Genetic Monitoring and Screening in the

Workplace

October 1990

OTA-BA-455

NTIS order #PB91-105940
Recommended Citation:

U.S. Congress, Office of Technology Assessment, Genetic Monitoring and Screening in the

Workplace, OTA-BA-455 (Washington, DC: U.S. Government Printing Office, October

1990).

For sale by the Superintendent of Documents

U.S. Government Printing Office, Washington, DC 20402-9325

(order form can be found in the back of this report)
Foreword

Genetic monitoring and screening have the potential to significantly change the

workplace by detecting both occupational and nonoccupational diseases. These tests can

identify genetic abnormalities that maybe associated with inherited diseases, susceptibilities,

and traits in otherwise healthy, asymptomatic individuals. The ability to diagnose latent

conditions (both occupational and nonoccupational) through genetic monitoring and

screening raises policy questions about the proper use of such technologies. This report

describes the issues associated with genetic monitoring and screening in the workplace. It

examines the technologies used, analyzes the legal framework for the use of such tests,

assesses the ethical issues inherent in the use of these tools in the workplace setting, describes

how genetic information is conveyed by a genetic counselor, and, based on an OTA survey

of 1,500 U.S. companies and the largest unions, evaluates the current and future use of genetic

monitoring and screening in the workplace.

Genetic Monitoring and Screening in the Workplace was requested by the Senate

Committee on Commerce, Science, and Transportation; House Committee on Energy and

Commerce; and the House Committee on Science, Space, and Technology. It was also

endorsed by the Senate Committee on Labor and Human Resources. It illustrates a range of

options for action by the U.S. Congress on two central issues:

. the appropriate role of the Federal Government in the regulation, oversight, or

promotion of genetic monitoring and screening; and

. the adequacy of federally sponsored research on the relationships between genes and

the environment.

OTA was assisted in preparing this study by a panel of advisors and reviewers selected

for their expertise and diverse points of view on the issues covered in the assessment. Advisory

panelists and reviewers were drawn from industry, academia, labor organizations, legal

experts, scientific and professional organizations, research organizations, and Federal

agencies.

OTA gratefully acknowledges the contribution of each of these individuals. As with all

OTA assessments, however, responsibility for the content is OTA’s alone.

u JO~T H. GIBBONS

Director

iii
Genetic Monitoring and Screening in the Workplace

Judy Hayes Bernhardt

Professor and Department Chair

Community and Mental Health

Nursing

East Carolina University

Greenville, NC

Patricia A. Buffler

Professor of Epidemiology

University of Texas School of

Public Health

Houston, TX

Martin G. Cherniack

Director

Occupational Health Center

Lawrence and Memorial Hospital

New London, CT

Kurt R. Fenolio

Genetic Counselor

Maternal-Fetal Medical Associates

San Francisco, CA

Theodore Friedmann

Professor of Pediatrics and Molecular

Genetics

University of California, San Diego

La Jolla, CA

Elizabeth Evans Gresch

Senior Occupational Health Associate

The Dow Chemical Company

Midland, MI

Bruce W. Karrh

Vice President

Safety, Health and Environmental

Affairs

E.I. du Pent de Nemours & Company

Wilmington, DE

Advisory Panel

Elena O. Nightingale, Panel Chair

Special Advisor to the President

Carnegie Corporation of New York

Washington, DC

Marvin S. Legator

Professor and Director

Division of Environmental Toxicology

University of Texas Medical

Branch-Galveston

Galveston, TX

Lewis L. Maltby

Director of Office Services

Drexelbrook Engineering Company

Horsham, PA

Tony Mazzocchi

Secretary-Treasurer

Oil, Chemical and Atomic Workers

Union

Denver, CO

Kenneth B. Miller

Director

Occupational and Environmental

Medicine

Ithaca, NY

Benjamin w. Mintz

Associate Professor of Law

Columbus School of Law

The Catholic University of America

Washington, DC

Robert F. Murray, Jr.

Professor of Pediatrics, Medicine and

Genetics

Howard University College of

Medicine

Washington, DC

Thomas H. Murray

Professor and Director

Center for Biomedical Ethics

Case Western Reserve University

Cleveland, OH

Vincent M. Riccardi

Medical Director

Alfigen--The Genetics Institute

Pasadena, CA

Anthony Robbins

Professor of Public Health

Boston University School of Public

Health

Boston, MA

Stanley D. Rose

Reagent Business Unit Manager

Perkin-Elmer Cetus

Emeryville, CA

Mark A. Rothstein

Professor of Law and Director

Law Foundation

Houston, TX

Sheldon W. Samuels

Executive Vice President

Workplace Health Fund

Industrial Union Department,

AFL-CIO

Washington, DC

NOTE: OTA appreciates and is grateful for the valuable assistance and thoughtful critiques provided by the advisory panel members.

The panel does not, however, necessarily approve, disapprove, or endorse this report. OTA assumes full responsibility for the

report and the accuracy of its contents.
OTA Project Staff—Genetic Monitoring and Screening in the Workplace

Roger C. Herdman, Assistant Director, OTA Health and Life Sciences Division

Gretchen S. Kolsrud, Biological Applications Program Manager1

Margaret A. Anderson, Project Director

Joyce Ann Brentley, Legal Analyst

Claire L. Pouncey, Research Assistant

Robyn Y. Nishimi, Project Director2

Gladys B. White, Analyst 3

Kathi E. Hanna, Analyst 4

R. Alta Charo, Analyst5

Gianna M. Bosko, Intern6

David H. Keller, Intern7

Support Staff

Cecile Parker, Office Administrator

Linda Ray ford-Journiette, Administrative Secretary

Jene Lewis, Secretary

Sharon Kay Oatman, Administrative Assistant8

Lori B. Idian, Secretary/Word Processing Specialist

Editor

Carter R. Blakey, Bethesda, MD

Contractors

Lori B. Andrews, American Bar Foundation, Chicago, IL

Paul R. Billings, Pacific Presbyterian Medical Center, San Francisco, CA

Baruch A. Brody, Baylor College of Medicine, Houston, TX

Edward J. Calabrese, University of Massachusetts, Amherst, MA

R. Alta Charo, University of Wisconsin, Madison, WI

Sharon L. Dorfman, Focus Technologies, Inc., Washington, DC

Robert I. Field, Dilworth, Paxson, Kalish & Kauffman, Philadelphia, PA

Alan Gewirth, The University of Chicago, Chicago, IL

Kathi E. Hanna, Churchton, MD

Schulman, Ronca, & Bucuvalas, Inc., John M. Boyle, Principal Investigator, Washington, DC

Schulman, Ronca, & Bucuvalas, Inc., Ken John, Research Associate, Washington, DC

Marja Sorsa, Institute of Occupational Health, Helsinki, Finland

Hastings S. Trigg, Jr., E.I. du Pent de Nemours & Co., Wilmington, DE

Imou@ September 19*9.

z~ou~ oetober 1989.

3~ou~ June 1989.

%OU@ Much 1989.

%’hOU@ August 1988.

6Apnl 1990- Au~st 1~.

7Septemkr 1988- December 1988.

Wh.rough February 1989.

%’hOU@ July 1989.
Contents

Page

Chapter 1: Summary, policy Issues, and Options for Congressiona1 Action . . . . . . . . . . 3

Chapter 2: Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31

Chapter 3: Occupational Health and Genetic Monitoring and Screening: An Overview. 41

Chapter 4: The State-of-the-Art of Genetic Monitoring . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55

Chapter 5: The State-of-the-Art of Genetic Screening . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77

Chapter 6: Legal Considerations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103

Chapter 7: Ethical Issues . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 139

Chapter 8: The Worker as a Person: Individual Uses of Genetic Information . . . . . . . . . 157

Chapter 9: Genetics in the Workplace: Perceptions and Practice . . . . . . . . . . . . . . . . . . . . . 171

Appendix A: Basic Tenets of Human Genetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 191

Appendix B: Survey Methodology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .197

Appendix C: 1982 Survey of the Use of Genetic Testing in the Workplace . . . . . . . . . . . 201

Appendix D: Federal Research in Genetic Monitoring and Screening . . . . . . . . . . . . . . . . 209

Appendix E: Survey Instrument: Corporate Health Officers . . . . . . . . . . . . . . . . . . . . . . . . . 213

Appendix F: Survey Instrument: Corporate Personnel Officers . . . . . . . . . . . . . . . . . . . . . . 225

Appendix G: Survey Instrument: Union Presidents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 233

Appendix H: Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .247

Appendix I: List of Contractor Documents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 249

Appendix J: Acronyms and Glossary of Terms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 250

Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 257
Chapter 1

Summary, Policy Issues, and

Options for Congressional Action
CONTENTS

Page

DEFINING GENETIC TESTING . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . . . . . . . . . . 3

What is Genetic Monitoring? . . . . . . . . . . .

. . . . . . .

... .., .+. ... ... .*** ,+e Q*4**, ,+e .*4 4

What is Genetic Screening? ... ... ... ... ... ... ..+

. ... ... ... ..*. +**. .o*. moo.**.*.** * 5

DIFFERENCES BETWEEN GENETIC MONITORING AND SCREENING ...........5

HISTORY OF GENETIC! MONITORING AND SCREENING . . . . . . . . . . . . . . . . . . . . . . . . 6

GENETIC MONITORING AND SCREENING IN THE WORKPLACE:

A HISTORY OF CONGRESSIONAL CONCERN . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

The 1983 Office of Technology Assessment Report . . . . . . . . . . . . . . . . . . . . . . 6

Impacts of the Human Genome Project

● . . . . . . . . .

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

THE STATE-OF-THE-ART

. . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .8

Genetic Monitoring Technologies . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

Genetic Screening Technologies ... ... ... ... ... .*. ... ... ... *.. .,. .., .,.4, *o

, .+++ a 10

WHAT LEGAL CONSIDERATIONS ARE INVOLVED? . . . . . . . . . . . . . . . . . . . . . . . . . . . 12

Federal Regulatory Framework . . . . . . . . . . . . . . . . . . . . .

. ...........,,.........++**,* 15

State Responsibility ... ... ... ... ... +

.. .*. ... ... ... ... **. +c*Q. +**+ Q * * * . * * *.***..+< 16

WHAT ETHICAL ISSUES ARE INVOLVED? ... ... ... ... .,,.,. ,.. ... ..+* qe *$***,, 17

GENETIC COUNSELING FOR INDIVIDUAL USES OF GENETIC!

INFORMATION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . 19

SURVEY OF THE USE OF GENETIC MONITORING AND SCREENING . . . . . . . . . . 20

POLICY ISSUES AND OPTIONS FOR CONGRESSIONAL ACTION . . . . . . . ....,,..24

Boxes

Box Page

l-A. Cancer Detection in the Workplace . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

l-B. Genetics and Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .14

l-C. An International Survey of Attitudes of Medical Geneticists Toward Workplace

Genetic Screening and Access to Results . ....................,,.,..,...,,.,.6++ 18

1-D. Huntington’s Disease . . . . . . . . . . . . . . . . . . . . . . . . . . .

● . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20

Figures

Figure Page

1-1. The Structure of DNA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ....*...........**+.*+,+ 3

1-2. DNA Base Pairing . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4

1-3. Components of Genetic Testing in the Workplace

. . . . . . . . . . . . .

. * . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4

1-4. Biological Consequences of Exposure to Mutagenic Agents

. . . . . . . . . . . . . . . . . . . . . 9

1-5. Detection of Restriction Fragment Length Polymorphisms Using Radioactively

Labeled DNA Probes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

● . . . . . . . . . . . . . . . . . . . . . . . 11

1-6. The Polymerase Chain Reaction . . . . .

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12

Tables

Table Page

1-1. Identification and Quantification of Genetic Factors Affecting Susceptibility to

Environmental Agents ... ... ..** ... ... ... .,, .**, +*** o+, ,,o. **c* o*t. **4*,,,.**. 13

1-2. Genetic Tests Available and Total Americans Affected . . . . . . . . . . . . . . . . . . . . . . . . . . 15

1-3. Summary of Methodology ... ... ... ... ... ... ..*. +., *,. ,.***. ,+. e+q, u*,**., 21

1-4. Current Use of Genetic Monitoring by Fortune 500 Companies . . . . . . . . . . . . . . . . . . 21

. . . .

1-5. Current Use of Genetic Screening by Fortune 500 Companies . . . . . . . . . . . . . . . . . . . 21

1-6. Past Use of Genetic Monitoring Tests by Fortune 500 Companies 22

1-7. Past Use of Genetic Screening Tests by Fortune 500 Companies

. . . . . . . . . . . . . . . .

. . . . . . . . . . . . 22 1-8. Combined Testing: Current v. Past Monitoring and Screening by Fortune 500 . . . . .

Companies . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22

1-9. Use of Genetic Monitoring or Screening: 1989 v. 1982 Survey Results . . . . . . . . . . . 23

1-10. Consideration To Conduct Genetic Monitoring and Screening in the Next Five

Years: Health Officers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
Chapter 1

Summary, Policy Issues, and Options for Congressional Action

During the past three decades, our understanding

of genetics has advanced remarkably as new methods for identifying, manipulating, and analyzing

deoxyribonucleic acid (DNA) have developed. Less

well understood, however, is the interaction between

the environment and heredity, and the roles each

plays in sickness and health. It has long been

recognized that genetic risks are associated with

certain workplace environments, such as exposure to

radiation or certain chemicals. Recognition of genetic factors in disease presents new opportunities

for detection, prevention, and treatment. This concept has provoked debate in recent years about

whether genetic monitoring and screening of workers to identify outwardly healthy individuals (or

populations) at risk for or susceptible to a variety of

work-related conditions is appropriate or even feasible.

Genetic monitoring and screening have the potential to significantly change the workplace by detecting both occupational and nonoccupational diseases.

They can identify genetic abnormalities which may

be associated with inherited diseases, susceptibilities, and traits in otherwise healthy, asymptomatic individuals. The ability to diagnose latent

conditions (both occupationally and nonoccupationally related) through genetic monitoring and

screening raises policy questions about the proper

use of such technologies.

This report examines the potential applications

and limitations of genetic monitoring and screening

in the workplace. In response to requests from the

Senate Committee on Commerce, Science, and

Transportation, the House Committee on Energy

and Commerce, and the House Committee on

Science, Space, and Technology, this assessment

presents the scientific, legal, ethical, and social

issues surrounding the use of genetic monitoring and

screening in the workplace. It also evaluates the

results of a 1989 Office of Technology Assessment

(OTA) survey on genetic monitoring and screening

in the workplace of 1,500 U.S. companies, the 50

largest utilities, and the 33 largest unions. These

survey results will also be interpreted in the context

of a 1982 OTA survey on genetic monitoring and

screening (part of a 1983 OTA assessment of genetic

monitoring and screening).

DEFINING GENETIC TESTING

Genetic testing includes a number of technologies

to detect genetic traits, changes in chromosomes, or

changes in DNA. DNA is the chemical bearer of

genetic information, which takes the structural form

of a double-stranded helix (figure l-l). It is composed, in part, of four chemical subunits called

bases. These four bases—guanine (G), adenine (A),

thymine (T), and cytosine (C)---are the coding units

of genetic information that form the DNA double

helix structure (figure 1-2).

As used in the workplace, genetic testing encompasses two activities: genetic monitoring and genetic

screening. Thus, genetic testing of employee populations involves both examining persons for evidence of induced change in their genetic material

(monitoring) and identifying individuals with particular inherited traits or disorders (screening). The

general term “genetic testing” is not used in this

report; rather the more specific terms “genetic

monitoring” and “genetic screening” are used

(figure 1-3).

Figure l-l—The Structure of DNA

SOURCE: Office of 1 Assessment, 1990.

–3–
4 ● Genetic Monitoring and Screening in the Workplace

 

Figure 1-2—DNA Base Pairing

Phosphate Molecule

/

Deox 

Sugar Molecule

/ Nitrogenous

-0”

0 ,

-o”’

o . . . . 

 . . . . . . . >.. . ... . . . . . . 

. .. .””

CH

o 0 . . . . . , . . . . . .. . 

 ,.. . . . 

o 0 . . . . .

.. . . . . . . . . . .. . . : . ..,. 

. . . . . .

Weak Bonds Between

Base Pairs

o -

‘0

.o -

‘ 0

ro-

‘ 0

Figure 1-3-Components of Genetic Testing in

the Workplace

Genetic monitoring

Workers

Job applicants

Occupationally related Nonoccupationally

disease related disease I

Occupationally related Nonoccupationally

susceptibility related susceptibility

SOURCE: Office of Technology Assessment, 1990.

I 1

SOURCE: Office of Technology Assessment, 1990.

What is Genetic Monitoring?

Genetic monitoring involves periodically examining employees to evaluate modifications of their

genetic material--e.g., chromosomal damage or

evidence of increased occurrence of molecular

mutations—that might have evolved in the course of

employment. The putative cause is workplace exposure to hazardous substances. The premise is that

such changes could indicate increased risk of future

illness.

Because ambient exposures, personal habits and

lifestyle decisions (e.g., tobacco use, etc.), and age

can also induce changes in genetic material, genetic

monitoring could detect changes that arise from

exposures outside of the workplace. In short, genetic

I monitoring ascertains whether the genetic material

 The Sugar-Phosphate 

Backbone

The four nitrogenous bases, adenine (A), guanine (G), cytosine (C), and thymine (T), form the four letters in the alphabet

of the genetic code. The pairing of the four bases is A with

T and G with C. The sequence of the bases along the sugarphosphate backbone encodes the genetic information.

of a group of individuals has altered over time. In

general, current techniques are not exposurespecific, but serve merely as an indicator of recent

exposure.

Genetic monitoring could be performed on groups

of employees to identify the risk for the exposed

group as a whole, to target work areas for increased

safety and health precautions, and to indicate a need

to lower exposure levels for a group exposed to a

previously unknown hazard.
Chapter I-Summary, Policy Issues, and Options for Congressional Action ● 5

What is Genetic Screening?

Genetic screening involves assays to examine the

genetic makeup of employees or job applicants for

certain inherited characteristics. (Employees could

be screened on different occasions for different traits

or with improved technology, but generally only

once per characteristic.) Genetic screening can be

used in two distinct ways. First, employees or job

applicants could be screened for the presence of

genetically determined traits that render them susceptible to a pathological effect if exposed to

specific agents. For example, an employee or a job

applicant could be tested to identify a genetic

predisposition to an occupationally related disease.

Second, employees or job applicants could be

screened to detect general heritable conditions, not

just conditions associated with occupational illness.

Reasons for using the different classes of tests vary.

In either case, whether screening for an occupationally related trait or one unrelated to job exposure,

genetic screening tests involve examinations for

inherited traits where a single measure is usually

sufficient because these inherited characteristics, as

a rule, do not change.

Genetic screening for occupationally related traits

could be performed to ensure appropriate worksite

placement of employees susceptible to certain occupational diseases, and ensure that employers place

those workers most susceptible to a specific risk in

the least hazardous environments. Both genetic

screening for occupationally related traits and for

nonoccupationally related traits could be performed

to: improve employee productivity and lower workers’ compensation costs through better worker

health; promote and encourage general health

awareness; and improve employers’ health care

cost-containment efforts, especially for health insurance. This could be done through exclusion (i.e., not

hiring those with deleterious genes because of the

potential drain on health insurance).

Genetic screening differs significantly from

genetic monitoring. With screening, a one-time

test to detect a single trait in a worker or job

applicant is usually sufficient, while monitoring

generally involves multiple tests of a worker over

time. Most importantly, genetic screening focuses

on the preexisting genetic makeup that workers

or job applicants bring to the job. This is distinct

from genetic monitoring which focuses on hazardous workplace exposures that induce changes

in the genetic material in an exposed population

as a whole.

DIFFERENCES BETWEEN

GENETIC MONITORING AND

SCREENING

From a policy standpoint, these differences—

genetic monitoring v. genetic screening and occupational illness v. nonoccupational illness or general

health--could be significant. Some criticize all

types of genetic monitoring and screening in the

workplace as paternalistic and discriminatory, while

others advocate that, properly implemented, genetic

monitoring and screening programs benefit both

workers and industry. Others, however, maintain

that it is one thing to monitor or screen workers

because they are at increased risk for occupational

illness induced by the workplace, but quite another

to screen persons because they or their offspring—

who could be covered on an employee’s health

plan—are at high risk for a disease unrelated to

occupational exposure. Finally, some argue that

genetic screening per se, even if to reduce occupational illness, is unfair because it a priori measures

heritable conditions beyond an individual’s control.

Genetic monitoring is perceived by others as less

threatening because it mirrors other forms of successful biological monitoring (e.g., benzene or lead

exposure) performed on body fluids or tissue samples. The use of either technology, however, raises

serious legal and ethical questions.

Screening for nonoccupationally related diseases-e. g., Huntington’s disease or neurofibromatosis—raises new issues for containing health care

expenses, for both the employer and employee.

Increasingly, costs to U.S. employers of healthrelated benefits have skyrocketed. In particular, to

avoid rising health care costs, many large companies

are adopting self-insurance plans, which are not

subject to State insurance regulation. Self-insurance

refers to the practice of employers, particularly large

employers, assuming the risks for the health care

expenses of their employees instead of purchasing

health insurance through insurance companies.

Companies concerned about health insurance costs

could be interested in screening workers and job

applicants who are likely to develop genetically

based diseases and could impose high costs on a

company’s self-insured health program. Similarly,

companies could engage in genetic monitoring—
6 ● Genetic Monitoring and Screening in the Workplace

again, to safeguard workers’ health while simultaneously reducing the burden of occupational illness

on their health care costs. Corporate “wellness”

programs, or other company-sponsored health promotion programs (box l-A) that emphasize prevention and encourage employees to adopt healthier

lifestyles, are one way companies can limit their

health care expenses.

In addition to the obvious and significant benefits

from preventing serious illnesses, genetic monitoring and screening for occupationally related disease

could provide indirect benefits, such as a reduction

in the costs associated with occupational illnesses

for employees and their families, employers, the

insurance industry, and society. Workplace health

risks can produce financial costs to the worker in the

form of medical bills, changes in insurance status,

lost wages, ill health, and, in some cases, premature

death. When a worker incurs an occupational illness,

the employer experiences lower productivity levels,

higher insurance premiums, workers’ compensation

claims, and potential lawsuits. Insurance companies

either sustain a loss or raise others’ premiums. And,

society pays for the care and compensation of some

with occupational illnesses through Federal health

programs. The magnitude and distribution among

the sectors of society of the benefits and costs of

genetic monitoring and screening will help determine the desirability of this approach to improving

occupational health.

HISTORY OF GENETIC

MONITORING AND SCREENING

The concept of genetic monitoring and screening

surfaced before the discovery of DNA by Watson

and Crick in 1953. As early as 1938, noted geneticist

J.B.S. Haldane introduced the idea of sorting workers according to their susceptibilities. One of the first

cases of an individual’s genetic condition reacting to

either a chemical agent or drug was reported in the

1950s, when some American soldiers in Korea

experienced hemolysis (the destruction of red blood

cells). The hemolysis was attributed to their carrier

status of glucose-6-phosphate dehydrogenase (G-6-

PD) deficiency, which results in less of the enzyme

G-6-PD in their red blood cells. It was later

postulated that carriers of G-6-PD deficiency could

also undergo hemolysis after exposure to certain

chemicals. The possibility of conducting a preplacement examination to detect employees with the trait

was considered.

In the 1970s, there was considerable public

interest in nonoccupational screening programs for

sickle cell anemia. These programs became the

focus of controversy and criticism because proper

genetic counseling was not always provided, and

results were not always kept confidential. As a

result, discrimination sometimes occurred in the

workplace, and from insurance companies. (Federal

and State legislation in this area is discussed in a

later section.)

Incidents of industry involvement in genetic

monitoring or screening since the 1960s have been

reported. They have varied from research programs

using genetic monitoring techniques for evaluating

chromosomal damage to efforts in genetic screening

to detect conditions such as G-6-PD deficiency or

sickle cell trait.

GENETIC MONITORING AND

SCREENING IN THE

WORKPLACE: A HISTORY OF

CONGRESSIONAL CONCERN

Congressional interest in human genetics, genetic

diseases, and genetic technologies is not new. In

1972, Congress passed the National Sickle Cell

Anemia Control Act (Public Law 92-294), amending it 4 years later to the National Sickle Cell

Anemia, Cooley’s Anemia, Tay-Sachs, and Genetic

Diseases Act (Public Law 94-278). The goals of both

pieces of legislation included increased levels of

basic and applied research, training, testing, counseling, and public education in the area of screening

for sickle cell anemia and other genetic diseases.

More recently, congressional interest in human

genetics has focused on the mapping and sequencing

of the human genome.

The 1983 Office of Technology Assessment

Report

In the late 1970s and early 1980s, reports surfacing about genetic monitoring and screening in

occupational settings captured the interest of Congress. Concern about scientific and social issues of

such testing prompted the House Committee on

Science and Technology to hold hearings and

request an OTA assessment of The Role of Genetic

Testing in the Prevention of Occupational Disease.
Chapter l--Summary, Policy Issues, and Options for Congressional Action . 7

Box 1-A+ancer Detection in the Workplace

Among the greatest fears of industrial workers is the risk of cancer from exposure to hazardous

substances. Although employees are concerned about cancer risk, they are not always informed about the

specific dangers of the chemicals with which they work. By increasing employee and employer involvement

m cancer prevention and detection, both groups stand to benefit: employees with gains m personal health, and

employers with higher worker morale and productivity and reduced health expenditures. Because cancer risks

vary from worksite to worksite, worker perceptions of various job hazards related to cancer and chemical

exposure are important. From 1978 through 1987, the National Cancer Institute (NCI) allocated $14 million

to the Occupational Safety and Health Administration (CM-IA) for cancer prevention training and education

of workers. In 1983, NCI awarded grants to five unions, that had participated in OSHA’s education program,

to evaluate the impact of the unions’ cancer prevention and education programs.

A 1987 study by the International United Rubber, Cork, Linoleum, and Plastic Workers of America, one

of the participating unions, questioned approximately 24,000 of its members about their knowledge of

chemical hazards, the location of engineering controls, and the usc of daily safety procedures. Prior to the

study, employees had participated in the industry’s cancer control program, which included worker education.

Despite the fact that over 10,000 different chemicals, many hazardous, are used by these workers, the

study found that 22 percent of workers were not sure whether they worked with dangerous chemicals, and

only 6 percent felt they were very informed about chemical hazards. Percentages of employees saying they

were well-informed varied widely from company to company, ranging from 16 percent at one company to

32 percent at another. Thus, for adequate cancer education, greater understanding of chemical-specific risks

is needed.

In addition to worker perception and involvement, management health programs can play an important

role. Currently, several companies offer employees cancer screening clinics and other cancer detection

programs. One such program, offered by Pennzoil (in conjunction with the Kelsey -Seybold Foundation) to

employees at a Texas facility, began in 1984 as a cancer awareness clinic for white-collar employees to

discover cancers unrelated to worksite exposure. The Pennzoil program, strictly voluntary and confidential,

has since been expanded to industrial petroleum workers and other locations in 22 States, where the cancer

detection procedure can include workplace risks.

The Pennzoil program involves an initial lecture on cancer risk and detection, and a personal cancer

examination for those requesting one. Corporate management strongly supports these meetings, and

encourages employees to attend the lectures. As part of the program, employees also complete questionnaires

about cancer risk behaviors and personal medical histories. Those employees showing an increased risk of

cancer are offered followup counseling sessions with Kelsey-Seybold Foundation Cancer Prevention Center

physicians and medical tests, if necessary, paid for by Pennzoil. AU employees also are offered yearly

screening or followup examinations. Pennzoil receives only summary data on participation, cancer detection,

and demographic information. Both increased employee morale and detection of potential tumors resulted

Along with Pennzoil's expansion of the program, Exxon Chemical Americas has undertaken a similar project

with the Kelsey-Seybold Foundation Cancer Prevention Center.

The experience of cancer screening in the workplace suggests that the cooperation of corporate

management and private organizations, together with an accurate assessment of employee understanding of

workplace risk can create a healthier, more productive working environment; one benefiting both employer

and employee. At present, genetic monitoring detects genetic changes that could result in greater risk of

cancer. Future advances in genetic technologies could result in increased cancer testing and education at

worksites. As genetic technologies make detection of cancer or other health risks more accurate, programs

such as those just described could seine as models. For genetic monitoring and screening in particular,

implementing successful worker education will be crucial.

SOURCES: Office of Technology Assessment, 1990, based on M. Minkoff, Keky-Seybold Foundation Cancer Prevention Center,

Houston, TX, personal communication, October 1988; A.P. Schenck, A.D. Kaluzny, G.M. Hochbaum, et al., “Worker

Perceptions and Actions Toward Cancer Control in the Workplace: An Analysis of Baseline Data, ” and L.. Zimmerman, G. G.

Jackson, J. Hughes, et al., ‘‘Cancer Education and Screening in the Workplace: The Corporate Perspective, Advances in

Cancer Control: The War on Cancer--l5 Years of Progress, P.F. Engstrom, L.E. Mortenson, and P.N. Anderson (eds.) (New

York, NY: Alan R. Liss, Inc., 1987).
8 ● Genetic Monitoring and Screening in the Workplace

As part of its study, OTA surveyed American

industry and unions to determine the extent and

nature of employer genetic monitoring and screening (the 1982 OTA survey results are compared to

the 1989 survey results in a later section).

In the intervening years, several developments

have led to renewed congressional interest in assessing the current extent of and issues surrounding

genetic monitoring and screening in the workplace.

Understanding of human molecular genetics and

biotechnologies applicable to the field have expanded enormously. Both the technical capability to

detect genetically based disorders and the number of

applications of such technologies have increased.

Finally, the use of other types of employee testing

(e.g., acquired immunodeficiency syndrome

(AIDS), drug, and polygraph) as well as the current

efforts to map the human genome, also combined to

stimulate congressional interest.

Impacts of the Human Genome Project

Efforts underway to map and sequence the human

genome stand to have a significant impact on many

aspects of biology, medicine, and health-including

genetic monitoring and screening. To date, genome

projects have accelerated the production of new

technologies, research tools, and basic knowledge.

At current or perhaps increased levels of effort, they

may eventually make possible the control of many

human diseases-first through more effective methods of predicting or detecting disease, and ultimately, in some cases, through development of

effective therapies based on improved understanding of disease mechanisms. Although not a direct

result of the genome project, advances in human

genetics and molecular biology have already provided insight into the origins of such diseases as

cystic fibrosis, hemophilia, sickle cell disease, and

hypercholesterolemia.

The new technologies developed through human

genome projects research will also be used to assess

public health needs. Techniques for rapidly sequencing DNA, for example, may facilitate the detection

of mutations following exposure to radiation or

environmental agents. Susceptibilities to environmental and workplace toxicants might be identified

as more detailed genetic linkage maps are developed. In addition, special methods of surveillance

could be used to monitor individuals at risk.

However, possible applications of and access to

these genetic data pose profound ethical questions.

The complexity and urgency of these issues will

increase in proportion to advances in mapping and

sequencing. The human genome project will certainly accelerate diagnostic applications. Progress to

date indicates that the ability to diagnose a genetic

abnormality precedes the development of therapeutic interventions and that this gap may be growing.

Access to this information by third-parties (e.g.,

insurance companies or employers) and how this

information is used are important related issues.

These questions are complex and are unlikely to be

resolved in the near future. As a means to explore

these issues a working group on ethics was established in January 1989 by the Program Advisory

Committee on the Human Genome. Additionally, a

percentage of the Federal genome budget will go

toward studying the ethical issues associated with

the genome research.

THE STATE-OF-THE-ART

In 1983, OTA found that none of the genetic tests

evaluated met established scientific criteria for

routine use in an occupational setting. However,

OTA determined that enough suggestive evidence

existed to merit further research. Since that time,

rapid progress in both human molecular genetics and

occupational medicine has increased understanding

of causal relationships between disease and environmental factors, including workplace exposure to a

variety of substances. This report reexamines the

technologies available and evaluated by OTA in

1983 in light of new developments and knowledge

in this area. In addition, this report more thoroughly

evaluates the area of genetic screening for nonoccupationally related traits and diseases. Finally, it also

examines novel techniques (e.g., restriction fragment length polymorphisms (RFLPs)) and tests

(e.g., Huntington’s disease).

Genetic Monitoring Technologies

Genetic monitoring ascertains whether an individual’s genetic material has altered over time.

Workplace genetic monitoring is designed to detect

the effects of a toxic substance or its byproducts, and

to evaluate the genetic damage caused by such a

substance. The objective of these techniques, ultimately, is to predict risk of disease due to genetic

damage. When hazards are identified via genetic

monitoring, prevention programs can be considered
Chapter I-Summary, Policy Issues, and Options for Congressional Action . 9

that will reduce exposures to hazards. This is of

particular concern for certain occupational groups

that are exposed to such hazardous substances over

many years at much higher concentrations than the

general population.

It is well-documented that exposure to some

chemical substances and to radiation at high doses

causes cancer and genetic mutations (changes in

genetic information). Not all mutations, however,

cause disease (figure 1-4). The relationships between genes, mutations, and disease are becoming

clearer with the development of molecular techniques. However, until the health effects of radiation and chemical exposures are better understood, genetic and biological monitoring of exposed populations can only provide a gross

indication that genetic changes have occurred

and that adverse health effects could follow.

Changes in a cell’s genetic material (DNA) can be

detected at either the chromosomal level, using

cytogenetic methods which detect major structural

changes in chromosomes, or at the molecular level

using noncytogenetic methods.

The application of cytogenetic tests to measure

chromosomal damage is based on the concept that

Figure 1-4-Biological Consequences of Exposure to

Mutagenic Agents

Genetic

damage

Repair Cell death

Mutation I

Germ cells Somatic cells

Heritable

disorder

Reproductive

loss

Cancer

Somatic cell

change

Immediate

effects of

exposure

Delayed

 adverse

health

outcomes

SOURCE: office of Technology Assessment, adapted from Ward,

‘Issues in Monitoring Population Exposures,” 

Mutagens in the Environment Volume //, The Workplace, Hans

F. (cd.) Raton, FL: CRC Press, 19S5).

Photo credit: U.S. Council for Energy Awareness

A Nuclear Power Worker: Controversy continues regarding

the carcinogenic effects of radiation in employees of the

nuclear weapons and nuclear power industries.

damage to cells’ genetic material represents initial

events in a process that may eventually lead to

disease. Cytogenetic methods can detect human

exposures at biologically significant levels in populations, but the interpretation of findings for the

individual remain uncertain. In some cases, detectable mutations result from gross changes in chromosome structure and can be visualized under the

microscope. The disruptive effects of mutagens on

chromosome structure, organization, and behavior

have long been studied by geneticists. However, the

connections between chromosomal damage and

disease are unclear except in a small number of

cancer cases. Most analysts agree that interpretation of cytogenetic results at the individual level

is questionable and recommend that until the

relationship between cytogenetic damage and

disease is better understood, interpretation

should be limited to the population level. In

addition, cytogenetic monitoring of human populations is expensive and time-consuming. There can

also be technical variations associated with both test

limitations and interpretations.

