideration of qualified persons of both sexes, 

so long as no selection is made to the IRB on the

basis of gender. No IRB may consist entirely of

members of one profession.

(c) Each IRB shall include at least one member whose

primary concerns are in scientific areas and at least

one member whose primary concerns are in nonscientific areas.

(d) Each IRB shall include at least one member who is

not otherwise affiliated with the institution and who

is not part of the immediate family of a person who

is affiliated with the institution.

(e) No IRB may have a member participate in the IRB’s

initial or continuing review of any project in which

the member has a conflicting interest, except to provide information requested by the IRB.

(f) An IRB may, in its discretion, invite individuals with

competence in special areas to assist in the review of

issues which require expertise beyond or in addition

to that available on the IRB. These individuals may

not vote with the IRB.
86

§46.108 IRB functions and operations.

In order to fulfill the requirements of this policy each 

IRB shall:

(a) Follow written procedures in the same detail as

described in §46.103(b)(4) and to the extent

required by §46.103(b)(5).

(b) Except when an expedited review procedure is used

(see §46.110), review proposed research at convened meetings at which a majority of the members

of the IRB are present, including at least one member whose primary concerns are in nonscientific

areas. In order for the research to be approved, it

shall receive the approval of a majority of those

members present at the meeting

§46.109 IRB review of research.

(a) An IRB shall review and have authority to approve,

require modifications in (to secure approval), or disapprove all research activities covered by this policy.

(b) An IRB shall require that information given to subjects as part of informed consent is in accordance

with §46.116. The IRB may require that information, in addition to that specifically mentioned in

§46.116, be given to the subjects when in the 

IRB’s judgment the information would meaningfully

add to the protection of the rights and welfare of

subjects.

(c) An IRB shall require documentation of informed

consent or may waive documentation in accordance

with §46.117.

(d) An IRB shall notify investigators and the institution

in writing of its decision to approve or disapprove

the proposed research activity, or of modifications

required to secure IRB approval of the research

activity. If the IRB decides to disapprove a research

activity, it shall include in its written notification a

statement of the reasons for its decision and give the

investigator an opportunity to respond in person or

in writing.

(e) An IRB shall conduct continuing review of research

covered by this policy at intervals appropriate to the

degree of risk, but not less than once per year, and

shall have authority to observe or have a third party

observe the consent process and the research.

(Approved by the Office of Management and Budget

under Control Number 9999-0020.)

§46.110 Expedited review procedures for 

certain kinds of research involving no more

than minimal risk, and for minor changes in

approved research.

(a) The Secretary, HHS, has established, and published

as a Notice in the Federal Register, a list of categories of research that may be reviewed by the IRB

through an expedited review procedure. The list will

be amended, as appropriate, after consultation with

other departments and agencies, through periodic

republication by the Secretary, HHS, in the Federal

Register. A copy of the list is available from the

Office for Protection from Research Risks, National

Institutes of Health, DHHS, Bethesda, Maryland

20892.

(b) An IRB may use the expedited review procedure to

review either or both of the following:

(1) some or all of the research appearing on the list

and found by the reviewer(s) to involve no more

than minimal risk,

(2) minor changes in previously approved research

during the period (of one year or less) for which

approval is authorized.

Under an expedited review procedure, the review may

be carried out by the IRB chairperson or by one or

more experienced reviewers designated by the chairperson from among members of the IRB. In reviewing

the research, the reviewers may exercise all of the

authorities of the IRB except that the reviewers may 

not disapprove the research. A research activity may be

disapproved only after review in accordance with the

non-expedited procedure set forth in §46.108(b).

(c) Each IRB which uses an expedited review procedure

shall adopt a method for keeping all members

advised of research proposals which have been

approved under the procedure.

(d) The Department or Agency head may restrict, 

suspend, terminate, or choose not to authorize an

institution’s or IRB’s use of the expedited review 

procedure.

§46.111 Criteria for IRB approval of research.

(a) In order to approve research covered by this policy

the IRB shall determine that all of the following

requirements are satisfied:
87

(1) Risks to subjects are minimized: (i) by using

procedures which are consistent with sound

research design and which do not unnecessarily

expose subjects to risk, and (ii) whenever 

appropriate, by using procedures already being

performed on the subjects for diagnostic or

treatment purposes.

(2) Risks to subjects are reasonable in relation to

anticipated benefits, if any, to subjects, and the

importance of the knowledge that may reasonably be expected to result. In evaluating risks

and benefits, the IRB should consider only those

risks and benefits that may result from the

research (as distinguished from risks and benefits of therapies subjects would receive even if

not participating in the research). The IRB

should not consider possible long-range effects

of applying knowledge gained in the research

(for example, the possible effects of the research

on public policy) as among those research risks

that fall within the purview of its responsibility.

(3) Selection of subjects is equitable. In making this

assessment the IRB should take into account the

purposes of the research and the setting in

which the research will be conducted and

should be particularly cognizant of the special

problems of research involving vulnerable populations, such as children, prisoners, pregnant

women, mentally disabled persons, or economically or educationally disadvantaged persons.

(4) Informed consent will be sought from each

prospective subject or the subject’s legally

authorized representative, in accordance with,

and to the extent required by §46.116.

(5) Informed consent will be appropriately documented, in accordance with, and to the extent

required by §46.117.

(6) When appropriate, the research plan makes 

adequate provision for monitoring the data 

collected to ensure the safety of subjects.

(7) When appropriate, there are adequate provisions

to protect the privacy of subjects and to maintain the confidentiality of data.

(b) When some or all of the subjects are likely to be

vulnerable to coercion or undue influence, such as

children, prisoners, pregnant women, mentally 

disabled persons, or economically or educationally

disadvantaged persons, additional safeguards have

been included in the study to protect the rights and

welfare of these subjects.

§46.112 Review by institution.

Research covered by this policy that has been approved

by an IRB may be subject to further appropriate review

and approval or disapproval by officials of the institution. However, those officials may not approve the

research if it has not been approved by an IRB.

§46.113 Suspension or termination of IRB

approval of research.

An IRB shall have authority to suspend or terminate

approval of research that is not being conducted in

accordance with the IRB’s requirements or that has been

associated with unexpected serious harm to subjects.

Any suspension or termination of approval shall include

a statement of the reasons for the IRB’s action and shall

be reported promptly to the investigator, appropriate

institutional officials, and the Department or Agency

head.

(Approved by the Office of Management and Budget

under Control Number 9999-0020.)

§46.114 Cooperative research.

Cooperative research projects are those projects covered

by this policy which involve more than one institution.

In the conduct of cooperative research projects, each

institution is responsible for safeguarding the rights 

and welfare of human subjects and for complying with

this policy. With the approval of the Department or

Agency head, an institution participating in a cooperative project may enter into a joint review arrangement,

rely upon the review of another qualified IRB, or make

similar arrangements for avoiding duplication of effort.

§46.115 IRB records.

(a) An institution, or when appropriate an IRB, shall

prepare and maintain adequate documentation of

IRB activities, including the following:

(1) Copies of all research proposals reviewed, 

scientific evaluations, if any, that accompany the

proposals, approved sample consent documents,

progress reports submitted by investigators, and

reports of injuries to subjects.
88

(2) Minutes of IRB meetings which shall be in sufficient detail to show attendance at the meetings;

actions taken by the IRB; the vote on these

actions including the number of members voting

for, against, and abstaining; the basis for requiring changes in or disapproving research; and a

written summary of the discussion of controverted issues and their resolution.

(3) Records of continuing review activities.

(4) Copies of all correspondence between the IRB

and the investigators.

(5) A list of IRB members in the same detail as

described in §46.103(b)(3).

(6) Written procedures for the IRB in the same detail

as described in §46.103(b)(4) and

§46.103(b)(5).

(7) Statements of significant new findings provided

to subjects, as required by §46.116(b)(5).

(b) The records required by this policy shall be retained

for at least 3 years, and records relating to research

which is conducted shall be retained for at least 3

years after completion of the research. All records

shall be accessible for inspection and copying by

authorized representatives of the Department or

Agency at reasonable times and in a reasonable 

manner.

(Approved by the Office of Management and Budget

under Control Number 9999-0020.)

§46.116 General requirements 

for informed consent.

Except as provided elsewhere in this policy, no investigator may involve a human being as a subject in

research covered by this policy unless the investigator

has obtained the legally effective informed consent of

the subject or the subject’s legally authorized representative. An investigator shall seek such consent only under

circumstances that provide the prospective subject or

the representative sufficient opportunity to consider

whether or not to participate and that minimize the

possibility of coercion or undue influence. The information that is given to the subject or the representative

shall be in language understandable to the subject or

the representative. No informed consent, whether oral

or written, may include any exculpatory language

through which the subject or the representative is made

to waive or appear to waive any of the subject’s legal

rights, or releases or appears to release the investigator,

the sponsor, the institution or its agents from liability

for negligence.

(a) Basic elements of informed consent. Except as 

provided in paragraph (c) or (d) of this section, in

seeking informed consent the following information

shall be provided to each subject:

(1) a statement that the study involves research, an

explanation of the purposes of the research and

the expected duration of the subject’s participation, a description of the procedures to be followed, and identification of any procedures

which are experimental;

(2) a description of any reasonably foreseeable risks

or discomforts to the subject;

(3) a description of any benefits to the subject or to

others which may reasonably be expected from

the research;

(4) a disclosure of appropriate alternative procedures or courses of treatment, if any, that might

be advantageous to the subject;

(5) a statement describing the extent, if any, to

which confidentiality of records identifying the

subject will be maintained;

(6) for research involving more than minimal risk,

an explanation as to whether any compensation

and an explanation as to whether any medical

treatments are available if injury occurs and, if

so, what they consist of, or where further information may be obtained;

(7) an explanation of whom to contact for answers

to pertinent questions about the research and

research subjects’ rights, and whom to contact in

the event of a research-related injury to the subject; and

(8) a statement that participation is voluntary,

refusal to participate will involve no penalty or

loss of benefits to which the subject is otherwise

entitled, and the subject may discontinue participation at any time without penalty or loss of

benefits to which the subject is otherwise 

entitled.

(b) additional elements of informed consent. When

appropriate, one or more of the following elements
89

of information shall also be provided to each 

subject:

(1) a statement that the particular treatment or procedure may involve risks to the subject (or to the

embryo or fetus, if the subject is or may become

pregnant) which are currently unforeseeable;

(2) anticipated circumstances under which the 

subject’s participation may be terminated by 

the investigator without regard to the subject’s

consent;

(3) any additional costs to the subject that may

result from participation in the research;

(4) the consequences of a subject’s decision to 

withdraw from the research and procedures 

for orderly termination of participation by the

subject;

(5) A statement that significant new findings developed during the course of the research which

may relate to the subject’s willingness to continue participation will be provided to the subject;

and

(6) the approximate number of subjects involved in

the study.

(c) An IRB may approve a consent procedure which

does not include, or which alters, some or all of the

elements of informed consent set forth above, or

waive the requirement to obtain informed consent

provided the IRB finds and documents that:

(1) the research or demonstration project is to be

conducted by or subject to the approval of state

or local government officials and is designed to

study, evaluate, or otherwise examine: (i) public

benefit or service programs; (ii) procedures for

obtaining benefits or services under those programs; (iii) possible changes in or alternatives to

those programs or procedures; or (iv) possible

changes in methods or levels of payment for

benefits or services under those programs; and

(2) the research could not practicably be carried out

without the waiver or alteration.

(d) An IRB may approve a consent procedure which

does not include, or which alters, some or all of the

elements of informed consent set forth in this section, or waive the requirements to obtain informed

consent provided the IRB finds and documents that:

(1) the research involves no more than minimal risk

to the subjects;

(2) the waiver or alteration will not adversely affect

the rights and welfare of the subjects;

(3) the research could not practicably be carried out

without the waiver or alteration; and

(4) whenever appropriate, the subjects will be 

provided with additional pertinent information

after participation.

(e) The informed consent requirements in this policy

are not intended to preempt any applicable Federal,

State, or local laws which require additional information to be disclosed in order for informed consent

to be legally effective.

(f) Nothing in this policy is intended to limit the

authority of a physician to provide emergency medical care, to the extent the physician is permitted to

do so under applicable Federal, State, or local law.

(Approved by the Office of Management and Budget

under Control Number 9999-0020.)

§46.117 Documentation of informed consent.

(a) Except as provided in paragraph (c) of this section,

informed consent shall be documented by the use 

of a written consent form approved by the IRB and

signed by the subject or the subject’s legally authorized representative. A copy shall be given to the 

person signing the form.

(b) Except as provided in paragraph (c) of this section,

the consent form may be either of the following:

(1) A written consent document that embodies the

elements of informed consent required by

§46.116. This form may be read to the subject

or the subject’s legally authorized representative,

but in any event, the investigator shall give

either the subject or the representative adequate

opportunity to read it before it is signed; or

(2) A short form written consent document stating

that the elements of informed consent required

by §46.116 have been presented orally to the

subject or the subject’s legally authorized representative. When this method is used, there shall

be a witness to the oral presentation. Also, the

IRB shall approve a written summary of what is

to be said to the subject or the representative.
90

Only the short form itself is to be signed by the

subject or the representative. However, the witness shall sign both the short form and a copy of

the summary, and the person actually obtaining

consent shall sign a copy of the summary. A

copy of the summary shall be given to the subject or the representative, in addition to a copy

of the short form.

(c) An IRB may waive the requirement for the investigator to obtain a signed consent form for some or all

subjects if it finds either:

(1) That the only record linking the subject and the

research would be the consent document and

the principal risk would be potential harm

resulting from a breach of confidentiality. Each

subject will be asked whether the subject wants

documentation linking the subject with the

research, and the subject’s wishes will govern; or

(2) That the research presents no more than minimal risk of harm to subjects and involves no

procedures for which written consent is normally

required outside of the research context.

In cases in which the documentation requirement is

waived, the IRB may require the investigator to provide

subjects with a written statement regarding the research.

(Approved by the Office of Management and Budget

under Control Number 9999-0020.)

§46.118 Applications and proposals lacking

definite plans for involvement of human 

subjects.

Certain types of applications for grants, cooperative

agreements, or contracts are submitted to departments

or agencies with the knowledge that subjects may be

involved within the period of support, but definite

plans would not normally be set forth in the application

or proposal. These include activities such as institutional type grants when selection of specific projects is the

institution’s responsibility; research training grants in

which the activities involving subjects remain to be

selected; and projects in which human subjects’ involvement will depend upon completion of instruments,

prior animal studies, or purification of compounds.

These applications need not be reviewed by an IRB

before an award may be made. However, except for

research exempted or waived under §46.101 (b) or (i),

no human subjects may be involved in any project 

supported by these awards until the project has been

reviewed and approved by the IRB, as provided in this

policy, and certification submitted, by the institution, to

the Department or Agency.

§46.119 Research undertaken without the

intention of involving human subjects.

In the event research is undertaken without the intention of involving human subjects, but it is later proposed to involve human subjects in the research, the

research shall first be reviewed and approved by an IRB,

as provided in this policy, a certification submitted, by

the institution, to the Department or Agency, and final

approval given to the proposed change by the

Department or Agency.

§46.120 Evaluation and disposition of applications and proposals for research to be conducted or supported by a Federal Department

or Agency.

(a) The Department or Agency head will evaluate all

applications and proposals involving human subjects

submitted to the Department or Agency through

such officers and employees of the Department or

Agency and such experts and consultants as the

Department or Agency head determines to be appropriate. This evaluation will take into consideration

the risks to the subjects, the adequacy of protection

against these risks, the potential benefits of the

research to the subjects and others, and the importance of the knowledge gained or to be gained.

(b) On the basis of this evaluation, the Department 

or Agency head may approve or disapprove the

application or proposal, or enter into negotiations 

to develop an approvable one.

§46.121 [Reserved]

§46.122 Use of Federal funds.

Federal funds administered by a Department or Agency

may not be expended for research involving human

subjects unless the requirements of this policy have

been satisfied.

§46.123 Early termination of research support:

Evaluation of applications and proposals.

(a) The Department or Agency head may require that

Department or Agency support for any project be 

terminated or suspended in the manner prescribed 
91

in applicable program requirements, when the

Department or Agency head finds an institution has

materially failed to comply with the terms of this 

policy.

(b) In making decisions about supporting or approving

applications or proposals covered by this policy the

Department or Agency head may take into account,

in addition to all other eligibility requirements and

program criteria, factors such as whether the applicant has been subject to a termination or suspension

under paragraph (a) of this section and whether the

applicant or the person or persons who would direct

or has/have directed the scientific and technical

aspects of an activity has/have, in the judgment of

the Department or Agency head, materially failed to

discharge responsibility for the protection of the

rights and welfare of human subjects (whether or

not the research was subject to Federal regulation).

§46.124 Conditions.