Until recently, most tests for mutagenicity have

been merely indicators of exposure, only providing

evidence that exposure has occurred. This limitation

is diminishing with the development of more techniques at the molecular level, thus refining the

ability to document exposure and, in some cases,

providing qualitative information. New molecular

assays of mutagenicity, e.g., hypoxanthine-guanine

phosphoribosyltransferase and oncogene protein

detection, are providing greater specificity and will
10 ● Genetic Monitoring and Screening in the Workplace

augment tests already in use, e.g., the Ames test.

New methods may provide better estimates of the

health effects of low doses of some mutagens, as

well as providing qualitative data on the nature of

mutation. Detecting activated oncogenes and DNA

adducts has the potential of predicting disease in

asymptomatic individuals. As the nature of mutation

becomes more clearly defined, the connection between mutation and disease will also become better

understood.

A genetic monitoring or screening test must be

proved valid and reliable before a decision can be

made on its value. Validity is the probability that a

test will correctly classify true “positive” and true

‘‘negative’ results. Tests of the same specimen

must repeatedly give the same result whether

performed by several different laboratories or by the

same laboratory on several occasions to be reliable.

If the tests are valid and reliable, establishing

procedural safeguards and designing wellconceptualized test protocols can avert erroneous

and misleading conclusions. The use of genetic

monitoring methods in epidemiologic studies will

continue to be plagued by problems associated with

classical approaches to determining hazardous exposures in the workplace. Eliminating biases, obtaining controls, and keeping good records are procedural difficulties that may be encountered. The

employment of more specific and sensitive tests,

rather than the reliance on any one test for valid and

reliable results, will lead us closer to understanding

the relationships between exposure, mutation, and

disease.

Genetic Screening Technologies

It has long been speculated that genetically

determined variation in susceptibility may predispose some workers to occupational disease while

others in the same environment seem to be unaffected. Genetic influences may be exaggerated or

diminished by one’s age, diet, or overall health

status. Recognition of genetic factors in disease

(both occupationally and nonoccupationally related

disease) presents new opportunities for detection,

prevention, and treatment.

In assessing the state-of-the-art in screening tests

for use at worksites, three different questions must

be discussed:

● What general techniques are presently available that could be used for genetic screening?

. What is known about the association among

heritable traits, exposure to hazardous materials, and subsequent occupational illness?

. What genetic disorders unrelated to job exposures that are important to general health can be

detected?

Since the 1983 OTA report, there have been

several technical advances in genetic screening tests.

In addition, several new susceptibilities to occupational disease have been identified, and progress in

detecting some nonoccupationally related disorders

has been made. These nonoccupationally related

disorders, which are likely to affect large populations, might be of interest to an employer if they can

be detected through preemployment screening.

Biochemical and molecular techniques for detecting genetic disease are discussed in this report.

Biochemical genetics refers to the analysis of mutant

genes on the basis of altered proteins or metabolizes.

If diagnosed, some of these “inborn errors of

metabolism” can be treated with enzyme replacement or dietary control. An example of such a

biochemical disorder is phenylketonuria, which can

be controlled by restricting dietary intake of the

amino acid phenylalanine. In general, biochemical

techniques for diagnosing genetic disease are often

restricted to indirect analysis of gene products rather

than diagnosis targeted at the gene itself.

Advances in DNA technology have greatly enhanced our ability to directly examine the genetic

basis for disease and to predict and diagnose such

diseases in larger populations. Until recently, most

available tests for genetic conditions were not based

on recombinant DNA techniques. Today, DNAbased tests encompass a variety of standard diagnostic techniques that allow examination of regions

very near the genes (e.g., Huntington’s disease) or

direct examination of the genes themselves (e.g.,

sickle cell anemia and cystic fibrosis).

Two important tools, RFLPs, which serve as

markers for the presence of a diseased gene, and

cloned DNA probes, represent the major advances

responsible for improved diagnosis of genetic disease (figure 1-5). Another technology, polymerase

chain reaction (PCR) has also facilitated the ability

to detect genetic disorders. PCR can be thought of as

molecular photocopying (figure 1-6). PCR itself is

not used directly to analyze DNA, but allows a

scientist to take a sample that ordinarily would be

insufficient to detect the characteristics of the DNA,
Chapter 1--Summary, Policy Issues, and Options for Congressional Action . 11

Figure 1-5-Detection of Restriction Fragment

Length Polymorphisms Using Radioactively

Labeled DNA Probes

Genomic DNA From Three Blood Samples

A

The obstacles to understanding associations between predisposition and disease are slowly eroding

as the use of synthetic probes, PCR, and automated

DNA-sequencing machines increase the efficiency

and lower the cost of mass screening. However,

before widespread screening of populations is

begun, the validity of the tests should be determined.

Also, quality control is likely to become a major

issue as the volume of tests performed at laboratories

grows. These are already issues in forensic applications of DNA-based tests.

At present, there are approximately 50 diseases

‘/. y / that have the potential to enhance an individual’s

I

Agorose Gel Electrophesis

Gel

Denature DNA

 Transfer to Nylon

 Membrane

ylon Membrane

 A&l Radioactively Labeled

 DNA to Nylon Membrane for

 Hybridization

 Expose on X-Ray Film

 For Autoradiography

Film

Variations in DNA sequences at particular marker sites are

observed as differences in numbers and sizes of DNA fragments

among samples taken from different individuals (shown here as

samples A, B, and C).

SOURCE: Office of Assessment, 1990.

and reproduce it until enough DNA copies are

available for examination by a number of technologies, including RFLP analysis. Chapter 5 discusses

RFLP analysis and PCR in greater detail.

susceptibility to the toxic or carcinogenic effects of

environmental agents. These occupationally related

diseases include: G-6-PD deficiency, sickle cell

trait, and the thalassemias (see table 1-1 for more

examples).

Molecular biology has enhanced the traditional

determination of “predisposition to disease’ (previously based on physical examination, family history,

and lifestyle habits) by seeking out and finding

genes or markers associated with disease. Individuals found to have the gene or the marker can then be

identified, sometimes with near certainty, to be

candidates for disease. Often, predisposition only

manifests in disease when there is an accompanying

environmental insult, e.g. toxic substances, viruses,

or other disease. The influence of the environment,

however, remains the wild card in most cases,

because possession of the genetic predisposition

alone may be insufficient to cause disease. It is

likely that for some time modern science will be

more successful in identifying the genes and the

markers than in identifying the environmental

agent(s) necessary for activation of the predisposing genes.

Predispositions to certain cancers have been the

focus of much research in the past few years. As the

associations between carcinogenesis and genetics

become clearer, the boundaries between occupational and genetic disease may become more

blurred. (Box 1-B describes some of the connections

between genetic damage and cancer.) Research on

the predispositions to atherosclerosis, diabetes,

mental illness, and chemical addiction has also

progressed in recent years. In addition, research is

providing insight into possible genetic predispositions to such common ailments as lower back

injuries, obesity, allergies, and arthritis. While
12 ● Genetic Monitoring and Screening in the Workplace

Figure 1-6-The Polymerase Chain Reaction

Individual A Individual B Unknown C

AMPLIFICATION

(Molecular Photocopying of DNA)

Each sample is amplified

manually or in a machine.

Original DNA Sample

 ----- ._ Denature and Synthesize

-/- - --- - - -\-Denature and Synthesize

 - - - - 7 and 

Multiple copies of DNA Sample

(20-25 cycles of the PCR yields about

one million-fold reproduction)

DOT BLOT

Membrane

The amplified DNA is

spotted onto a membrane

The membrane is

challenged with a DNA

probe that has a key

sequence specific to an

HLA DQ-Alpha Allele.

in a color developer

There are 21 different types

at HLA DQ Alpha Locus

(most frequent is 1 in 5,

least 1 in 800).

SOURCE: Office of Assessment, 1990.

predictive tests are not immediately foreseeable in

any of those areas, as more populations are studied

and more linkage maps prepared, it is possible that

screening tests will be developed.

With accelerating interest in tests to detect abroad

range of genetic disorders and increasing investment

in biotechnology industries, the market demand for

tests, especially DNA-probe tests, is expected to

expand. While the population affected by genetic

conditions for which tests are available is still

somewhat small, the potential future test population

for multifactorial diseases is enormous (see table

1-2).

WHAT LEGAL CONSIDERATIONS

ARE INVOLVED?

Existing legal concepts must strain to keep pace

with the scientific advances of genetic monitoring

and screening. Only a limited body of law dealing

directly with genetic monitoring and screening in the

workplace exists. There is, however, a substantial

body of law pertaining to the related practice of

medical testing of workers, which may influence the

legal issues associated with genetic monitoring and

screening in the workplace.

Because an individual’s genetic makeup is not

chosen, legal questions of the most sensitive sort are

raised in seeking to analyze these personal characteristics. Genetic monitoring and screening raise

legal questions related to workplace safety and

employee rights. Among the fundamental legal

issues arising from genetic monitoring and screening in the workplace are:

. privacy from unwanted monitoring or screening;

. confidentiality of the information obtained;

. potential discrimination in employment opportunities; and

. ultimately, the health of the subject.

OTA examined common and statutory law—both

of which have a bearing on genetic monitoring and

screening in the workplace. Changes in the common

law relating to workplace genetic monitoring and

screening have been incremental over recent years.

An increasing body of case law is developing,

however, over employer screening for drug use and

AIDS.
Chapter 1--Summary, Policy Issues, and Options for Congressional Action ● 13

Table I-l-Identification and Quantification of Genetic Factors Affecting Susceptibility to Environmental Agents

Environmental agents to which group

High-risk groups Estimated occurrence is (may be) at increased risk

RBC conditions

G-6-PD deficiency . . . . . . . . . . . .

Sickle cell trait . . . . . . . . . . . . . . . . .

The thalassemias . . . . . . . . . . . . . .

NADH dehydrogenase deficiency

(MetHb reductase deficiency) . . . .

Catalase Hypocatalasemia . . . . . . .

Acatalasemia . . . . . . . . . . . . . . . . . .

Low SOD activity. . . . . . . . . . . . . . .

ALA dehydratase deficiency . . . . . .

Hb M . . . . . . . . . . . . . . . . . . . . . . . .

Erythrocyte potphyria . . . . . . . . . .

GHS-Px deficiency . . . . . . . . . . . . .

GSH deficiency . . . . . . . . . . . . . . . .

Liver metabolism

Defect in gluocuronidation

Gilbert’s syndrome . . . . . . . . .

Crigler-Najjar syndrome . . . . .

Defect in sulfation . . . . . . . . . . . .

Acetylation phenotype, slow v.

fast . . . . . . . . . . . . . . . . . . . . . .

Gout . . . . . . . . . . . . . . . . . . . . . . .

Oxidation center defects . . . . . . . . .

OCT deficiency . . . . . . . . . . . . . . . .

Paraxonase variant . . . . . . . . . . . . .

Rhodanese variant . . . . . . . . . . . . .

Sulfite oxidase deficiency

heterozygotes . . . . . . . . . . . . . . . . .

Inadequate carbon disulfide

metabolism . . . . . . . . . . . . . . . . .

Alcohol dehydrogenase variant. . . .

Wilson’s disease . . . . . . . . . . . . . . .

Serum variants

Albumin variants . . . . . . . . . . . . .

Pseudocholinesterase

variants . . . . . . . . . . . . . . . . . .

American Black males 16%; Mediterranean

Jewish males 119’.; Greeks 17.-2%; Sardinians 1%-8% 

7Y0-13Y0 of American Blacks are heterozygotes

Alpha: 4%-5% in Americans of Italian and

Greek descent; Beta: 2%-7% American

Blacks and 2%-3% American Greeks

Estimated 1% of population are heterozygotes

About 2% of U.S. population based on Swiss

gene frequency

1/10,000-20,000 of U.S. population based on

Swiss gene frequency

Frequency of genetic variants in population 1 to

2/10,000; normal population exhibits unimodal distribution; persons at low end of distribution may beat increased risk

Unknown, but thought to be rare

Unknown, but rare

1.5/100,000 in Sweden, Denmark, Ireland,

West Australia; 3/1 ,000 in South African

Whites; rare in Blacks

Rare

Rare

6% of normal, healthy adult population

Few persons live to adulthood

Unknown

Slow: 50% Whites; 50% Blacks; 10% Japanese

Fast: 50% Whites; 50% Blacks; 90% Japanese

0.27%-0 .3%. prevalence in U.S. and Europe

9% of British Whites; 8% of Nigerians; 6%

Ghanians; 1%. Saudi and Egyptians are poor

oxidizers

Unknown, but thought to be rare

25%-30% of population

Unknown

Unknown

Upward Of 30%-40%

5%. English; 20% Swiss; 70% Japanese

Homozygous 1/100,000 while the heterozygote

may approach 1/500

Less than 1/1 ,000 in Europeans, much higher

frequency in North American and Mexican

Indians

Highly sensitive homozygous and heterozygous persons of European ancestry have combined frequency of about 1/1,250; moderately

sensitive genotypic variants of European ancestry have frequency of 1/1 5,000

Environmental oxidants such as ozone, nitrogen dioxide, and chlorite

Aromatic amino and nitro compounds; carbon monoxiode, cyanide

Lead; benzene

MetHb-forming substances

Ozone; radiation

Wide variety of environmental oxidants; paraquat;

radiation; ozone

Lead

Carbon monoxide

Chloroquine; hexacholorobenzene; lead; various

drugs, including barbiturates, sulfonamides, others

Environmental oxidants

Environmental oxidants

Wide variety of xenobiotics including polychlorinated

biphenyls

Wide variety of xenobiotics; best association is with

tyramine-containing foods

Aromatic amine-induced cancer; numerous drugs,

e.g., isoniazid and hepatitis

Lead

Numerous xenobiotics requiring oxidative metabolism

for detoxification

Insect repellant (DET)

Parathion

Cyanide

Sulfite, bisulfite, sulfur dioxide

Carbon disulfide

Metabolize (e.g., ethanol) more quickly than normal

Cooper, vanadium

Unknown

Organophosphate and carbamate insecticides; muscle

relaxant drugs
14 ● Genetic Monitoring and screening in the Workplace

Box 1-B--Genetics and Cancer

Cancer is a genetic disease arising from genetic damage of diverse sorts—recessive and dominant mutations,

large rearrangements of DNA and point mutations--all leading to distortions of either the expression or

biochemical function of genes. The growing field of cancer genetics aims to uncover the genetic alterations

responsible for uncontrolled growth of cancer cells. Many types of human cancer occur in familial as well as

sporadic forms. Discrete genetic changes have been associated with different types of neoplasm, and are thought

to initiate or cause progression of cancer. Chromosome studies in more than 10,000 cases of neoplasm have

reported specific anomalies. The identification of genetic changes, therefore, presents the major diagnostic

challenge in cancer.

Both dominant and recessive forms of cancer have been found. The genetics of the common cancers--breast,

colon, and lung-are beginning to fit a pattern, Approximately 5 percent of cancer cases constitute a hereditary

cancer syndrome in which a dominant gene predisposes to cancers of the breast, ovary, brain, gastrointestinal

system, and white blood cell precursors. These are referred to as “cancer families’ (see ch. 5 for further discussion).

Apart from these, each type of cancer appears to have a small group of cases that fits the pattern of a major

predisposing gene and a much larger group that seems to be largely environmenta1 in origin.

In addition, examples such as xeroderma pigmentosa imply that there is a connection between susceptibility

to cancer and impaired ability of cells to repair damaged DNA. It is a reasonable expectation that if cancer is related

to alterations in somatic cell genes, then the rate at which those changes occur could serve as a barometer of changes

in the gem-dine that may not be expressed for many generations to come.

Certain cancers, e.g., lung, laryngeal, bladder, and testicular, have repeatedly been linked to environmental

exposures. The effects on chromosomes of such chemicals as arsenic, asbestos, chromium, nickel, and vinyl

chloride are well-documented. Substances that cause chromosomal abnormalities are called ‘‘clastogens. The

reader is referred to the 1983 Office of Technology Assessment report for more detail on the specific effects of those

agents. Chapter 5 describes recent advances in detecting predisposition to some common cancers.

SOURCES: Office of Technology Assessment, 1990, based on J.M. Bishop, “The Molecular Genetics of Cancer, ” Science 235:305-311, 1987;

F. Mitelman and J.D. Rowley, “Genes, Chromosomes and Cancer: A New Forum for Research in Cancer Genetics,” Genes,

Chromosomes & Cancer 1:1-2, 1989; J.J. Nora and F.C. Fraser, Medical Genetics: Principles and Practice (Philadelphia, PA: Lea

& Febiger, 1989); R. Parshad, K.K. Sanford, K.H. Kraemer, et al., ‘ ‘Carrier Detection in Xeroderma Pigmentosum," The Journal

of Clinical Investigation 85: 135-138, 1990; U.S. Congress, Office of Technology Assessment,The Role of Genetic Testing in the

Prevention of Occupational Disease, OTA-BA- 194 (Washington, DC: U.S. Government Printing office, April 1983).

Of particular interest in terms of common law grown to cover different grounds for dismissal, they

developments is the apparent continuing expansion

of the public policy exception to the employment

at-will doctrine for dismissal from employment.

This rule forms the basis for most employment

relationships, absent an explicit contract between

the parties, and gives the employer virtually unlimited authority to terminate the employment relationship at any time. It includes the right to refuse to

hire an individual because of a perceived physical

inability to perform the job and the right to terminate

employment because of a belief that the employee is

no longer able to perform adequately. With respect

to genetic monitoring and screening, this would

allow an employer to use either in any way,

including personnel decisions. Even if test results

were inaccurate or unreliable, the employer would

be protected in basing employment actions on them.

In recent years, however, courts have begun to erode

the scope of the at-will doctrine by creating exceptions. While exceptions to employment-at-will have

have not been applied to other kinds of employment

actions. This trend may also play an important role

in forming judicial attitudes toward employment

decisions based on genetic monitoring and screening

results.

Beyond the role of occupational health and safety

regulation, common law decisions regarding confidentiality and privacy are relevant to genetic monitoring and screening in the workplace. An area of

concern is the role of the occupational health

physician in genetic monitoring and screening.

Because the occupational health physician is hired

by the employer, there can be some question whether

legal precedents protecting confidentiality in the

physician-patient relationship apply, Occupational

health physicians must balance patient privacy and

confidentiality on the one hand with employer

need-to-know on the other.
Chapter I-Summary, Policy Issues, and Options for Congressional Action ● 15

Table 1-2—Genetic Tests Available and Total

Americans Affected

Genetic condition Total cases

Currently available:

Adult polycystic kidney disease . . . . . . .

Fragile X Syndrome . . . . . . . . . . . . . . . . .

Sickle cell anemia . . . . . . . . . . . . . . . . . .

Duchenne muscular dystrophy . . . . . . . .

Cystic fibrosis . . . . . . . . . . . . . . . . . . . . .

Huntington’s disease . . . . . . . . . . . . . . . .

Hemophilia . . . . . . . . . . . . . . . . . . . . . . . .

Phenylketonuria . . . . . . . . . . . . . . . . . . . .

Retinoblastoma . . . . . . . . . . . . . . . . . . . .

Total . . . . . . . . . . . . . . . . . . . . . . . . . . .

Potential future tests:

Hypertension . . . . . . . . . . . . . . . . . . . . . .

Dyslexia . . . . . . . . . . . . . . . . . . . . . . . . . .

Atherosclerosis . . . . . . . . . . . . . . . . . . . . .

Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . .

Manic-depressive illness . . . . . . . . . . . . .

Schizophrenia. . . . . . . . . . . . . . . . . . . . . .

Type 1 diabetes . . . . . . . . . . . . . . . . . . . .

Familial Alzheimer’s . . . . . . . . . . . . . . . . .

Multiple sclerosis . . . . . . . . . . . . . . . . . . .

Myotonic muscular dystrophy . . . . . . . . .

Total . . . . . . . . . . . . . . . . . . . . . . . . . . .

500,000

100,000

65,000

32,000

30,000

25,000

20,000

16,000

10,000

798,000

58,000,000

15,000,000

6,700,000

5,000,000

2,000,000

1,500,000

1,000,000

250,000

250,000

100,000

89,800,000

SOURCE: p.58,Apr. ll,1988.

Federal Regulatory Framework

Federal legislation ranging from the Occupational

Safety and Health Act (OSH Act) (Public Law

91-596), the Rehabilitation Act of 1973 (29 U.S.C.

791 et seq.), Title VII of the Civil Rights Act of 1964

(42 U.S.C. 2000e), the National Labor Relations Act

(NLRA) (29U.S.C. 151 et seq.), and the Americans

with Disabilities Act (ADA) (Public Law 101-336)

provide some protections against abuses, particularly those relating to unilateral employer imposition of genetic monitoring and screening, discrimination based on monitoring and screening results,

and breaches of confidentiality concerning results.

The OSH Act contains several federally imposed

statutory duties related to occupational safety and

health that must be carried out by the employer. The

Occupational Safety and Health Administration

(OSHA) has regulated some employer practices that

could have a bearing on genetic monitoring and

screening, including employee access to medical

records and communications about hazards by

employers to employees.

Title VII of the Civil Rights Act of 1964 prohibits

discrimination in employment practices based on

race, color, religion, sex, or national origin. In

Photo credit: Margaret Anderson

U.S. Department of Labor, Washington, DC: Headquarters

of the Occupational Safety and Health Administration.

addition to intentionally discriminatory actions,

neutral employment practices that have a disparate

impact on a protected group may violate Title VII.

A Supreme Court decision, Wards Cove v. Atonio,

recently placed stringent standards on workers

attempting to use statistics to prove discriminatory

employment practices. This decision could make it

more difficult for an employee to prove that an

employer’s employment practices are discriminatory. Many genetic screening procedures (e.g., sickle

cell disease, G-6-PD deficiency) have a disparate

impact that could fall under the protection of Title

VII.

The Rehabilitation Act of 1973 bans discrimination against handicapped individuals by employers

who are government contractors or recipients of

Federal assistance. In order to fall under its protection, an employee must prove that his or her genetic

trait is or is regarded as an impairment, and in

addition, he or she must otherwise be qualified.

Accordingly, an individual with a genetic

predisposition for a disease may not be denied

employment or promotion simply because of the

predisposition so long as the individual is otherwise

qualified for the position. In such a case, the
16 . Genetic Monitoring and Screening in the Workplace

Photo credit: Earl Dotter

The use of protective clothing can help prevent

occupational illness and injury.

employer would have to make reasonable accommodation for the person.

ADA, which was recently signed into law and

whose enforcing regulations have yet to be drafted

and approved, extends a clear and comprehensive

prohibition of discrimination on the basis of disability to the private sector. It bans discrimination

against individuals with disabilities in hiring, discharge, compensation, or any term, condition, or

privilege of employment by an employer engaged in

an industry affecting commerce. By 1994, this

legislation will apply to all employers with 15 or

more employees. Whether a genetic marker or a trait

constitutes an ‘impairment’ under ADA is unclear.

Preemployment medical examinations or inquiries

are to be used only as a tool for determining the

applicant’s ability to do the job. Thus, genetic

screening for nonoccupationally related conditions

would seem to be prohibited. ADA language,

however, does not specifically address genetic

monitoring or screening.

NLRA governs the relationships of employees,

labor organizations (unions), and employers engaged in businesses affecting interstate commerce.

Safety and health matters, including fitness-for-duty

physical examinations and medical testing are considered mandatory subjects of bargaining between

these parties. Thus, genetic monitoring and screening could be considered mandatory subjects of

collective bargaining. In this context however,

preemployment screening of job applicants would

not be covered. Additionally, not all employees are

union members and therefore would not be covered

under collective bargaining agreements.

The protections provided by current Federal

legislation are somewhat disjointed, applying at

times to applicants and at times to workers, or

offering protections of which applicants and workers

may be unaware. The exact role of each will depend

on the nature of the tests that are developed and their

application. While it is clear that many legal tools

presently exist, it is probable that new ones will be

needed as unexpected challenges arise.

On the whole, it appears that Federal regulatory law, as administered by OSHA, is likely to

have the most immediate impact on the use of

genetic monitoring and screening in the

workplace. OSHA has dealt extensively with related

practices of biological monitoring that could forma

ready source of rules for genetic monitoring and

screening. OSHA’s rules on access to medical

records and hazard communication are among the

most directly applicable sources of existing law.

Thus, OSHA is the most appropriate candidate for

regulating in the area of genetic monitoring and

screening in the workplace. It could call on the

National Institute for Occupational Safety and

Health (NIOSH) to provide research and recommendations for regulatory development. However, at this

time the OSH Act neither prohibits nor requires

genetic monitoring or screening.

State Responsibility

States have a role in a variety of areas concerning

genetic monitoring and screening. One of these areas

is workers’ compensation programs which are designed to provide no-fault compensation to workers

suffering harm as a result of their employment. A

particular challenge is posed, however, by diseases

with long latency periods between exposure to a

causative agent and onset of illness. It is the

compensation of such long latency conditions that

presents the most likely opportunity for the application of genetic monitoring and screening. Many

issues concerning genetic monitoring and screening

and workers’ compensation (e.g., the role of genetic
Chapter 1--Summary, Policy Issues, and Options for Congressional Action ● 17

data as evidence and their admissibility, and the

coverage of a susceptible employee) are unresolved.

Some States have directly addressed genetic

discrimination. OTA found in 1983 that four States

had passed statutes limiting the use of genetic

information in employment decisions. In three of

these States—Florida, Louisiana, and North Carolina-the laws are specific to testing for sickle cell

trait. In New Jersey, however, a fairly broad measure

was passed banning employment discrimination

based on genetic traits. If this measure becomes a

model for other jurisdictions, the adverse impact,

and perhaps benefits, of genetic monitoring and

screening results on employees could be severely

curtailed. The New Jersey experience will be interesting to observe as more genetic monitoring and

screening tests become available.

WHAT ETHICAL ISSUES ARE

INVOLVED?

Genetic monitoring and screening involve the

acquisition of personal information in the

workplace. Several important ethical issues arise

when discussing the interests of employees, job

applicants, employers, and society, including the

potential for discrimination. Many of these issues

express the same concerns as current laws: legal and

ethical arguments often share common ground.

Yet, while legal and ethical issues can be similar,

approaches to resolve dilemmas raised differ. Law

does not reflect all moral values held by members of

society, nor can it necessarily be used to resolve

ethical dilemmas. Ethical arguments about the use of

genetic monitoring and screening in the workplace

often address obligations, rights, or values not

explicitly covered by law. Awareness of the ethical

issues surrounding new technology is essential for

formulating and implementing policies that reflect

the greatest possible regard for human values.

Although the ethical issues show little change

since the 1983 OTA study, the emphasis placed on

some concerns about genetic monitoring and screening has shifted. In 1983, OTA found that genetic

monitoring and screening were not inherently unethical, and that if they were used to enhance worker

health in a reamer consistent with ethical principles,

they could be morally justified. Whether the tests

were consistent with ethical principles depended on

how they were done and how the resulting information was used. Since that time, there has been

increased pessimism in public debate about the risks

genetic screening for nonoccupationally related

disease could have for employees’ autonomy and

privacy. Attention has shifted from the uncertain

technical efficacy of genetic monitoring and screening in predicting or identifying illness to the

potential abuses of genetic monitoring and screening

in the workplace.

At least three parties play a role and have an

interest in genetic monitoring and screening in the

workplace--job applicants and workers, employers,

and society. For these parties, three principal issues

exist:

●

●

●

the implementation of genetic monitoring and

screening tests in the workplace and the use of

the information they generate;

the dissemination and storage of information

gained from genetic monitoring and screening;

and

the role of genetic counseling for both employers and employees in genetic monitoring and

screening programs.

Each of these issues is probably viewed differently by job applicants and employees, employers,

and society, since each group has different interests

to protect. In addition, the ethical issues associated

with genetic monitoring and screening in the

workplace vary according to whether the test performed is genetic monitoring for chromosomal

damage, genetic screening for susceptibilities to

occupational illness, or genetic screening for inherited conditions or traits unrelated to the workplace.

Employees and job applicants, for example, want

to protect their autonomy and privacy. They could

feel that all genetic information should remain

confidential under any circumstance, especially if it

might be used to deprive them of a job, health

insurance, or other benefit (box l-C). Employers, in

desiring to preserve their liberty to make their own

hiring decisions, might want to be free to conduct

monitoring or screening programs. They might also

wish to establish the conditions for employee

participation and consequences for those who refuse

to participate. Such practice would be consistent

with current preemployment medical testing practices. Society has an interest in promoting a safe

workplace, and fair treatment of individuals, as well

as economic efficiency.
18 ● Genetic Monitoring and Screening in the workplace

Box 1-C-An International Survey of Attitudes of Medical Geneticists Toward

Workplace Genetic Screening and Access to Results

A survey on mass genetic screening was sent to 1,053 medical geneticists in 18 nations, of whom 677

responded. Geneticists strongly preferred voluntary over mandatory workplace screening,by a 72 percent majority.

In the United States, there was consensus (greater than 75 percent) that screening should be voluntary. Geneticists

who thought screening should be voluntary cited the worker’s autonomy or right to decide (74 percent), and the

danger of stigmatization, discrimination in employment, or misuse of information by institutional third-parties (41

percent). Advocates of mandatory screening cited protecting the individual worker’s health (64 percent), protecting

public health (51 percent), and efficiency or cost-benefit arguments (22 percent). Nine percent of those who

advocated voluntary screening and 12 percent of those who advocated mandatory screening based their responses

in part on concern for economic interests of employers.

In advocating voluntary versus mandatory screening, a clear difference of opinion on whose welfare the

respondent placed foremost was reported. Ninety-seven percent who advocated voluntary screening and 58 percent

who advocated mandatory screening placed the worker’s welfare as most important. Three percent who advocated

voluntary screening and 37 percent who believed in mandatory screening placed societal interests first. Only 1

percent placed the employer’s welfare first.

Advocates of voluntary screening were more likely than supporters of mandatory screening to describe a

conflict of interest between worker and employer, 34 percent described such conflicts, as opposed to 13 percent who

advocated mandatory screening. A majority of both groups, however, described no conflicts.

Ninety-eight percent of respondents said the worker should have access to test results, including 86 percent

who said the worker should be told the results even if he or she did not ask for them. When asked whether the

employer should have access to geneticscreening results, 81 percent said employers should have no access without

the worker’s consent, including 22 percent who believed that employers should have no access at all.

Thirty percent of respondents who gave reasons for their choices about access believed it would be to the

worker’s benefit if the employer had some form of access, e.g., employers could shift susceptible workers to less

dangerous jobs. Only 6 percent of respondents, however, thought that working conditions m general would be

improved. Nineteen percent described potential economic disc rimination, stigmatization, or other misuse of test

results by employers. Ten percent based their responses on the economic interests of the employer.

When asked whether government health departments should have access, 68 percent said there should be no

access without worker consent. There was a strong consensus on this issue in six nations, including the United

states.

These differences in perception indicate that geneticists-those in a position to conduct genetic screening

tests-share concerns about how genetic screening might be used in the workplace. A large majority of geneticists

ranked the interests of workers and society above those of employers in importance, but they disagree about how

those interests can be best protected. Many geneticists believe that workplace screening should be voluntary and

that workers should make autonomous decisions about whether to undergo genetic screening. Almost all geneticists

believed workers should receive genetic screening results, but that employers’ access should be restricted ‘hey

expressed concern that genetic screening results may be used to justify personnel actions that may stigmatize or

discrimina te against some workers.

SOURCE: D.C. Wertz and J.C. Fletcher, “An International Survey of Attitudes of Medical Geneticists Toward Mass Screening and Access to

Results,” Public Health Reports 104(1):35-44, 1989.

A balance must be struck between promoting one Employer and employee interests can conflict at

party’s autonomy and compromising that of another. three points in the processes of genetic monitoring

If employers are free to implement and enforce and screening:

genetic monitoring or screening policies, the auton- ●

omy of job applicants and employees will be limited.

Conversely, giving the applicant or employee com- ●

plete freedom to protect his or her own interests

would restrict the freedom of the employer and, in ●

some instances, present risk to co-workers or family.

the decision to undergo genetic monitoring or

screening;

access to information gained from genetic

monitoring or screening; and

the communication and interpretation of genetic monitoring or screening results.
Chapter 1--Summary, Policy Issues, and Options for Congressional Action . 19

Certain broad guidelines for the use of genetic

monitoring and screening could at least partially

address the concerns of all parties. Such guidelines

could produce maximal benefits to all parties—

minimizing occupational illness without threatening

privacy or confidentiality, denying equality of opportunity, or stigmatizing workers.

GENETIC COUNSELING FOR

INDIVIDUAL USES OF GENETIC

INFORMATION

The effects and results of genetic monitoring or

screening transcend the workplace, and raise issues

for the individual who is tested-not just as a

worker—but as a person and family member. As a

result of new technical capabilities to diagnose and

predict genetically based disease, pathways for

informed decisionmaking about ourselves and our

family’s health have expanded. However, these

capabilities often create moral, ethical, and psychological dilemmas for which no easy solutions

exist. Receiving such personal information in the

workplace setting differs from the way most people

learn about their genetic identity, because the

individual may not have sought to be tested. When

tests are conducted in a medical setting, a context

is provided in which certain assumptions and

expectations can reasonably be held by the

person being tested. These factors might be

different when the workplace becomes the background for receiving genetic information.

For many individuals, even considering whether

to undergo genetic monitoring or screening constitutes a life crisis because of the possible outcomes.

If the results are positive, the crisis obviously is

exacerbated. How the results will affect the individual has much to do with the individual’s own frame

of reference, but also with the implications of the

condition and its prognosis. Psychological issues

permeate every aspect of genetic consultation. In

addition to the intrapsychic consequences of receiving genetic information, there are potential impacts

on family. Genetic information affects not only the

individual, but also the spouse, parents, grandparents, siblings, and children. Social and psychological stress, as well as future financial and

emotional burdens, can strain family functioning. In

addition to coping with their own uncertain future,

individuals may experience guilt or grief if they find

they have unknowingly passed a deleterious trait to

their offspring.

Obviously, the psychological impact of a positive

diagnosis varies with its severity and treatability,

and the fact that different families will react

uniquely to similar situations. Support, counseling,

and followup are likely to assist individuals and their

families in coping with positive test results. The

knowledge and skills of a properly trained counselor

can help the individual understand the diagnosis,

recurrence risk, prognosis, relevant preventive and

therapeutic measures, and also aid in communicating important information to other family members.