With respect to any research project or any class of

research projects the Department or Agency head may

impose additional conditions prior to or at the time of

approval when in the judgment of the Department or

Agency head additional conditions are necessary for the

protection of human subjects.

Subpart B: Additional DHHS Protections

Pertaining to Research, Development,

and Related Activities Involving

Fetuses, Pregnant Women, and Human

In Vitro Fertilization

Source: 40 FR 33528, Aug. 8, 1975; 43 FR 1758, 

January 11, 1978; 43 FR 51559, November 3, 1978.

§46.201 Applicability.

(a) The regulations in this subpart are applicable to 

all Department of Health and Human Services 

grants and contracts supporting research, development, and related activities involving: (1) the 

fetus, (2) pregnant women, and (3) human in 

vitro fertilization.

(b) Nothing in this subpart shall be construed as indicating that compliance with the procedures set forth

herein will in any way render inapplicable pertinent

State or local laws bearing upon activities covered by

this subpart.

(c) The requirements of this subpart are in addition to

those imposed under the other subparts of this part.

§46.202 Purpose.

It is the purpose of this subpart to provide additional

safeguards in reviewing activities to which this subpart

is applicable to assure that they conform to appropriate

ethical standards and relate to important societal needs.

§46.203 Definitions.

As used in this subpart:

(a) “Secretary” means the Secretary of Health and

Human Services and any other officer or employee

of the Department of Health and Human Services

(DHHS) to whom authority has been delegated.

(b) “Pregnancy” encompasses the period of time from

confirmation of implantation (through any of the

presumptive signs of pregnancy, such as missed

menses, or by a medically acceptable pregnancy

test), until expulsion or extraction of the fetus.

(c) “Fetus” means the product of conception from the

time of implantation (as evidenced by any of the

presumptive signs of pregnancy, such as missed

menses, or a medically acceptable pregnancy test),

until a determination is made, following expulsion

or extraction of the fetus, that it is viable.

(d) “Viable” as it pertains to the fetus means being able,

after either spontaneous or induced delivery, to survive (given the benefit of available medical therapy)

to the point of independently maintaining heart beat

and respiration. The Secretary may from time to

time, taking into account medical advances, publish

in the Federal Register guidelines to assist in determining whether a fetus is viable for purposes of this

subpart. If a fetus is viable after delivery, it is a 

premature infant.

(e) “Nonviable fetus” means a fetus ex utero which,

although living, is not viable.

(f) “Dead fetus” means a fetus ex utero which exhibits

neither heart beat, spontaneous respiratory activity,

spontaneous movement of voluntary muscles, nor

pulsation of the umbilical cord (if still attached).

(g) “In vitro fertilization” means any fertilization of

human ova which occurs outside the body of a
92

female, either through admixture of donor human

sperm and ova or by any other means.

§46.204 Ethical Advisory Boards.

(a) One or more Ethical Advisory Boards shall be 

established by the Secretary. Members of these

Board(s) shall be so selected that the Board(s) will 

be competent to deal with medical, legal, social, 

ethical, and related issues and may include, for

example, research scientists, physicians, psychologists, sociologists, educators, lawyers, and ethicists,

as well as representatives of the general public. No

Board member may be a regular, full-time employee

of the Department of Health and Human Services.

(b) At the request of the Secretary, the Ethical Advisory

Board shall render advice consistent with the policies and requirements of this part as to ethical

issues, involving activities covered by this subpart,

raised by individual applications or proposals. In

addition, upon request by the Secretary, the Board

shall render advice as to classes of applications or

proposals and general policies, guidelines, and 

procedures.

(c) A Board may establish, with the approval of the

Secretary, classes of applications or proposals which:

(1) must be submitted to the Board, or (2) need not

be submitted to the Board. Where the Board so

establishes a class of applications or proposals which

must be submitted, no application or proposal 

within the class may be funded by the Department

or any component thereof until the application or

proposal has been reviewed by the Board and the

Board has rendered advice as to its acceptability

from an ethical standpoint.

(d) [Nullified under Public Law 103-43, June 10, 1993]

§46.205 Additional duties of the Institutional

Review Boards in connection with activities

involving fetuses, pregnant women, or human

in vitro fertilization.

(a) In addition to the responsibilities prescribed for

Institutional Review Boards under Subpart A of this

part, the applicant’s or offeror’s Board shall, with

respect to activities covered by this subpart, carry

out the following additional duties:

(1) determine that all aspects of the activity meet the

requirements of this subpart;

(2) determine that adequate consideration has been

given to the manner in which potential subjects

will be selected, and adequate provision has

been made by the applicant or offeror for monitoring the actual informed consent process (e.g.,

through such mechanisms, when appropriate, 

as participation by the Institutional Review

Board or subject advocates in: (i) overseeing the

actual process by which individual consents

required by this subpart are secured either by

approving induction of each individual into the

activity or verifying, perhaps through sampling,

that approved procedures for induction of individuals into the activity are being followed, and

(ii) monitoring the progress of the activity and

intervening as necessary through such steps as

visits to the activity site and continuing evaluation to determine if any unanticipated risks have

arisen);

(3) carry out such other responsibilities as may be

assigned by the Secretary.

(b) No award may be issued until the applicant or offeror has certified to the Secretary that the Institutional

Review Board has made the determinations required

under paragraph (a) of this section and the Secretary

has approved these determinations, as provided in

§46.120 of Subpart A of this part.

(c) Applicants or offerors seeking support for activities

covered by this subpart must provide for the designation of an Institutional Review Board, subject to

approval by the Secretary, where no such Board has

been established under Subpart A of this part.

§46.206 General limitations.

(a) No activity to which this subpart is applicable may

be undertaken unless:

(1) appropriate studies on animals and nonpregnant

individuals have been completed;

(2) except where the purpose of the activity is to

meet the health needs of the mother or the particular fetus, the risk to the fetus is minimal and,

in all cases, is the least possible risk for achieving the objectives of the activity;
93

(3) individuals engaged in the activity will have no

part in: (i) any decisions as to the timing,

method, and procedures used to terminate the

pregnancy, and (ii) determining the viability of

the fetus at the termination of the pregnancy;

and

(4) no procedural changes which may cause greater

than minimal risk to the fetus or the pregnant

woman will be introduced into the procedure for

terminating the pregnancy solely in the interest

of the activity.

(b) No inducements, monetary or otherwise, may be

offered to terminate pregnancy for purposes of the

activity.

Source: 40 FR 33528, Aug. 8, 1975, as amended at

40 FR 51638, Nov. 6, 1975.

§46.207 Activities directed toward pregnant

women as subjects.

(a) No pregnant woman may be involved as a subject in

an activity covered by this subpart unless: (1) the

purpose of the activity is to meet the health needs of

the mother and the fetus will be placed at risk only

to the minimum extent necessary to meet such

needs, or (2) the risk to the fetus is minimal.

(b) An activity permitted under paragraph (a) of this

section may be conducted only if the mother and

father are legally competent and have given their

informed consent after having been fully informed

regarding possible impact on the fetus, except that

the father’s informed consent need not be secured if:

(1) the purpose of the activity is to meet the health

needs of the mother; (2) his identity or whereabouts

cannot reasonably be ascertained; (3) he is not reasonably available; or (4) the pregnancy resulted 

from rape.

§46.208 Activities directed toward fetuses 

in utero as subjects.

(a) No fetus in utero may be involved as a subject in 

any activity covered by this subpart unless: (1) the

purpose of the activity is to meet the health needs 

of the particular fetus and the fetus will be placed at

risk only to the minimum extent necessary to meet

such needs, or (2) the risk to the fetus imposed by

the research is minimal and the purpose of the 

activity is the development of important biomedical

knowledge which cannot be obtained by other

means.

(b) An activity permitted under paragraph (a) of this

section may be conducted only if the mother and

father are legally competent and have given their

informed consent, except that the father’s consent

need not be secured if: (1) his identity or whereabouts cannot reasonably be ascertained, (2) he is

not reasonably available, or (3) the pregnancy 

resulted from rape.

§46.209 Activities directed toward fetuses ex

utero, including nonviable fetuses, as subjects.

(a) Until it has been ascertained whether or not a 

fetus ex utero is viable, a fetus ex utero may not be

involved as a subject in an activity covered by this

subpart unless:

(1) there will be no added risk to the fetus resulting

from the activity, and the purpose of the activity

is the development of important biomedical

knowledge which cannot be obtained by other

means, or

(2) the purpose of the activity is to enhance the 

possibility of survival of the particular fetus to

the point of viability.