However, doubts can be introduced into the lives

of those tested because genetic monitoring and

screening tests often convey a probability, but not a

certainty, that disease will appear. When it is not

possible to give an accurate recurrence risk or more

than a general diagnosis, the interactions between

the test subject and the test administrator are even

more complex. In the case of genetic monitoring,

it is likely that nonspecificity of diagnosis and

prognosis will predominate. Further complicating the use of monitoring and screening tests is

the fact that for most genetic diseases, effective

Photo Diane 

A genetic counselor showing a chromosome chart to a

client. Genetic counseling may assist individuals and

families cope with positive test results.
20 ● Genetic Monitoring and screening in the Workplace

Box 1-D--Huntington’s Disease

Huntington’s disease is a chronic, progressive, degenerative disorder, beginning usually between the ages of

30 and 50 years. It is characterized by uncontrollable, spasmodic movements in the face and extremities, as well

as gradual loss of mental faculties, ending in dementia. The disease is lethal and incurable; death usually occurs on

average 15 to 17 years after disease onset. The disease is transmitted as an autosomal dominant trait; offspring of

an affected individual have a 50 percent chance of developing the disease. The test for the Huntington’s gene is most

often performed on an asymtomatic individual. If someone has the gene, that person will definitely develop the

disease. Symptoms for the disease usually begin past the typical childbearing years, between ages 35 to 45.

The test provokes considerable anxiety among those at risk who elect to take it. Not all of those at risk choose

to be tested, even though there is a 50 percent chance that they will receive good news Prior to the availability of

a predictive teat for Huntington’s disease, surveys indicated that between 56 and 85 percent of those at risk would

avail themselves of the test. In a survey conducted after the test became available, less than 14 percent of the sample

population at risk elected to take the test.

In another survey, 66 percent of the sample population at risk said they wanted the test. Of that group, 15

percent said they might commit suicide if the test were positive. Of the group that chose not to be tested, 30 percent

feared they might be suicidal and therefore did not want their fears confirmed. For some people, uncertainty appears

to be preferable to certainty.

A recent study on the psychological reaction of people being tested for the disease found no clear increase in

psychiatric illness among people who tested positive for the Huntington’s gene. People’s reactions to their test

results ranged from “extreme joy and relief to disappointment, sadness and demoralization.” This study suggests

that people cope well with this type of information if they are carefully screend, counseled, and provided followup

care. In addition, it suggests that those who test positive should be given appropriate long-term monitoring.

SOURCES: Office of Technology assessment, 1990; based on C. Mastromauro, R.H. Myers, and B. Berkman, “Attitudes Toward

Presymtomatic Testing in Huntington’s Disease," American Journal of Medical Genetics 26:271-282, 1987; K. A. Quaid, J.

Brandt, and S.E. Folstein, “The Decision To Be Tested for Huntington's Disease," Journal of the American Medical Association

257:3362 (letter), 1987; B. Teltacher and S. Polgar, “Objective Knowledge About Huntington's Disease and Attitudes Toward

Predictive Tests of Persons at Risk,” Journal of Medical Genetics 18:31-39, 1981; A. Tyler and P.S. Harper, “Attitudes of Subjects

at Risk and Their Relatives Toward Genetic Counseling in Huntington's Chorea,” Journal of Genetics 20:179-188, 1983.

interventions are not yet feasible (box l-D). SURVEY OF THE USE OF

Employers undertaking genetic monitoring and

screening programs should anticipate the com- GENETIC MONITORING AND

plexity of interpretation and communication of SCREENING

test results.

The workplace is an atypical setting for receiving

information of such personal importance. It should

not be overlooked that when genetic monitoring or

screening are used in the workplace, the focus of the

tests--the person—is being provided with information that could have a significant impact on

decisions unrelated to employment: marriage, procreation, and lifestyle. The absence of referrals to

trained professionals and reimbursement for the

costs of additional tests or counseling may be

prohibitive factors influencing an individual’s ability to obtain additional information. Genetic counseling and appropriate referrals for those at risk

should accompany the use of either genetic monitoring or screening.

To assess the current practice of genetic monitoring and screening by U.S. employers, a survey was

conducted for OTA from March 24 to July 15, 1989,

by Schulman, Ronca, & Bucuvalas, Inc. This effort

is a followup to a 1982 survey that was part of the

1983 OTA report. As with the earlier survey, the

core remained a national survey of the 500 largest

U.S. industries (Fortune 500), 50 largest utilities,

and 33 major unions. The 1989 survey was designed

to provide comparability to the earlier survey in

terms of populations sampled and the questionnaire

content. The 1989 survey, however, did not exactly

duplicate the 1982 questionnaire. Rather, it was

designed to remove ambiguities that might have

been present in the initial survey, but could be

detected only in hindsight. It also was designed to

include a representative sample of all other compa-
Chapter I-Summary, Policy Issues, and Options for Congressional Action ● 21

Table 1-3-Summary of Methodology

Samples

Fortune 500 companies . .

50 largest utilities . . . . . . .

Unions . . . . . . . . . . . . . . . .

Sampled in 1989 and 1982.

Sampled in 1989 and 1982.

33 unions in 1989 and 11 unions in

1982.

Companies with 1,000+

employees . . . . . . . . . . .

Designated respondent

Private companies:

Chief health officer . . . .

Chief personnel officer. .

Unions:

Union president . . . . . . .

Followup methodology

Reminder letters . . . . . . . .

Remailing questionnaires

to nonresponders . . . . .

Telephone followup to

nonresponders . . . . . . .

Actual telephone interviews with nonresponders to mail

survey . . . . . . . . . . . . . . .

1,000 sampled in 1989. Not sampled

in 1982.

Designated respondent in 1989 and

1982.

Received version of questionnaire

for health officers.

Designated respondent in 1989 only.

Received different questionnaire

version for personnel officers.

Designated respondent in 1989 and

1982.

Sent in 1989 and 1982.

Sent to all nonresponders in 1989

and 1982.

All Fortune 500 and utilities in 1989.

Only 200 largest companies in

1982.

Done as a last resort in 1989 and

1982.

SOURCE: Office of Technology Assessment, 1990.

nies with 1,000 or more employees so that broader

estimates could be made of the use and pattern of

genetic monitoring and screening in the workplace.

(See table 1-3 for a summary of the methodology of

the 1989 and 1982 surveys.)

Table 1-4-Current Use of Genetic Monitoring by

Q.15.

Q.18.

Fortune 500 Companies

Is your company currently conducting cytogenetic monitoring of any employees or job applicants, for research or any

other reason?

Is your company currently conducting direct-DNA monitoring of any employees or job applicants, for research or any

other reason?

(Base: Health officers)

Number of companies

currently conducting

Cytogenetic Direct-DNA

monitoring monitoring

Total . . . . . . . . . . . . . . . . . . . . . . . . 1 0

Type of business

Electrical utility . . . . . . . . . . . . . . . . 0 0

Pharmaceutical . . . . . . . . . . . . . . . . 0 0

Other chemical . . . . . . . . . . . . . . . . 0 0

Petroleum. . . . . . . . . . . . . . . . . . . . 1 0

Electronic . . . . . . . . . . . . . . . . . . . . O 0

Other manufacturing . . . . . . . . . . . 0 0

Nonmanufacturing . . . . . . . . . . . . . 0 0

Number of employees

Less than 5,000 . . . . . . . . . . . . . . . O 0

5,000-9,999 . . . . . . . . . . . . . . . . . . 0 0

10,000 or more . . . . . . . . . . . . . . . . 1 0

SOURCE: Office of T~noiogy Assessment, 1990.

Table 1-5--Current Use of Genetic Screening by

Fortune 500 Companies

Q.13. Is your company currently conducting biochemical genetic

screening of any employees or job applicants, for research

or any other reason?

Q.17. Is your company currently conducting direct-DNA screening of any employees or job applicants, for research or any

other reason?

(Base: Health officers)

Number of companies

currently conducting

Biochemical

genetic Direct-DNA

screening screening

To flesh out the details of the data from the 1989

survey, OTA added questions that explored the use

of genetic monitoring and screening in greater depth.

Questions were asked about genetic monitoring and

screening tests that might have been conducted as

part of a voluntary wellness program, at the request

of the employee, or for diagnosis. Including the

results of the new questions produced a broader

definition of genetic monitoring and screening

for the 1989 survey. OTA believes the increased

specificity attained an accurate measure of genetic monitoring and screening in 1989, established a firm base for future comparisons, and

preserved general comparability to the 1982

study.

Total . . . . . . . . . . . . . . . . . . . . . . . . 12 0

Type of business

Electrical utility . . . . . . . . . . . . . . . . 0 0

Phar maceutical . . . . . . . . . . . . . . . . 0 0

Other chemical . . . . . . . . . . . . . . . . 4 0

Petroleum . . . . . . . . . . . . . . . . . . . . 1 0

Electronic . . . . . . . . . . . . . . . . . . . . O 0

Other manufacturing . . . . . . . . . . . 2 0

Nonmanufacturing . . . . . . . . . . . . . 5 0

Number of employees

LOSS than 5,000 . . . . . . . . . . . . . . . 1 0

5,000-9,999 . . . . . . . . . . . . . . . . . . 2 0

10,000 or more . . . . . . . . . . . . . . . . 9 0

SOURCE: Office of Technology Assessment, 1990.

Before presenting the trend data from 1982 to

1989, the current, past, and combined use of genetic

monitoring and screening will be discussed. Following those sections, the overall use of genetic
22 ● Genetic Monitoring and Screening in the Workplace

Table 1-6-Past Use of Genetic Monitoring Tests by

Fortune 500 Companies

Q.16. Has your company conducted any cytogenetic monitoring

of any employees or job applicants, for research or any

other reason in the past 19 years?

(Base: Health officers)

Number of companies

conduoced in past

Cytogenic monitoring

Total . . . . . . . . . . . . . . . . . . 5

Type of business

Electrical utility . . . . . . . . . . 0

Pharmaceutical . . . . . . . . . . 0

Other chemical . . . . . . . . . . 1

Petroleum . . . . . . . . . . . . . . 0

Electronic . . . . . . . . . . . . . . . 0

Other manufacturing. . . . . . 1

Nonmanufacturing . . . . . . . 3

Number of employees

Less than 5,000 . . . . . . . . . 0

5,000-9,999 . . . . . . . . . . . . . 0

10,000 or more . . . . . . . . . . 5

SOURCE: Office of Technology Assessment, 1990.

monitoring and screening in 1989 and 1982 will be

discussed.

In the 1982 survey, six health officers (1.6

percent) reported their companies currently conducted genetic monitoring or screening. In 1989, 12

health officers (5 percent) reported their companies

currently conducted genetic monitoring or screening

(1 of the companies used genetic monitoring and

screening while 11 used only genetic screening) (see

tables 1-4 and 1-5). (These numbers do not directly

correlate because of different sized survey populations in 1982 and 1989.) The increase in the number

of ‘‘current users’ in 1989 could reflect slight

differences in question wording between the 1989

and 1982 surveys.

The 1989 survey asked health officers whether

their companies had conducted genetic monitoring

tests in the past 19 years, for research or any other

reason. Five health officers in Fortune 500 companies reported that their companies had conducted

cytogenetic monitoring in the past 19 years of any

employees or job applicants, for research or any

other reason (table 1-6). All five companies that

formerly conducted cytogenetic monitoring reported

no current use of genetic monitoring or screening. A

total of eight health officers in the Fortune 500

companies reported that their companies had conducted biochemical genetic screening of any employees or job applicants in the past 19 years (table

Table 1-7—Past Use of Genetic Screening Tests by

Fortune 500 Companies

Q.14. Has your company conducted any biochemical genetic

screening of any employees or job applicants, for research

or any other reason in the past 19 years?

(Base: Health officers)

Number of companies

conducted in past

Biochemical genetic screening*

Total . . . . . . . . . . . . . . . . . . 8

Type of business o

Electrical utility . . . . . . . . . .

Pharmaceutical . . . . . . . . . . 0

Other chemical . . . . . . . . . . 4

Petroleum . . . . . . . . . . . . . . 0

Electronic . . . . . . . . . . . . . . . 0

Other manufacturing. . . . . . 2

Nonmanufacturing . . . . . . . 2

Number of employees

Less than 5,000 . . . . . . . . . 0

5,000-9,999 . . . . . . . . . . . . . 1

10,000 or more . . . . . . . . . . 7

● NOTE: Includes companies currently conducting genetic screening.

SOURCE: Office of T~nology Assessment, 1990.

Table 1-8-Combined Testing: Current v. Past

Monitoring and Screening by Fortune 500 Companies

(Base: Health officers)

Number of

companies

Conducted genetic monitoring or screening for

research or any other reason, at present or

in past 19 years. . . . . . . . . . . . . . . . . . . . . . . . .

Currently conducting genetic monitoring or

screening . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Conducted monitoring or screening in past

only . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Conducted genetic screening for research or any

other reason at present or in past 19 years . .

Currently conducting genetic screening . . . . . . .

Conducted genetic screening in past only . . . . .

Conducted cytogenetic monitoring for research or

any other reason at present or in past 19

years . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Currently conducting cytogenetic monitoring . . .

Conducted cytogenetic monitoring in past

only . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Currently conducting direct-DNA screening for

research or any other reason . . . . . . . . . . . . . . .

Currently conducting direct-DNA monitoring for

research or any other reason . . . . . . . . . . . . . . .

SOURCE: Office of Technology Assessment, 1990.

20

12

8

16

12

4

6

1

5

0

0

1-7). This included four health officers in Fortune

500 companies that reported they were currently

conducting biochemical genetic screening.

A total of 20 health officers reported that their

companies had conducted cytogenetic monitoring or
Chapter I-Summary, Policy Issues, and Options for Congressional Action .23

Table 1-9-Use of Genetic Monitoring or Screening: 1989 v. 1982 Survey Results

(Base: Health officers)

Number of companies

1989 1982

Conducted genetic monitoring or

screening for research or any other

reason, at present or in the past* . . . . 20 18

Currently conducting genetic

monitoring or screening . . . . . . . . . 12 6

Conducted monitoring or screening in

past only . . . . . . . . . . . . . . . . . . . . . . 8 12

● Defined as past 19 years in 1989 survey and past 12 years in 1982 survey.

SOURCE: Office of Technology Assessment, 1990.

Table l-10-Consideration To Conduct Genetic Monitoring and Screening in the Next Five Years: Health Officers

Q.33. Does your company anticipate conducting any biochemical genetic screening, for any reason, in the next 5 years?

Q.34. Does your company anticipate conducting any cytogenetic monitoring, for any reason, in the next 5 years?

Q.35. Does your company anticipate conducting any direct-DNA screening, for any reason, in the next 5 years?

Q.36. Does your company anticipate conducting any direct-DNA monitoring, for any reason, in the next 5 years?

(Base: Health officers)

Percent

Yes No Not sure No answer

Biochemical genetic screening . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 218 25 3

Cytogenetic monitoring . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 219 27 3

Direct-DNA screening . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 224 23 3

Direct-DNA monitoring . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 218 27 4

SOURCE: Office of Technology Assessment, 1990.

biochemical genetic screening, either currently or in

the past 19 years. This includes 12 health officers

who reported that genetic monitoring or screening

was currently conducted, and 8 who reported that

genetic monitoring or screening had been conducted

in the past 19 years, but not currently (table 1-8). (In

the 1982 OTA survey, past was defined as 12 years,

and in the 1989 survey, as 19 years.)

Trend data on the use of genetic monitoring or

screening can be obtained by tabulating comparable

questions in the 1989 and 1982 surveys. These do

not include the previously mentioned items added in

1989. Using this narrow definition, of the 330

companies (62.4 percent) responding to the 1989

survey, 20 health officers reported that their companies had conducted genetic monitoring or screening,

either currently or in the past 19 years. In comparison, the 1982 survey found 18 health officers in the

Fortune 500 sample who reported current or past use

of genetic monitoring or screening (table 1-9). Thus,

there has been little change between 1989 and 1982

in the number of companies that had used genetic

monitoring or screening in the workplace.

In summary, the 1989 survey found 12 companies

reporting current use of genetic monitoring or

screening for research or any other reason. The ratio

of current to past use of monitoring or screening was

reversed in 1982, with 6 companies indicating

current use of genetic monitoring or screening and

12 companies indicating past but not current use.

Overall, OTA found that 20 companies had used

genetic monitoring or screening in 1989, as compared to 18 companies in 1982.

If there has been little or no growth in the number

of companies conducting genetic monitoring and

screening in the workplace, what do companies

foresee for the future? In 1982,, OTA found that 4

companies (1. 1 percent) anticipated using the tests in
24 ● Genetic Monitoring and Screening in the Workplace

the next 5 years, and 55 companies (15 percent)

stated they would “possibly” use the tests in the

next 5 years. The 1989 OTA survey provided the

response categories “yes,” “no,” and “not sure”

for the same questions to avoid classifying an

indefinite answer as a positive response to future

genetic monitoring or screening.

OTA found one Fortune 500 company that

anticipated cytogenetic monitoring, one company

that anticipated direct-DNA monitoring, and four

companies that anticipated biochemical genetic

screening. No company anticipated using directDNA screening in the next 5 years. Twenty-seven

companies in 1989 indicated they were not sure

whether they anticipated cytogenetic monitoring,

and 27 were not sure whether they anticipated

direct-DNA monitoring. For biochemical genetic

screening, 25 companies were not sure whether they

anticipated using it, and 23 were not sure about

future direct-DNA screening (table 1-lO).l In 1982,

55 companies said they would possibly use such test

in the next 5 years. Although this number cannot be

directly compared to the current survey, the 1989

OTA survey appears to indicate fewer companies

anticipate using genetic monitoring or screening.

POLICY ISSUES AND OPTIONS

FOR CONGRESSIONAL ACTION

While technologies associated with genetic monitoring and screening in the workplace have continued to advance, OTA found no significant change in

the use of these technologies since 1983. Thus,

several of the policy issues and options for congressional action offered in the 1983 OTA report are still

valid and remain unchanged.

Two central issues related to genetic monitoring

and screening in the workplace were identified

during the course of this assessment. They are:

the appropriate role of the Federal Government

in the regulation, oversight, or promotion of

genetic tests (both monitoring and screening);

and

the adequacy of federally sponsored research

on the relationships between genes and the

environment.

Associated with each policy issue are several

options for congressional action, ranging in each

case from taking no specific steps to making major

changes. Some of the options involve direct legislative action. Others involve the executive branch but

with congressional oversight or direction. The order

in which the options are presented does not imply

their priority. Moreover, the options are not generally mutually exclusive; adopting one does not

necessarily disqualify others that pertain to the same

or other issues, although changes in one area could

have repercussions in others. A careful combination

of options might produce the most desirable effects.

ISSUE: Is there a role for the Federal Government in genetic monitoring in the workplace?

Option 1: Take no action.

Congress could take no action to prohibit, regulate, or promote the use of genetic monitoring in the

workplace. This would allow employers, employees, and their representative trade groups and unions

to regulate its use through negotiation, arbitration,

and litigation.

Thus far, executive agencies involved in workplace health and safety have not regulated against

the use of genetic monitoring in workplace settings.

OSHA has regulated some employer practices that

could affect the use of genetic monitoring, such as

medical records access by the employee. Congress

could take no action if it determines that present

Federal regulation is adequate in this area. Under

this scenario, constraints on the use of genetic

monitoring would develop through court rulings in

suits between pa-ties or by negotiations between

companies and unions.

Option 2: Prohibit genetic monitoring in the

workplace.

To prevent all possibilities for discrimination and

breach of confidentiality, Congress could prohibit

genetic monitoring in the workplace. In light of the

many discrete changes needed in the OSH Act,

NLRA, and Rehabilitation Act to achieve this degree

of protection through regulation, Congress could

decide to prohibit all genetic monitoring until further

research into the methods is conducted. Such a

l~ese n-rs cannot be added because of cross counting, nor do they directly correlate to the 55 COJIIpaIIieS because of question wording. rn

retrospect those who chose “possibly’ in 1982 might not have meant to indicate that genetic monitoring or screeningwas anticipated, they simply could

not rule out the possibility they would use it in the future.
Chapter 1-Summary, Policy Issues, and Options for Congressional Action ● 25

prohibition could shift the focus of the issue to levels

of exposure in the workplace.

Prohibiting genetic monitoring, however, will

delay the accumulation of data needed to make the

judgment whether certain genetic monitoring tests

are useful. By slowing the development of these

data, prohibition might threaten efforts to identify

workplace hazards, whether they are to be minimized through cleanup or worker selection. In

addition, some workers who might have avoided

dangerous exposures had they known of a susceptibility will sicken unnecessarily. Finally, this option

clearly eliminates the possibility for mandatory

worker protection under those discrete circumstances where overall worksite hazard reduction

is not technologically or economically feasible.

Option 3: Promote genetic monitoring in the workplace.

Congress could decide that genetic monitoring in

the workplace should be promoted because of its

potential to improve the work environment and

worker health conditions. This could be done by

providing additional funding to those Federal agencies currently performing research into genetic

monitoring methods, as well as basic research on the

cause of occupational disease, in general, and the

relationships between environmental exposures and

health effects arising from genetic mutation. Such

projects could identify useful occupational genetic

monitoring tests and develop protocols for their use.

However, many questions about the use of genetic

monitoring remain unanswered. Because the interpretation of genetic monitoring is only considered to

be reliable at the population level, rather than the

individual level, the current usefulness of genetic

monitoring in the workplace is questionable.

ISSUE: Is there a role for the Federal Government in genetic screening in the workplace?

Option 1: Take no action.

Congress could choose to take no action in the

area of genetic screening in the workplace. As with

genetic monitoring, any constraints on the use of

genetic screening would develop through court

rulings in lawsuits between employers and employees, or by negotiations between companies and

unions. In support of this option is the viewpoint that

congressional action is not currently warranted at

this time. Use of genetic screening in the workplace

has not changed greatly since the 1983 OTA report.

However, there have been several newly recognized susceptibilities to occupational illness since

that time. In addition, advances have been made in

the area of molecular techniques for genetic screening for both occupationally and nonoccupationally

related disease.

If Congress takes no action in this area, those

identified as susceptible to occupational illness

through genetic screening could be seen as unfit for

work. In addition, those identified as being susceptible to a nonoccupationally related disease could be

seen as a health insurance burden. Without proper

restrictions, the use of genetic screening to detect

either type of disease risk could make job discrimination a possibility.

Option 2: Prohibit genetic screening in the workplace.

The principal reason for prohibiting genetic

screening in the workplace would be the concern

over its potential misuse. Such potential for misuse

probably would be greater for genetic screening than

genetic monitoring because the former is targeted

toward identifying individuals at increased risk

while the latter focuses on groups at increased risk.

The existing legal framework may offer protection

in some circumstances, but many questions have not

resolved.

A drawback to this option is that by prohibiting

both types of genetic screening in the workplace,

employers could not utilize screening for occupationally related disease. This type of screening offers

some protection of the worker.

Option 3: Promote genetic screening in the workplace.

Congress could stimulate the research and development of genetic screening tools by providing

funds for research into occupationally related disease, nonoccupationally related disease, or both.

Useful screening tests for occupationally related

disease could be developed which could have direct

benefits for the individual worker and indirect

benefits for the employer. In addition, more money

could be provided in the area of research on

occupationally related traits. NIOSH could be authorized to do research in this area, and to certify

procedures for medical technologies that are of

sufficient value to be used in an occupational setting.

If such research were promoted, however, employers

might be prone to use those screening tests to screen
26 ● Genetic Monitoring and Screening in the Workplace

out susceptible employees in lieu of cleaning up the

workplace.

If research in the area of nonoccupationally

related disease was promoted beyond current Federal research levels, employers might be prone to

using such screening tests to discriminate against

employees or job applicants who might increase the

company health care costs.

ISSUE: Should the Federal Government regulate

genetic monitoring or screening in the workplace?

If Congress determines that the current regulatory

framework addressing genetic monitoring and

screening is adequate, it could take no action and let

the current regulatory framework stand. However, if

Congress determines that the current regulatory

framework is inadequate, it could pursue several

avenues. A framework established by several major

pieces of legislation exists on which to build: OSH

Act; NLRA; Title VII of the Civil Rights Act of

1964; Rehabilitation Act of 1973; and ADA. The

following options are discussed according to

whether they apply to genetic monitoring, genetic

screening, or both.

Genetic Monitoring and Screening

Option 1: Congress could amend Section 6(b)(7) of

the OSH Act which states that OSHA standards

shall prescribe the type and frequency of medical

examinations or other tests to be made available,

to specify whether genetic monitoring and

screening tests are to be included.

To either prohibit or promote genetic monitoring

and screening, Congress could amend this section’s

coverage with respect to genetic monitoring and

screening. To contain abuses, Congress could include language directing OSHA to prescribe or

recommend genetic monitoring or screening only

when less intrusive medical tests will not provide

information of substantially the same value. Thus,

for example, tests for sickle cell anemia would not

be permitted unless other tests of lung fiction and

blood oxygenation were incapable of giving an

employer the information needed to decide whether

a particular worker could safely manage a particular

task.

A principal drawback of this option is that

performin g genetic monitoring and screening tests

on employees could be financially prohibitive for

some employers. In addition, mandating genetic

monitoring or screening tests could be burdensome

for both the employer and the employee. Such an

action could require the employer to hire new

medical staff to perform them. Furthermore, the

employee might not wish to undergo genetic monitoring or screening.

Option 2: Congress could amend the OSH Act to

guarantee the confidentiality of genetic monitoring and screening results.

Congress could amend the OSH Act to specifically guarantee that genetic monitoring and screening results not be disseminated, except in

nonidentifying, statistical forms for research purposes, to any third-party without specific authorization from the worker. Further, employers could

receive only the conclusion of the occupational

physician, i.e., whether the worker is fit for the job

in question, without receiving details or results of

the genetic monitoring or screening tests. The

worker, on the other hand, would receive both the

test results and the conclusions drawn from them by

the examining physician. Several State statutes

provide a model for such legislation.

Advantages of this option are the ability to shield

workers from misuse of genetic information by

immediate and potential employers, and the maintenance of adequate authority to provide statistical

information needed for ongoing improvement of

health and safety practices. As with the option just

mentioned concerning recordkeeping, however, this

amendment would logically be appropriate to all

medical records, and not merely those concerning

genetic monitoring and screening tests. Thus, evaluating this option requires a larger consideration of

whether the OSH Act should guarantee the confidentiality of all medical testing in this fashion. If this

option is adopted, consideration would also need to

be given to remedies for breach of confidentiality

and an examination of the role of the occupational

physician employed by the company.

Option 3: Require full disclosure to employees and

job applicants of the nature and purpose of all

medical procedures performed on them.

Current law does not require employers to disclose the nature and purpose of medical procedures

conducted on employees or job applicants, or how

the results are to be used. Although employees are

given access to their medical records, they may not
Chapter 1--Summary, Policy Issues, and Options for Congressional Action ● 27

be able to interpret the data within the records, or

challenge incorrect information. A congressionally

mandated requirement that employers provide detailed information of what procedures were performed and why they were performed might serve as

a deterrent to abuses. This would also protect the

employees’ autonomy by allowing them to be part of

a decisionmaking process that affects their health

and economic interests. If the test were genetic in

nature, the assistance of a genetic counselor would

be important to fully explain the procedure and the

meaning of a positive result.

On the other hand, by requiring full disclosure,

Congress would place requirements on employers

that might be perceived as burdensome and expensive. Additionally, arguments might be made that

such a requirement would intrude on the judgment of

the occupational health physician.

Genetic Monitoring

Option 4: Congress could direct OSHA

that genetic changes shall be included

definition of occupational illness.

to clarify

under the

OSHA’s definition of occupational illness now

includes ‘‘abnormal condition,’ but does not

specifically cover genetic changes. Taking this

action could ensure that data on worker exposures

and subsequent genetic changes would be recorded

in worksites where employers are using genetic

monitoring. This would help with ongoing efforts to

assess the effects of potentially hazardous substances, as well as offer the opportunity to more

closely monitor the health of a particular worker.

Yet including genetic changes in the definition of

occupational illness would implicitly equate all

genetic changes with “illness.” Many changes are

likely to be without immediate symptomatic effect.

Therefore, gathering and distributing this information might be unduly alarming, particularly to the

workers in question. Also, all genetic change is not

definitely a result of the workplace. Changes can be

induced by personal habits and lifestyle decisions

(e.g., smoking, diet) as well. Equating genetic

changes with illness, may encourage employers to

view such employees as somehow disabled or unfit

for work, making job discrimination a distinct

possibility.

Genetic Screening

Option 5: Congress could amend section 504 of the

Rehabilitation Act to prohibit discrimination in

hiring against otherwise qualified applicants

because their genetic screening results reveal a

proclivity toward certain diseases in the future.

Amending section 504 in this manner would

address several potential concerns. First, it tackles

the problem of discrimination against job applicants,

a topic left largely untouched by the OSH Act and

NLRA protections. Second, it addresses what is

perhaps the most likely area of abuse for the use of

genetic screening. Third, it focuses on one of the

possible uses of genetic screening, i.e., identification

of applicants who are qualified but likely in the

future to suffer from a disease that will require full

use of sick leave or even early retirement. Finally,

amending section 504 also permits Congress to

address the use of genetic screening in the workplace

to detect nonoccupationally related illnesses.

By focusing on this section, rather than with

section 503, Congress could avoid the problem of

directing employers to include those with genetic

variants that do not otherwise qualify them as

“handicapped” under their affirmative action programs.

The disadvantage, however, is the uncertainty

associated with section 504’s requirement that

employers provide a reasonable accommodation for

handicapped workers. It may be clear what accommodation is necessary to make a job accessible to

one who is deaf or blind, and in turn to make a

judgment whether that accommodation is reasonable to require of an employer. It may be more

difficult, however, to judge what is necessary for

someone with a currently asymptomatic genetic

illness or susceptibility.

Option 6: Congress could direct the National Labor

Relations Board to make preemployment genetic

screening a mandatory subject of bargaining, in

order to increase the possibilities for workers to

protect themselves against what they and their

representatives perceive as abuses of genetic

screening.

Fitness-for-duty physicals and medical tests are

already regarded as mandatory subjects of bargaining between unions and employers when applied to

current workers. Thus, extending the concept to

preemployment physicals and genetic screening
28 ● Genetic Monitoring and Screening in the Workplace

would not require markedly different concerns to be

placed on the bargaining table, and would provide

some protection for job applicants.

A disadvantage to this option, however, is that

unions do not represent the majority of American

workers, so this action would not protect all affected

persons. Additionally, in light of interest in “twotiered” systems of compensation, it is possible that

unions and employers may trade protections for

current workers from potentially discriminatory

genetic screening tests for the privilege of screening

job applicants more stringently.

ISSUE: Is the current Federal research agenda

addressing genetic monitoring and screening

adequately?

The current Federal research framework for addressing genetic monitoring and screening is composed of extramural and intramural programs sponsored by several agencies, including the Department

of Energy (DOE), NIOSH, National Institutes of

Health (NlH), National Center for Toxicological

Research, Center for Environmental Health and

Injury Control, and Agency for Toxic Substances

and Disease Registry. OTA found that, in general,

Federal research programs do not adequately address genetic monitoring or screening technologies

for use in the workplace.

Option J: Take no action.

In the absence of congressional directives encouraging more research on the relationships between

environmental exposures and health, information on

gene-environment interactions will continue to be

gathered piecemeal by the Federal agencies involved in this area. Some of the research funded by

the National Center for Human Genome Research at

NIH will contribute to the development of more

valid and reliable tests. Research agendas of the

National Cancer Institute and the National Institute

of Environmental Health Sciences include studies

relevant to this report. Work being conducted

internationally is also contributing to knowledge in

this area. Congress could decide that existing

research capabilities will provide an adequate and

appropriate level of information in this area and that

no additional action needs to be taken. If Congress,

however, decides that it is important to determine

these relationships in order to provide for a safe and

healthy workplace, and that the cost of occupational

illness warrants more extensive examination, taking

no action will result in incremental and disjointed

progress in reaching these goals.

Option 2: Encourage the appropriate agencies to

pursue studies that will provide a better understanding of the link between mutagenesis and

carcinogenesis through larger, better controlled

epidemiologic studies.

Over the years, an increasing number of health

effects have been attributed to mutations caused by

toxicants. The diseases most often associated with

genotoxic substances are various forms of cancer.

Mutational changes such as point mutations and

chromosomal rearrangements have been associated

with early stage tumor development. However, not

all mutations cause disease. Because the relationship

between mutation and health effect is often indirect

and not well understood, more research needs to be

conducted in this area. Epidemiologic studies in an

occupational setting can address this problem.

Option 3: Direct the Secretary of the DOE to report

on past and current research efforts directed by

DOE toward identifying the genetic risks of

radiation exposure.

Open-ended data collection by DOE, and problems of access to data, have stalled an open

discussion of the real risks of radiation exposure to

American workers in high- and low-level environments. DOE has recognized this problem and could

be encouraged to share data with interested investigators.

Option 4: Ensure that the Food and Drug Administration (FDA) and the relevant offices of NIH

properly evaluate new genetic monitoring and

screening tests for reliability and validity.

There is some concern that the unique nature of

many genetic diseases-which may present heterogeneity, reduced penetrance, and variable expressivity-pose significantly different challenges to diagnostic tests. Tests made available to employers or

physicians need not only to be safe and effective, but

to clearly explain the limitations in careful labeling

so as to avoid misuse and misinterpretation. As more

tests become available for both occupationally and

nonoccupationally related diseases, issues of quality

control must be addressed. NIH and FDA could

cosponsor a Consensus Development Conference(s)

on genetic monitoring and screening that could

evaluate the accuracy, safety, labeling, and potential

misuses and abuses of new tests.
Chapter 2

Introduction
CONTENTS

Page

WHAT IS GENETIC TESTING? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31

WHY USE GENETIC MONITORING AND SCREENING IN THE

WORKPLACE? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32

GENETICS IN THE WORKPLACE: A HISTORY OF CONGRESSIONAL

CONCERN . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .36

The 1983 OTA Report . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36

Impacts of the Human Genome Project . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36

THIS OTA REPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37

CHAPTER 2 REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37

Box

Box Page

2-A. Cancer Detection in the Workplace . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34

Figure

Figure Page

2-1. Components of Genetic Testing in the Workplace . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32
Chapter 2

Introduction

Genetically determined individuality is a fact of

life. Yet not long ago, the factors affecting heritability were, by today’s standards, ill-defined and only

partially known by scientists. During the past three

decades our understanding of genetics has advanced

remarkably as new methods for identifying, manipulating, and analyzing DNA have developed. Today,

the secrets of inheritance are revealed by modern

biology. At the same time, public awareness of the

role that genetics play in daily lives is increasing.

Less well understood by both scientists and the

public is interaction of the environment with genetics, and the role each plays in sickness and health.

Nevertheless, it has long been recognized that

genetic risks are posed by various workplace environments, such as exposure to radiation or certain

chemicals. In an effort to reduce occupational

illness, some have advocated genetic testing of

workers to identify healthy individuals (or populations) at risk for, or susceptible to, a variety o f

work-related conditions. Such genetic testing has

been heretofore viewed strictly as a tool to prevent

occupational disease (23). However, recent progress

in developing genetic tests to detect inborn conditions not obviously associated with worksite exposures--e.g., Huntington’s disease or heart disease--

and the advances expected to be made from the

human genome project, has been coupled increasingly with the notion of using these tests in the

workplace. A new dimension has been added to the

debate surrounding genetic testing conducted at the

workplace (1,2,3).

This report covers the scientific, ethical, legal, and

social issues of genetic testing of workers. While the

report is limited to issues central to use of genetic

technologies, some discussion of other medical and

biological testing of workers is presented to place

genetic testing in context. What is excluded are

job-associated injuries, nongenetic technologies to

prevent occupational disease, and reproductive hazards in the workplace, which have all been assessed

in previous Office of Technology Assessment

(OTA) reports (21,22). Similarly, acquired immunodeficiency syndrome (AIDS) testing, the implications of genetic testing for health insurance, regulating carcinogens, technologies to detect heritable

mutations, identifying and regulating neurotoxins,

and nonmedical uses of genetic tests are topics of

other OTA reports (9,10,1 1,13,20,24).

WHAT IS GENETIC TESTING?

Genetic testing includes a number of technologies

to detect genetic traits, changes in chromosomes, or

changes in DNA. As used in the workplace, it

encompasses two activities: monitoring and screening. Thus, genetic testing of employee populations

involves both examining persons for evidence of

induced change in their genetic material (monitoring) and methods to identify individuals with

particular inherited traits or disorders (screening). To

avoid confusion, the general term “genetic testing” will not be used in the text, rather, the more

specific terms genetic monitoring and screening

will be used instead.

Genetic monitoring involves periodically examining employees to evaluate modifications of their

genetic material-e. g., chromosomal damage or

evidence of increased occurrence of molecular

mutations—that may have evolved in the course of

employment. The premise is that such changes could

indicate increased risk of future illness. The putative

cause is workplace exposure to hazardous substances. Because ambient exposures, personal habits

and lifestyle decisions (e.g., tobacco use, etc.), and

age can also induce changes in genetic material,

genetic monitoring can be used to periodically

monitor risk arising outside of the workplace. In

short, genetic monitoring ascertains whether the

genetic material of the group of individuals has

altered over time. In general, current techniques are

not exposure-specific but serve merely as an indicator of recent exposure.

Genetic screening is a process to examine the

genetic makeup of employees or job applicants for

certain inherited characteristics. (Employees could

be screened on different occasions for different traits

or with improved technology, but generally only

once for each characteristic.) Genetic screening can

be used in two distinct ways. First, employees could

be screened for the presence of genetically determined traits that render them susceptible to a

pathological effect if exposed to specific agents. An

example of such genetic screening would be a test

–31–
32 ● Genetic Monitoring and Screening in the Workplace

for traits that might identify an employee with a

genetic predisposition to an occupationally related

disease. (Similarly, job applicants could be screened

for a trait prior to being hired for a position where

exposure could occur.) Second, employees or job

applicants could be screened to detect general

heritable conditions, not just conditions associated

with occupational illness. Reasons for using the

different classes of tests vary, and are discussed in

the following section. In either case, whether screening for an occupationally related trait or one not

related to job exposure, genetic screening tests

involve examinations for inherited traits where a

single measure is usually sufficient because generally these inherited characteristics do not change.

Genetic screening differs significantly from

genetic monitoring. In most cases, screening

requires a one-time test to detect a single trait in

a worker or job applicant, while monitoring

generally involves multiple tests of a worker over

time. Most importantly, in genetic screening the

focus is on the preexisting genetic makeup that

workers or job applicants bring to the job. This

is distinct from genetic monitoring, where the

focus is on changes in the genetic material

induced from hazardous exposures at the

workplace (see figure 2-l).

WHY USE GENETIC

MONITORING AND SCREENING

IN THE WORKPLACE?

As mentioned, genetic monitoring and screening

tests are methods for identifying individuals or

groups for evidence of alteration in the genetic

material or with particular inherited traits. Detecting

modifications or traits can inform individuals that

they are potentially at increased risk for disease, or

could pass a trait to their offspring. By applying

genetic monitoring and screening tests to a group of

apparently well persons and identifying those who

have a greater probability of developing a disease,

counseling, prevention, or early treatment (if available) become possible. The use of genetic monitoring

and screening of selected individuals or groups at

high risk through employers has not been a longstanding practice.

The recent development of tests for human

genetic disorders (14) has fueled interest in genetic

monitoring and screening of workers. To some

extent, as interest in AIDS and drug testing of

Figure 2-l-Components of Genetic Testing in the

Workplace

Genetic monitoring

*

Workers

T

Occupationally related ————————— Occupationally related

exposure disease

Genetic screening

8

Workers

Job applicants

Occupationally related

1+ l-+

Nonoccupationally

disease related disease

“EZEY

SOURCE: Office of Technology Assessment, 1990.

E

workers has increased, so has interest in genetic

monitoring and screening by employers (4). Nevertheless, many aspects of genetic monitoring and

screening in the workplace differ from other types of

testing of workers and remain controversial. Many

of the objections raised-scientific and social-are

discussed in following chapters. In spite of objections, why consider using genetic monitoring and

screening tests in the workplace? Genetic monitoring of employees could be performed on groups of

employees to identify work areas for increased

safety and health precautions, and to indicate a need

to lower exposure levels for a group exposed to a

previously unknown hazard. Genetic screening for

occupationally related traits could be performed to

ensure appropriate worksite placement of employees

susceptible to certain occupational diseases, and

ensure that employers place those workers most

susceptible to a specific risk in the least hazardous

environments. Both types of genetic screening

(occupational and nonoccupational) could be performed to improve employee productivity and lower

workers’ compensation costs through better worker

health; promote and encourage general health

awareness; and improve employers’ health care

cost-containment efforts, especially for health insurance.
Chapter 2-introduction ● 33

 U.S. News & World Report, 1987

Media coverage of genetic monitoring and screening.

Worksite risks create costs to employers, who

might be required to compensate individuals

through workers’ compensation for lost earnings, or

workers’ estates through tort liability claims for

premature death. Genetic screening of workers or

job applicants could be a tool to identify individuals

with a particular genetic trait that indicates susceptibility to occupational illness if they are exposed to

specific hazards, such as radiation or certain chemicals. Periodic genetic monitoring of employees

could be used to detect induced genetic change that

could indicate an increased risk for certain diseases,

in particular cancer. Thus, genetic monitoring and

screening could lead to improved worker health and

payment of lower workers’ compensation costs. On

the other hand, without clear correlations between

workplace hazards and occupational illnesses and

without cost-effective tests, any expectations of

money saved by genetic monitoring and screening

for job-related conditions could be minor.

Increasingly, costs to U.S. employers of healthrelated benefits have skyrocketed. In particular, to

avoid rising health care costs, many large companies

are adopting self-insurance plans. Self-insurance

plans are exempt from State mandates and other

forms of State regulation (6). Business health

spending between 1980 and 1987 almost doubled,

from $68.1 billion to $134.6 billion (6). One

company of 70 employees says that, in 16 years its

health insurance premiums will exceed its payroll if

both continue their present growth rates (5). Companies concerned about health insurance costs could be

interested in screening workers and job applicants

who are likely to develop genetically based diseases

and could impose high costs on a company’s

self-insured health program. Similarly, companies

could engage in genetic monitoring-again, to

safeguard workers’ health while simultaneously

reducing the burden of occupational illness on their

health costs.

In this respect, genetic monitoring and screening

in the workplace differ. Genetic monitoring can be

viewed as an extension of several types of biological

monitoring in the workplace to detect changes or

assess exposures that could be associated with

increased exposure to occupational or nonoccupational risk. Genetic screening, on the other hand, can

be used to detect both traits that indicate a predisposition to occupational disease, as well as traits not

associated with workplace illness. Some argue from

an economic standpoint that genetic monitoring and

screening in the workplace to limit occupational

illnesses could be less important in the long run than

genetic screening by employers to limit general

company health care expenses (2). A window on this

development could be corporate “wellness” programs, or other company-sponsored health promotion programs (see box 2-A) that emphasize

prevention and encourage employees to adopt

healthier lifestyles (2).

From a policy standpoint, these differences—

monitoring v. screening and occupational illness v.

general health-could be significant. Some criticize

all types of genetic monitoring and screening in the

workplace as paternalistic and discriminatory, while

others advocate that, properly implemented, genetic

monitoring and screening (for both purposes) programs benefit both workers and employers. Others,

however, maintain that it is one thing to monitor or

screen workers because they are at increased risk for

occupational illness induced by the workplace, but

quite another to screen persons because they or their

offspring-who could be covered on an employee’s
34 ● Genetic Monitoring and Screening in the Workplace

Box 2-A--Cancer Detection in the Workplace

Among the greatest fears of industrial workers is the risk of cancer from exposure to hazardous

substances. Although employees are concerned about cancer risk, they are not always informed about the

specific dangers of the chemicals with which they work. By increasing employee and employer involvement

in cancer prevention and detection, both groups stand to benefit: employees with gains in personal health, and

employers with higher worker morale and productivity and reduced health expenditures. Because cancer risks

vary from worksite to worksite, worker perceptions of various job hazards related to cancer and chemical

exposure are important. From 1978 through 1987, the National Cancer Institute (NCI) allocated $14 million

to the Occupational Safety and Health Administration (OSHA) for cancer prevention training and education

of workers. In 1983, NCI awarded grants to five unions, that had participated in OSHA’s education program,

to evaluate the impact of the unions’ cancer prevention and education programs.

A 1987 study by the International United Rubber, Cork, Linoleum, and Plastic Workers of America, one

of the participating unions, questioned approximately 24,000 of its members about their knowledge of

chemical hazards, the location of engineering controls, and the use of daily safety procedures. Prior to the

study, employees had participated in the industry’s cancer control program, which included worker education.

Despite the fact that over 10,000 different chemicals, many hazardous, are used by these workers, the

study found that 22 percent of workers were not sure whether they worked with dangerous chemicals, and

only 6 percent felt they were very informed about chemical hazards. Percentages of employees saying they

were well-informed varied widely from company to company, ranging from 16 percent at one company to

32 percent at another. Thus, for adequate cancer education, greater understanding of chemical-specific risks

is needed.

In addition to worker perception and involvement, management health programs can play an important

role. Currently, several companies offer employees cancer screening clinics and other cancer detection

programs. One such program, offered by Pennzoil (in conjunction with the Kelsey-Seybold Foundation) to

employees at a Texas facility, began m 1984 as a cancer awareness clinic for white-collar employees to

discover cancers unrelated to worksite exposure. The Pennzoil program, strictly voluntary and confidential,

has since been expanded to industrial petroleum workers and other locations in 22 States, where the cancer

detection procedure can include workplace risks.

The Pennzoil program involves an initial lecture on cancer risk and detection, and a personal cancer

examination for those requesting one. Corporate management strongly supports these meetings, and

encourages employees to attend the lectures. As part of the program, employees also complete questionnaires

about cancer risk behaviors and personal medical histories. Those employees showing an increased risk of

cancer are offered followup counseling sessions with Kelsey-Seybold Foundation Cancer Prevention Center

physicians and medical tests, if necessary, paid for by Pennzoil. All employees also are offered yearly

screening or followup examinations. Pennzoil receives only summary data on participation, cancer detection,

and demographic information. Both increased employee morale and detection of potential tumors resulted.

Along with Pennzoil’s expansion of the program, Exxon Chemical Americas has undertaken a similar project

with the Kelsey -Seybold Foundation Cancer prevention Center.

The experience of cancer screening in the workplace suggests that the cooperation of corporate

management and private organizations, together with an accurate assessment of employee understanding of

workplace risk, can create a healthier, more productive working environment one benefiting both employer

and employee. At present, genetic monitoring detects genetic changes that could result m greater risk of

cancer. Future advances in genetic technologies could result in increased cancer testing and education at

worksites. As genetic technologies make detection of cancer or other health risks more accurate, programs

such as those just described could serve as models. For genetic monitoring and screening, in particular,

implementing successful worker education will be crucial.

SOURCES: Office of Technology Assessmcnt, 1990, based on M. Minkoff, Kelsey-Seybold Foundation Cancer prevention Center,

Houston, TX, personal communication, October 1988; A.P. Schenck, A.D. Kaluzny, G.M. Hochbaum, et al., “Worker

Perceptions and Actions Toward Cancer Control in the Workplace: An Analysis of Baseline Data”; and L. Zimmerman, G.

Jackson, J. Hughes, et al., 4

‘CanCer Education and Screening in the Workplace: The Corporate Perspective, ” Advances in

Cancer Control: The War on Cancer—15 Years of Progress, P.F. Engstrom, LE. Mortenson and P.N. Anderson (eds.) (New

York, NY: Alan R. Liss, Inc., 1987).
Chapter 2--Introduction ● 35

FORM (31 2602 PENNZOIL COMPANY

HEALTH RISK APPRAISAL

NAME HOME ADDRESS

SOCIAL SECURITY NUMBER BIRTH DATE COMPANY NUMBER TODAY’S DATE

Health Risk Appraisal Is an educational tool. It shows you choices you can make to keep good health and avoid the most common causes of

death for a person your age and sex. This Health Risk Appraisal Is not a substitute for a check-up or physical exam that you get from a doctor

or nurse. It only gives you some ideas for Iowering your risk of getting sick or injured In the future.

DIRECTIONS: To get the most accurate results answer as many questions as you can and as best you can. If you do not know the answer

leave it blank, Questions with a ● (star symbol) are important to your health, but are not used by the computer to calculate your risks.

However, your answers may be helpful in planning your health and fitness program.

Please check or fill-in the appropriate numbers.

1. SEX

2. AGE Years

(Without shoes)

3. HEIGHT (No fractions) Feet Inches

4. WEIGHT

(Without shoes)

(No fractions) Pounds

5 Body frame size

7. Are you now taking medicine for high blood pressure?

Systolic Diastolic

8. What is your blood pressure now? (High number) I (Low number)

9. If you do not know the numbers, check the box that describes your blood pressure.

10. What is your TOTAL cholesterol level (based on a blood test)? mg/dl

11. What is your HDL cholesterol (based on a blood test)? mg/dl

12. How many cigars do you usually smoke per day? cigars per day

13. How many pipes of tobacco do you usually smoke per day’? pipes per day

14. How many times per day do you usually use smokeless tobacco? (Chewing tobac

co, snuff, pouches, etc.) times per day

16. STILL SMOKE. How many cigarettes a day do you smoke? cigarettes per day (go to question 18)

17. USED TO SMOKE -a. How many years has it been since you smoked cigarettes

fairly regularly? years

b. What was the average number of cigarettes per day that

you smoked in the years before you quit? 2 cigarettes per day

Photo credit: Pennzoil Co.

Health risk appraisal form from the Pennzoil program.
36 ● Genetic Monitoring and Screening in the Workplace

health plan—are at high risk for a disease not related

to occupational exposure. Finally, some argue that

screening per se, even if to reduce occupational

illness, is unfair because it a priori measures

heritable conditions beyond an individual’s control,

while genetic monitoring is similar to other forms of

successful biological monitoring (e.g., benzene or

lead exposure) that are performed from body fluids

or tissue samples.

GENETICS IN THE WORKPLACE:

A HISTORY OF CONGRESSIONAL

CONCERN

Congressional interest in human genetics, genetic

diseases, and genetic technologies is not new. In

1972, Congress passed the National Sickle Cell

Anemia Control Act (Public Law 92-294), amending it 4 years later to the National Sickle Cell

Anemia, Cooley’s Anemia, Tay-Sachs, and Genetic

Diseases Act (Public Law 94-278).

Beginning in the early 1980s, a public debate

began about the feasibility of mapping, and perhaps

sequencing, the human genome. Congress held

several hearings on this issue and requested an OTA

assessment on the subject (12). Two agencies, the

National Institutes of Health and the Department of

Energy, received funding to perform research for the

human genome project (25). Much of the research

done for the genome project will be important to the

scientific advancement of genetic monitoring and

screening techniques.

The 1983 OTA Report

In the late 1970s and early 1980s, reports surfacing about genetic monitoring and screening in

occupational settings captured the interest of Congress. Concern about the scientific and social issues

of such testing prompted the House Committee on

Science and Technology to hold hearings and

request an OTA assessment of the role of genetic

testing in preventing occupational disease (7,8,23).

As part of its study, OTA surveyed American

industry and unions to determine the extent and

nature of employer genetic monitoring and screening.

In the intervening years, understanding of human

molecular genetics and biotechnologies applicable

to the field have expanded enormously. Both the

number of applications of such technologies and the

technical capability to detect genetically based

disorders have increased, linked to rapid scientific

developments in recombinant DNA and cell culture

techniques. This has heightened congressional concern about their applications (12,14,15,16,17,18,

19). Debates surrounding the changing climate of

employee testing (e.g., AIDS, drugs, and polygraph)

(4) and, as described in the following section, efforts

to map the human genome, also combined to

stimulate congressional interest in reassessing the

extent of and issues surrounding genetic monitoring

and screening in the workplace.

Impacts of the Human Genome Project

Efforts underway to map and sequence the human

genome stand to have a significant impact on many

aspects of biology, medicine, and health-including

genetic monitoring and screening. (The history and

debate surrounding mapping and sequencing the

human genome have been analyzed in a separate

OTA report (12).) To date, genome projects have

accelerated the production of new technologies,

research tools, and basic knowledge. At current or

perhaps increased levels of effort, they may eventually make possible the control of many human

diseases-first through more effective methods of

predicting or detecting disease, then, in some cases,

through development of effective therapies based on

improved understanding of disease mechanisms.

Although not a direct result of the genome project,

advances in human genetics and molecular biology

have already provided insight into the origins of

such diseases as cystic fibrosis, hemophilia, sickle

cell disease, and hypercholesterolemia.

The new technologies developed through human

genome projects research will also be used to assess

public health needs. Techniques for rapidly sequencing DNA, for example, may facilitate the detection

of mutations following exposure to radiation or

environmental agents. Susceptibilities to environmental and workplace toxicants might be identified

as more detailed genetic linkage maps are developed, and special methods of surveillance could be

used to monitor individuals at risk.

However, profound ethical questions are posed by

possible applications of and access to these genetic

data. The complexity and urgency of these issues

will increase in proportion to advances in mapping

and sequencing. There is no doubt that continuing

scientific advances in mapping and sequencing the
Chapter 2--Introduction .37

human genome accelerate diagnostic applications.

Progress to date indicates that the ability to diagnose

a genetic abnormality precedes the development of

therapeutic interventions and that this gap may be

growing. An important related issue is that of access

to this information by third-parties such as insurance

companies or employers and how this information is

used. These questions are complex and are not likely

to be resolved in the near future. It will therefore be

necessary to ensure that some means for explicitly

addressing ethical issues accompanies such scientific research. A working group on ethics was

established in January 1989 by the Program Advisory Committee on the Human Genome, and a

percentage of the genome budget will go toward

studying ethical issues associated with the genome

research (25).

THIS OTA REPORT

Health and safety of the U.S. workforce involves

many components. This report presents the technological, ethical, legal, and personal implications of

employers using, genetic technologies. Where applicable, other types of medical testing are discussed to

place genetic technologies in context. This report

addresses two entirely different purposes of genetic

monitoring and screening in the workplace: to

prevent occupational disease and to detect nonoccupationally linked conditions related to general employee health. To place both genetics and worker

health in context, historical perspectives of genetic

monitoring and screening in this country are presented, as are perspectives on the evolution of

occupational health.

With this report, OTA assesses the current practice of genetic monitoring and screening by U.S.

employers, as determined by surveys of 1,500

companies, the 50 largest utilities, and 33 unions.

Beyond determining the extent of genetic monitoring and screening, the report also examines the

attitudes of employers toward using genetic procedures in the workplace. In addition, it examines the

very notion of “genetic normality,’ and explores

what role both genetics and a person’s job play in his

or her identity-and how these two parameters could

conflict.

For policymakers, this report presents a series of

policy issues and options for congressional action

aimed at addressing the concerns that arise when

personal identity, corporate interests, and Federal

regulation and oversight collide over genetic monitoring and screening in the workplace.

1.

2.

3.

4.

5.

6.

7.

8.

9.

10.

11.

12.

13.

CHAPTER 2 REFERENCES

Hamilton, J.O’C., and Rhein, Jr., R., “The Giant

Strides in Spotting Genetic Disorder Early,” Business Week 2921:82-85, 1985.

Hoerr, J., Hafner, K. M., DeGeorge, G., et al.,

‘‘Privacy,“ Business Week 3044:61-68, 1988.

Kolata, G., “Genetic Screening Raises Questions for

Employers and Insurers,” Science 232:317-319,

1986.

Patterson, W. P., “Genetic Screening: How Much

Should We Test Employees?” Industry Week

233:45-50, 1987.

Stipp, D., ‘‘Laws on Health Benefits Raise Firms’ Ire:

Mandates Pose Unfair Burden, Employers Say,” The

Wall Street Journal, Dec. 28, 1988.

U.S. Congress, General /wcounting Office, Health

Insurance: Cost Increases Lead to Coverage Limitations and Cost Shijling, Report to the Committee on

Energy and Commerce, House of Representatives,

U.S. Congress, HRD-90-68 (Washington, DC: U.S.

Government Printing Office, 1990).

tJ.S. Congress, House Committee on Science and

Technology, Subcommittee on Investigations and

Oversight, Genetic Screening in the Workplace,

hearing June 22, 1982 (Washington, DC: U.S.

Government Printing Office, 1982).

U.S. Congress, House Committee on Science and

Technology, Subcommittee on Investigations and

Oversight, Genetic Screening of Workers, hearing

Oct. 6, 1982 (Washington, DC: U.S. Government

Printing Office, 1982).

U.S. Congress, Office of Technology Assessment,

AIDS and Health Insurance: An OTA Survey, SW

paper, February 1988.

U.S. Congress, Office of Technology Assessment,

Genetic Witness: Forensic Uses of DNA Tests,

OTA-BA-438 (Washington, DC: U.S. Government

Printing Office, July 1990).

U.S. Congress, Office of Technology Assessment,

Identi~ing and Regulating Carcinogens+Background Paper, OTA-BP-H-42 (Washington, DC:

U.S. Government Printing Office, November 1987).

U.S. Congress, Office of Technology Assessment,

Mapping Our Genes—The Genome Projects: How

Big, How Fast? OTA-BA-373 (Washington, DC:

U.S. Government Printing Office, April 1988).

U.S. Congress, Office of Tedmology Assessment,

Medical Testing and Health Insurance, OTA-H-384

(Washington, DC: U.S. Government Printing Office,

August 1988).
38 ● Genetic Monitoring and Screening in the Workplace

14.

15.

16.

17.

18.

19.

U.S. Congress, Office of Technology Assessment,

New Developments in Biotechnology: The Commercial Development of Tests for Human Genetic

Disorders, staff paper, February 1988.

U.S. Congress, Office of Technology Assessment,

New Developments in Biotechnology: Field-Testing

Engineered Organisms: Genetic and Ecological

Issues, OTA-BA-350 (Washington, DC: U.S. Government Printing Office, May 1988).

U.S. Congress, Office of Technology Assessment,

New Developments in Biotechnology: Ownership of

Human Tissues and Ceils, OTA-BA-337 (Washington, DC: U.S. Government Printing Office, March

1987).

U.S. Congress, Office of Technology Assessment,

New Developments in Biotechnology: Patenting Life,

OTA-BA-370 (Washington, DC: U.S. Government

Printing Office, April 1989).

U.S. Congress, Office of Technology Assessment,

New Developments in Biotechnology: Public Perceptions of Biotechnology41a ckground Paper, OTABP-BA-45 (Washington, DC: U.S. Government

Printing Office, May 1987).

U.S. Congress, Office of Technology Assessment,

New Developments in Biotechnology: U.S. Investment in Biotechnology, OTA-BA-337 (Washington,

DC: U.S. Government Printing Office, July 1988).

20.

21.

22.

23.

24.

25.

U.S. Congress, Office of Technology Assessment,

New Developments in Neuroscience: Neurotoxicit#dentifying and Controlling Poisons of the

Nervous System, OTA-BA-436 (Washington, DC:

U.S. Government Printing Office, May 1990).

U.S. Congress, Office of Technology Assessment,

Preventing Illness and Injury in the Workplace,

OTA-H-256 (Washington, DC: U.S. Govemrnent

Printing Office, April 1985).

U.S. Congress, Office of Technology Assessment,

Reproductive Health Hazards in the Workplace,

OTA-BA-266 (Washington, DC: U.S. Government

Printing Office, December 1985).

U.S. Congress, Office of Technology Assessment,

The Role of Genetic Testing in the Prevention of

Occupational Disease, OTA-BA-194 (Washington,

DC: U.S. Government Printing Office, April 1983).

U.S. Congress, Office of Technology Assessment,

Technologies for Detecting Heritable Mutations in

Human Beings, OTA-H-298 (Washington, DC: U.S.

Government Printing Office, September 1986).

U.S. Department of Health and Human Services, U.S.

Department of Energy, Understanding Our Genetic

Inheritance: The U.S. Human Genome Project, The

First Five Years 1991-1995, DOE/ER-0452P, April

1990.
Chapter 3

Occupational Health and

Genetic Monitoring and Screening:

An Overview
CONTENTS

Page

HISTORY OF GENETIC MONITORING AND SCREENING . . . . . . . . . . . . . . . . . . . . ...41

Screening Programs for Sickle Cell Anemia and Trait . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41

Industry Involvement in Genetic Monitoring and Screening . . . . . . . . . . . . . . . . . . . . . . . . 44

INTRODUCTION TO OCCUPATIONAL ILLNESS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45

Costs of Occupational Illness to the Employee . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46

Costs of Occupational Illness to the Employer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46

Costs of Occupational illness to Insurance Industry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46

Costs of Occupational Illness to Society . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .46

FEDERAL AGENCIES INVOLVED IN OCCUPATIONAL SAFETY AND

HEALTH . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .46

Occupational Safety and Health Administration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46

National Institute for Occupational Safety and Health . . . . . . . . . . . . . . . . . . . . . . . ,,,.... 47

National Labor Relations Board . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48

Environmental Protection Agency . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .50

SUMMARY AND CONCLUSIONS ● . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50

CHAPTER 3 REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .50

Boxes

Box Page

3-A. Community Screening for Tay-Sachs Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43

3-B. Occupational Safety and Health in Finland . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48

3-C. NIOSH Surveys of the Workplace . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49
Chapter 3

Occupational Health and Genetic Monitoring

and Screening: An Overview

The concept of genetic monitoring and screening

emerged prior to the discovery of the molecular

structure of DNA by Watson and Crick in 1953.

Although not always tied to the workplace, an

examination of the evolution of genetic monitoring

and screening can provide valuable insight to the

procedures’ current and potential employment applications. This chapter discusses the history of genetic

monitoring and screening as they have been used in

both workplace and nonoccupational settings. In

addition, the economics of genetic monitoring and

screening are examined by evaluating the costs of

occupational illness to the employee, the employer,

the insurance industry, and society. Finally, the

Federal agencies either currently involved or potentially involved in the policy matters associated with

genetic monitoring and screening in the workplace

are introduced.

HISTORY OF GENETIC

MONITORING AND SCREENING

As early as 1938, noted geneticist J.B.S. Haldane

discussed “sorting out workers according to their

susceptibility to occupational hazards” (7). He

suggested, for example, screening out potters who

had “constitutions” that could make them susceptible to bronchitis. Haldane went onto suggest that the

entry into the workplace of those with the hereditary

trait for bronchitis could be regulated.

One of the frost cases of an individual’s genetic

condition reacting to either a chemical agent or drug

was reported in the 1950s. During the Korean

conflict, some American soldiers taking the antimalarial drug, primaquine, experienced hemolysis (the

destruction of red blood cells) (4). The hemolysis

was attributed to their carrier status of glucose-6-

phosphate dehydrogenase (G-6-PD) deficiency,

which results in less of the enzyme G-6-PD in their

red blood cells (see ch. 5 for further discussion).

People with this trait are often found in malariaridden regions, and it is common among Blacks and

those with Mediterranean origins. The trait protects

people somewhat against contracting malaria, but

also can result in hemolysis when triggered by eating

fava beans or by taking certain drugs such as

antimalarial medication. The soldiers in Korea who

reacted to the antimalarial medication, as a result of

G-6-PD deficiency, were characterized as “hypersusceptible.

It was believed by the early 1960s that carriers of

G-6-PD deficiency could also undergo hemolysis

after exposure to certain chemicals. Since then, some

employers believe that those with G-6-PD deficiency should not handle aromatic nitro or amino

compounds, industrial chemicals prevalent in dynamite factories. The concept of “hypersusceptibility" was being applied to the workplace. One idea

considered was the use of a preplacement examination to detect susceptible employees (3 1). Once such

employees were discovered, their susceptibility

would be factored into their workplace assignment.

By the early 1970s, performing “hypersusceptibility" screens had been proposed for five conditions,

including G-6-PD deficiency, sickle cell disease,

and alpha-1-antitrypsin deficiency (32). Approximately 50 human genetic diseases have been identified as having the potential to enhance an individual’s susceptibility to toxic or carcinogenic effects

of environmental agents (4) (see ch. 5). Genetic

screening may be justified depending on the type

and severity of the condition, as well as the difficulty

or the expense of performing the genetic screening

test (17).

Screening Programs for

Sickle Cell Anemia and Trait

Sickle cell anemia in the United States was the

subject of a great deal of public attention in the early

1970s. The Black community felt that it had become

a‘ ‘neglected disease’ and that it had received little

Federal research funding. As a result of public

debate, considerable Federal interest developed in

sickle cell anemia (22). President Nixon made an

appeal for an effort to combat sickle cell anemia in

his 1971 health address to Congress (9). Laws

requiring sickle cell screening were eventually

passed in at least 20 States (l). These laws targeted

newborns, schoolchildren, marriage license applicants, and inmates of penal institutions (19,22).

-41-
42 ● Genetic Monitoring and Screening in the Workplace

TAY-SACHS FACTS:

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DISORDER OF INFANCY

● A CHILD WITH THE DISEASE CAN BE BORN TO

HEALTHY PARENTS WHO ARE CARRIERS OF THE

TAY-SACHS GENE

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Photo CJedit: Alpha Epsilon Pi

An advertisement for Tay-Sachs screening.

Many who participated in screening programs

found the resulting information difficult to interpret.

A 1975 study by the National Academy of Sciences

(NAS) reinforced this notion. The study found that

many of the sickle cell screening programs initially

established did not provide proper genetic counseling, and did not always keep the results confidential

(19). For many, the difference between sickle cell

anemia and sickle cell trait was not made clear in the

screening program process. (Sickle cell anemia

occurs when the patient inherits the gene for sickle

hemoglobin from both parents; sickle cell trait

occurs when the gene for sickle hemoglobin is

passed on from only one parent.)

Some who participated in screening programs and

were found to be carriers of sickle cell trait

experienced discrimination at work and from insurance companies that raised their premiums (9).

Apparently, discrimination in the workplace sometimes occurred because it was believed that those

with sickle cell trait could experience the painful

episodes characteristic of sickle cell disease (which

occur when sickle-shaped red blood cells occlude

the normal flow of blood) (2,24). The result for some

job applicants was denial of employment based on

their carrier status and removal for some who were

already employed. In some cases, life insurance

companies either raised premiums for carriers or

denied coverage for applicants with sickle cell trait

(9). At that time, laws were enacted in Florida,

Louisiana, and North Carolina that prohibited such

discrimination (26). Since the mid- 1970s, many of

the State laws requiring mandatory sickle cell testing

have been repealed. The sickle cell screening

programs of the 1970s are often compared to

Tay-Sachs disease screening programs (see box

3-A).

Controversy still exists over whether the carriers

of sickle cell trait are at risk of having sickling

episodes. A 1974 NAS report concluded “there was

insufficient scientific information to forma basis for

excluding carriers from the armed forces or for

limiting their activities or duties” (20). However, it

was not until 1981 that the U.S. Air Force Academy

reversed its policy of excluding Blacks with sickle

cell trait from pilot training, based on the belief that

a low-oxygen environment (e.g., high-altitude exer-
Chapter 3-Occupational Health and Genetic Monitoring and Screening: An Overview ● 43

Box 3-A-Community Screening for Tay-Sachs Disease

Tay-Sachs disease (TSD) screening programs were initiated in the early 1970s, around the same time the

Nation’s sickle cell screening programs began. While mass sickle cell screening eventually ended because of the

belief that the information was sometimes used to the detriment of participants, TSD screening has been cited as

a model in professional-community cooperation. TSD is a rare inherited, incurable, neurological disease most

prevalent in Jews of Ashkenazi origin. It results in progressive necrologic deterioration and results in death within

a child’s first few years.

Many screening programs at the local level were initiated following the development of the blood test to detect

TSD carrier status in 1970. Screening can determine whether one or both parents are carriers for TSD. If both are

carriers, they have a risk of 1 in 4 in each pregnancy of having a child affected with TSD.

A mass screening program involving some 7,000 individuals was initiated in the Baltimore-Greater

Washington, DC area in the early 1970s, Six to eight weeks prior to this program, the community received some

education about TSD. Information was disseminated through the press, TV, radio, letters from religious, medical

and community groups, medical presentations, and telephone contact. Eventually, similar screening programs were

initiated in at least five countries.

In one survey, one-half of the TSD carriers were still uneasy with the information even though they had been

informed of the meaning of carrier status through extensive educational efforts and genetic counseling. Current

emphasis is on hospital- or physician-based screening for TSD with individual couples. Overall in the United States,

TSD screening has reduced the incidence of TSD in the Jewish population by at least 70 percent.

SOURCES: Officee of Technology Assessment 1990, based on M.J. Goodman and L.E. Goodman, ‘‘The Overselling of Genetic Anxiety, The

Hastings Center Report, October 1982; R.H. Kenen and R.M. Schmidt “Stigmatization of carrier status: social replications of

Heterozygote Genetic Screening Program, “ American Journal of Public Health 68:1116-1120, 1978.

tion or flights, or deep-water activity) would cause this legislation was on voluntary participation in

a carrier to undergo a sickling episode (8,14).

While States were passing sickle cell screening

laws, Congress passed the National Sickle Cell

Anemia Control Act (Public Law 92-294) in 1972.

Only States that met the requirements of the act were

eligible for Federal funds. To receive funds, a State

program had to be voluntary, a requirement designed

to defuse the controversy over mandatory screening

programs. Although the intent of the law was to

reduce stigmatization of and discrimination against

the carriers of sickle cell trait, many saw these

concerns as continuing unabated (23).

The National Sickle Cell Anemia Control Act was

updated in 1976 and renamed the National Sickle

Cell Anemia, Cooley’s Anemia, Tay-Sachs, and

Genetic Diseases Act (Public Law 94-278; hereinafter, The National Genetic Disease Act). Much

broader in scope, it authorized increased Federal

funds to be awarded as grants and contracts by the

Secretary of the Department of Health, Education,

and Welfare. Goals of the National Genetic Disease

Act included increased levels of basic and applied

research, training, testing, counseling, and education

programs on genetic disease. Again, the emphasis of

testing programs. It also emphasized using proper

guidelines for confidentiality of results, and stressed

the availability of genetic counseling for all participants (23).