(b) No nonviable fetus may be involved as a subject in

an activity covered by this subpart unless:

(1) vital functions of the fetus will not be artificially

maintained,

(2) experimental activities which of themselves

would terminate the heartbeat or respiration of

the fetus will not be employed, and

(3) the purpose of the activity is the development of

important biomedical knowledge which cannot

be obtained by other means.

(c) In the event the fetus ex utero is found to be viable,

it may be included as a subject in the activity only to

the extent permitted by and in accordance with the

requirements of other subparts of this part.

(d) An activity permitted under paragraph (a) or (b) of

this section may be conducted only if the mother

and father are legally competent and have given

their informed consent, except that the father’s

informed consent need not be secured if: (1) his
94

identity or whereabouts cannot reasonably be ascertained, (2) he is not reasonably available, or (3) the

pregnancy resulted from rape.

§46.210 Activities involving the dead fetus,

fetal material, or the placenta.

Activities involving the dead fetus, mascerated fetal

material, or cells, tissue, or organs excised from a dead

fetus shall be conducted only in accordance with any

applicable State or local laws regarding such activities.

§46.211 Modification or waiver of specific

requirements.

Upon the request of an applicant or offeror (with the

approval of its Institutional Review Board), the Secretary

may modify or waive specific requirements of this subpart, with the approval of the Ethical Advisory Board

after such opportunity for public comment as the

Ethical Advisory Board considers appropriate in the 

particular instance. In making such decisions, the

Secretary will consider whether the risks to the subject

are so outweighed by the sum of the benefit to the subject and the importance of the knowledge to be gained

as to warrant such modification or waiver and that such

benefits cannot be gained except through a modification

or waiver. Any such modifications or waivers will be

published as notices in the Federal Register.

Subpart C: Additional DHHS Protections

Pertaining to Biomedical and

Behavioral Research Involving

Prisoners as Subjects

Source: 43 FR 53655, Nov. 16, 1978.

§46.301 Applicability.

(a) The regulations in this subpart are applicable to all

biomedical and behavioral research conducted or

supported by the Department of Health and Human

Services involving prisoners as subjects.

(b) Nothing in this subpart shall be construed as indicating that compliance with the procedures set forth

herein will authorize research involving prisoners as

subjects, to the extent such research is limited or

barred by applicable State or local law.

(c) The requirements of this subpart are in addition to

those imposed under the other subparts of this part.

§46.302 Purpose.

Inasmuch as prisoners may be under constraints

because of their incarceration which could affect their

ability to make a truly voluntary and uncoerced decision whether or not to participate as subjects in

research, it is the purpose of this subpart to provide

additional safeguards for the protection of prisoners

involved in activities to which this subpart is applicable.

§46.303 Definitions.

As used in this subpart:

(a) “Secretary” means the Secretary of Health and

Human Services and any other officer or employee

of the Department of Health and Human Services 

to whom authority has been delegated.

(b) “DHHS” means the Department of Health and

Human Services.

(c) “Prisoner” means any individual involuntarily confined or detained in a penal institution. The term is

intended to encompass individuals sentenced to

such an institution under a criminal or civil statute,

individuals detained in other facilities by virtue of

statutes or commitment procedures which provide

alternatives to criminal prosecution or incarceration

in a penal institution, and individuals detained

pending arraignment, trial, or sentencing.

(d) “Minimal risk” is the probability and magnitude of

physical or psychological harm that is normally

encountered in the daily lives, or in the routine

medical, dental, or psychological examination of

healthy persons.

§46.304 Composition of Institutional Review

Boards where prisoners are involved.

In addition to satisfying the requirements in §46.107 of

this part, an Institutional Review Board, carrying out

responsibilities under this part with respect to research

covered by this subpart, shall also meet the following

specific requirements:

(a) A majority of the Board (exclusive of prisoner members) shall have no association with the prison(s)

involved, apart from their membership on the

Board.

(b) At least one member of the Board shall be a prisoner, or a prisoner representative with appropriate

background and experience to serve in that capacity,
95

except that where a particular research project is

reviewed by more than one Board only one Board

need satisfy this requirement.

§46.305 Additional duties of the Institutional

Review Boards where prisoners are involved.

(a) In addition to all other responsibilities prescribed 

for Institutional Review Boards under this part, the

Board shall review research covered by this subpart

and approve such research only if it finds that:

(1) the research under review represents one of the

categories of research permissible under

§46.306(a)(2);

(2) any possible advantages accruing to the prisoner

through his or her participation in the research,

when compared to the general living conditions,

medical care, quality of food, amenities and

opportunity for earnings in the prison, are not of

such a magnitude that his or her ability to weigh

the risks of the research against the value of such

advantages in the limited choice environment of

the prison is impaired;

(3) the risks involved in the research are commensurate with risks that would be accepted by nonprisoner volunteers;

(4) procedures for the selection of subjects within

the prison are fair to all prisoners and immune

from arbitrary intervention by prison authorities

or prisoners. Unless the principal investigator

provides to the Board justification in writing for

following some other procedures, control subjects must be selected randomly from the group

of available prisoners who meet the characteristics needed for that particular research project;

(5) the information is presented in language which

is understandable to the subject population;

(6) adequate assurance exists that parole boards will

not take into account a prisoner’s participation in

the research in making decisions regarding

parole, and each prisoner is clearly informed in

advance that participation in the research will

have no effect on his or her parole; and

(7) where the Board finds there may be a need for

follow-up examination or care of participants

after the end of their participation, adequate 

provision has been made for such examination

or care, taking into account the varying lengths

of individual prisoners’ sentences, and for

informing participants of this fact.

(b) The Board shall carry out such other duties as may

be assigned by the Secretary.

(c) The institution shall certify to the Secretary, in such

form and manner as the Secretary may require, that

the duties of the Board under this section have been

fulfilled.

§46.306 Permitted research involving prisoners.

(a) Biomedical or behavioral research conducted or supported by DHHS may involve prisoners as subjects

only if:

(1) the institution responsible for the conduct of 

the research has certified to the Secretary that

the Institutional Review Board has approved the

research under §46.305 of this subpart; and

(2) in the judgment of the Secretary the proposed

research involves solely the following:

(A) study of the possible causes, effects, and

processes of incarceration, and of criminal

behavior, provided that the study presents

no more than minimal risk and no more

than inconvenience to the subjects;

(B) study of prisons as institutional structures 

or of prisoners as incarcerated persons, 

provided that the study presents no more

than minimal risk and no more than 

inconvenience to the subjects;

(C) research on conditions particularly affecting

prisoners as a class (for example, vaccine trials and other research on hepatitis which is

much more prevalent in prisons than elsewhere; and research on social and psychological problems such as alcoholism, drug

addiction, and sexual assaults) provided that

the study may proceed only after the

Secretary has consulted with appropriate

experts including experts in penology, medicine, and ethics, and published notice, in the

Federal Register, of his intent to approve

such research; or

(D) research on practices, both innovative 
96

and accepted, which have the intent and 

reasonable probability of improving the

health or well-being of the subject. In cases

in which those studies require the assignment of prisoners in a manner consistent

with protocols approved by the IRB to 

control groups which may not benefit from

the research, the study may proceed only

after the Secretary has consulted with appropriate experts, including experts in penology,

medicine, and ethics, and published notice,

in the Federal Register, of the intent to

approve such research.

(b) Except as provided in paragraph (a) of this section,

biomedical or behavioral research conducted or 

supported by DHHS shall not involve prisoners as

subjects.

Subpart D: Additional DHHS Protections

for Children Involved as Subjects in

Research

Source: 48 FR 9818, March 8, 1983; 56 FR 28032, 

June 18, 1991.

§46.401 To what do these regulations apply?

(a) This subpart applies to all research involving children as subjects, conducted or supported by the

Department of Health and Human Services.

(1) This includes research conducted by Department employees, except that each head of an

Operating Division of the Department may

adopt such nonsubstantive, procedural modifications as may be appropriate from an 

administrative standpoint.

(2) It also includes research conducted or supported

by the Department of Health and Human

Services outside the United States, but in appropriate circumstances, the Secretary may, under

paragraph (i) of §46.101 of Subpart A, waive the

applicability of some or all of the requirements

of these regulations for research of this type.

(b) Exemptions at §46.101(b)(1) and (b)(3) through

(b)(6) are applicable to this subpart. The exemption

at §46.101(b)(2) regarding educational tests is also

applicable to this subpart. However, the exemption

at §46.101(b)(2) for research involving survey or

interview procedures or observations of public

behavior does not apply to research covered by this

subpart, except for research involving observation 

of public behavior when the investigator(s) do not

participate in the activities being observed.