Advances in the treatment of sickle cell anemia

have prompted renewed interest in screening newborns. A certain percentage of infants with sickle

cell anemia are at risk of overwhelming infection

and sudden death in the first few years of life. If their

sickle cell disease is identified early on, affected

infants can be given prophylactic antibiotics that

significantly reduce the risk of infection and lower

the overall mortality rate from the disease in early

life (6). A 1987 National Institutes of Health

conference on newborn screening for sickle cell

disease concluded that every child should be

screened to prevent the potentially fatal complications of sickle cell disease in infancy. In addition, for

a program to be effective, proper followup capabilities should be in place prior to instituting a screening

program. The services available to the patients and

their families should include medical care, psychosocial support, and genetic counseling (35).
44 ● Genetic Monitoring arid Screening in the Workplace

WHAT...

Is

CELL

Photo credit: Howard University

Pamphlets describing sickle cell anemia and

sickle cell trait.

Industry Involvement in Genetic

Monitoring and Screening

Although the concept of screening out unhealthy

workers has been around since the early part of this

century, most screening technologies have only

recently become available. Several incidents of

industry involvement in genetic monitoring and

screening since the 1960s have been reported. They

have varied from research programs using genetic

monitoring techniques for evaluating chromosomal

damage to efforts in genetic screening to detect

genetic conditions such as G-6-PD deficiency or

sickle cell trait. Each use brings with it its own set of

scientific, legal, and ethical issues.

An early pilot program of cytogenetic monitoring

was initiated by Dow Chemical in 1964. (See ch. 4

for a discussion of cytogenetic monitoring.) Within

10 years, some 43,044 chromosomal profiles had

been performed on 1,689 employees involved in the

chemical production process. In addition, 25,104

chromosomal profiles were conducted on 1,302

applicants as part of a preemployment exam (13).

These cytogenetic analyses and preemployment

exams provided a baseline for future cytogenetic

analyses of an individual. By comparing an employee’s current data to that taken previously, the

employee served as his or her own control. In 1977,

Dow conducted an evaluation of workers exposed to

both epichlorohydrin and benzene which, due to the

ambiguity of the findings, gave rise to a controversy

regarding use of cytogenetics for population monitoring (3).

Their efforts were criticized for several reasons,

which included failure to take into account the

effects of personal habits and lifestyle decisions

(e.g., tobacco use, etc.), and age on chromosomal

change. Also, the results of these profiles were given

to those employees involved without properly explaining what the results meant in terms of their risk

of cancer and genetic disease in their offspring

(3,1 1). The program was terminated in 1977 by Dow

Chemical in response to the questions about the

validity and reliability of the results, and the

interpretation of differences in results between

employee groups.

Another corporation, Johnson & Johnson, conducted some cytogenetic monitoring research in

1980 to examine the effects of ethylene oxide, a

sterilant gas, on workers (12). The project’s intent

was to determine whether workers exposed to

ethylene oxide experienced any more chromosomal

changes than those not exposed. This was done by

analyzing sister chromatid exchanges and chromosomal aberrations in workers at three plants where

three levels of exposure existed (see ch. 4). These

groups were then compared to three control groups

not exposed to ethylene oxide. After 6 months, the

study found that employees working with the

highest concentrations of ethylene oxide had a

significantly greater incidence of sister chromatid

exchange than the control group. This prompted

Johnson & Johnson to discontinue the use of

ethylene oxide at that particular plant (8).

A genetic screening program for sickle cell trait

took place at the DuPont Corp. in the 1970s.

According to company officials, the program was

initiated at the request of a group of Black employees. The resulting information was not used for

employment decisions, officials later stated. Rather

it was for the “information and edification” of the

employees (8). DuPont was criticized by some

because, although there were many employees of
Chapter 3--Occupational Health and Genetic Monitoring and Screening: An Overview . 45

Mediterranean origin at the facility, only Blacks

were given the sickle cell test. (People of Mediterranean origin as well as Blacks have a higher incidence

of sickle cell anemia.)

Both the Dow cytogenetics program and DuPont’s sickle cell screening program were later to

become the focus of a great deal of controversy. A

series of newspaper reports in 1980 argued that

genetic monitoring and screening programs were

widespread in industry and had been used in

industrial settings for several years (29). Much was

made over whether DuPont was actually using the

information derived from the sickle cell screening

program to make hiring or job placement decisions.

The Federal response to genetic monitoring and

screening was also examined. The newspaper series

identified a section on medical surveillance found in

the Code of Federal Regulations that stated that in a

preassignment examination before exposure to certain carcinogens, a worker’s personal history that

included genetic and environmental factors could be

taken. As mentioned in chapter 2, these events

heightened congressional interest.

INTRODUCTION TO

OCCUPATIONAL ILLNESS

It has long been recognized that there are substantial health risks posed by various workplace environments, risks often associated with exposure to

harmful agents such as chemicals and radiation.

These risks can produce costs to the workers in terms

of loss of earnings, ill health, and even premature

death. Such risks are costly to employers who may

have to compensate workers through workers’

compensation schemes for lost earnings and through

health insurance schemes for the costs of the medical

care they require, and who may have to compensate

the workers’ estates (through tort liability) for the

premature death of the workers.

An occupational illness is defined by the Department of Labor’s (DOL) Bureau of Labor Statistics

(BLS) as any abnormal condition or disorder, other

than one resulting from an occupational injury,

caused by exposure to environmental factors associated with employment (37). This includes acute and

chronic illnesses or disease that can be caused by

inhalation, absorption, ingestion, or direct contact.

The prevalence of occupational illness is unknown. On the Federal level, BLS is responsible for

collecting statistical data on occupational injury and

illness. BLS statistics on occupational illness incidence rates represent only new cases that occur in a

given year. Continuing conditions that were reported

in previous BLS occupational injury and illness

surveys are not reported (36). Gathering data on the

incidence of occupational disease in the United

States is extremely difficult for several reasons.

Often the relationship between exposure to a health

hazard and the risk of, or even onset of, disease is not

well understood. Because occupational diseases

may have long latency periods, it is difficult to

gather the information necessary to link workers’

employment history with their medical diagnostic

records. Personal physicians are often not aware of

their patients’ prior chemical exposures or work

environments, and therefore may not recognize and

diagnose an occupational disease (5,10). It has been

suggested that the BLS Annual Survey be modified

to improve data collection and analyses (18).

Approximately 190,000 cases of occupational

disease were reported in 1987 by BLS (37). This was

a 39 percent increase over the 136,800 cases

recorded in 1986, which represented a 9 percent

increase over the 125,600 cases reported in 1985

(36). An explanation offered by BLS for the increase

in illness rates was improved recordkeeping by

industry as a result of new government guidelines, as

well as an effort on the part of BLS to improve its

statistics (41).

Costs of occupational illness affect several parties—the employee, the employer, the insurance

industry, and society. The employee experiences

physical pain and suffering, emotional costs, and

financial costs in the form of medical bills, changes

in insurance status, and loss of salary. When a

member of the work force incurs an occupational

disease, the employer experiences lower productivity levels, higher insurance premiums, workers’

compensation claims, and potential legal fees and

monetary damage assessed from any lawsuits (27).

Insurance companies compensate occupational disease victims, and thereby either sustain a loss or raise

others’ premiums. Finally, society pays for a large

portion of the care and compensation of occupational disease victims through Federal health programs.
46 ● Genetic Monitoring and Screening in the Workplace

Costs of Occupational Illness to the Employee

Costs of occupational illness for the individual

employee can include loss of potential earnings

(including those fringe benefits used for disability

days); transfer to a lower paying job; early retirement; and direct medical expenses. In addition, the

costs of such intangibles as premature death, pain

and suffering, and family bereavement if an occupational illness victim dies cannot be estimated.

Costs of Occupational Illness to the Employer

An employer’s costs associated with occupational

illness include direct health care expenses, higher

workers’ compensation premiums, excess absenteeism, worker turnover, reduced productivity, and

possible civil liability suits. Compensation for

work-related illness can prove to be a contentious

issue. Once an illness can be pinpointed to a

particular employer, it is possible that employer can

be sued by the employee affected even though

workers’ compensation is the ‘‘exclusive remedy’

for such claims (28). Even within the employer’s

staff there may be disagreement as to the protocol for

treating and compensating occupational illness

cases. While occupational physicians and other

employer-provided health professionals may be

interested in the prevention and control of workrelated disease from a purely medical standpoint, the

employer may be interested in causality, and ultimately in compensation and liability from a legal

standpoint. Thus, work-relatedness is defined as

both a medical and a legal concept (40). Employers

have a financial interest in using their resources

efficiently; an interest that could be cited by

members of industry as proper justification for

monitoring and screening employees for genetic

conditions or damage.

Costs of Occupational Illness to

Insurance Industry

For the majority of Americans, access to health

care, and the health insurance that makes such access

possible, is provided through their jobs. Containment of ever-increasing health care costs, whether or

not they are related to occupational illness, is a high

priority for employers. The increasing propensity of

employers to self-insure their employees’ health

care expenses is a reflection of this. Because these

plans are not regulated by the States, there are fewer

restraints on them than on traditional health insurance plans.

Companies concerned about insurance costs may

be more interested in genetic screening for workers

who are likely to develop both occupational and

nonoccupational diseases. Many argue that genetic

monitoring and screening in the workplace to limit

occupational illnesses may be less important to them

in the long run than monitoring and screening in the

workplace to limit company health insurance costs

(21,26).

Costs of Occupational Illness to Society

Society absorbs costs of occupational illness from

the private sector. These include: transfer payments

and services to disabled individuals and families

(e.g., social security benefits and public assistance);

health care costs not paid by the individual or the

company which are then passed onto Medicare and

Medicaid; and the administrative costs of related

government programs.

FEDERAL AGENCIES INVOLVED

IN OCCUPATIONAL SAFETY

AND HEALTH

Although the principal Federal organization responsible for the occupational safety and health

regulatory process is DOL’s Occupational Safety

and Health Administration (OSHA), there are several other agencies involved. In this section, the

activities of OSHA, the National Institute for

Occupational Safety and Health (NIOSH), the Environmental Protection Agency (EPA), and the National Labor Relations Board (NLRB) are discussed

as they relate to both general occupational safety and

health and genetic monitoring and screening in the

workplace.

Occupational Safety and Health

Administration

In 1970, Congress passed the Occupational Safety

and Health Act (Public Law 91-596) (OSH Act) “to

assure as far as possible every working man and

woman in the Nation safe and healthful working

conditions and to preserve our human resources.

Within the OSH Act there are several federally

imposed statutory duties that must be undertaken by

the employer.
Chapter 3-Occupational Health and Genetic Monitoring and Screening: An Overview . 47

Photo credit: Margaret Anderson

U.S. Department of Labor, Washington, DC: Headquarters

of the Occupational Safety and Health Administration.

Coverage under the OSH Act does not include

State and local government employees, or those

covered under other occupational health and safety

legislation. Prior to the passage of the OSH Act,

States were responsible for regulating occupational

safety and health. Little uniformity among safety

codes or enforcement practices existed, with no

standardized reporting and recordkeeping system for

occupational illnesses and injuries (25). In addition

to Federal enforcement, OSHA now oversees 23

State OSHA programs. If a State plan is approved by

OSHA, the State may receive up to 50 percent of its

operating costs from OSHA. OSHA will only grant

this approval if it can assure that the State performance will be as effective as its own (33).

Contained in the OSH Act was a provision to

create OSHA within DOL headed by a presidentially

appointed Assistant Secretary of Labor. OSHA is

responsible for setting health and safety standards

for workplaces, inspecting worksites to ensure

proper compliance with those standards, issuing

citations for violations of the standards, providing

educational and consultation services and programs,

and monitoring State programs. Perhaps the two

most important OSHA duties are standard-setting

and the enforcement of these standards. Effective

March 1989, OSHA adopted new exposure standards for over 350 substances (15). Compliance with

these standards is expected to reduce the number of

workplace fatalities, illnesses, and lost workdays

caused by work-related illnesses (38). Prior to this

action, the bulk of OSHA’s existing health standards

were adopted when it was first formed.

At this time, OSHA does not have a formal policy

on the use of genetic monitoring and screening in the

workplace. Some argue that the OSH Act already

provides statutory authority for the evaluation of the

accuracy of genetic tests and could implement such

genetic monitoring and screening programs, by

having NIOSH formulate the criteria for acceptability of genetic monitoring tools and screening tests.

Critics of using genetic monitoring and screening in

workplace settings maintain, however, that if OSHA

adopted a standard mandating genetic monitoring or

screening, employers would exclude workers, rather

than make the workplace safe for all.

National Institute for Occupational

Safety and Health

NIOSH is a research agency of the Centers for

Disease Control of the U.S. Public Health Service,

which is within the Department of Health and

Human Services. It was created under the OSH Act

to conduct research designed to identify and evaluate workplace hazards, research concerning measurement techniques and control technologies, and

education of occupational health and safety professionals. NIOSH also assists OSHA by developing

criteria and recommendations to be used by OSHA

in setting standards, and conducting Health Hazard

Evaluations. (See box 3-B for information on an

international agency similar to NIOSH.)

Congress deliberately separated the research and

regulatory functions of the OSH Act to protect the

neutrality of the science. However, some say the

result has been less than ideal and point to lack of

coordination between OSHA and NIOSH. In setting

standards, OSHA is not required to follow NIOSH

scientific recommendations; OSHA also considers

other nonscientific factors, such as economic, social,

and political factors, in its regulatory decisions (28).

Some NIOSH research requires on-site workplace

investigations to gather testimony from both employers and employees, and to conduct medical

examinations and tests to detect exposure to hazard-
48 ● Genetic Monitoring and Screening in the Workplace

Box 3-B--Occupational Safety and Health in Finland

In 1987, Finland’s Parliament passed the Labour Protection Act which specifically directs employers to

consider “possible risk for the genetic material" of the employee. Prior to the passage of this legislation, Finland’s

Institute of Occupational Health (101-1) was pursuing research opportunities in genetic monitoring. IOH oversees

a register of employees who have been occupationally exposed to chemicals listed as potential cancer-causing

agents. This enables researchers to monitor those workers for cancer. Another Federal organization, the National

Institute of Radiation Protection and Safety, is conducting a longitudinal study to determine whether workers m four

Finnish nuclear powerplants have suffered any chromosomal damage.

The main emphasis of IOH research is on prevention of occupational disease and injury. Projects are designed

to be “multidisciplinary, problem-oriented and aimed at solving national problems.” Research areas include:

epidemiology, medicine, physiology, ergonomics, psychology, occupational safety, industrial hygiene, and

toxicology. Most of the research in genetic monitoring and screening is performed within the Department of

Industrial Hygiene and Toxicology through a wide range of toxicological, epidemiological, and medical studies.

Scientists currently are using various methods of genetic monitoring techniques such as chromosomal aberrations,

sister chromatid exchange, micronuclei detection and adduct formation in proteins, ribonucleic acid, and DNA, In

addition, some “susceptibility assessments” have been conducted using genetic screening methods.

Scientists at IOH conduct some research and informational exchange with the international scientific

community. This can be done through formal bilateral agreements with international research institutions or

agencies, as NIOSH, or through international organizations as the World Health Organization. An example of a

collaborative project currently underway with the other Nordic nations is a study to assess the health significance

of somatic chromosome damage. Utilizing a cohort of 3,000 individuals, the project is aimed at determining g worker

exposure to genotoxins, and whether or not this predisposes them to ill health, particularly cancer.

SOURCES: Office of Technology Assessment, 1990 based on A. Brogger, L. Hagmar, I.L. Hansteen, et al., “An Inter-Nordic Prospective Study

on Cytogenetic Endpoints and Cancer Risk,” Cancer Genetics and Cytogenetics 45:85-92, 1990 Finnish Institute of Occupational

Health, Annual Report 1987 (Helsinki Finland: 1988); Finnish Institute of Occupational Health, Institute of Occupational Health

(Helsinki, Finland 1988); Finland’s Parliament “The Labor Protection Act of 1987,” n. 27/87.

ous agents (see box 3-C). Employees can contact

NIOSH to request that the agency conduct worksite

investigations.

At this time, because NIOSH is a research and not

a regulatory agency, it cannot require usage of

genetic monitoring or screening in the workplace.

However, it currently conducts some research in this

area (see app. D). NIOSH could be requested to

formulate the criteria necessary for determining the

acceptability of genetic monitoring or screening

tests for use in the workplace setting (39).

National Labor Relations Board

One of the central pieces of legislation regulating

labor-management relations is the National Labor

Relations Act (NLRA) of 1935 (29 U.S.C. 151 et

seq.). It encouraged the practice of collective bargaining, and offered protection to workers of full

freedom of association, self-organization, and designation of representatives. Amendments to the law in

Photo credit: Kathy Goldberg 1947, 1959, and 1974 clarified NLRB organization

U.S. Department of Health and Human Services, and procedures, and increased the protection of

National Institute for Occupational Safety and Health, workers and enhanced their right not to participate in

Robert A. Taft Laboratories, Cincinnati, OH. union activity (16).
Chapter Occupational Health and Genetic Monitoring and Screening: An Overview ● 49

Box 3-C-NIOSH Surveys of the Workplace

NIOSH conducted the National Occupational Hazard Survey of 4,636 facilities in 67 metropolitan areas from

1972 to 1974. The purpose was to survey American workplaces to determine to what occupational hazards the

Nation’s workers were being exposed, and to examine companies’ health and safety programs. NIOSH conducted

a similar survey, the National Occupational Exposure Survey (NOES) from 1981 to 1983. The NOES surveyed

4,490 facilities in 98 geographic areas. A facility site visit included completion of a standardized survey

questionnaire by the facility management, and a walk-through survey taken by a NIOSH employee to inventory

chemical and physical agents present in that particular work environment.

Among the issues the NOES attempted to answer were: what occupational groups are exposed to what types

of potential health hazards in the United States? In what types of industries are these hazards found? What control

technologies are present to prevent work-related disease in terms of plant operation and occupational safety and

health practice? W are the exposures by intensity, duration, and type of control? And what trade name products

were present?

Both surveys gathered a representative sample from all of the nonagricultural, nonmining, and nongovernmental businesses, with eight or more employees, that were covered under the OSH Act. One difficulty of the survey

has been that it has taken several years to analyze the data. This has been due, in part, to the length of time it has

taken to track down the components of trade name products seen on the walk-through surveys. During the NOES

walk-through investigations, NIOSH representatives saw more than 10,000 different potential exposure agents and

over 100,000 trade name products. Comparisons to the data collected from 1972 to 1974 will provide NIOSH with

a valuable database that can be used to identify areas for further occupational health and safety research.

By comparing the data from both surveys, NIOSH has been able to analyze some of the trends in worker access

to health care in the United States. NIOSH found two related events occurring simultaneously. First, facilities are

increasingly substituting other health care professionals, primarily nurses and allied medical personnel, for on-site

occupational physicians. Health units staffed only by paramedics or nurses are becoming increasingly common. If

physician care is needed, the worker is often sent to an off-site medical facility through contractual agreements

between the employer and the medical care provider. In comparing the figures from the two NIOSH surveys, the

percentage of physician care offered off-site increased from 19.1 to 57.8 percent. Worker access to health care is

increasing but much of it is being offered off-site.

The NOES also gathered data concerning some screening tests, preemployment exams, and the recording of

health information. The screening tests used were: ophthalmology, audiology, blood urine, and pulmonary function

tests, and chest x-rays. Overall, worker access to one or more screening tests increased slightly. This increase would

have been greater, except that the number of immunizations given by employers decreased. Data on recording of

health information showed a decrease in recording by employers because of the increased use of off-site medical

facilities. This responsibility is being left to the off-site physician. This analysis suggests that while worker access

to health care is increasing, the delivery mechanism is changing from on-site to off-site, a circumstance that could

have implications for the field of occupational medicine.

SOURCES: Office of Technology Assessment, 1990; based on D.H. Pedersen and W.K. Sieber, Jr., “Some Trends in Worker Access to Health

Care in the United States (1974- 1983), "Journal of Industrial Medicine 15(2): 151-165, 1989; U.S. Departmcntof Health and Human

Services, Public Health Service, Centers for Disease Control, National Institute for Occupational Safety and Hcalth, National

Occupational Exposure Survey: Volume 1 Survey Manual, J. Seta, D. Sundin, and D. Pedersen(eds.), DHHS Pub. No. (PHS) 88-106

(Washington, DC: 1988).

Under NLRA, NLRB administers the law and acts Although the law was enacted to assist the

as an intermediary between workers and man- organization of unions, some members of the labor

agement. NLRB is responsible for preventing and community have said that they would be better off if

remedying unfair labor practices, and conducting the law were repealed. Much of the criticism stems

secret ballot elections to determine whether employ- from what some see as the Board’s lack of remedies

ees wish to be represented by a union. NLRB’s to deal with unfair labor practices, as well as its

Office of the General Counsel is charged with the backlog of pending cases (28,30). It is also argued by

responsibility of investigating and prosecuting un- labor groups that they feel inadequately protected by

fair labor practices. NLRB when they confront management. In order for
50 ● Genetic Monitoring and Screening in the Workplace

an employer to have a duty to deal with a union to

bargain over the issue of genetic monitoring or

screening, it would have to be considered a mandatory subject of bargaining (39). Because health and

safety issues are considered to be mandatory subjects of bargaining, it has been argued that health and

safety includes genetic monitoring and screening

(39). The extent to which unions and employers

could bargain and come up with solutions to the

many questions that would arise over the use of

genetic monitoring or screening depends on answers

to a variety of questions. These questions include

issues such as the accuracy and predictive value of

the tests, clinical significance of the results, access

to results, how the tests are used, and who will pay

for them.

Environmental Protection Agency

Established in 1970, EPA was created to protect

and enhance the environment. EPA administers

several environmental health statutes that include

broad mandates to protect the public from environmental hazards (34) (see ch. 6). EPA has pollution

abatement and control programs in the areas of air,

water, solid waste, hazardous wastes, pesticides,

radiation, and toxic substances. In addition, it

reinforces other Federal agencies’ efforts with respect to their operations’ impact on the environment.

EPA performs research in the area of genetic

monitoring (see app. D).

SUMMARY AND CONCLUSIONS

The concept of genetic monitoring and screening

is not new. Over 50 years ago, the idea of sorting

workers according to their individual susceptibilities

to occupational hazards was discussed. The idea of

factoring “hypersusceptibility” into workplace assignments was again discussed in the early 1970s,

and screens for five conditions, including G-6-PD

deficiency, sickle cell disease, and alpha-1-

antitrypsin deficiency were proposed.

Controversy over the negative impacts that could

result from genetic screening arose following the

introduction of a national sickle cell screening

program in the early 1970s. The resulting information caused some carriers of the trait to be confused

about their health status, as well as to be discriminated against by employers and insurance companies. As a result of this experience, some have

concluded that widespread genetic monitoring and

screening in the absence of clear guidelines on how

the screening results will be interpreted and used has

the potential for great abuse. At the same time,

legislation concerning sickle cell anemia and other

genetic diseases was passed at the Federal level

authorizing funds for research, training, testing,

counseling, and education.

In addition to mass screening programs, there

have been reported cases where genetic monitoring

or screening have been used to smaller extents in the

workplace. The use of these technologies in the

workplace brings with it its own set of scientific,

legal, and ethical issues. Discussions concerning the

use by employers of genetic monitoring and screening are being heard again, partly in response to the

soaring costs of health insurance and also because of

new scientific discoveries in genetics that could be

applied to the practice of occupational medicine and

public health. Because occupational illnesses are

costly to all parties involved, there is increasing

interest in using genetic screening methods to detect

genetic traits that would make a worker susceptible

to certain illnesses. Currently there are at least four

Federal agencies involved in occupational safety

and health, and perhaps genetic monitoring and

screening in the workplace.

1.

2.

3.

4

5.

6.

7.

8.

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Buffler, P., University of Texas at Houston, Houston,

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Directions,’ contract document for the Office of

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1989.

Cullen, M.R., and Cherniack, M.G., “Spectrum of

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Gaston, M.H., Verter, J.J., Woods, G., et al.,

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the Resolution and Closure of Disputes in Science

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Mine, M. P., “Industrial Screening Programs for

Workers,” Environment 24:26-38, 1982.

Long, J., “Workplace Health: OSHA Sets New

Exposure Standards,” Chemical & Engineering

News, p. 4, Jan. 23, 1989.

McGuiness, K. C., and Norris, J. A., How To Take a

Case Before the NLRB (Washington, DC: Bureau of

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Murray, R.F., ‘‘Tests of So-Called Genetic Susceptibility, ’ Journal of Occupational Medicine

28(10):1103-1107, 1986.

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Programs, Principles, and Research (Washington,

DC: National Academy Press, 1975).

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Forces (Washington, DC: National Academy Press,

1974).

Nelkin, D., and Tancredi, L., Dangerous Diagnostics: The Social Power of Biological Information

(New York, NY: Basic Books, Inc., 1989).

President’s Commission for the Study of Ethical

Problems in Medicine and Biomedical and Behavioral Research, Screening and Counseling for Genetic Conditions (Washington, DC: U.S. Government Printing Office, February 1983).

Reilly, P., “Government Support of Genetic Services,” Social Biology 25:23-32, 1978.

Reilly, P., ‘ ‘There’s Another Side to Genetic Screening,” Prism 55-57, January 1976.

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Safety and Health in Twentieth Century America

(Bloomington, IN: Indiana University Press, 1987).

Rothstein, M. A., Med”cal Screening and the Employee Health Cost Crisis (Washington, DC: Bureau

of National Affairs, Inc., 1989).

Rothstein, M.A., “Medical Screening of Workers:

Genetics, AIDS, and Beyond,” Labor Lawyer

2(4):675-682, 1988.

Rothstein, M. A., University of Houston Law Center,

Houston, TX, personal communications, February

1989, March 1990.

Severe, R., “The Genetic Barrier: Job Benefit or Job

Bias?” The New York Times, Feb. 3-6, 1980.

Silver, E., and McAvoy, J., “The National Labor

Relations Act at the Crossroads,” Fordham Luw

Review 56:181-208, 1987.

Stokinger, H.E., and Mountain, J.T., “Tests for

Hypersusceptibility to Hemolytic Chemicals,” Archives of Environmental Health 6:57-64, 1%3.

Stokinger, H.E., and Scheel, L.D., “Hypersusceptibility and Genetic Problems in Occupational MedicirIo-A Consensus Report,” Journal of Occupational Medicine 15:564-573, 1973.

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Employer Injury and Illness Records, Report to the

Subcommittee on Labor, Health and Human Services, and Education, Committee on Appropriations,

U.S. Senate, HRD-89-23 (Washington, DC: U.S.

Government Printing Office, 1989).

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Technologies for Detecting Heritable Mutations in

Human Beings, OTA-H-298 (Washington, DC: U.S.

Government Printing Office, September 1986).

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National Institutes of Health, Consensus Development Conference Statement, ‘‘Newborn Screening

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U.S. Department of Labor, Occupational Injuries

and Illnesses in the United States by Industry, 1986,

Bulletin 2308 (Washington, DC: U.S. Government

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Printing Office, 1989).

Weisskopf, M., “Chemical-Exposure Rules Updated,” Washington Post, p. A7, June 8, 1988.

Williams, J. F., “A Regulatory Model for Genetic

Testing in Employment,” Oklahoma L.uw Review

40(2):181-208, 1987.

World Health Organization, ldentzjication and Control of Work-Related Diseases, Report of a WHO
52 ● Genetic Monitoring and Screening in the Workplace

Expert Committee, Technical Report Series 714 41. Yancey, M., “RateofJob Injuries, Disease on Rise,”

(Geneva, Switzerland: 1985). AP Wire Service, Nov. 11, 1988.
Chapter 4

The State-of-the-Art of

Genetic Monitoring
CONTENTS

Page

MUTATION AND HEALTH EFFECTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .55

Mutagenic Effects of Radiation v. Chemicals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56

TECHNOLOGIES FOR GENETIC MONITORING . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58

Tests of Mutagenicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60

Studies of Effects on Sperm . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. .. .. .. .. ... ... .+..... 62

Cytogenetic Indicators . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62

Limitations of Cytogenetic Tests . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64

Application of Cytogenetic Tests to Occupational Exposures . . . . . . . . . . . . . . . . . . . . . . . 65

Analysis of Mutagenesis at the Molecular Level .. .. .. .. .. .. .. ... ... ......+. . . . . . . . 66

METHODOLOGIC CONSIDERATIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69

Validity, Reliability, and Predictive Value . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69

Procedural Safeguards and Difficulties. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70

The Battery Approach to Genetic Monitoring . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70

SUMMARY AND CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. ... ... ......+ 71

CHAPTER PREFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71

Boxes

Box Page

4-A. Genetics and Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59

4-B. The Ames Test . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .,...,.. . 61

4-C. A Battery

Figure

4-1. Biological

4-2. The Ames

Table

Approach To Determining Exposure-Disease Associations . . . . . . . . . . . . 70

Figures

Page

Consequences of Exposure to Mutagenic Agents . . . . . . . . . . . . . . . . . . . 60

Test .. ...........:..

4-1. Major DNA Lesions Produced by

Their Genotoxic Consequences .

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60

Tables

Page

Chemical Interaction and

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58

4-2. Main Confounders and Limitations of Occupational Cytogenetic Studies and

Ways to Control Them . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64

4-3. Occupational Hazards Reported To Increase the Frequency of

Cytogenetic Abnormalities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65

4-4. Pitfalls of Classical Epidemiological Studies in Identifying Hazardous

in the Workplace . .=. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69
Chapter 4

The State-of-the-Art of Genetic Monitoring

With the advent of molecular biology, the field of

human genetics has undergone an extraordinary

metamorphosis. Progress in molecular biology and

human genetics clearly has transformed society on

many levels—medical, social, economic, legal, and

ethical. Because biotechniques are having such

profound and practical impacts on daily living, it is

important to appreciate the nature of the technologies in order to understand potential applications,

such as genetic monitoring and screening by employers. The techniques used in genetic monitoring

v. genetic screening for the most part are distinct,

although the two areas tend to merge in the detection

and diagnosis of cancer.

The term “genetic disease” is used broadly in this

and the following chapter, referring to those conditions for which the major causative factor is genetic.

There are over 3,000 diseases known to be caused by

a single-gene defect and chromosomal anomalies are

found in over 1 in 700 live births (44). In addition,

research has demonstrated that genetic viability

affects many aspects of health, ranging from heart

disease to cancer (2,19). It has long been speculated

that genetically determined variation in susceptibility may predispose some workers to occupational

disease while others in the same environment seem

to be unaffected (26,52,65). Additionally, certain

environmental agents are known to mutate previously normal somatic cells that could, in some cases,

cause disease.

Recognition of genetic factors in disease presents

new opportunities for detection, prevention, and

treatment. Because of uncertainties about the exact

nature of the relationship between genes and environment, genetic monitoring and screening of otherwise healthy populations remain problematic.

Medical screening in the workplace involves

evaluating employees before they begin work. It can

range from a cursory questionnaire to an oral history

to a full preemployment physical. (See chs. 3 and 9

for industry practice.) Genetic screening is a

process that considers attributes or indices of

altered DNA that may put an employee at high

risk for developing disease, whether workrelated or not. An extensive discussion of the

state-of-the-art in genetic screening for inherited

disorders appears in chapter 5. Monitoring, on the

other hand, involves the periodic evaluation of

employees for either the effects of a toxic substance or its byproducts (60). Genetic monitoring

evaluates the genetic damage caused by such

substances. In short, genetic monitoring ascertains

whether an individual’s genetic material has altered

over time. Basic human genetics information necessary to understanding this chapter is contained in

appendix A. Several documents have presented

background material on human genetics and the

techniques often used in this field (68,69,70,71,

72,73). The state-of-the-art in genetic monitoring,

methodological and reliability issues in monitoring,

and the interpretive value of monitoring are also

discussed.

MUTATION AND HEALTH

EFFECTS

Over the past 15 years an increasing number of

health effects have been attributed to mutations

caused by toxic agents (26). These mutational

effects occur at a rate significantly above the normal

background rate found in human cells. The relationships between genes, mutations, and disease are

becoming clearer with the development of molecular

techniques that enhance both the quantitative and

qualitative evaluation of mutation.

The diseases most associated with genotoxic

substances are various forms of cancer. Several

types of mutational changes (i.e., point mutations,

chromosomal rearrangements) have been associated

with the early stage of tumor development, as well

as with the following steps of tumor promotion and

progression (36).

The emphasis on the relationships between genotoxins and cancer may be due to the fact that most

studies have focused on somatic cell changes and

because germline effects may take generations to

appear. Genetic effects on human germ cells are

imprecise. More research is needed. Most validation

efforts undertaken in genetic monitoring have been

designed to quantify the correlation of mutagenesis

with carcinogenesis (46). Thus, genetic monitoring

involves, for the most part, search for mutations in

the somatic cells.

–55–
56 ● Genetic Monitoring and Screening in the Workplace

There are two classes of genotoxic agents commonly found in the workplace--chemicals and

radiation. The differences between these agents are

described below.

Mutagenic Effects of Radiation v. Chemicals

It has been documented for over 40 years that

radiation at high doses causes significant carcinogenic and genetic effects. Less clear and certainly

more controversial are the effects of low-level doses.

The effects of radiation on chromosomes are described in the 1983 Office of Technology Assessment (OTA) report (72) and will not be discussed

again here. However, two new topics are worth

examination. The first is the extent to which research

findings have affected the setting of limits for

exposure for chemicals v. radiation. Second is the

continuing debate about the effects of low-level

radiation.

The finding that ionizing radiation induces chromosomal aberrations (CAs) may help elucidate the

means by which certain chemicals alter DNA.

Radiation-induced damage can be observed in cells

within a few hours following exposure. In general,

chemically induced lesions, however, are not converted into aberrations until the cells containing

them undergo DNA replication (19). Meanwhile,

some chemically induced damage may be repaired

long before replication. Because of the lack of good

baseline information on chromosomal damage as

an effect of chemical mutagens, enthusiasm differs on recommending cytogenetic surveillance

for exposed individuals. This has led some to assert

that chemical exposures should be evaluated differently from radiation exposures (24).

For example, groups such as the International

Commission on Radiological Protection use different rationales in setting limits for exposures to

radiation than does the American Conference of

Governmental Industrial Hygienists, which sets

standards for chemical exposures. There are basic

scientific and philosophical differences underlying

these discrepancies (24).

External radiation dosimetry can be done on a

continuous basis, providing a cumulative dose

reading as well as the possibility of periodic

readings. Dosimeters of this type are not available

for chemical exposures. Thus, relation of dose to

genetic monitoring results is much more difficult

with chemicals (39).

More data exist on the genetic and health effects

of radiation, based largely on studies of Japanese

atomic bomb survivors, as well as biological experimentation. The data on radiation have been collected

over several generations and have led to the consideration of radiation as a somatic and germinal

genotoxic agent. Chemical standards, on the other

hand, are based on far fewer data, and tend to

consider acute, rather than long-term and germinal

effects of exposures. Such analysis has led, in many

cases, to differences in evaluating exposures.

Internal biological doses are often determined for

workers exposed to radiation whereas most limits for

workplace chemicals are established in terms of

airborne concentration or external exposures (24).