(c) The exceptions, additions, and provisions for waiver

as they appear in paragraphs (c) through (i) of

§46.101 of Subpart A are applicable to this subpart.

§46.402 Definitions.

The definitions in §46.102 of Subpart A shall be 

applicable to this subpart as well. In addition, as used

in this subpart:

(a) “Children” are persons who have not attained

the legal age for consent to treatments or 

procedures involved in the research, under the

applicable law of the jurisdiction in which the

research will be conducted.

(b) “Assent” means a child’s affirmative agreement to

participate in research. Mere failure to object

should not, absent affirmative agreement, be

construed as assent.

(c) “Permission” means the agreement of parent(s)

or guardian to the participation of their child or

ward in research.

(d) “Parent” means a child’s biological or adoptive

parent.

(e) “Guardian” means an individual who is authorized under applicable State or local law to consent on behalf of a child to general medical care.

§46.403 IRB duties.

In addition to other responsibilities assigned to IRBs

under this part, each IRB shall review research covered

by this subpart and approve only research which satisfies the conditions of all applicable sections of this 

subpart.

§46.404 Research not involving greater than

minimal risk.

DHHS will conduct or fund research in which the IRB

finds that no greater than minimal risk to children is

presented, only if the IRB finds that adequate provisions

are made for soliciting the assent of the children and the

permission of their parents or guardians, as set forth in
97

§46.408.

§46.405 Research involving greater than minimal risk but presenting the prospect of direct

benefit to the individual subjects.

DHHS will conduct or fund research in which the IRB

finds that more than minimal risk to children is presented by an intervention or procedure that holds out

the prospect of direct benefit for the individual subject,

or by a monitoring procedure that is likely to contribute

to the subject’s well-being, only if the IRB finds that:

(a) the risk is justified by the anticipated benefit to the

subjects;

(b) the relation of the anticipated benefit to the risk is at

least as favorable to the subjects as that presented by

available alternative approaches; and

(c) adequate provisions are made for soliciting the

assent of the children and permission of their 

parents or guardians, as set forth in §46.408.

§46.406 Research involving greater than minimal risk and no prospect of direct benefit to

individual subjects, but likely to yield generalizable knowledge about the subject’s disorder

or condition.

DHHS will conduct or fund research in which the IRB

finds that more than minimal risk to children is presented by an intervention or procedure that does not

hold out the prospect of direct benefit for the individual

subject, or by a monitoring procedure which is not likely to contribute to the well-being of the subject, only if

the IRB finds that:

(a) the risk represents a minor increase over minimal

risk;

(b) the intervention or procedure presents experiences

to subjects that are reasonably commensurate with

those inherent in their actual or expected medical,

dental, psychological, social, or educational 

situations;

(c) the intervention or procedure is likely to yield 

generalizable knowledge about the subjects’ disorder

or condition which is of vital importance for the

understanding or amelioration of the subjects’ 

disorder or condition; and

(d) adequate provisions are made for soliciting assent 

of the children and permission of their parents or

guardians, as set forth in §46.408.

§46.407 Research not otherwise approvable

which presents an opportunity to understand,

prevent, or alleviate a serious problem affecting the health or welfare of children.

DHHS will conduct or fund research that the IRB does

not believe meets the requirements of §46.404,

§46.405, or §46.406 only if:

(a) the IRB finds that the research presents a reasonable

opportunity to further the understanding, prevention, or alleviation of a serious problem affecting the

health or welfare of children; and

(b) the Secretary, after consultation with a panel of

experts in pertinent disciplines (for example: 

science, medicine, education, ethics, law) and 

following opportunity for public review and 

comment, has determined either:

(1) that the research in fact satisfies the conditions

of §46.404, §46.405, or §46.406, as applicable,

or (2) the following:

(i) the research presents a reasonable opportunity 

to further the understanding, prevention, or 

alleviation of a serious problem affecting the

health or welfare of children;

(ii) the research will be conducted in accordance

with sound ethical principles;

(iii)adequate provisions are made for soliciting the

assent of children and the permission of their

parents or guardians, as set forth in §46.408.

§46.408 Requirements for permission by parents or guardians and for assent by children.

(a) In addition to the determinations required under

other applicable sections of this subpart, the IRB

shall determine that adequate provisions are made

for soliciting the assent of the children, when in the

judgment of the IRB the children are capable of providing assent. In determining whether children are

capable of assenting, the IRB shall take into account

the ages, maturity, and psychological state of the

children involved. This judgment may be made for

all children to be involved in research under a particular protocol, or for each child, as the IRB deems

appropriate. If the IRB determines that the capability

of some or all of the children is so limited that they
98

cannot reasonably be consulted or that the intervention or procedure involved in the research

holds out a prospect of direct benefit that is important to the health or well-being of the children and

is available only in the context of the research, the

assent of the children is not a necessary condition

for proceeding with the research. Even where the

IRB determines that the subjects are capable of

assenting, the IRB may still waive the assent requirement under circumstances in which consent may be

waived in accord with §46.116 of Subpart A.

(b) In addition to the determinations required under

other applicable sections of this subpart, the IRB

shall determine, in accordance with and to the

extent that consent is required by §46.116 of

Subpart A, that adequate provisions are made for

soliciting the permission of each child’s parents or

guardian. Where parental permission is to be

obtained, the IRB may find that the permission of

one parent is sufficient for research to be conducted

under §46.404 or §46.405. Where research is covered by §46.406 and §46.407 and permission is to

be obtained from parents, both parents must give

their permission unless one parent is deceased,

unknown, incompetent, or not reasonably available,

or when only one parent has legal responsibility for

the care and custody of the child.

(c) In addition to the provisions for waiver contained in

§46.116 of Subpart A, if the IRB determines that a

research protocol is designed for conditions or for a

subject population for which parental or guardian

permission is not a reasonable requirement to protect the subjects (for example, neglected or abused

children), it may waive the consent requirements in

Subpart A of this part and paragraph (b) of this section, provided an appropriate mechanism for protecting the children who will participate as subjects

in the research is substituted, and provided further

that the waiver is not inconsistent with Federal,

State, or local law. The choice of anappropriate

mechanism would depend upon the nature and purpose of the activities described in the protocol, the

risk and anticipated benefit to the research subjects,

and their age, maturity, status, and condition.

(d) Permission by parents or guardians shall be documented in accordance with and to the extent

required by §46.117 of Subpart A.

(e) When the IRB determines that assent is required, it

shall also determine whether and how assent must

be documented.

§46.409 Wards.

(a) Children who are wards of the State or any other

agency, institution, or entity can be included in

research approved under §46.406 or §46.407 only if

such research is:

(1) related to their status as wards; or

(2) conducted in schools, camps, hospitals, institutions, or similar settings in which the majority of

children involved as subjects are not wards.

(b) If the research is approved under paragraph (a) of

this section, the IRB shall require appointment of an

advocate for each child who is a ward, in addition to

any other individual acting on behalf of the child as

guardian or in loco parentis. One individual may

serve as advocate for more than one child. The

advocate shall be an individual who has the background and experience to act in, and agrees to act

in, the best interests of the child for the duration of

the child’s participation in the research and who is

not associated in any way (except in the role as

advocate or member of the IRB) with the research,
Comparison Table 

of Professional Statements

Appendix C

99

Organization Protections for Permissible Use of Existing Materials Protections for Future Material Collection

Anonymous Identifiable Anonymous Identifiable

Coded Directly Identified Coded Directly Identified

American Policy statement speaks only to future use. Informed Informed Informed

Association Informed consent: consent: consent: consent:

of Medical Statement not explicit YES YES YES

Colleges General consent General consent Specific

1997 IRB review:

Statement not explicit IRB review: IRB review: IRB review:

Statement not Statement not Statement not

explicit explicit explicit

American Informed consent: Informed consent:

College of “The following factors, among others, should be YES for all above categories

Medical considered in deciding whether it is appropriate to Consent for use of all clinical and research samples.

Genetics use previously collected samples without contacting

1995 the individual: IRB review:

■ are or will the samples be made anonymous?; Statement not explicit

■ the degree to which the burden of contacting 

individuals may make it impracticable to conduct 

research; 

■ existence and content of prior consent; and

■ risks and benefits.”

IRB review:

Statement not explicit

American Informed Informed Informed Informed Informed Informed

Society of consent: consent: consent: consent: consent: consent:

Human “Not applicable” YES1 YES NO YES - Layered YES - Layered

Genetics

1996 IRB review: IRB review: IRB review: IRB review: IRB review: IRB review:

Statement not Statement not Statement not Statement not Statement not Statement not

explicit explicit explicit explicit explicit explicit

Biotechnology Informed Informed Informed Informed consent:

Industry consent: consent: consent: Statement not explicit

Organization NO NO2 YES

1997

IRB review: IRB review: IRB review: IRB review:

Statement not Statement not Statement not Statement not explicit

explicit explicit explicit
100

Organization Protections for Permissible Use of Existing Materials Protections for Future Material Collection

Anonymous Identifiable Anonymous Identifiable

Coded Directly Identified Coded Directly Identified

College of Informed Informed Informed Informed Informed Informed

American consent: consent: consent: consent: consent: consent:

Pathologists Statement not Statement not Statement not YES YES YES

1997 explicit explicit explicit

IRB review: IRB review: IRB review: General consent General consent May not

YES YES3 YES for research, for research, identify

teaching and teaching and individuals in

quality control quality control publications

without specific

IRB review: IRB review: consent

YES YES

IRB review:

YES

ELSI Working Informed Informed consent: Informed consent:

Group consent: YES4 YES5

1995 NO 

Informed

consent may be

considered if 

identifiers are IRB review: IRB review:

to be removed YES YES

from currently 

linkable samples

IRB review:

YES

Department Informed Informed Informed Informed consent: 

of Health and consent: consent: consent: Statement not explicit

Human Services Statement not Generally Generally

1997 explicit requires requires IRB review:

informed consent informed consent Statement not explicit

IRB review: IRB review: IRB review:

Statement not YES YES

explicit

Human Genome Informed Informed Informed Informed Informed Informed

Organziation consent: consent: consent: consent: consent: consent:

1998 NO6,7 YES (Clinical) YES YES YES YES

NO (Research)

IRB review: IRB review: IRB review: IRB review: IRB review: IRB review: 

YES YES YES YES YES YES

U.S. National Informed consent: Informed Do not construct identifiable

Center for YES consent: sample collections.

Human Genome Continue to use existing libraries for large-scale YES8

Research and sequencing, only if IRB approval and consent for 

U.S. Department continued use are obtained and approval by the

of Energy funding agency is granted.

IRB may determine that recontact should be made IRB review:

by a third party. YES

IRB review:

YES

1996
101

Organization Protections for Permissible Use of Existing Materials Protections for Future Material Collection

Anonymous Identifiable Anonymous Identifiable

Coded Directly Identified Coded Directly Identified

National Heart, Informed Informed Informed Informed consent:

Lung, and Blood consent: consent: consent: YES - Layered

Institute Use of sample Use of sample IRB must judge

1997 must not violate must not violate adequacy of 

original consent original consent previous 

consent9

IRB review: IRB review: IRB review:

Statement not YES IRB review: Statement not explicit

explicit YES

Office for Informed consent: Informed consent: 

Protection from YES10 YES

Research Risks

1997 IRB review: IRB review:

YES11 YES

Pathologists Informed Informed Informed Informed Informed Informed

Consensus consent: consent: consent: consent: consent: consent:

Statement NO NO YES YES Statement not YES

Revised General explicit

1997 IRB review: IRB review: IRB review: consent12, 13 IRB review:

NO NO Statement not IRBs should Statement not

(includes explicit IRB review: be permitted to explicit

anonymized NO have broader

samples) latitude to waive

requirement for 

informed consent 

on coded samples.

IRB review:

NO

Review of

procedure

PRIM&R/ARENA Principles apply to prospective collection with the Informed consent:

Tissue Banking intent that pathologists will adapt them to apply to YES for all above categories

Working Group existing collections.

1997 IRB review:

Informed consent: YES for all above categories

Statement not explicit

IRB review:

Statement not explicit

Trans-NIH Informed Informed Informed Informed

Bioethics consent: consent: consent: consent:

Subcommittee Statement not Generally Generally Statement not explicit

1993 explicit requires requires

informed informed IRB review:

IRB review: consent consent Statement not explicit

Statement not

explicit IRB review: IRB review:

YES YES
102

Notes

1 “Waivers may be granted, although the waivers will be difficult

to justify by the above criteria [45 CFR § 46.116] if identifiers are

retained.”

2 “In the context of when to require informed consent, we recommend that the bill’s provisions apply only to samples that are personally-identifiable, not to ones that are anonymous or encoded.

We believe that it would burden the process without providing

patients with additional protections if the informed consent provisions were to be required for the use of non-identifiable samples in

research. As long as there is an appropriate ‘firewall’ between the

data and identifiers, the use of the data for further research should

not breach confidentiality.”

3 “Each institution that controls or uses specimens of human tissue

should have and enforce a written policy on confidentiality. For

issues involving research, this policy should be approved by an

institutional review board. Institutions should strive to maintain

separation of information—that is, keeping patient identity and

clinical information separate from research data through means

such as coding.”

4 “Before requiring recontact: IRB determines if proposed research

was agreed to at time of original sample collection. Implied consent sufficient. No consent if conditions for waiver are met under

45 CFR § 46.116.”

5 “Obtain informed consent for all samples likely to be used for

research in the future. Present options of whether samples can be

1.linked and whether they want to be recontacted with results

(should inform them about benefits and risks, confidentiality

and ability to withdraw from studies);

2.stripped of identifiers;

3.shared with other investigators, whether linked or anonymous;

or

4. used to study certain classes of diseases.”

6 “Routine samples obtained during medical care and stored may

be used for research if there is general notification of such a policy,

the patient has not objected, and the sample to be used by the

researcher has been coded or anonymized. Routine samples

obtained during medical care and stored before such notification of

such a policy may be used for research if the sample has been

anonymized prior to use....”

7 “Research samples obtained with consent and stored may be

used for other research if there is general notification of such a policy, the participant has not yet objected, and the sample to be used

by the researcher has been coded or anonymized. For the use of

research samples obtained before notification of a policy, these

samples may be used for other research if the sample has been

coded or anonymized prior to use.”

8 “In addition, there are several other disclosures that are of special

importance for donors of DNA for large-scale sequencing. These

include:

■ The meaning of confidentiality and privacy of information in 

the context of large-scale DNA sequencing, and how these issues

will be addressed;

■ The lack of opportunity for the donor to later withdraw the

libraries made from his/her DNA or his/her DNA sequence 

information from public use;

■ The absence of opportunity for information of clinical relevance

to be provided to the donor or his/her family;

■ The possibility of unforeseen risks; and

■ The possible extension of risk to family members of the donor

or to any group or community of interest (e.g., gender, race, 

ethnicity) to which a donor might belong.”

9 In judging the adequacy of a previous informed consent, 

IRBs and funding agencies should consider “1. The nature of the

proposed study, 2. The likelihood that knowing results of the

research will harm or benefit individual, 3. The availability of 

effective treatment or prevention for the disorder, and 4. The 

burden of such treatment.”

10 Regarding the submittal of materials to the repository: “A written submittal agreement for tissue collectors should require written

informed consent of the donor-subjects....It should also contain 

an acknowledgment that collectors are prohibited from providing

recipient-investigators with access to the identities of donorsubjects or to information through which the identities of donorsubjects may readily be ascertained.”

11 “A written usage agreement for recipient-investigators should

include the following: ‘Recipient acknowledges that the conditions

for use of this research material are governed by the cell repository

Institutional Review Board (IRB) in accordance with Department of

Health and Human Services regulations at 45 CFR 46.’”

12 “To give a description of each and every research protocol

which might be performed in the (sometimes distant) future on a

patient’s tissue is an unreasonable burden for the patient and the

researcher....Provided that written nondisclosure, confidentiality,

and security policies have been IRB-approved...we recommend

that the appropriate regulatory agencies modify the current Federal

regulations so that simple consent for research should be sufficient

for the use of all samples that are anonymous or anonymized.”

13 “Specific informed consent must be obtained from the donor

when specimens are collected specifically for research.”
103

References

American Association of Medical Colleges

American Association of Medical Colleges. Executive Council.

1997. Medical Records and Genetic Privacy, Health Data Security,

Patient Privacy, and the Use of Archival Patient Materials in Research.

Washington, DC: American Medical Association.

American College of Medical Genetics

American College of Medical Genetics. Storage of Genetics

Materials Committee. 1995. “Statement on Storage and Use of

Genetic Materials.” American Journal of Human Genetics

57(6):1499–1500.

American Society of Human Genetics

American Society of Human Genetics. Rapid Action Task Force 

on Informed Consent for Genetic Research. 1996. “Statement on

Informed Consent for Genetic Research.” American Journal of

Human Genetics 59:471–474.