Finally, radiation standards assume that biological

damage caused by low doses of radiation is cumulative and is not repaired as rapidly as damage caused

by chemicals, whereas standards set for chemical

exposure are based on the assumption that biological

damage caused by exposures to low doses is not

cumulative and is frequently repaired. While the
Chapter 4--The State-of-the-Art of Genetic Monitoring ● 57

effects of low-level, long-term exposure to chemicals are hardly understood, the debate in this area

relative to ionizing radiation still rages.

Until the health effects of radiation and chemical exposures are better understood, genetic and

biological monitoring of exposed populations can

only provide a gross indication of health risks.

Health effects may not appear for as many as 30

years following initial exposure.

Low-Level Radiation

In the past few years, science has offered sharply

conflicting opinions about the dangers of low levels

of radioactivity. This divergence is due, in part, to

the different assessments of radiation doses received

by those studied, and to insufficient understanding

about how small doses of radiation increase cancer

risk (55).

The debate has been rekindled, in part, because of

the nuclear accidents at Three Mile Island and

Chernobyl, and current concerns about the effects of

radon (74). Concern about the carcinogenic effects

of radiation in employees of the nuclear weapons

and nuclear power industries has also fueled the

debate (14,55). And, most recently, an association

between low-dose exposure to radiation and leukemia in the offspring of men employed in a nuclear

facility was reported (20).

In a study of mortality among workers at a nuclear

fuels production facility, the rate of cancer was

found to be normal or below normal except for

leukemia (16). This, and similar studies, have led

some to the conclusion that very low doses of

ionizing radiation are not harmful after all, or might

even have net benefits, a phenomenon called

“hormesis” (57). This net benefit is attributed to an

overprotective response involving enhanced DNA
58 ● Genetic Monitoring and Screening in the Workplace

Table 4-1—Major DNA Lesions Produced by Chemical Interaction and Their Genotoxic Consequences

Primary lesion Description Consequence

Alkylation . . . . . . . . . . . . . Covalent adduct formed, involving the genotoxic agent Alteration of base pairing, Ioss of the base, stimulation

and a DNA base or phosphodiester bridge of error-prone repair

Intercalation . . . . . . . . . . . Noncovalent stacking of the genotoxic agent between Alteration of DNA transcription, replication, or repair

adjacent base pairs in the DNA helix

Cross-linkage . . . . . . . . . . Formation of two covalent bonds between bases within Dimer formation, alteration of replication

(intrastrand) or between (interstrand) DNA strands

Breakage . . . . . . . . . . . . . Scission of either a single or both strands of the DNA DNA rearrangements forming chromosomal aberrahelix tions after mitotic cell division

SOURCE: R.W. Hart and D. Brusick, “Assessment of the Hazard of Genetic Toxicity,” Toxic Substances and Human Risk, R.G. Tardiff and J.V. Rodricks (eds.)

(New York, NY: Plenum Press, 1987).

repair of arising mutations that more than compensates for the harmful effects of radiation.

Critics of this theory argue that radiation-induced

mutations have not been proven to be beneficial (in

fact, the preponderance of evidence is quite the

opposite (79)). Although an adaptive response was

detected after exposure to very low doses of ionizing

radiation, the protective effects remain to be determined (35). Also, studies reporting no increase in

cancer after radiation exposure have not waited long

enough before drawing conclusions. Leukemias

typically start to appear about 2 years after a dose of

radiation, compared with about 15 years for other

cancers. Forty years after Hiroshima and Nagasaki,

most cases of leukemia have already occurred,

whereas other cancers are still being reported (55).

Thus, studies that report “only” an increase in

leukemias could be reporting the beginning of the

trend toward more cancer reporting years away.

In late 1989, a panel of the National Research

Council (NRC) concluded that exposure to low

levels of radiation, such as that from x-rays or radon,

is at least three to four times more likely to cause

fatal cancer than is commonly believed. This dramatic about-face from previous NRC reports is due

to a reevaluation of dose data from atomic bomb

populations. Reconstructions of the original bomb

designs revealed much lower radiation doses than

originally thought. Also, as the surviving population

has aged, more fatal cancers have developed than

expected, including cancers of the breast, lung,

stomach, ovary, throat, colon, and bladder, as well as

leukemia, the standard “canary in the mine” (43).

The effect of the NRC conclusions is to at least

quadruple estimates of the number of radiation

deaths expected among workers in the nuclear power

and nuclear weapons industries, those who frequently undergo radiation therapy and x-rays for

diagnosis, and those who are routinely exposed to

radioactive elements in certain natural gases, building materials, or tobacco. These revised estimates,

however, do not change the difficulty or impossibility of doing definitive epidemiological studies of

low-level radiation effects (63).

TECHNOLOGIES FOR

GENETIC MONITORING

In simple terms, a mutagen is a substance capable

of inducing a heritable change in the genetic material

of cells. The changes can be detected at the

molecular or chromosomal level through measurement of sister chromatid exchange (SCE), unscheduled DNA synthesis, point mutations, CAs, formation of DNA adducts, and oncogene activation,

described in this section. Much progress has been

made in measuring these endpoints and understanding the role of these processes in the induction of

mutagenesis. Table 4-1 summarizes the major DNA

lesions produced by genotoxic substances. In many

cases, mutagens are also carcinogens, so at high

exposure levels, the most common manifestation of

genetic damage is in the form of cancer (75). Box

4-A describes some of the connections between

genetic damage and cancer.

Exposure to genetically toxic agents initiates a

process which is illustrated in figure 4-1. The

damage will be resolved in one of three ways: cell

death, successful DNA repair, or viable mutation. It

is difficult to establish the causal relationships

between the mutation and cancer because of the long

latency of human cancer. Nonetheless, the rationale behind the use of genetic damage assays as

indicators of exposure is that events observed

initially and at high frequencies are the start of a

process that may ultimately produce abnormal

growth (neoplastic changes) in a smaller subset of

cells.
Chapter 4--The State-of-the-Art of Genetic Monitoring ● 5 9

Box 4-A--Genetics and Cancer

Cancer is a genetic disease arising from genetic damage of diverse sorts-recessive and dominant mutations,

large rearrangements of DNA, and point mutations-all leading to distortions of either the expression or

biochemical function of genes. The growing field of cancer genetics aims to uncover the genetic alterations

responsible for uncontrolled growth of cancer cells. Many types of human cancer occur in familial as well as

sporadic forms, Discrete genetic changes have been associated with different types of neoplasm, and are thought

to initiate or cause progression of cancer. Chromosome studies in more than 10,000 cases of neoplasms have

reported specific anomalies. The identification of genetic changes, therefore, presents the major diagnostic

challenge in cancer.

Both dominant and recessive forms of cancer have been found. The genetics of the common cancers-breast,

colon, and lung—are beginning to fit a pattern. Approximately 5 percent of cancer cases constitute a hereditary

cancer syndrome in which a dominant gene predisposes to cancers of the breast, ovary, brain, gastrointestinal

system, and white blood cell precursors. These are referred to as ‘cancer families’ (see ch. 5 for further discussion).

Apart from these, each type of cancer appears to have a small group of cases that fits the pattern of a major

predisposing gene and a much larger group that seems to be largely environmental in origin.

In addition, examples such as xeroderma pigmentosa imply that there is a connection between susceptibility

to cancer and impaired ability of cells to repair damaged DNA. It is a reasonable expectation that if cancer is related

to alterations in somatic cell genes, then the rate at which those changes occur could serve as a barometer of changes

in the gem-dine that may not be expressed for many generations to come.

Certain cancers, e.g., lung, laryngeal, bladder, and testicular, have repeatedly been linked to environmental

exposures. The effects on chromosomes of such chemicals as arsenic, asbestos, chromium, nickel, and vinyl

chloride are well-documented. Substances that cause chromosomal abnormalities are called ‘‘clastogens. The

reader is referred to the 1983 Office of Technology Assessment report for more detail on the specific effects of those

agents. Chapter 5 describes recent advances in detecting predisposition to some common cancers.

SOURCES: Office of Technology Assessment, 1990, based on J.M. Bishop, “he Molecular Genetics of Cancer,” Science 235:305-311, 1987;

F. Mitelman and J.D. Rowley, ‘‘Genes, Chromosomes and Cancer: A New Forum for Research in Cancer Genetics,” Genes,

Chromosomes & Cancer 1:1-2, 1989; J.J. Nom and F.C. Fraser, Medical Genetics: Principles and Practice (Philadelphia% PA: Lea

& Febiger, 1989); R. Parshad, K.K. Sanford,, K.H. Kraemer, et al., ‘‘Carrier Detection in Xeroderma Pigmentosum," The Journal

of Clinical Investigation 85: 135-138, 1990.

Thus, the purpose of monitoring tests is to Yet, the whole process of making carcinogenic risk

detect biologically significant exposures early, estimates is based on the assumption that there is a

even though the results are currently unsuitable

as a basis of quantitative risk assessment. A d -

vances in testing at the molecular level (discussed

below) will most likely provide better predictors of

neoplasia, as the relationships between mutation and

neoplasia become better understood.

Environmental agents can increase the risk of

genetic disease and cancer in exposed populations.

Humans are exposed to over 25,000 toxic compounds that are potentially or demonstrably mutagenic in lower organisms (44). The fundamental

problem of evaluating genetic risk from environmental exposures rests with the ability to identify a

chemical as a somatic or germ cell mutagen in

humans (67). Because this cannot be done ethically

or legally in humans, most studies rely on animal

models. Problems arise in trying to extrapolate from

animal studies to human populations because of

genetic differences and dose-response relationships.

qualitative and quantitative correlation between the

results of animal mutagenicity and carcinogenicity

tests and expected effects in humans. Most Federal

and State regulations are based on this premise (17):

that is, if mutagenic activity is observed for a

chemical, even in bacteria, it is possible that it or its

metabolizes could be carcinogenic.

Reduction of risk requires, among other things,

sensitive methods for detecting harmful agents.

Mutagenesis can be measured in many ways, the

most conventional methods are cytogenetic and

biochemical. Molecular methods, however, are increasingly being developed and will shed further

light on the nature of mutagenesis and its relationship to carcinogenesis (see also ch. 5).

A previous OTA report discusses in greater detail

technologies for detecting heritable mutations (73).

The reader is referred to that publication for elabora32-799 - 90 - 3 : QL 3
60 ● Genetic Monitoring and Screening in the Workplace

Figure 4-l—Biological Consequences of Exposure —

to Mutagenic Agents

T

Exposure

1

Genetic

damage

I Repair Cell death

Mutation 1

Germ cells I Somatic cells

+, Ei71

1 Immediate

F etfects of

1

exposure

1 Delayed

I

adverse

health

outcomes

-

SOURCE: Office of Technology Assessment, adapted from J.B. Ward,

“Issues in Monitoring Population Exposures,” Carcinogens and

Mutagens in the Environment Volume 11, The Workplace, Hans

F. Stich (cd.) (Boca Raton, FL: CRC Press, 19S5).

tion of techniques and methodological considerations relevant to tests for mutagenicity. Other than a

brief discussion of biological monitoring, the remainder of this section will address tests used

specifically for monitoring occupational populations for genotoxic effects. The focus is on detection

of genetic changes, not just the presence of chemicals, in workers.

Tests of Mutagenicity

The more traditional approach to testing for

exposure to mutagens has been to measure the

chemical itself (or a byproduct) in blood, breath, and

urine. Mutagenic activity in urine can be shown by

using rapid screening tests developed for bacterial or

in vitro cell culture systems. Standard analysis of

body fluids for the presence of mutagens was

discussed in greater detail in the 1983 OTA report

and will not be covered further here. The most

common short-term test for mutagenicity conducted

on body fluids is the Ames/Salmonella test (see

figure 4-2). Because the specificity of the procedure

has come under fire in recent years it is discussed in

detail in box 4-B.

Figure 4-2—The Ames Test

IIi-l

Culture of Salmonella bacteria

that require histidine to grow

owing to a mutation in a gene

I for histidine biosynthesis

~

I 106 cells are spread on Petri

‘ishescontaininoaoarwith

No additions

to medium

Colonies arising from

spontaneous revertants

+

nutrients, but n; hfitidine

Suspected mutagen added

to medium in sugar

12 hours 4

Colonies of revertants

induced by the mutagens

The Ames testis used to determine whether a chemical can cause

mutations in bacteria Mutant bacteria that have lost the ability to

synthesize the amino acid histidine and cannot grow in its

absence are treated with the test chemical. Potent mutagens can

cause mutations that reverse the hismutation, resulting in bacteria

that can grow in the absence of histidine.

SOURCE: Office of Technology Assesment, 1990.

Testing for the presence of mutagens in blood and

urine is more suited to occupational settings as a

complement to ambient measurements, thereby

providing an indicator of exposure and absorption.

The presence of mutagens only serves as an indicator

of recent exposure and provides no information

regarding the health effect on the individual.

Biological monitoring, therefore, involves examining the worker for absorption of a toxic substance

or its byproduct as an indicator of internal dose.

Most work to date has focused on the relationship

between internal dose and external exposure, rather

than between internal dose and adverse effects (58).

Detection of mutagens in urine has been reported in

several types of workers including oncology nurses

and pharmacists involved in preparing and administering cancer chemotherapeutic drugs (65).
Chapter 4-The State-of-the-Art of Genetic Monitoring . 61

Box 4-B—The Ames Test

Most current studies of mutagenesis are based on the pioneering work of Ames et al. The

general procedure involves treating a bacterial cell population containing a designated genetic

marker with a mutagen. The mutagen kills off a fraction of the cell population with survivors

growing back into a larger population. Within this survivor population, a fraction of the cells will

have lost the marker. This fraction, expressed as a percentage, is taken as a measure of the

mutagenic action suffered by the original population. Since about 85 percent of compounds

known to be carcinogenic in rodents arc also mutagenic in the Ames test, some have suggested

that the Ames test is a belter indirect test of carcinogenicity than a direct test of mutagenicity. In

fact, because of the correlation between mutagenicity and carcinogenicity, some statutes, such as

the Toxic Substances Control Act (Public Law 94-469), require chemical manufacturers to

demonstrate negative mutagenicity of a chemical via the Ames test as a substitute for long-term,

more expensive bioassays for carcinogenicity.

The limitations of the Ames test, however, are many. First, only mutations in viable cells are

scored. Those m cells killed by the agent are not measurable. While such mutations could be lethal

in the particular chromosome containing the marker gene, similar mutations at loci on other

chromosomes could produce viable but genetically damaged cells. Furthermore, mutants often

possess reduced rates of cell multiplication. Thus, the fraction of mutated cells in the test

population will be materially decreased from the original value.

The Ames test also fails to measure large mutations such as deletions, because such lesions

have a high probability of extending into vital genes on the marker chromosome and causing the

death of the cell. Large mutations are known to be extremely important in the activation of

oncogenes and in the induction of genetic disease.

In addition, critics argue that the Ames testis not specific, as large doses of mutagenic agent

are required before significant measurements can be made. The low specificity produces a high

false positive rate and a less than desirable predictive value. Finally, in order to calculate

mutagenic effects for low dosages, it is necessary to resort to extrapolation over a large dosage

interval. Whether this extrapolation should be linear or based on a threshold region has been

widely debated. So far, regulatory agencies have favored the threshold hypothesis which

postulates that there are low dosages with no mutagenic effect.

Efforts have been made to correct for these deficiencies, including use of a plasmid

unnecessary for reproduction as the carrier of the marker, use of several markers, and use of lower

dosages on a more variable cell population. Some feel that the current reliance on the Ames test

and its requisite extrapolation may underestimate the health effects of low doses of some

mutagens.

A method by which to recover and analyze the mutated genes could facilitate the molecular

analysis of mutagenesis in intact organisms as well as in cultured cells. This approach uses

chromosomally integrated shuttle vector genes that are integrated into the mammalian cell’s

chromosomes and replicated in synchrony with the chromosomal DNA. Pure clones of

mammalian cells containing the mutant genes can then be isolated, recovered, and sequenced.

SOURCES: Office of Technology Assessment, 1990, based on B.N. Ames, J. McCann, and E. Yamasaki, “Methods for

Detecting Carcinogens and Mutagens with the Salmonella/Mammalian-Microsome Mutagenicity Test”

Mutation Research 31(6):347-364, 1975; RI... Davidson and C.R. Ashman, “Chromosomally Integrated

Shuttle Vectors and Molecular Analysis of Mutagenesis in Mammalian Cells," Somatic Cell and Molecular

Genetics 13(4):415-417, 1987; J.J. Nom and F.C. Fraser, Medical Genetics: Principles and Practice

(Philadelphia, PA: Lea & Febiger, 1989); T.T. Puck and C.A. Waldren, “Mutation in Mammalian Cells:

Theory and Implications,"Somatic Celland Molecular Genetics 13(4):405-409, 1987; R.W. Tennant, B.H.

Margolin, M.D. Shelby, et al., “Prediction of Cbemical Carcinogenicity in Rodents From In Vitro Genetic

Toxicity Assays,” Science 236:933-941, 1987; C.A. Waldren and T.T. Puck, “Steps Toward Experimental

Measurement of Total Mutations Relevant to Human Disease,’ Somatic Cell and Molecular Genetics

13(4):411-414, 1987.
62 ● Genetic Monitoring and Screening in the Workplace

Biological monitoring techniques are frequently

used for chemicals known to have adverse health

effects, as well as mutagenic effects. For example,

the recognition of the neurotoxic and narcotic

properties of toluene--a product of crude oil used as

a solvent in oils, resins, rubber, and paints, and as a

basic material in many synthetic chemicals-has

lead to the development of biological monitoring

methods for assessing toluene uptake. Short-term

exposure to high concentrations of toluene can cause

drowsiness, dizziness, and headaches. Breath,

blood, and urine tests can be used to check and

control levels of exposures (11).

Studies of Effects on Sperm

Traditionally, most studies of chromosomal abnormalities are performed on cultured white blood

cells. But to assess the effect of mutagens on

reproduction, analysis must be done on germ cells.

Knowledge about adverse effects of toxic exposures

on reproduction is limited, but some credible associations have emerged.

The potential for occupational exposure to have

an adverse effect on sperm was shown when workers

exposed to dibromochloropropane had markedly

reduced sperm counts and a decrease in number of

offspring (34,78). Sperm count can be affected by a

multitude of factors, so direct causal relationships

between decreased counts and particular exposures

are difficult to establish. Some studies, however,

have shown that certain physical abnormalities of

sperm are produced by environmental exposure,

such as atypical shape, nondisjunction of the Y

chromosome, and abnormal motility (54).

Abnormal sperm morphology has been associated

with exposure to lead and carbaryl (32,80). Adriamycin, a cancer drug effective against a broad

spectrum of neoplasias, has been shown to cause

reduced sperm count and increased CAs in mouse

germinal cells (3). Solvents such as ethylene glycol

ethers, pesticides such as ethylene dibromide, metals

such as mercury and arsenic, and alkylating agents

such as ethylene oxide, have demonstrated spermatotoxic effects in animals (18).

Cytogenetic Indicators

Results from extensive animal and human studies

show an empirical association between chromosomal damage and mutagenic-carcinogenic agents.

CAs and SCEs are the principal cytogenetic indicators used to estimate exposures to carcinogens. The

efficiency of these indicators can potentially be

improved by the application of developing computer

image analysis for the scoring of CAs (35). It has not

been determined whether these indicators of exposure are predictors of disease risk except as a

diagnostic tool for some tumors, so the clinical

significance for individual workers is unclear.

Studies of some occupational exposures reveal

associations between exposures and chromosomal

effects (12,65). The results of cytogenetic techniques that use blood cultures to study the in vivo

response of people exposed to mutagens are compelling but inconclusive. The main conceptual basis for

the application of cytogenetic tests to measure

chromosomal damage is that damage to the genetic

material of cells represents initial events in a process

that may eventually lead to disease. Cytogenetic

methods can detect human exposures at biologically

significant levels in populations, but the interpretation of findings for the individual remain uncertain.

Detectable mutations result from gross changes in

chromosome structure and can be visualized under

the microscope. The disruptive effects of mutagens

on chromosome structure, organization, and behavior have long been studied by geneticists. The

relationship between CAs, spontaneous abortions,

and birth defects is well-documented. But, the

connections between chromosomal damage and

disease are unclear except in a small number of

cancer cases. Again, cancer is the disease most

commonly hypothesized to be associated with induced CAs because of their presence in lymphoproliferative disorders such as leukemia, and in solid

tumors (62). Most analysts agree that interpretation of cytogenetic results at the individual level

is questionable and recommend that until the

relationship between cytogenetic damage and

disease is better understood, interpretation

should be maintained at the population level. In

addition, cytogenetic monitoring of human populations is expensive and time-consuming (12).

Chromosomal Aberrations

One of the few direct methods for measuring gross

changes in DNA involves visualization of the

chromosomes through the light microscope. The

viewer might see overt breakage and rearrangement

of the chromosomes within the cell as well as more

subtle changes involving the exchange of material

between chromatics of a chromosome. The type of
Chapter 4--The State-of-the-Art of Genetic Monitoring ● 63

alteration produced by physical and chemical agents

depends on the lesions induced in the DNA and,

therefore, on the chemical structure of the genotoxic

substance (12).

CAs are usually induced by agents that can

directly break the DNA duplex such as different

types of radiation chemicals that imitate the effects

of radiation. CAs therefore serve as a biological

dosimeter in individuals exposed to ionizing radiation. The same is not true for cases of chemical

exposure, however, since most chromosomebreaking (clastogenic) chemicals require metabolic

activation and are dependent on a critical time in

DNA replication. CAs have been demonstrated for

a large number of chemicals in vitro, but relatively

few chemicals have been convincingly shown to

increase CAs in vivo (15). On the other hand, some

investigators have reported that in vivo cytogenetic

assay is a very accurate assay system to identify

carcinogens from non-carcinogens (4).

For chemical exposures, chromosome analysis is,

for the most part, a low sensitivity method. This

stems from the low frequency of CAs, thereby

requiring that large numbers of individuals and cells

be studied to detect a statistically significant increase in CAs. Detecting effects at low exposure

levels or in small groups is not informative (15).

Application of this method to ionizing radiation, on

the other hand, is well-established. It continues to be

applied routinely to all suspected cases of radiation

exposure in several countries, most notably by the

National Radiological Protection Board in the

United Kingdom (7).

Recently, two studies have demonstrated that

cancer developed more frequently among individuals having CAs (22,64). These data suggest a direct

relationships between CAs and development of

disease.

Sister Chromatid Exchange

The study of SCEs is an indirect indicator of

mutation, although the biological significance is

unknown. Unlike CA measurements, SCE can be a

sensitive marker for the measurement of DNA

damage and repair (76). Sister chromatics are the

two daughter strands of a duplicated chromosome.

SCEs are events that occur when apparently equivalent sections of the sister chromatics of the same

chromosome are exchanged during cell division

(mitosis). SCEs occur in cells at a normal rate, but

Photo credit: U.S. Council for Energy Awareness

A Nuclear Power Worker: Controversy continues regarding

the carcinogenic effects of radiation in employees of the

nuclear weapons and nuclear power industries.

appear to be elevated when exposed to agents that

damage DNA. Of importance from a practical

standpoint, SCEs appear to result only as an

effect of chemical mutagens, not radiation. They

are most efficiently induced by substances that form

covalent adducts to the DNA, distort the DNA helix,

or interfere with DNA precursor metabolism or

repair (33).

Detecting SCEs in peripheral blood lymphocytes

is one way of monitoring chemically induced

chromosomal damage and is less costly than tests of

CAs because SCEs are easily scored. Because CA

and SCE represent different types of genetic damage, however, it would be misleading to replace one

assay with the other.

SCE analysis has the potential for being useful in

both screening and monitoring, because in addition

to the tendency toward increased SCE as a result of

exposure to genotoxic chemicals, certain inherited

conditions demonstrate increased SCE (13). On the

other hand, caution must be taken to protect against

confounding factors such as cigarette smoking,

alcohol consumption, drug intake, chemotherapy,

infections, and vaccination, as all have been shown

to induce SCEs.

As mentioned previously, chemically induced

lesions are often repaired and therefore would not

show up in the SCE assay. The frequencies of SCEs,

therefore, can fall off rapidly with time after an acute

exposure, and the time at which the SCEs are scored

becomes a confounding variable in interpretation.

Nevertheless, elevated SCE frequencies may pro-
64 ● Genetic Monitoring and Screening in the Workplace

vide a good indication of prior exposure to chemical

mutagens. Although, because the effect of chemicals

on induction of SCEs varies, calibration curves have

to be derived for each agent for SCEs to be

quantitative predictors of mutation induction (13).

To date, many studies of the effects of occupational chemicals on SCE frequencies have been

conducted; often with contradictory results (76). The

contradictions could be due to unidentified confounding factors related to lifestyle of those tested.

Some evidence also exists that SCE frequencies do

not necessarily increase with level of exposure. At

relatively low levels, certain chemicals, such as

benzene, mainly affect DNA repair at the replication

point, inhibiting, rather than inducing the formation

of SCEs (76). Thus, without accounting accurately

for exposure levels, separate studies could yield

conflicting results. Finally, for a given exposure, it

is not known whether higher or lower frequencies of

SCEs is better, i.e., a sign of damage or a sign of

repair (47).

At present, many known carcinogens produce

SCEs, but no systematic sampling of chemical

agents has been conducted to determine whether

correlations for certain chemicals are truly predictive of health risk (66).

Micronuclei Assay

One consequence of the induction of CAs is the

formation of micronuclei, which result from the

exclusion of fragments of/or whole chromosomes

from nuclei formed at mitosis. The presence of

micronuclei can be taken as an indication of the

previous existence of CAs. Micronuclei are far

easier to score than CAs at metaphase (although less

frequent) and provide a simple means for estimating

induced genetic damage. In addition, micronuclei

persist for varying lengths of time after their

formation so they can be detected in nondividing

descendants of cells. Early studies of the effects of

ionizing radiation on mitosis showed that the

frequency of micronuclei was dependent on radiation dose (19).

One of the most dramatic presentations of micronuclei has been demonstrated in worker populations

exposed to cytostatic drugs such as cyclophosphamide, a chemotherapeutic agent. Increased numbers

of micronuclei were observed in lymphocytes of

groups of workers from industry and hospitals where

the drug is processed and administered (81).

Table 4-2—Main Confounders and Limitations of

Occupational Cytogenetic Studies and

Ways To Control Them

Control efforts

Confounders

Exposure conditions:

Identification of correct chemical

exposure . . . . . . . . . . . . . . . .

Estimate of dose of exposure . .

Individual variations:

Genetic factors . . . . . . . . . . . . . .

Lifestyle factors . . . . . . . . . . . . .

Health factors . . . . . . . . . . . . . . .

Limitations

Culture conditions:

Culture time . . . . . . . . . . . . . . . .

Culture medium and chemicals..

Time between sampling and

culture . . . . . . . . . . . . . . . . . . .

Persistence of mutagens in the

blood sample . . . . . . . . . . . . .

Analysis and scoring:

Scorer variation . . . . . . . . . . . . .

Interpretation of damage

scored . . . . . . . . . . . . . . . . . . .

Factory record checking

Industrial hygiene survey

Unknown before analysis

Match with controls

Check medical records

CAs: First division metaphrases

SCEs: Second division metaphases

Keep constant

Keep constant

In vitro experimentation

Coded slides, one scorer

Strict scoring criteria

SOURCE: M. Sorsa and J.W. Yager, “Cytogenetic Surveillance of Occupational Exposures,” Cytogerretics, G, Obe and A. Basler (eds.)

(Berfin, West Germany: Springer Verlag, 1987).

Limitations of Cytogenetic Tests

In cytogenetic studies, at least two major types of

technical variations exist. The first includes factors

associated with differences in slide reading, culture

conditions, and concentrations of test chemicals.

The second involves sampling times and differences

in cell populations being tested (65).

Test Limitations

Scoring, or counting of the cells, is also an

extremely important element in cytogenetic toxicology. Slides must be randomized and coded to avoid

scorer bias. Accurate results depend on slides

prepared at a specific time during the analysis to

ensure that the proper time in the lifecycle of the cell

is reached. Consistent scoring criteria and statistical

analyses must be maintained to obtain reliable and

valid results. Table 4-2 summarizes some of the

major limitations and confounders of occupational

cytogenetic studies.

Test Interpretation

Baseline data for the effects of various chemicals

on SCEs and micronuclei formation are inadequate.

In particular, quantitative data on the normal back-
Chapter 4--The State-of-the-Art of Genetic Monitoring ● 65

ground frequencies of micronuclei are unavailable,

making it difficult to set standards for exposed

populations. Theoretically any increase detected

between preemployment data and post-exposure

data would suggest that exposures are too high.

Micronuclei are associated with increasing age

and smoking (29). All measurements must establish

a background level of alterations that is seldom, if

ever, zero. The background incidence of all genetic

events varies with time and between individuals. To

date, there is no international standard for the

conduct of human cytogenetic surveillance studies,

although guidelines have been developed by the

International Commission for Protection Against

Environmental Mutagens and Carcinogens (31). The

U.S. Environmental Protection Agency has also

provided guidelines for cytogenetic evaluations

(51).

Application of Cytogenetic Tests to

Occupational Exposures

Elevated cytogenetic abnormalities of the three

types previously described may be associated with

occupational exposures to ionizing radiation or

some chemicals, particularly where long-lived alterations are involved. The nature and longevity of the

alterations vary from one agent to another. For some

chemicals such as benzene, the alterations may

persist for years and probably represent a cumulative

exposure. For others, such as vinyl chloride, the

alterations disappear quickly after reduction of

exposure; thus cytogenetic assays can monitor

exposure only over a short period of time.

Over 100 cytogenetic studies have been reported

from various occupational exposure groups (65).

Among the occupational chemicals with best documented positive cytogenetic tests are ethylene oxide,

styrene, benzene, and alkylating anticancer agents.

Occupational cytogenetic studies of arsenic, benzene, epichlorohydrin, ethylene oxide, lead, cadmium, zinc, and vinyl chloride were described in the

1983 OTA report. They are not discussed again here,

but summaries of those findings appear in table 4-3,

which lists the most common occupational exposures that induce cytogenetic abnormalities.

Since the 1983 OTA report, increased CAs have

been reported in individuals exposed to phosphine,

a common grain fumigant (21), and a range of

pesticides, including organophosphorous, organoTable 4-3-Occupational Hazards Reported To

Increase the Frequency of Cytogenetic Abnormalities

Alkylating anticancer DDT (CA)

agents (CA, SCE) Epichlorohydrin (CA)

Arsenic and arsenic Ethylene oxide (CA, SCE)

compounds (CA) Mineral oils (CA)

Asbestos (CA, SCE) Nickel refining (CA)

Benzene (CA) Organophosphorous insectiBenzidine (CA) cides (CA, SCE)

Bis(chloromethyl)ether (CA) Pentachlorophenol

Cadmium/lead/zinc (CA) (CA,SCE)

Chromium (CA, SCE) Rubber industry (CA, SCE)

Coal gasification (CA) Shale oils (SCE)

Coal tars (CA) Styrene (CA)

Coke production (SCE) Sulphite (wood pulp) (CA)

Diesel fumes (CA) Trichloroethylene (CA, SCE)

Dimethylformamide (CA) Vinyl chloride (CA, SCE)

KEY: CA E chromosomal aberrations; SCE = sister chromatid exchanges.

SOURCES: J. Ashby and C.R. Richardson, ‘Tabulation and Assessment

of 113 Human Surveillance Cytogenetic Studies Conducted

Between 1965 and 1984,” Mutation Research 154:1 11-133,

1985; M. Sorsa and J.W. Yager, “Cytogenetic Surveillance of

Occupational Exposures,” Cyfogenetks, G. Obe and A.

Basler (eds.) (Berfin, West Germany: Springer Verlag, 1987).

chlorinated, and carbamate groups (56). Animal

studies have demonstrated elevated SCE and CA

frequencies in rat cells exposed to a common

household insecticide known as DDVP (37).

As mentioned previously, chemical agents are

more likely to induce SCEs than CAs, which are

more likely to be induced by ionizing radiation. A

few notable exceptions exist. Workers exposed to

vinyl chloride exhibit increased CAs and are at risk

for developing hepatic angiosarcoma, a form of liver

cancer. Workers exposed to benzene also show

elevated CAs and are at increased risk for developing leukemia (7). Steelworkers with a history of coke

oven exposure have an increased SCE frequency as

well as significantly elevated CAs (8) and are at

increased risk of developing lung cancer.

Frequently, both elevated SCE and CA frequencies are demonstrated for a particular genotoxic

agent. In approximately 30 percent of studies

conducted, however, there is disagreement between

these two endpoints for the same chemical, indicating that the fundamental way in which a particular

chemical interacts with the DNA to produce SCEs is

likely to be different from the mechanism that

produces CAs (72).

The conclusions of the 1983 OTA report pertaining to the appropriate use of cytogenetic assays for

occupational testing still hold true and are summarized as follows:
66 ● Genetic Monitoring and Screening in the Workplace

●

●

●

●

the appropriateness of cytogenetic tests for

occupational monitoring needs to be considered on a case-by-case basis for each chemical;

a monitoring program should be instituted

when in vitro and animal tests have proved that

the chemical in question is mutagenic or

carcinogenic;

no occupational studies, to date, directly relate

cytogenetic abnormalities to increased individual risk for disease; and

at the present time, cytogenetic monitoring is

insufficient to predict health risks for an

individual although it may have predictive

value for a group.

For industrial practice this implies that when

workers are in the vicinity of an established genotoxin, exposures should be reduced to a level that

does not affect their chromosome morphology or

DNA. In a sequence of cytogenetic studies on vinyl

chloride exposed workers, a reduction of CAs was

detected when the exposure level to the agent was

decreased (l). To date, data on CAs are routinely

used by regulatory agencies as contributing information for setting safe exposure standards. In view of

the lack of a threshold level where there is zero risk,

there is no safe level of exposure. Thus, this should

apply to all workers, not just to those determined by

some test to be susceptible (39).

It is likely that new populations of workers who

have been exposed to significant levels of a

genotoxin are yet to be discerned: data are now

available for only 500 of the more than 100,000

major environmental and industrial chemicals (39).

In the case of major synthetic genotoxins it is likely

that improved hygiene measures will be undertaken

before a surveillance study is begun, as was the case

in vinyl chloride and ethylene oxide, where the

greatest cytogenetic damage was observed at the

early stages of surveillance before hygienic measures reduced exposure levels for later sample dates

(2).

Analysis of Mutagenesis at the

Molecular Level

Until recently, most tests for mutagenicity have

been merely indicators of exposure, only providing

evidence that exposure has occurred. This limitation

is being removed as more techniques at the molecular level are being developed, refining the ability to

document exposure and, in some cases, providing

qualitative information about the nature of the

mutation. As the nature of mutation becomes more

clearly defined, the connection between mutation

and disease will also become better understood. This

section describes the more common molecular

approaches to analysis of mutagenesis.

HPRT Lymphocyte Selection System

One method used for detecting gene mutations is

a T-cell assay that uses the hypoxanthine-guanine

phosphoribosyltransferase (HPRT) gene as a mutation indicator, because there is an easy selection

method to distinguish those cells in which mutations

have inactivated the HPRT gene. Thus, the assay

determines the frequency of T-cells carrying the

HPRT-inactivating mutations. Mutation frequencies

are elevated in people exposed to such mutagens as

chemotherapeutic drugs, cigarette smoke, and ionizing radiation (38). In fact, HPRT mutations inhuman

T-cells can be detected in atomic bomb survivors 40

years after the presumed mutational event (23). The

test is extremely sensitive, permitting study of

effects of very low doses of environmental mutagens

(40).

At the laboratory investigation level, individual

mutant T-cells have been cloned and their HPRT

genes analyzed to identify the specific sequence

changes they have undergone. As a means to better

understand mutagenesis, this approach is useful, but

is obviously not practical for populations. A second

laboratory approach involves electrophoresis to

separate mutated strands of DNA, amplification of

the mutated DNA through the polymerase chain

reaction (PCR) (see ch. 5), and determination of their

specific DNA sequence. This approach has lead to

the establishment of an “HPRT Mutational Spectra

Repository” that is collecting data on HPRT mutations together with information on types of environmental exposures experienced by the individuals

whose cells manifested the mutations (38). The use

of this technique requires that an individual’s

spontaneous mutation rate be determined as well as

the rate of changes induced by environmental

mutagens.

It is unclear whether HPRT mutations are related

both to exposures and a subsequent cancer; HPRT

may just be a sentinel event in a pathway not related

to a specific cancer (59).
Chapter 4--The State-of-the-Art of Genetic Monitoring ● 67

DNA Adducts

One type of DNA alteration involves the binding

of exogenous and xenobiotic materials to DNA to

form additional products, or adducts (42). Radiolabeling, immunochemical, and physical methods

can detect adducts at extremely low concentrations.

Adducts can form in many tissues but are not stable

since they are easily removed by DNA repair

systems. DNA adducts have special significance

in view of their potential to force replication or

repair errors and thus be chemical progenitors of

genetic alterations that can be passed on to

offspring (5).

The toxicological significance of adducts is

unclear, but they can be used as markers of

exposures to specific toxicants. Current evidence

suggests an association between the onset of specific

types of toxicity (e.g., mutation, cancer, developmental effects) and the concentration of DNA

adducts (42). Recent studies have suggested that for

DNA adduct formation, it may be more meaningful

to relate tumor response to the target organ concentration of DNA adducts than to applied dose (6).

Adducts exist at variable background levels

between individuals differing by age, race, sex, and

interference factors. Adducts can be measured using

blood, semen, urine, buccal mucosa, or skin biopsy

specimens (42).

The relationship between DNA adducts and tumor

initiation depends heavily on the nature of the

chemical exposure. The use of DNA adducts as

molecular dosimeters will provide better information about individual differences in absorption,

distribution, biotransformation, cell proliferation,

and DNA repair and detoxification between highand low-dose exposures and between tissues (42).

Further research must correlate specific toxic

effects of specific DNA adducts with the induction

of gene mutation or tumor formation before they

will be useful beyond dosimetry studies. It may be

simplistic to assume that specific adducts will ever

be good predictors of tumor formation, since there

are so many other intermediary steps and modifying

factors between adduct formation and the development of a detectable tumor (63).

Most studies of DNA adducts in humans have

been in populations where the exposure was to a

ubiquitous compound producing delayed clinical

effects, making the cumulative exposure unknown

Photo credit: American Cancer Society

DNA from lung cancer patients who smoke cigarettes

shows a DNA adduct pattern that intensifies with the

amount and duration of smoking.

and the identification of unexposed control populations impossible.

However, certain cohorts reveal reliable dose

relationships. Testicular and ovarian cancer patients

receiving cisplatin, a platinum-based chemotherapeutic agent, show a dose-response relationship for

adduct formation (50). Roofers and foundry workers

have tested adduct positive for benzopyrene (25,61).

Lung cancer patients have tested positive for

adducts, probably from a variety of hydrocarbons

(49). In fact, DNA from cancer patients who smoke

cigarettes shows an adduct pattern that intensifies

with the amount and duration of smoking. Traces of

this adduct pattern can persist for at least 14 years

(53). Furthermore, while DNA from heart and lung

tissue shows the highest adduct levels, the bladder,

kidney, aorta, and liver of longtime smokers showed

the same pattern of adducts, indicating widespread

damage.

Results in most studies show individual rates of

metabolic activation of carcinogens and repair

capacities. The same chemical exposure, therefore,

can produce wide variability in the numbers of

adducts. More baseline data are needed before

adducts will be a reliable form of risk assessment. In

addition, there is an appreciable amount of background DNA adducts that needs to be more carefully

assessed in all individuals.

Most of the assays for detecting adducts resulting

from occupational exposures are sufficiently sensitive and will be improved by three methods currently
68 ● Genetic Monitoring and Screening in the Workplace

under investigation: tandem mass spectrometry,

32P-postlabeling, and accelerator mass spectrometry, which provide the additional advantage of

detecting low levels of interactive genotoxic agents

(63).

In general, protein adducts, as compared to DNA

adducts, are stable for the lifetime of the protein and

can be used as indicators for recent exposure. They

can be found in the hemoglobin of red blood cells

and in sperm. They are considered a form of

biological monitoring rather than a test of mutagenicity because they allow for direct measurement of

the relationship between external exposure and

internal dose. The unique features of this approach

are the sample size and the ease of obtaining red

blood cells. As in other tests, however, there will be

considerable differences between chemicals and

their effect on adduct formation and data must be

collected on each chemical.

Determination of DNA Repair

Determining DNA repair in lymphocytes can

indirectly estimate some types of damage to genetic

material. DNA repair systems probably arose as

evolutionary consequences of DNA damage resulting from ultraviolet radiation and naturally occurring mutagens. The method detects damage susceptible to excision repair, but some other mutagenic

lesions may not be detected. DNA repair is an

ongoing normal cellular process; monitoring methods detect elevated levels of DNA repair activity.

Increased DNA repair activity probably reflects

recent exposure to a genotoxic compound.

Sensitivity of the DNA repair assay to detect

abnormality from low-dose exposure has not been

demonstrated. Since this assay as used routinely

cannot determine whether the damage is correctly

repaired or not, the biological significance of detectable induced repair cannot be determined (35).

DNA Quantification

Two cytometric methods to measure the DNA

content of individual cells could provide a means for

identifying workers who are at increased risk in

occupational groups exposed to certain carcinogens.

Most recently these methods-called simple filter

microfluorometry and quantitative fluorescence

image analysis-have been applied to groups exposed to bladder carcinogens (27). Collectively the

methods are referred to as absolute nuclear fluorescence intensity, or ANFI. The value of ANFI is

Photo U.S. Environmental Protection Agency

Increased chromosomal aberrations have been reported in

individuals exposed to phosphine, a common grain

fumigant, and a range of pesticides.

based on the finding that tumors contain cells with

abnormal, elevated amounts of chromosomes, and

therefore, DNA. These aneuploid cells may be

cancerous or premalignant.

In the ANFI technique, cellular DNA obtained

from exposed populations is treated with a fluorescent stain. Quantitative spectrofluorometry is then

used to detect excess DNA. The intensity of the

fluorescence is proportional to the DNA content of

the cell. Fluorescence in excess of a standard norm

may be a useful diagnostic criterion. In fact, DNA

changes have been observed in asymptomatic patients prior to biopsy-confined clinical disease

(27).

The real power of the technique could likely be

its ability to detect disease in asymptomatic

individuals. If tumors can be detected while still

noninvasive and nonmetastatic, then screening

could become valuable for treatment success (77). In

1981, a study was conducted of 1,385 chemical

production workers exposed to aromatic amines,

primarily 2-naphthylamine, to assess the predictive

value of this technique. Of a cohort of 67 individuals

tested positive via ANFI, 33 have been diagnosed

histologically positive for bladder cancer (48).

Serum Oncogene Proteins

Oncogenes, or cancer-causing genes, are discussed in greater detail in chapter 5 because of their

importance in detecting early stages of cancer.

Oncogene detection, however, may become in-
Chapter 4--The State-of-the-Art of Genetic Monitoring . 69

creasingly important in monitoring situations

because of the effect of genotoxic agents on the

induction of oncogene activity. Oncogenes can be

activated by translocations, breaks, and deletions

caused by clastogens. The presence of activated

oncogenes can be identified by molecular methods

such as restriction fragment length polymorphisms

(see ch. 5) or by screening of serum for oncogenerelated proteins in conjunction with PCR sequencing.

This approach was recently used in a study of

workers exposed to polychlorinated biphenyls

(PCBs) (9). PCBs are a group of chlorinated aromatic hydrocarbons found in the past in transformer

and capacitor fluids, plastics, pump oils, hydraulic

systems, printing ink, flame retardants, pesticides,

and copy paper. They have well-documented acute

and chronic health effects on skin, neurophysiology,

and reproduction.

Municipal workers exposed to PCBs in cleaning

of a transformer were tested for oncogene-related

proteins in their serum. While the connection

between exposure to PCBs and elevated serum

oncogene proteins was not substantial, the relationship between cigarette smokers exposed to PCBs

and elevated proteins was remarkable, indicating a

strong effect of smoking on oncogene activity.

Serum oncogene protein detection may offer a tool

for early diagnosis of cancer.

METHODOLOGIC

CONSIDERATIONS

Before a decision can be made on the value of any

genetic test, it must be valid and reliable. In

considering the application of genetic monitoring to

detect job-related illness, the additional criteria of

cause and effect between a particular trait (or genetic

change) and occupational illness must be evaluated.

The 1983 OTA report presented a full discussion

of the concepts of validity, reliability, predictive

value, and relative risk (72). Because these fundamental criteria have not altered since that report,

basic aspects are only summarized here. Similarly,

general criteria for evaluating the acceptability of

genetic tests linked to environmental exposure have

been discussed elsewhere (41,72). Certain variables

such as age, sex, race, and lifestyle will continue to

confuse establishing causal linkages between exposures and subsequent disease. If the tests are valid

Table 4-4-Pitfalls of Classical Epidemiological

Studies in Identifying Hazardous Chemicals

in the Workplace

Difficulty identifying suitable study populations:

. inadequate size

. unreliability of death or birth medical records

● lack of reliable incidence data

Long latency period in onset of effects (excluding in utero

exposure for major anomalies):

● complicates data collection

● prevents detection of effects of new exposures

. requires assessment of current risks based on much earlier

exposures

Lack of sensitivity:

● normal incidence of specific diseases can obscure increased

rates

. multiple exposures confound attempts to establish causeeffect relationship

. effects of ubiquitous exposure are difficult to detect

● large populations are required to detect common effects

Substantial population exposure to agent prior to detection:

● dilution of exposed population

● failure to consider power of study

SOURCE: M. Legator, University of Texas Medical Branch, Galveston, TX,

written communication, August 1990.

and reliable, establishing procedural safeguards and

designing well-conceptualized test protocols can

avert erroneous and misleading conclusions. Table

4-4 presents some of the pitfalls encountered in any

epidemiology study, whether genetic or not, attempting to identify hazardous agents in the

workplace.

Validity, Reliability, and Predictive Value

The validity of genetic testing (i.e., the probability

that a test will correctly classify true susceptible and

true nonsusceptible individuals) should be evaluated

before any test is placed into routine use. Few tests

are 100 percent valid because of the influences of

variable test performance and genetic and environmental factors. Sensitivity and specificity are the

two characteristics subsumed under validity. Sensitivity is the frequency with which the test will be

positive when the genotype in question is present.

Specificity is the frequency with which the test will

be negative when the genotype in question is absent.

Sensitivity and specificity are usually inversely

related.

In addition to validity, reliability under conditions

of routine use must also be demonstrated. That is,

tests of the same specimen must repeatedly give the

same result whether performed by several different

laboratories or by the same laboratory on several

occasions.
70 ● Genetic Monitoring and Screening in the Workplace

Predictive value of the test is determined by

sensitivity and specificity, as well as the prevalence

of the trait or genetic damage in the population.

Prevalence is the percentage of the population that is

affected with a particular disease at a given time.

When the prevalence of a particular traitor genetic

damage is low in the population, even a highly

specific test will give a relatively large number of

false positives because many persons being tested

will not have the endpoint.

Procedural Safeguards and Difficulties

In undertaking any testing of exposed populations—whether cytogenetic, biochemical, or DNAbased tests—good sampling and data collection are

essential. Individual factors that can affect test

results include such confounding variables as sex,

age, race, ethnic group, work history, diet, genotype,

medication, alcohol and drug consumption, and

smoking. These factors play a role in the induction

of CAs and must be considered when drawing

conclusions about the effects of genotoxic agents.

For example, smoking and alcohol consumption

have been shown to increase the frequency of CAs

and SCEs (30,45). Thus, they must be controlled for

any population study.

In all cases, certain precautions should be taken

before employing these techniques in wide-scale

population monitoring. They are:

documentation of clastogenicity of the chemical in question in vitro and in vivo;

determination of the duration and level of

exposure;

establishment of an appropriate matched control population;

determination of the history and habits of the

individuals to be tested (i.e., smoker, medication and drug use, other exposures, nutrition)

(12); and

determination of test variability and sample

size requirements to detect a true difference

(lo).

The greatest difficulties in monitoring may not be

technical but procedural. Eliminating biases, obtaining suitable control groups, and obtaining good

records may be the greatest obstacles, made especially difficult with chemical carcinogens because of

the long latency period between exposure and

resultant malignancy (a problem with retrospective

cohort studies). Adequate protocols (enough subBox 4-C-A Battery Approach To

Determining Exposure-Disease Associations

The use of biological markers in a battery of tests

over time allows for the resolution of more detail in

exposure-disease associations. For instance, instead

of waiting to identify a worker who has developed

bladder cancer and had been exposed to benzidine,

a researcher might: 1) ascertain the worker’s

predisposition by determining whether he or she is

a slow or fast acetylator (see ch. 5); 2) determine

early biologic effect by measuring the amount of the

H-ras oncogene expression product, p-21 protein in

the urine; 3) quantify the degree to which bladder

cells are in a premalignant aneuploid state by using

quantitative fluorescence image analysis; and 4)

evaluate the prognosis of early tumors by measuring the glycosaminoglycans on bladder cell surfaces. Additionally, the current contribution of

cigarette smoking, a confounder to the benzidinebladder cancer association, can be assessed by

evaluation of macromolecule adducts to a representative cigarette smoke component such as 4-

aminobiphenyl. The implications of this example

are that the exposure-disease association can now,

in some cases, be resolved into detailed and

quantifiable components. This resolution has implications for understanding basic mechanisms and for

intervention.

SOURCE: P.A. Schulte, “Methodologic Issues in the Use of

Biologic Markers in Epidemiologic Research”

.4merican .Journal of Epidemiology 126(6):1006-

1016, 1987.

jects used and cells scored) must be used to ensure

that the results are reliable.

The Battery Approach to Genetic Monitoring

The most sensible approach to genetic monitoring, if validated, would be to employ a battery of

relevant and sensitive tests, rather than rely on any

one test for valid and reliable information. Genetic

monitoring is based on epiderniological methods,

using the observation of immediate effects such as

sperm morphology, urine mutagenicity, and cytogenetics. Immediate effects can be measured in

tandem and more long-term health outcomes, such

as appearance of neoplasia and reproductive effects,

should follow in the study design. It should be borne

in mind that the frequencies of immediate effects

will always be higher than frequencies of adverse

health outcomes (28).
Chapter 4-The State-of-the-Art of Genetic Monitoring ● 71

In an ideal study, types and durations of external

exposures should be determined as best possible.

Mutagenicity assays, such as the Ames or HPRT

tests, could be conducted to determine if mutagenic

agents were present. Cytogenetic analysis examining overall CA rates and SCE or micronuclei

frequencies could be conducted as indicators of

mutation. Tests of sperm morphology could be done

to estimate potential germline mutations. Molecular

studies, such as DNA adduct formation, DNA

quantification, or serum oncogene protein detection

can serve as direct measures of mutagenicity and

toxicity. Combined, these tests can provide a qualitative association between occupational exposure

and abnormalities in endpoints. This approach is

likely to be extremely costly.

If the tests are conducted in parallel, sensitivity

increases while specificity decreases. If they are

conducted in sequence, sensitivity decreases while

specificity increases. The investigator would have to

decide which characteristic was more desirable

given the exposure and the circumstances.

The intelligent use of a combination of tests may

yield a finer resolution of exposure-disease associations. Box 4-C gives an example of such an

approach.

SUMMARY AND CONCLUSIONS

Occupational exposures to certain substances can

alter genetic makeup through structural damage to

both genes and chromosomes. Genetic damage,

regardless of cause, appears as recessive and dominant mutations, large rearrangements of DNA, point

mutations, and loss of genetic material, leading to

distortions of either the expression or biochemical

function of genes. But not all mutations cause

disease. In addition, most occupational exposures

are likely to cause principally nonheritable damage

to somatic cells, rather than germline or heritable

damage. The relationship between mutation and

health effect is often indirect and not well understood. Cancer, a disease of somatic cells, is the most

common class of genetic disease correlated with

genotoxic substances.

Until the health effects of exposures are better

understood, monitoring can only provide a gross

indication that genetic changes have occurred and

that adverse health effects could follow. The rationale behind the use of assays of genetic damage stems

from historical evidence that events observed initially and at high frequency could be the start of a

process that ultimately produces neoplasm in a

smaller number of cells.

New molecular assays of mutagenicity, such as

HPRT and oncogene protein detection, are providing greater specificity and will augment tests already

in use, such as the Ames test. New methods may

provide better estimates of the health effects of low

doses of some mutagens, as well as providing

qualitative data on the nature of mutation. Detecting

activated oncogenes and DNA adducts has the

potential of predicting disease in asymptomatic

individuals. The use of genetic monitoring methods

in epidemiologic studies will continue to be plagued

by some of the pitfalls associated with classical

approaches to determining hazardous exposures in

the workplace. The greatest difficulties may not be

technical but procedural-eliminating biases, obtaining controls, and keeping good records. Methods

for determining types and levels of exposures must

be improved, and certain methodological and procedural safeguards should be adhered to. In addition,

the employment of more specific and sensitive tests,

rather than relying on any one test for valid and

reliable results, will lead us closer to understanding

the relationships between exposure, mutation, and

disease.

1.

2.

3.

4.

5.

6.

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Chapter 5

The State-of-the-Art in

Genetic Screening
CONTENTS

Page

BIOCHEMICAL TECHNIQUES FOR DETECTING GENETIC DISEASE ...........77

MOLECULAR TECHNIQUES FOR GENETIC SCREENING . . . . . . . . . . . . . . . . . . . . . . . 77

Restriction Fragment Length Polymorphisms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 78

Polymerase Chain Reaction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . 81

Automation of DNA Diagnostic Procedures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82

SCREENING FOR SUSCEPTIBILITY TO WORKPLACE EXPOSURES . . . . . . . . . . . . 83

Glucose-6-Phosphate Dehydrogenase Deficiency . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85

Sickle Cell Anemia and Sickle Cell Trait . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85

The Thalassemias . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85

Acetylation Phenotype . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .85

Serum Alpha- 1-Antitrypsin Deficiency . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 86

Aryl Hydrocarbon Hydroxylase and Cytochrome P-450 . . . . . . . . . . . . . . . . . . . . . . . . . . . . 86

Ataxia Telangiectasia Heterozygosity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 86

Paraoxonase Variants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .,. . 87

HLA Associations . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87

SCREENING FOR NONOCCUPATIONALLY RELATED DISEASE . . . . . . . . . . . . . . . . 87

Predisposition to Cancers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 88

Predisposition to Mental and Addictive Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 92

Predisposition to Atherosclerosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93

Predisposition to Diabetes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 94

COMMERCIAL DEVELOPMENT OF GENETIC TESTS . . . . . . . . . . . . . . . . . . . . . . . . . . . 94

SUMMARY AND CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95

CHAPTER 5 REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .95

Box

Box Page

5-A. Adult Polycystic Kidney Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 80

Figures

Figure Page

5-1. Detection of Restriction Fragment Length Polymorphisms Using

Radioactively Labeled DNA Probes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79

5-2. The Polymerase Chain Reaction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82

Tables

Table Page

5-1. Common Monogenic Disorders for Which DNA Diagnosis Is Possible or

Within Reach ... .*. ... ... ... ... ..+

. ... ... ... ... ... ... *+. .***   ** ** **. *. #** 80

5-2. Identification and Quantification of Genetic Factors Affecting Susceptibility to

Environmental Agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 84

5-3. Some Companies Offering DNA-Based Diagnostic Tests

. . . .

. . . . . . . . . . . . . . . . . . . . . . 94

5-4. Genetic Tests Available and Total Americans Affected . . . . . . . . . . . . . . . . . . . . . . . . . 95
Chapter 5

The State-of-the-Art in Genetic Screening

As mentioned in chapter 2, genetic screening in

the workplace can be used in two distinct ways.

First, genetic screening can detect traits that may

indicate an increased susceptibility to occupational

illness after exposure to specific agents. Second,

screening tests can be used to identify genetic

disorders not associated with specific job exposures.

Thus, in assessing the state-of-the-art of screening

tests for use at worksites, three different questions

must be discussed. Namely, what general techniques

are presently available that could be used for genetic

screening? What is known about the association

among heritable traits, exposure to hazardous materials, and subsequent occupational illness? And,

what genetic disorders can be detected unrelated to

job exposures that are important to general health?

The following sections address the recent technical advances in genetic screening tests, with an

emphasis on recombinant DNA tests. Important

background information on human genetics and

disease can be found in appendix A. In evaluating

the interaction of occupational exposure and genetic

influences, the discussion focuses on traits evaluated

in the 1983 Office of Technology Assessment

(OTA) report (111), but also assesses several newly

recognized susceptibilities to occupational disease.

Finally, progress in detecting some nonoccupationally related disorders is presented. These disorders

are presented because they are likely to affect large

populations, screening tests for them are under

investigation or being developed, and they might be

of interest to an employer if available through

preemployment screening.

BIOCHEMICAL TECHNIQUES

FOR DETECTING GENETIC

DISEASE

Biochemical genetics refers to the analysis of

mutant genes on the basis of altered proteins or

metabolizes. If diagnosed, some of these “inborn

errors of metabolism” can be treated with enzyme

replacement or dietary control.

Phenylketonuria is the classic example of an

inborn error of metabolism, inherited as an autosomal recessive, that can be controlled by restricting dietary intake of phenylalanine. In this disease,

the individual lacks the enzyme necessary to convert

phenylalanine to tyrosine. Retardation and seizures

are common symptoms. Carriers, or heterozygotes,

for the disease tend to have the enzyme at a level

about half that found in individuals who are homozygous for the normal gene. Affected individuals

have almost none of the necessary enzyme. Most

inborn errors of metabolism, for which the enzyme

defect is known, lend themselves to biochemical

tests for the detection of affected and carrier

individuals.

Sickle cell disease is a form of chronic hemolytic

anemia characterized by the presence of crescentshaped (or sickled) red blood cells that cause

peripheral oxygen deficit by blocking the terminal

arterioles. It is a biochemical disorder of hemoglobin

for which the mutant gene has been found. The

disease has an extraordinarily high frequency in

populations of West African origin, occurring in

about 1 in 625 U.S. Blacks at birth (87). One in eight

Blacks is a carrier for the disease, a condition

referred to as “sickle cell trait. ’ The trait can be

detected biochemically by hemoglobin electrophoresis, or by testing for the gene itself, now that

the gene has been cloned (see subsequent discussion

of cloning) (66,99).

In general, biochemical techniques for diagnosing genetic disease are often restricted to

indirect analysis. Only for fewer than 10 percent

of monogenic disorders has the fundamental

biochemical defect been elucidated (85). Advances in DNA technology (described below) have

greatly advanced our ability to directly examine the

genetic basis for disease and to predict and diagnose

such diseases.

MOLECULAR TECHNIQUES FOR

GENETIC SCREENING

Until recently, most available tests for genetic

conditions were not based on recombinant DNA

techniques. Traditionally, enzyme or other proteinbased assays that identified abnormal gene products

(or the consequences of abnormal gene function) are

more commonly performed. For example, in the case

of Tay-Sachs disease, reduced activity of a particular

enzyme signals the carrier state, and absence, the

–1 l–
78 . Genetic Monitoring and Screening in the Workplace

Photo credit: Lawrence Laboratory, CA

Direct image of chemically unaltered strand of DNA

obtained using a scanning tunneling microscope. (Light

microscopes magnify objects up to about 1,000 times;

electron microscopes about 300,000 times. Scanning

tunneling microscopes can magnify images

up to 1 million times.)

disease state. Today, DNA-based tests encompass a

variety of standard diagnostic techniques that allow

examination of regions very near the genes (e.g.,

Huntington’s disease) or direct examination of the

genes themselves (e.g., sickle cell anemia and cystic

fibrosis).

DNA can be extracted from any tissue containing

nucleated cells, including blood. Once extracted, the

DNA is stable and can be stored indefinitely so that

samples from people with genetic disorders can be

collected and saved for investigations to diagnose

future family members.

The remainder of this section describes the types

of techniques that can be used for genetic screening,

with emphasis on molecular methods developed

since the 1983 OTA report, including restriction

fragment length polymorphisms (RFLPs), allelespecific oligonucleotide (ASO) probes, polymerase

chain reaction (PCR), and automation of these and

other technologies useful to DNA-based genetic

diagnostics.

Two major tools, recognition of RFLPs and

development of cloned DNA probes are the major

advances responsible for improved diagnosis of

genetic disease.

Restriction Fragment Length Polymorphisms

Variations in the DNA sequence of two individuals are likely to occur on average every 300 to 500

base pairs (49). These variations occur both within

and outside of genes and usually do not lead to

functional changes in the protein products of genes.

In the 1970s, it was demonstrated that certain

bacterial enzymes, called restriction endonucleases,

could be used to map genes by cleaving DNA at

specific sites. This discovery led researchers to

propose that natural differences in DNA sequence

(polymorphisms) might replace other chemical and

morphological markers as a way to track chromosomes through a family (linkage analysis) (50).

Because of the naturally occurring variation in the

DNA sequences of individuals, the lengths of DNA

resulting from cuts by the endonucleases will differ.

This phenomenon is referred to as RFLP. RFLP

analysis is a relatively straightforward process, and

over 3,000 RFLP loci have been identified, including more than 100 highly polymorphic loci at which

many alleles exist in the population. Some of these

loci are located so close to a gene of interest that they

are nearly always inherited with the gene. So even

when a gene associated with disease has not been

identified and even when a disease gene’s locus is

not precisely known, the inheritance of an associated

RFLP can be used as an indicator of inheritance of

the gene.

Briefly, the method involves cutting the DNA

with a restriction enzyme, and sorting out various

fragments by electrophoresis in a gel in which the

DNA fragments will migrate according to length.

The double-stranded fragments are then converted

into single strands and transferred onto a nylon

membrane, to which the fragments adhere. This

technique is referredtoasa‘‘Southern blot’ after its

inventor, E.M. Southern (96). The membrane is then

soaked in a solution containing a radiolabeled DNA

probe which binds to the particular fragment containing its complementary sequence. The probe is

obtained through cloning the gene of interest or by

chemical synthesis. The nonspecifically bound

probe is washed away and the falter is placed on a

piece of x-ray film. The radioactively labeled bands

expose the x-ray film and their locations indicate the
Chapter 5—The State-of-the-Art in Genetic Screening ● 79

size of the fragments complementary to the gene

probe under study (figure 5-l).

A new probe technology, using fluorescence

rather than radioactivity, is expected to speed up the

time it takes to make a diagnosis while simultaneously decreasing the incidence of false positives

(37). Enzyme-linked dye methods are already available commercially (87). These methods do not

necessarily improve accuracy, but provide greater

safety in the laboratory.

As stated previously, the RFLP itself is not the

cause of disease.1 Rather, RFLPs serve as flags, or

markers for the presence of the disease gene. The

general location of many genes has been determined

and located on or near a specific restriction fragment. The segregation pattern of the RFLP within a

family is analyzed and the inheritance of specific

alleles of the RFLP is then used to predict the

inheritance of the disease gene. One of the first

applications of this technology came in 1983 when

genetic linkage between a RFLP marker on chromosome 4 and Huntington’s disease was described

(39,50).

Thus, RFLP analysis can be useful for families

where the precise mutation is unknown but general

location of the locus of the mutation is known to be

linked to a RFLP marker. Indirect analysis of this

type is most often used in prenatal diagnosis, but is

likely to be used in other diseases, such as adultonset polycystic kidney disease (see box 5-A) and

Wilson’s disease. Linkage analysis is limited for

three primary reasons: 1) at least one living

affected family member is usually required; 2)

genetic heterogeneity will confound the analysis

if an affected member is not available because

different mutations at different loci may produce

indistinguishable disease manifestations, or phenotypes; and 3) paternity must be known. Successful linkage studies have also been completed for

cystic fibrosis (for which the gene has now been

found), myotonic dystrophy, familial amyloidotic

polyneuropathy, familial Alzheimer’s disease, and

Duchenne muscular dystrophy. Table 5-1 lists selected diseases for which DNA diagnosis is possible

or within reach.

Figure 5-l—Detection of Restriction Fragment

Length Polymorphisms Using Radioactively

Labeled DNA Probes

Genomic DNA From Three Blood Samples

A

Agorose Gel Electrophesis

Gel

+

Denature DNA

ii Transfer to Nylon

~Membrane

ylon Membrane

~ Add Radioactively Labeled

~ DNA to Nylon Membrane for

.] ~ H ybridization

Vy

z Expose on X-Ray Film

] For Autoradiography

Y

Film

Variations in DNA sequences at particular marker sites are

observed as differences in numbers and sizes of DNA fragments

among samples taken from different individuals (shown here as

samples A, B, and C).

SOURCE: Office of Technology Assessment, 1990.

lk sic~e cell, tie mutation that causes tie disease results in an aIteration in a restriction site so the restriction analysis constitutes a *Ct t=t for

the disease.
80 ● Genetic Monitoring and Screening in the Workplace

BOX 5-A—Adult Polycystic Kidney Disease

Adult polycystic kidney disease (APKD) is a

dominant disorder with age of onset between 20 and

35 in most families. Renal dialysis or transplantation are the primary treatment modalities. The

disorder can be diagnosed by ultrasonography, but

false negatives are common, For example, a 20-

year-old at risk may have a negative ultrasound but

develop the disease 10 years later.

A number of flanking DNA linkage markers have

been identified very close to the disease locus on

chromosome 16. If multiple affected and unaffected

individuals in an APKD family can be tested for the

presence of the marker, the coupling phase between

the marker and the disease gene can be set, and

predictive diagnoses can be made. his constitutes

a presymptomatic diagnosis. The physician can

then be alerted to monitor the blood pressure, renal

function, and weight status of the patient knowing

that he or she is markedly at risk for ultimately

manifesting the disease.

SOURCE: Office of Technology Assessment, 1990.

Use of RFLPs in Population Studies

Population differences are important to recognize in both genetic screening and monitoring. In

screening, it is important to remember that certain

rare alleles are often concentrated within certain

ethnic groups, e.g., Tay-Sachs and Gaucher’s diseases affect Jewish people of Ashkenazi descent. An

individual of this background, therefore, would

more appropriately be screened for these traits than

would individuals of different ethnic or racial

backgrounds. In the case of monitoring, the ethnic

composition of the population being tested might be

an important consideration in deterrnining allelic

frequencies.

In addition to using RFLPs in clinical diagnosis,

they provide the potential for elucidating a range of

information in the study of human populations.

Population-specific alleles or allele frequencies

have been found. For example, the number of

polymorphisms due to the presence or absence of a

dihydrofolate reductase gene has been found to

differ between Blacks and Caucasians. And one of

the six known RFLPs in the human growth hormone

cluster was found only in Blacks although the other

five were present in Caucasians. RFLPs linked to the

alpha-1 -antitrypsin Z allele (which is associated

Table 5-l-Common Monogenic Disorders for Which

DNA Diagnosis Is Possible or Within Reach

Autosomal dominant . . . . . . . . .

Autosomal recessive . . . . . . . . .

X-linked . . . . . . . . . . . . . . . . . . . .

hypercholesterolemia

polycystic kidney disease

Huntington’s disease

neurofibromatosis

myotonic dystrophy

polyposis coli

tuberous sclerosis

hemochromatosis

alpha-1 -antitrypsin deficiency

cystic fibrosis

phenylketonuria

adrenogenital syndrome

retinitis pigmentosa

retinoblastoma

sickle cell anemia

thalassemias

fragile X mental retardation

Duchenne muscular dystrophy

hemophilia A and B

ichthyosis vulgaris

adrenoleukodystrophy

SOURCE: Adapted from H.H. Ropers and B. Wieringa, ‘The Recombinant

DNA Revolution: Implications for Diagnosis and Prevention of

Inherited Disease,” European Journal of Obstetrics and Gynecology and Reproductive Biology 32:15-27, 1989.

with increased risk of emphysema and liver disease

and is an occupationally important marker) have

only been described in Europeans. RFLPs linked to

clinical hypertriglyceridemia differ between Caucasians and Japanese (100). Population differences in

RFLPs are attributed to racial divergences and

explain, in part, ethnic and racial differences in

disease morbidity.

HLA Typing and Genetic Disease

More recently, linkage analysis relying on the

genetic organization of the major histocompatibility

complex (the genes that regulate and control the

immune system) has provided useful information for

organ and tissue transplantation, paternity determinations, and disease susceptibility (26). The utility

of typing of the human leukocyte antigens (HLA) for

genetic studies is due to the high degree of genetic

polymorphism in the HLA region (i.e., HLA antigens are among the most variable proteins of the

human genome).

Genetic susceptibility to a variety of diseases has

been linked in family studies with specific HLA

types. Polymorphisms of the HLA loci have been

associated with specific diseases such as insulindependent diabetes mellitus, rheumatoid arthritis,

multiple sclerosis, and myasthenia gravis. As more

polymorphisms in the HLA complex are identified,
Chapter 5—The State-of-the-Art in Genetic Screening . 81

Photo credit: Nishimi

Gel electrophoresis of DNA samples.

HLA-based probes will provide an additional tool

for linkage studies, and possibly direct analysis of

mutant genes. The high degree of variability at the

DNA level in the HLA loci suggests that DNA

markers in the region are of great importance in

characterizing population groups.

Direct Analysis of Mutant Genes

In a small percentage of cases (5 to 10 percent),

point mutations responsible for genetic disease can

be directly detected by restriction analysis and the

use of synthetic oligonucleotides as probes (4).

Sickle cell disease is one such example. Direct

analysis of mutant genes involves cloning the

mutant allele and sequencing through the mutation.

This is a laborious process because most genes are

large (the globin genes have been sequenced because

they are small). If the gene can be sequenced,

oligonucleotide probes can be synthesized that

specifically recognize the mutant or normal alleles.

DNA probes have been in use for nearly 10 years

to detect point mutations. A probe is a short

sequence of single-stranded DNA that is complementary to the DNA sequence being sought. If short,

they may be chemically synthesized DNA segments.