Biotechnology Industry Organization

Statement of Alan R. Goldhammer. February 4, 1997.

www.bio.org/laws/bioethics_welcome. html.

College of American Pathologists

“Quality Assurance and Confidentiality in Genetic Testing.” 1997.

www.cap.org/html/advocacy/cappoints/posgen.html.

ELSI Working Group

Clayton, E.W., K.K. Steinberg, M.J. Khoury, E. Thomson, L.

Andrews, M.J.E. Kahn, L.M. Kopelman, and J.O. Weiss. 1995.

“Informed Consent for Genetic Research on Stored Tissue

Samples.” Journal of the American Medical Association

274:1786–1792.

Department of Health and Human Services

U. S. Department of Health and Human Services (DHHS). 1997.

Confidentiality of Individually Identifiable Health Information:

Recommendations of the Secretary of HHS, Pursuant to Section 264 

of the Health Insurance Portability and Accountability Act of 1996.

Washington, DC: U.S. Government Printing Office.

Human Genome Organization

Human Genome Organization Ethics Committee (HUGO). 1998.

Statement on DNA Sampling: Control and Access. London: HUGO.

U.S. National Center for Human Genome Research and

U.S. Department of Energy

U.S. National Center for Human Genome Research and U.S.

Department of Energy. 1996. “Guidance on Human Subjects Issues

in Large-Scale DNA Sequencing.” www.ornl.gov/ techresources/

human_genome/archive/nchg/doe.html.

National Heart, Lung, and Blood Institute

National Heart, Lung, and Blood Institute (NHLBI), NIH. 1997.

Report of the Special Emphasis Panel: Opportunities and Obstacles 

to Genetic Research in NHLBI Clinical Studies. Bethesda, MD: NIH. 

Office for Protection from Research Risks

Office for Protection from Research Risks (OPRR), NIH. 1997.

“Issues to Consider in the Research Use of Stored Data or Tissues.”

November 7. www.nih.gov/grants/oprr/humansubjects/guidance/

reposit.htm.

Pathologists Consensus Statement

Grizzle, W., W.W. Grody, W.W. Noll, M.E. Sobel, S.A. Stass, 

T. Trainer, H. Travers, V. Weedn, and K. Woodruff. 1997. Ad Hoc

Committee on Stored Tissues. College of American Pathologists.

“Recommended Policies for Uses of Human Tissue in Research,

Education, and Quality Control.” Archives of Pathological Laboratory

Medicine 123(4):296–300. 

PRIM&R/ARENA Tissue Banking Working Group

National Action Plan on Breast Cancer Tissue Banking Working

Group with comments by the PRIM&R/ARENA Tissue Banking

Working Group. 1997. Model Consent Forms and Related Information

on Tissue Banking from Routine Biopsies. December 4.

Trans-NIH Bioethics Subcommittee

Discussions and Recommendations: Protecting the Confidentiality of

Individually-Identifiable Research Information. Draft. February 4, 1993.

Guidance for Institutional

Review Boards Reviewing

Research Using Human

Biological Materials

■ NBAC’s Proposed Process for Research Using Human Biological Materials

■ Human Subject as Currently Defined by OPRR

■ IRB Review for Research with Human Biological Materials

■ NBAC’s Proposed Informed Consent Requirements for Research with 

Human Biological Materials

Appendix D

105
106

Chart 1: NBAC’s Proposed Process for Research Using Human Biological Materials

Key to Guidance in the Report

1) Is the research subject to human subjects regulations and IRB review? See Recommendations 1, 3, 4, and 5.

2) Is the research eligible for expedited review? See Recommendation 2.

3) Is consent required? See Recommendations 10, 11, 12, and 13.

4) Is the proposed use of the sample consistent with the subject’s likely understanding of how it would be used? 

See Recommendations 6, 7, 8, 9, and 18. See Recommendations 14, 15, and 16 for disclosure of research results to subjects.

5) Samples may legally be used without obtaining (additional) consent (subject to applicable state law, if any).

See Recommendations 19–23.

6) Obtain consent or consider appropriateness of retaining identifiers. See Recommendations 3, 6, 7, 8, 9, and 18.

Yes, the samples are

coded or identified.

2. Is the research 

eligible for expedited

review?

3. Is consent required? Yes

Yes

Yes

No

No

No

4. Is the proposed use of the sample 

consistent with the subject’s likely 

understanding of how it would be used?

5. Samples may legally be used without

obtaining (additional) consent (subject to

applicable state law, if any).

6. Obtain consent or consider 

appropriateness of retaining identifiers.

7. Samples may legally be used 

without informed consent or 

IRB review.

Do previous consent documents exist?

No, the 

samples are

publicly 

available.

No, the samples 

are unidentified.

No, the subject

is deceased.

No, the

process 

of unlinking 

the 

samples is

sound.

1. Is the research subject to human subjects regulations and IRB review?
107

Chart 2: Human Subject as Currently Defined by OPRR1

1 Adapted from Memorandum, Gary B. Ellis to Office for Protection from Research Risks (OPRR) Staff. April 17, 1996. 

2 “That is, the identity of the subject is or may readily be ascertained or associated with the information.” Ibid.

3 See Recommendation 1.

Yes No

Yes No

Is the definition of “human subject” at Section 46.102 (f) met in this research activity?

Is there an intervention or an interaction with a living person that would not be occurring

or would be occurring in some other fashion, but for this research?

Will identifiable private data/information be obtained 

for this research in a form associable2 with the 

living individual?3

Human subjects involved. 

Follow 45 CFR Part 46 or 

meet criteria for exemptions.

SEE CHART 3

45 CFR Part 46 does not apply.
108

Chart 3: IRB Review for Research with Human Biological Materials

Is the research contained within one of

the categories listed on the Expedited

Review List (46 Federal Register 8392)

issued by the Department of Health and

Human Services?

Will information be recorded by the 

investigator in such a way that it cannot

be linked to the subject?3

Yes

No

Full IRB review.

Full IRB 

review.6

Yes

No

Yes

No Yes No Yes

No

Eligible for

expedited 

IRB review.

Full IRB

review.7

Eligible for

expedited 

IRB review.

Research is

exempt from 45

CFR Part 46.

Will the research in its

entirety involve greater

than minimal risk?5

Will the research in its 

entirety involve greater than

minimal risk?4

Will the research involve solely the study of existing1 data or specimens?

Guidelines for applying the exemption stated at 45 CFR 46.101(b)(4) and criteria for expedited review at §46.110.

1 “Existing” means collected (i.e., on the shelf) at the time the research is proposed. It includes data or specimens collected in

research and nonresearch activities.

2 See Recommendation 1.

3 See Recommendations 1 and 3. This question is relevant to determine both (1) Is the definition of “human subject” at 

Section 46.102 (f) met in this research activity? and (2) Is the research exempt in accordance with Section 46.101 (b)(4)?

4 See Recommendations 2, 5, and 10.

5 See Recommendations 2, 5, and 10.

6 Research also is eligible for expedited IRB review if the subject of review involves exclusively minor changes in previously

approved research during the period (of one year or less) for which approval is authorized.

7 See fn 6.

No

Are those data or specimens publicly 

available?2
109

Chart 4: NBAC’s Proposed Informed Consent Requirements for Research 

with Human Biological Materials1

Will the research in its entirety involve greater than minimal risk?1

No Yes

No waiver or alteration.

No waiver or 

alteration.

No Yes

Waiver or alteration possible,

if IRB documents these two

findings and approves the

waiver or alteration.

Will waiving/altering informed consent adversely affect

subjects’ rights and welfare?2

1 See Recommendations 2, 5, and 10.

2 See Recommendations 11 and 12.

Public Comments on NBAC’s

February 22, 1999, Draft

Appendix E

Bruce S. Alpert, University of Tennessee, Clinical Research

Center (Memphis, TN)

Sheri Alpert, George Mason University (Alexandria, VA)

Philip L. Bereano, Department of Technical Communication,

University of Washington (Seattle, WA)

William R. Brinkley, Federation of Societies for

Experimental Biology (Bethesda, MD)

Allen Buchanan, Department of Philosophy, University of

Arizona (Tucson, AZ)

Courtney S. Campbell, Department of Philosophy, Oregon

State University (Corvallis, OR)

David Chesnut (Poway, CA)

Ellen Wright Clayton, Vanderbilt University (Nashville, TN)

Jordan J. Cohen, Association of American Medical Colleges

(Washington, DC)

The College of American Pathologists (Washington, DC)

Jeffrey Cossman, Georgetown University Medical Center

(Washington, DC)

Ethics Advisory Committee, The Endocrine Society

(Bethesda, MD)

John C. Fletcher, School of Medicine and Division of

Continuing Education, University of Virginia (Kenswick, VA)

Uta Franke, Stanford University School of Medicine

(Stanford, CA)

Matthew Giannandrea, U.S. Army (Manhattan, KS)

Sid Gilman, Department of Neurology, University of Michigan

(Ann Arbor, MI)

Kenneth W. Goodman, University of Miami (Miami, FL)

Eric R. Grimes, Case Western Reserve School of

Medicine (Cleveland, OH)

William E. Grizzle, Department of Pathology, University of

Alabama at Birmingham (Birmingham, AL)

Sue Hamill, University of California, Davis (Davis, CA)

Erica Heath, Independent Review Consulting 

(San Anselmo, CA)

Paul V. Holland, Sacramento Medical Foundation Blood

Centers (Sacramento, CA)

C. Christopher Hook, Mayo Clinic (Rochester, MN)

Dianne N. Irving, University Faculty for Life 

(Bethesda, MD)

Anne Janin, Department of Pathology, Hospital Saint Louis

(Paris, France)

Marjorie Kagawa-Singer, University of California, 

School of Public Health and Asian American Studies 

(Los Angeles, CA)

Regina Kenen, Department of Sociology and Anthropology,

The College of New Jersey (Ewing, NJ)

Bartha Maria Knoppers, Faculty of Law, University of

Montréal (Québec, Canada)

Deena A. Koniver, Centers for Disease Control and 

Prevention (Atlanta, GA)

James Linder, American Society of Clinical Pathologists

(Washington, DC)

Virginia A. LiVolsi, Department of Pathology, University of

Pennsylvania Medical Center (Philadelphia, PA)

Mary B. Mahowald, University of Chicago (Chicago, IL)

Peter Marshall, Cleveland Veterans Affairs Medical Center

(Cleveland, OH)

Caroline D. McCoy, Illinois State University (Bloomington, IL)

Jean E. McEwen, Boston College Law School (Newton, MA)

Elizabeth McPherson, Glaxo Wellcome, Inc. (Research

Triangle Park, NC)

Jon F. Merz, University of Pennsylvania Center for Bioethics

(Philadelphia, PA)

111
112

Marsel Mesulam, The Cognitive Neurology and Alzheimer’s

Disease Center, Northwestern University Medical School

(Chicago, IL)

Abbey S. Meyers, National Organization for Rare Disorders

(New Fairfield, CT)

Vincent M. Monnier, Case Western Reserve University

(Cleveland, OH)

Donald E. Mosier, Department of Immunology, The Scripps

Research Institute (La Jolla, CA) 

Curtis R. Naser, Department of Philosophy, Fairfield

University (Fairfield, CT)

Stuart L. Nightingale, Food and Drug Administration, 

Office of Health Affairs (Rockville, MD)

Ari Patrinos, Biology and Environmental Research,

Department of Energy (Germantown, MD)

Carol K. Petito, Department of Pathology, University 

of Miami School of Medicine (Miami, FL)

Frances A. Pitlick, American Society for Investigative

Pathology (Bethesda, MD)

Joan Porter, National Science and Technology Council

(Washington, DC)

Rosalind Porter, National Community Advisory Board to the

AIDS Vaccine Evaluation Group (Montgomery, AL)

Karen H. Rothenberg, University of Maryland School of Law

(Baltimore, MD)

Marc A. Schuckit, Department of Psychiatry, San Diego

Veterans Affairs Medical Center, University of California, 

San Diego School of Medicine (San Diego, CA)

James D. Shelton, U.S. Agency for International Development

(Washington, DC)

Frank P. Simone, American Type Culture Collection

(Manassas, VA)

Lana R. Skirboll, National Institutes of Health, Office of

Science Policy (Bethesda, MD)

Mark E. Sobel, Association for Molecular Pathology

(Bethesda, MD)

Robert Sparkes, Department of Medicine, University of

California (Los Angeles, CA)

Donald Stablein, The EMMES Corporation (Potomac, MD)

Clive R. Taylor, Association of Pathology Chairs, Department

of Pathology, University of Southern California (Los Angeles,

CA)

Suzanne P. Tomlinson, Biotechnology Industry Organization

(Washington, DC)

Russell P. Tracy, University of Vermont, Laboratory for Clinical

Biochemistry (Colchester, VT)

John Q. Trojanowski, Department of Pathology and

Laboratory Medicine, University of Pennsylvania School of

Medicine (Philadelphia, PA)

David Wargowski, University of Wisconsin-Madison School

of Medicine (Madison, WI)

Beverly Woodward, Brandeis University (Waltham, MA)

Gillian R. Woollett, Pharmaceutical Research and

Manufacturers of America (Washington, DC)
Public and Expert Testimony

Appendix F

December 13, 1996 (Bethesda, MD)

Public:

George Gasparis, Office for Protection from Research Risks

Susan Pollin, Kennedy Institute of Ethics, Georgetown University 

January 9–10, 1997 (Washington, DC)

Expert:

David Korn, American Association of Medical Colleges

Debra Saslow, Office on Women’s Health, Department of 

Health and Human Services

Mark Guyer, National Center for Human Genome Research

March 5, 1997 (Bethesda, MD) – Genetics Subcommittee

Expert:

Dorothy Wertz, Shriver Center for Mental Retardation

Chuck Denk, Mathematica

Ronald Cole-Turner, Pittsburgh Theological Seminary

Public:

Mark Sobel, National Cancer Institute

July 14, 1997 (Bethesda, MD)

Expert:

Sheri Alpert, Office of the Privacy Advocate, 

Internal Revenue Service

September 18–19, 1997 (Bethesda, MD)

Expert:

Bartha M. Knoppers, University of Montréal

Elisa Eiseman, RAND Corporation

Courtney Campbell, Oregon State University

Public:

John Cavanaugh-O’Keefe, American Bioethics Advisory

Commission, American Life League

October 19, 1997 (Bethesda, MD)

Expert:

Robert Weir, University of Iowa

November 23, 1997 (Bethesda, MD)

Expert:

Elisa Eiseman, RAND Corporation

James Wells, Center for Health Policy Studies 

Sheri Alpert, Office of the Privacy Advocate, Internal 

Revenue Service

Robert Weir, University of Iowa

Mark Sobel, National Cancer Institute

Frances Pitlick, American Society for Investigative Pathology

December 9, 1997 (Arlington, VA)

Expert:

John Killen, National Institute of Allergy and Infectious Diseases

January 6–7, 1998 (Arlington, VA)

Expert:

Susan E. Old, National Heart, Lung, and Blood Institute

Patricia Barr, National Action Plan on Breast Cancer

Public:

Mark Sobel, National Cancer Institute

March 3–4, 1998 (McLean, VA)

Expert:

Lisa Brooks, National Human Genome Research Institute

Mark Guyer, National Human Genome Research Institute

Public:

Karen Rothenberg, University of Maryland

May 20, 1998 (Cleveland, OH)

Expert:

C. Christopher Hook, The Mayo Clinic

July 14–15, 1998 (Portland, OR)

Expert:

Allen Buchanan, University of Arizona

Frank C. Dukepoo, Northern Arizona University

Mary-Claire King, University of Washington

Public:

Ted Falk, Portland, OR

March 2–3, 1999 (Vienna, VA)

Expert:

John Fanning, Office of the Assistant Secretary for Planning 

and Evaluation, Department of Health and Human Services

113

Commissioned Papers

Appendix G

The following papers, prepared for the National Bioethics Advisory Commission, 

are available in Volume II of this report:

Privacy and the Analysis of Stored Tissues

Sheri Alpert

Alexandria, Virginia

An Ethical Framework for Biological Samples Policy

Allen Buchanan

University of Arizona

Research on Human Tissue: Religious Perspectives

Courtney S. Campbell

Oregon State University

Stored Tissue Samples: An Inventory of Sources in the United States 

Elisa Eiseman

RAND Critical Technologies Institute

Control of DNA Samples and Information

Bartha Maria Knoppers, Marie Hirtle, Sébastien Lormeau, Claude M. Laberge, Michelle

Laflamme

CRDP (Public Law Research Centre), Faculty of Law, Université de Montréal, Québec 

Contribution of the Human Tissue Archive to the Advancement of Medical 

Knowledge and the Public Health

David Korn

Stanford University School of Medicine

The Ongoing Debate About Stored Tissue Samples, Research, and Informed Consent

Robert F. Weir

University of Iowa

Mini-Hearings on Tissue Samples and Informed Consent

James A. Wells

Center for Health Policy Studies

115