ASO probes refine diagnostic accuracy by perfectly

matching the nucleotide sequence of a portion of the

gene in question (17). These probes are long enough

to represent unique sequences but short enough to be

specific to a target molecule. Before being used, the

probe is labeled with a fluorescent or radioactive

marker so it can be detected. A method of amplification, described below, can then be used to permit

extremely accurate identification of the target gene.

This approach has been applied successfully in

alpha-1-antitrypsin deficiency, sickle cell disease,

several of the thalassemias, cystic fibrosis, and

hemophilia A, to name a few. Because of the

difficulty of sequencing and producing probes for

large genes, indirect, or linkage analysis, is more

commonly used for diagnosis. The use of probes

for direct analysis has been limited because, for

most single-gene disorders, there are many different mutations that cause the same disease. As

in linkage studies, accurate diagnosis often depends

on the availability of several affected family members.

It is likely that the complete physical map of the

human genome will serve as the ultimate source of

DNA probes for any human gene (62).

Polymerase Chain Reaction

PCR, first reported by Cetus Corp. in 1985,

facilitates the use of probes by greatly increasing, or

amplifying, the number of copies of target DNA. For

example, selected areas of a gene can be amplified

through repeated cycles, a probe can be hybridized

directly to the amplified DNA and a rapid diagnosis

made. PCR produces enough of the target sequence

so that simple, rapid, and accurate methods for

identification can be employed (74). In some respects, it can be thought of as molecular photocopying (see figure 5-2).

PCR will probably be the method of choice for

identifying monogenic disorders in which point

mutations account for the majority of gene defects

and will make DNA diagnosis possible at any major

medical center (4). It has great potential value for

carrier screening programs. The possibilities for use

of PCR in diagnosing monogenic diseases through

linkage studies are also great (52).

Briefly, PCR involves using two specific sequences, called primers, that flank the area the

scientist wants to copy. The scientist then sets

conditions in the reaction that allow new copies of
82 ● Genetic Monitoring and Screening in the Workplace

Figure 5-2—The Polymerase Chain Reaction

Individual A Individual B Unknown C

AMPLIFICATION

(Molecular Photocopying of DNA)

Each sample is amplified

manually or in a machine.

Original DNA Sample

 . . Synthesize

New DNA -

PCR Primer

 Synthesize

-/- - - - - - Synthesize

 - - - - 7 and 

Multiple copies of DNA Sample

(20-25 cycles of the PCR yields about

one million-fold reproduction)

DOT BLOT

The membrane is

challenged with a DNA

probe that has a key

sequence specific to an

HLA DQ-Alpha Allele. washed and 

in a color developer

There are 21 different types

at HLA DQ Alpha Locus

(most frequent is 1 in 5,

least 1 in 800).

SOURCE: Office Technology Assessment, 1990.

Photo credit: 

DNA thermal cycler for automated PCR analysis.

the DNA of interest to be produced from the primers.

Because the products generated in one sample can

serve as templates in the next cycle, the number of

amplified copies doubles with each cycle. Thus, 20

cycles of PCR yields about a millionfold reproduction. This extraordinary ability is also PCR’s greatest weakness. PCR assays can lead investigators

astray when trace quantities of contaminating DNA

molecules find their way into the reaction sample.

Handling of samples when using PCR requires much

greater care than with routine RFLP analysis.

Automation of DNA Diagnostic Procedures

A number of instruments have been developed

that can increase the speed and volume of routine

DNA diagnostic procedures. Some examples include:

●

●

●

The DNA extractor prepares DNA suitable for

Southern blots from eight tissue samples in 3

hours. Future extractors will be able to handle

hundreds of samples daily (62).

The DNA synthesizer, or ‘gene machine, ’ can

assemble oligonucleotides up to 200 nucleotides in length with a synthesis rate of 12 to 15

minutes per cycle. The synthesizer is crucial for

probe development (43,62).

Laboratory robotic workstations are being developed that can rapidly and accurately perform

routine manipulations including RFLP analyses and DNA sequencing.
Chapter 5—The State-of-the-Art in Genetic Screening ● 83

Photo credit: Human Genome Center, Lawrence Berkeley Laboratory

Computerized robotics used to speed repetitive tasks of

●

mapping and sequencing DNA.

An instrument has been developed that can

size-separate very large DNA segments

through pulsed field gradient gel electrophoresis. This will be useful in identifying

deletions, translocations, and amplifications of

DNA sequences and in determining RFLPs

over large DNA segments (62).

Novel computing systems are being designed

specifically to handle the computational tasks of

sequencing. Automation of DNA diagnostic procedures will make large-scale screening faster and

more affordable.

The Limits of Molecularly Based Tests

No matter what the mode of screening, two

questions must be asked before administration of the

test: 1) does the test reliably identify either the

genetic trait or specific damage? and 2) does this

particular trait or damage cause the individual to be

at increased risk for disease? The frost question is

more easily answered than the second. To answer the

first question, the test must be subjected to scientifically recognized analytical criteria; validity, reliability, predictive value, and relative risk (111).

These issues are discussed in chapter 4 and will not

be repeated here.

As discussed previously, linkage studies are

limited by the requirement for samples from informative relatives and by variable expressivity. This

makes linkage testing uncertain for some individuals. Currently, widespread application of linkage

studies is limited by the number of probes available,

but this obstacle will gradually be overcome. And, as

more disease genes are cloned, linkage studies will

be replaced by direct tests.

Even with direct tests, however, variable expressivity, incomplete penetrance, and heterogeneity

will interfere with the ability to predict correctly that

certain individuals will develop disease (42). Heterogeneity lowers sensitivity and variable expressivity lowers specificity. (See ch. 4 for discussion of

specificity and sensitivity.)

In any case, before widespread screening of

populations is begun, the validity of the tests should

be determined in a large number of unrelated people

with clinical expression of the disease and in others

who have no signs of the disease. Such efforts will

require a large test population.

Reliability is measured by the ability of a test to

accurately detect that which it was designed to detect

and to do so in a consistent fashion. Other than the

routine laboratory problems that lead to unreliable

test results (human error, contamination), DNAbased tests can fail to yield reliable results for a

number of reasons, most often because of incomplete digestion of DNA, faulty hybridization in the

Southern blot, or contamination of the PCR amplification. Quality control is likely to become a major

issue as the volume of tests at laboratories grows

(42). These are already issues in forensics applications (109).

SCREENING FOR

SUSCEPTIBILITY TO

WORKPLACE EXPOSURES

At the end of the 1960s, some scientists sought to

provide perspectives for research on the interaction

of genetics, drugs, and environmental agents by

showing its application to the field of industrial

hygiene (98). Today, the term “ecogenetics” often

refers to the field dealing with genetic predispositions to drugs or any type of environmental agent

(10). At present, approximately 50 human genetic

diseases have been identified as having the

potential to enhance an individual’s susceptibility to toxic or carcinogenic effects of environmental agents (14) (see table 5-2 for examples).

This section briefly reviews selected genetic

conditions from the 1983 OTA report that some

believe enhance susceptibility to environmental
84 ● Genetic Monitoring and Screening in the Workplace

Table 5-2—ldentification and Quantification of Genetic Factors Affecting Susceptibility to Environmental Agents

Environmental agents to which group

High-risk groups Estimated occurrence is (may be) at increased risk

RBC conditions

G-6-PD deficiency . . . . . . . . . . . .

Sickle cell trait ., . . . . . . . . . . . . .

The thalassemias . . . . . . . . . . . .

NADH dehydrogenase deficiency

(MetHb reductase deficiency) . .

Catalase Hypocatalasemia . . . . .

Acatalasemia . . . . . . . . . . . . . . . .

Low SOD activity . . . . . . . . . . . . .

ALA dehydratase deficiency . . . .

Hb M . . . . . . . . . . . . . . . . . . . . . .

Erythrocyte porphyria . . . . . . . . .

. .

. .

. .

. .

. .

. .

. .

. .

. .

GHS-Px deficiency . . . . . . . . . . . . .

GSH deficiency . . . . . . . . . . . . . . . .

Liver metabolism

Defect in gluocuronidation

Gilbert’s syndrome . . . . . . . . .

Crigler-Najjar syndrome . . . . .

Defect in sulfation . . . . . . . . . . . .

Acetylation phenotype, slow v.

fast . . . . . . . . . . . . . . . . . . . . . .

Gout . . . . . . . . . . . . . . . . . . . . . . .

Oxidation center defects . . . . . . . . .

OCT deficiency . . . . . . . . . . . . . . . .

Paraxonase variant . . . . . . . . . . . . .

Rhodanese variant . . . . . . . . . . . . .

Sulfite oxidase deficiency

heterozygotes . . . . . . . . . . . . . . . . .

inadequate carbon disulfide

metabolism . . . . . . . . . . . . . . . . .

Alcohol dehydrogenase variant . . . .

Wilson’s disease . . . . . . . . . . . . . . .

Serum variants

Albumin variants . . . . . . . . . . . . .

Pseudocholinesterase

variants . . . . . . . . . . . . . . . . . .

American Black males 16%; Mediterranean

Jewish males 11%; Greeks 1%-2%.; Sardinians 1%-8%

7%-1 3% of American Blacks are heterozygotes

Alpha: 4%-5% in Americans of Italian and

Greek descent; Beta: 2%-7% American

Blacks and 2%-3% American Greeks

Estimated 1%. of population are heterozygotes

About 2% of U.S. population based on Swiss

gene frequency

1/10,000-20,000 of U.S. population based on

Swiss gene frequency

Frequency of genetic variants in population 1 to

2/10,000; normal population exhibits unimodal distribution; persons at low end of distribution may beat increased risk

Unknown, but thought to be rare

Unknown, but rare

1.5/100,000 in Sweden, Denmark, Ireland,

West Australia; 3/1 ,000 in South African

Whites; rare in Blacks

Rare

Rare

6% of normal, healthy adult population

Few persons live to adulthood

Unknown

Unknown

Upward of 30%-40%

5% English; 20% Swiss; 70% Japanese

Homozygous 1/100,000 while the heterozygote

may approach 1/500

Less than 1/1,000 in Europeans, much higher

frequency in North American and Mexican

Indians

Highly sensitive homozygous and heterozygous persons of European ancestry have

combined frequency of about 1/1,250; moderatelv sensitive genotypic variants of European ancestry have frequency of 1/15,000

Environmental oxidants such as ozone, nitrogen dioxide, and chlorite

Aromatic amino and nitro compounds; carbon monoxiode, cyanide

Lead; benzene

MetHb-forming substances

Ozone; radiation

Wide variety of environmental oxidants; paraquat;

radiation; ozone

Lead

Carbon monoxide

Chloroquine; hexacholorobenzene; lead; various

drugs, including barbiturates, sulfonamides, others

Environmental oxidants

Environmental oxidants

Wide variety of xenobiotics including polychlorinated

biphenyls

Wide variety of xenobiotics; best association is with

tyramine-captaining foods

Aromatic amine-induced cancer; numerous drugs,

e.g., isoniazid and hepatitis

Lead

Numerous xenobiotics requiring oxidative metabolism

for detoxification

insect repellant (DET)

Parathion

Cyanide

Sulfite, bisulfite, sulfur dioxide

Carbon disulfide

Metabolize (e.g., ethanol) more quickly than normal

Copper, vanadium

Unknown

Organophosphate and carbamate insecticides; muscle

relaxant drugs
Chapter 5—The State-of-the-Art in Genetic Screening ● 85

agents, and evaluates any progress made since that

report (111). Following that, several new associations between genetic traits and environmental

agents are analyzed.

Glucose-6-Phosphate Dehydrogenase

Deficiency

Individuals whose blood cells are deficient in the

enzyme glucose-6-phosphate dehydrogenase (G-6-

PD) are at enhanced risk for hemolysis (destruction

of red blood cells) if exposed to a number of oxidant

drugs and industrial chemicals, especially certain

aromatic amino and nitro compounds such as

naphthalene and TriNitroToluene. G-6-PD deficiency is inherited as an X-linked trait. Although

G-6-PD deficient persons could be at increased risk

of anemia if exposed to specific hazards in the

workplace, epidemiologic studies designed to actually assess G-6-PD deficient workers are lacking

(14). A direct DNA test for some mutants causing

G-6-PD deficiency is available (4).

Sickle Cell Anemia and Sickle Cell Trait

Sickle cell anemia and sickle cell trait result from

the presence in red blood cells of an abnormal

hemoglobin molecule (HbS v. normal HbA). Persons with sickle cell anemia are homozygous for

HbS, that is they have two copies of the abnormal

beta-globin gene, and 100 percent of red blood cells

contain HbS. Individuals who have sickle cell trait

have only one copy of the abnormal gene (i.e., are

heterozygous) and only 20 to 40 percent of their red

blood cells have HbS. Under certain conditions,

when the oxygen level or environmental temperature

drops, HbS-containing red blood cells can sickle.

This leads to varying degrees of adverse health

consequences, depending on the individual’s level

of HbS. Although the sickle cell gene has been

cloned, a simple, and relatively inexpensive, biochemical assay can detect HbS. The principal use of

both a DNA probe for sickle cell and PCR lies in

prenatal diagnosis (4).

Individuals with sickle cell anemia have reduced

lifespans and many health problems directly attributable to being homozygous for the sickle cell gene.

But as in the 1983 OTA report, whether sickle cell

trait carriers are at increased risk from the challenges

of rigorous training at high altitudes (where oxygen

is low) remains unresolved. Limited evidence suggests that possession of sickle cell trait is a

contributing factor in reported cases of injury or

death during or after vigorous exercise (51), but

other confounding factors are most likely present

(14). Neither the experimental or epidemiological

evidence has confirmed the hypothesis that persons

with sickle cell trait are at increased risk when

exposed to several chemicals (14).

The Thalassemias

Thalassemia is a deficiency in the production of

hemoglobin that results in smaller red blood cells.

The disease is inherited in an autosomal recessive

pattern and it varies in severity and type (there are

alpha and beta forms of the disease). It has been

suggested that beta thalassemic individuals are at

increased risk after exposure to several chemicals,

including benzene and lead. Again, while limited

clinical observations have suggested that persons

with thalassemia could be at increased toxic risk

from benzene and lead, data since 1983 remain

insufficient and unconvincing. Continued assessment, epidemiological investigations, and a predictive animal model to test lead- or benzene-induced

blood toxicity will be required before an association

can be made between this genetic trait and enhanced

occupational illness (14,15).

Acetylation Phenotype

Acetylation is a common liver pathway for

detoxification of a variety of compounds. The

enzyme involved in acetylation, N-acetyltransferase, is coded for by one gene, and humans are

either slow or fast acetylators. At the time of the

1983 OTA report, slow acetylation was implicated

in increased risk of bladder cancer, and susceptibility to bladder cancer was not equal among those

generally grouped as slow acetylators (16). Since

then, a growing body of epidemiologic studies

further suggests that slow acetylation is a predisposing factor for the recurrence of arylamine-induced

bladder cancer (115), and the hypothesis of increased susceptibility is well-characterized with

animal models (45,70,1 15). Epidemiologic studies

of industrial cancer populations are necessary (78).

Because 50 percent of North American Caucasian

and Black populations are slow acetylators, the

incentive to develop these studies is great.

On the other hand, in addition to the association

of slow acetylation with bladder cancer reported in

the 1983 OTA report, several recent studies reveal a

statistical link between fast acetylation and colorectal cancer (47,64).
86 ● Genetic Monitoring and Screening in the Workplace

Serum Alpha-1-Antitrypsin Deficiency

Homozygous serum alpha-l-antitrypsin (SAT)

deficiency is an important genetic factor in emphysema, and some research from animal and human

studies supports the hypothesis that an intermediate

deficiency of SAT deficiency is a contributing factor

in the development of emphysema in heterozygotes.

Nevertheless, it is now recognized that emphysema

has a multifactorial etiology and that the heterozygote state, by itself, is not a major predisposing

factor. Rather, in combination with other predisposing factors, intermediate SAT deficiency can enhance risk of emphysema. Since the 1983 OTA

report, data from several clinical and epidemiologic

studies indicate that heterozygotic carriers of SAT

deficiency display enhanced risk of developing

chronic obstructive pulmonary disease (COPD),

even in the absence of occupational or lifestyle

factors, such as smoking (44). The risk is, however,

exacerbated by smoking (25), occupational risk

factors, such as grain dust (44), and other nonidentified factors (55). Thus, while it would appear that a

genetic factor is important in risk of COPD for

carriers of SAT deficiency, a better understanding of

all aspects of emphysema is probably necessary

before implementing widespread SAT screening. A

DNA-based test for SAT has been used for direct

analysis of mutation (58), as well as in prenatal

diagnosis (57).

Homozygous alpha- l-antitrypsin deficiency, because it is so thoroughly understood at the molecular

level, is a good candidate for gene therapy. It has

been proposed that genetically engineered alpha-1 in

aerosol form could serve the function of shielding

against natural destruction of the respiratory tract.

Such therapy is in early experimental stages (19).

Aryl Hydrocarbon Hydroxylase and

Cytochrome P-450

Cytochrome P-450 enzymes play a central role in

metabolizing an enormous range of molecules,

including steroids, other drugs, carcinogens, and an

array of environmental agents. Both because of their

wide spectrum of action and their genetic variability

among humans, P-450 enzymes have a marked

potential to affect individual susceptibility. Research in cytochrome P-450 has exploded (75) and

information continues to mount about genetic differences in human P-450 enzymes, as well as the

relationship between P-450 enzymes and cancer

(35,75,76,117). This section examines two cytochrome P-450 enzymes: aryl hydrocarbon hydroxylase (AHH) and debrisoquine 4-hydroxylase (D4-

H),

The 1983 OTA report examined the role of

individual differences of AHH and lung cancer. A

key feature of this discussion relied on scientists’

ability to reliably measure AHH changes in white

blood cells and correlate those changes with changes

in lung cells. Experimental limitations to elucidate

the role of changes in enzyme levels of AHH in lung

cancer led investigators to identify the role of other

P-450 genetic markers in environmentally induced

cancers, including D4-H (5,13). Nevertheless, concrete evidence that enzyme levels of AHH or D-4H

could serve as markers for differential cancer

susceptibility to lung cancer (5) remained elusive

until recombinant DNA methods were used to define

the inheritance of a number of P-450 enzymes,

including AHH and D4-H.

With advances in molecular biology, scientists

anticipate clinical studies to correlate inheritance of

RFLPs associated with (or genetically linked to)

various P-450 enzymes with individual cancer risk

(75). In the case of D4-H deficiency, where 5 to 10

percent of people are affected, molecular characterization of the phenotype (36) shows promise of

revealing the relationship among individual differences in D4-H, environmental exposure to certain

agents, and cancer susceptibility (46). Characterization of other P-450 genes is likely to yield insight

into predicting individual toxicity to some types of

antibiotics, including erythromycin, a commonly

prescribed antibiotic, and other agents (14).

Ataxia Telangiectasia Heterozygosity

Ataxia telangiectasia (AT) is an autosomal recessive disorder displaying simultaneous neurological,

oculocutaneous, and immunological complications

(61,101). Diagnosis is usually made in childhood

based on the appearance of poor motor control and

telangiectasia, or spider-like lesions, on the skin and

eyes. Such individuals are predisposed to both

immune deficiencies and certain cancers (1,31,81).

The cancer risk is over 100 times greater than for

control groups. Patients usually die in early adulthood from respiratory ailments or lymphoproliferative disorders.

Several studies have noted that the AT gene may

have some clinical effects in persons who are
Chapter 5--The State-of-the-Art in Genetic Screening . 87

heterozygous. Among those effects found in some

AT heterozygotes are defective immunity, oculocutaneous telangiectasias, and enhanced cancer

susceptibility (31,102). AT heterozygotes are particularly sensitive to ionizing radiation.

AT homozygotes are relatively uncommon at

approximately 25 per million (or 1 in 40,000).

However, population-based studies have estimated

the incidence of the heterozygote in the United

States to be about 2.8 percent, or 6 to 7 million

Americans (14). For AT heterozygotes younger than

age 45, the risk of dying from a malignant neoplasm

is greater than five times the risk for the general

population. AT heterozygotes comprise more than 5

percent of all persons dying from cancer before age

45. The types of cancer increased in AT families are

ovarian, gastric, and biliary system carcinomas, and

leukemia and lymphoma. In addition, there is

evidence to support some predisposition of AT

heterozygotes to basal cell, breast, pancreatic, cervical, and colon cancers. AT heterozygotes appear to

be at markedly enhanced risk of breast cancer

(14,72,82).

The emphasis on environmental-occupational exposures and their effects on the AT heterozygote is

currently focused on radiation, x-rays in particular.

For example, occupational exposures of breast tissue

to x-rays, or even diagnostic exposures such as

mammography, have been raised as cause for

concern (102).

A test has been developed to detect AT heterozygotes. Progress in this area could lead to identification of individuals at risk for cancers as a result of

radiation exposure.

Paraoxonase Variants

Paraoxonase is one esterase found in human

serum that metabolizes paraoxon, a metabolize that

is the active ingredient of the organophosphate

insecticide parathion. Paraoxonase activity shows

considerable variability in human populations, with

significant interethnic differences (20,34,83). Individuals with variations in esterase activity are

expected to be at increased risk to organophosphate

toxicity from any given exposure and would require

longer recovery before resuming pesticide spray

work (32,79). Insufficient research has been done to

determine at what levels of exposure individuals

with decreased paraoxonase activity are at risk.

HLA Associations

Each individual has a specific set of proteins on

the surface of his or her cell membranes that make

him or her different from everyone else. This array

of cellular surface proteins is called the HLA system.

HLA typing has been used for several years in

matching tissue and organ donors with recipients

and for paternity determinations. Increasingly, various HLAs are being associated with specific human

diseases (106).

The classic and most striking example of an HLA

associated with disease is that between ankylosing

spondylitis (AS), an arthritis of the spine. Among

Europeans, approximately 90 percent of patients

with AS display the antigen HLA-B27, while it is

present in only 8 to 9 percent of the general

population. A number of other joint diseases also

display strong positive associations with the B27

antigen.

Allergies, cardiovascular disease, immune system

diseases, dermatological disorders, renal disease,

ophthalmologic disorders, gastrointestinal diseases,

and certain malignancies have been associated with

the presence of one or more HLA types (73,88).

Despite some striking statistical associations of

certain diseases with specific HLAs, any mechanistic relationship is yet to be determined, precluding

the possibility of knowing whether the relationship

is causal or merely statistical. Nevertheless, the

recognition of the statistical relationship of HLAs

with a wide range of human diseases—some of

which are known to also be occupationally related,

such as bladder cancer, asbestosis, and farmer’s

lung-suggests that inherent genetic factors are

affecting the occurrence of the disease within the

population (14).

SCREENING FOR

NONOCCUPATIONALLY

RELATED DISEASE

Recent progress in developing tests to detect

conditions not associated with worksite exposures—

e.g., Huntington’s disease or heart disease--raises

new issues for containing health care expenses, for

both the employer and employee, and for employee

“wellness programs. ” The implications of the

various motivations for screening for nonoccupationally related traits and disease are discussed more

extensively in chapter 2.
88 ● Genetic Monitoring and Screening in the Workplace

This section covers genetic traits that have been

identified and for which genes have been cloned

(table 5-l), or where the abnormal gene can be

detected indirectly through DNA-based tests. It is

not a comprehensive treatise on all genetic conditions that have been cloned, but rather a discussion

of selected conditions intended to illustrate the vast

progress in this field.

The determination of ‘predisposition to disease’

used to be based on gross physical examination,

family history, and lifestyle habits such as eating and

drinking. Molecular biology has enhanced this

determination by seeking out and finding genes or

markers associated with disease. Individuals found

to have the gene or the marker can then be identified,

sometimes with near certainty, to be candidates for

disease. The influence of environment remains

the wild card in most cases, because possession of

the genetic predisposition alone may not be

sufficient to cause disease. It is likely that for

some time modern science will be more successful

in identifying the genes and the markers than in

identifying the environmental agent(s) necessary

for activation of the predisposing genes.

Predispositions to certain cancers have been the

focus of much research in the past few years, as have

those to atherosclerosis, diabetes, mental illness, and

chemical addiction. Advances in those areas are

discussed below.

Research is also providing insight into possible

genetic predispositions to such common ailments as

lower back injuries, obesity, allergies, and arthritis.

While predictive tests are not immediately foreseeable in any of those areas, as more populations are

studied and more linkage maps prepared, it is not

improbable that screening tests will be developed.

Predisposition to Cancers

Cancers resemble other common diseases in-sofar as some forms are associated with chromosomal

anomalies, others with single mutant genes, or

environmental agents (as discussed in ch. 4). The

vast majority, however, are best explained by a

genetic-environmental interaction. Clearly, some

individuals are predisposed to certain types of

cancer given the right environmental exposure.

Thus, viruses and carcinogenic agents act as environmental triggers in individuals with a hereditary

predisposition to cancer. This “two-hit” theory,

first posed in the early 1970s (59), states that

sporadic v. inherited forms of cancer could both

result from mutations in the same gene. These

mutations act recessively at the cellular level, and

both copies of the normal gene must be altered or

lost for the cancer to develop. In sporadic cases, both

events occur somatically whereas in cancer families,

susceptibility is inherited through a germline mutation and the cancer develops after a somatic change

in the normal allele. Recent developments in the

study of oncogenes corroborate this theory (7,69).

Occupational exposures have been implicated in

lung, bladder, testicular, and laryngeal cancers, as

well as leukemias. As the connections between

cancer and genetics become clearer, so may the

relevance of occupational exposure to genetic

disease.

Increasingly, predisposition to certain cancers

will be detected through the identification of oncogenes, as well as DNA repair, metabolizing enzymes, and immune function. The following section

describes recent developments in identifying individuals predisposed to cancer. Evidence from studies of high-risk cohorts of workers exposed to

carcinogenic agents shows that some workers do not

develop tumors. Possible explanations for this

differential effect could be variation in exposure,

diet, or other lifestyle factors, or genetic factors.

Little is known about the role of genetic predisposition to cancer following exposure to carcinogenic

agents, but as the genetic defects of various neoplasms are identified, the prospects for better understanding improve.

Recent developments in the identification of

cancer genes, or oncogenes, and tumor-suppressor

genes are discussed below.

Oncogenes

One of the most spectacular results of the new

DNA techniques has been the discovery that certain

genes, called oncogenes, play a role in the development of cancer (40). Activation of individual oncogenes appear to be necessary, but not sufficient, to

trigger cancer. As many as 10 distinct mutations may

have to accumulate in a cell before it becomes

cancerous (68). In some cases, chromosomal breaks,

deletions, translocations, or insertions of foreign

DNA place a potential oncogene (also called a

proto-oncogene) near a regulatory element that

activates it (94). The clastogenic (chromosomebreaking) effects of radiation and certain chemi-
CANCE

Assessing

Your Risk

●

A PERSONALIZED TEST ,

with guides for

reducing your risks5/90 Copyright 1990

 SEX: a Male (2) b Female (1)

2 AGE: a. 39 or less (1) b 40-49 (2) c 50-59 (5) d 60+ (7)

REDUCING YOUR RISK

SUBTOTAL

TOTAl

8. Use or have used tanning beds or sun lamps Yes No

9 Have large, many, or moles Yes No

A written self-test that assesses an individual’s cancer risks.
90 ● Genetic Monitoring and Screening in the Workplace

cals, therefore, have the potential for activating

an oncogene (see ch. 4).

Approximately 40 dominant-acting oncogenes

have been found that can induce transformation

when introduced into a cell in a structurally altered

form or when improperly expressed. The most

commonly studied oncogene, called ‘‘ras, ” is found

in 50 percent of colon carcinomas, 30 percent of

adenocarcinomas of the lung, and more than 90

percent of cancers of the pancreas (3,28,54,90,113).

Most pancreatic carcinomas and about one-third of

colorectal cancers reveal the presence of a dominantacting oncogene activated by a single nucleotide

substitution.

Chronic myelogenous leukemia (CML) exhibits

the Philadelphia chromosome (named after the city

in which it was identified) which results from

chromosomal translocation. The translocation indirectly activates an oncogene. Biotechnology companies have developed probes for the CML and breast

cancer oncogenes.

In recessive oncogenesis, the cells appear to have

lost both copies of a tumor suppressor gene (62).

Suppressor genes, or “anti-oncogenes,” are necessary for the inactivation of the oncogene, and

therefore, the malignant cell growth. Suppressor

gene loss is at least as important in carcinogenesis as

oncogene activation. It usually takes two separate

mutagenic events to eliminate a suppressor gene,

because alleles are paired and both probably have to

be inactivated (68). Two candidate turner suppressor

genes have been cloned, for retinoblastoma and

Wilm’s tumor, but the existence of others has been

inferred from experiments in which specific chromosomal regions were deleted in turners (86,114).

Retinoblastoma (Rb) is an intraocular tumor of

early childhood that can be inherited in an autosomal

dominant fashion but is thought to result from a

recessive-acting oncogene. The Rb gene provides a

model system for recessive oncogenesis. This gene

also has been shown to be inactivated in some breast

cancer cell lines. Inheriting a mutant allele for the Rb

gene predisposes a recipient to Rb. The sporadic loss

of the Rb gene through mutation is correlated with

increased cell proliferation and oncogenesis (23).

Inactivation through mutation of the Rb susceptibility gene has been implicated in the genesis of Rb and

certain other human neoplasms, suggesting a broad

role for this gene in oncogenesis (65).

Recessive-acting oncogenes also have been associated with common solid tissue tumors such as

carcinomas of the bladder, colon, breast, and lung.

There is a significant distinction between dominant-acting oncogenes and recessive-acting suppressor genes. The oncogenes that have been identified

to date are activated through somatic mutations—

genetic changes occurring in one or another target

organs and not in the germ cells. Mutant, activated

oncogenes are therefore not transmitted from parent

to offspring and can be detected only in tumor cells.

In contrast, mutant forms of suppressor genes might

be found in sperm or eggs, and can be passed onto

future generations (116). This difference distinguishes those who are predisposed to cancer at birth

from those who are not.

The rapid development of synthetic probes and

gene amplification techniques will increase the

capability to detect the presence or recurrence of

malignant cells with genetic characteristics associated with oncogenes and tumor suppressor genes.

An experimental approach, termed “gene targeting,” proposes to stop or counter the action of

oncogenes by introducing a synthetic strand of DNA

to block the message arising from the activated

oncogene.

Colon Cancer

Colon cancer is the second most common cancer

in North America, estimated to account for about

62,000 deaths in 1988 (54). A recent study concluded that a gene inherited by a third of all

Caucasian Americans may be responsible for most

cancer of the colon and rectum. Inheriting the gene

does not mean that one is destined to have cancer.

Other factors, both genetic and environmental, play

a role in inducing cancer in those who inherit the

gene. One study found evidence that a series of four

to five genetic mutations and deletions are necessary

for colon or rectal cancer to occur. If it takes four or

five steps to get the cancer, those who have inherited

one of the mutations in those steps have, in a sense,

a ‘‘head start’ and are more likely to get the cancer

(54).

Two types of mutations have been detected in

colorectal tumors. The first involves point mutations

in ras proto-oncogenes. The second type involves

deletions of specific chromosomal regions. Deletions can be detected through RFLP analysis. The

deleted sequences have been hypothesized to in-
Chapter 5—The State-of-the-Art in Genetic Screening ● 91

elude tumor-suppressor genes necessary for inhibition of neoplastic growth (54,114).

Advances in this area will lead to earlier detection

and intervention and to greater understanding of

environmental influences on the activation of the

oncogene.

Lung Cancer

Lung cancer is the overall leading cause of cancer

death among Americans. There is evidence that a

genetic defect contributes to the development of an

important form of lung cancer that makes up at least

20 percent of all lung cancers. In some studies of

lung cancer patients, a portion of chromosome 3 is

deleted, possibly taking with it suppressor genes

(60). Some lung cancers also demonstrate loss of

heterozygosity on the short arm of chromosome 17.

The p53 gene located in chromosome 17 has the

features of a tumor suppressor gene (103).

Some occupational exposures are among the

known causes of lung cancer, as is cigarette smoking. It has been suggested that, in males, 15 percent

of lung cancers in the United States are due to

occupational exposure (21). Employees in asbestosrelated occupations, including asbestos production

workers, pipefitters, boilermakers, roofers, and shipyard workers, have long demonstrated above averPhoto credit: Gianna Bosko

A sign displayed at an asbestos removal site warning that

asbestos is a cancer and lung disease hazard.

age incidence of lung cancer (112). Workers exposed to polycyclic hydrocarbons, such as mechanics and railroad workers, also have a higher incidence of lung cancer. It is unclear how these

exposures might induce the mutation necessary for

initiation of carcinogenesis, but breakage and rearrangement of chromosomal material is the likely

predictor of the deletions containing the suppressor

genes.

Future research exploring the relationship between genetic predisposition to lung cancer and

environmental exposure will focus on these groups

of workers. It is conceivable that once a predisposing gene or set of genes is located, use of probes

and PCR will facilitate rapid identification of a

subpopulation of workers at higher risk if exposed to certain genotoxic agents. Recent use of

RFLPs and probes has detected marker antigens on

cells at least 2 years before the clinical appearance

of lung cancer (77). Widespread application of this

early test could dramatically improve prognosis for

cancer patients, whether or not the cancer was

attributed to environmental exposure.

Bladder Cancer

More than 49,000 Americans develop bladder

cancer each year and about 10,000 die annually.

Historically, the major known risk factors were

environmental, particularly occupational exposures

to aromatic amines. As described earlier in this

chapter, phenotypic variants of the autosomal recessive trait for the enzyme N-acetyltransferase have

been associated with bladder cancer in workers

exposed to aromatic amines. Various genetic polymorphisms have been associated with bladder cancer, including an excess of the A gene of the ABO

blood group and an excess of two HLA genes, B5

and CW4 (92). But much of this latter work has not

been corroborated.

Activated oncogenes and chromosomal changes

have recently been identified with bladder cancer. It

has been demonstrated that cells from urogenital

tissue derived from patients with bladder cancer are

missing genes on the short arm of chromosome 11.

As in colorectal and lung cancers, it is theorized that

among those missing genes are genes responsible for

suppression of growth (27). A transforming oncogene (H-ras-1) has been isolated from a cell line of

human bladder cancer cells (89).
92 . Genetic Monitoring and Screening in the Workplace

If a genetic component in bladder cancer can

be confirmed, screening programs could be targeted to worker populations at high risk. The

National Cancer Institute (NCI) estimates that

one out of four cases of bladder cancer in

Caucasian male Americans is related to occupational exposure. The risk is highest among painters,

truckdrivers, employees of the oil, aluminum, and

railroad industries, and drill press operators (18).

Future research on these populations might lead to

a better understanding of the subtleties of predisposition and environmental insult. Some analysts,

however, feel that the NCI figures are based on soft,

or insufficient data (2,95).

Hereditary Cancer Syndromes

Human cancers that are associated with autosomal dominant mutations have been collectively

referred to as hereditary cancer syndromes (HCS)

(29). Approximately 60 to 90 percent of individuals

with HCS develop a specific type of cancer at an

early age. Family members with HCS tend to

develop the same type of neoplasm at multiple

stages in the same organ or bilaterally in paired

organs (3). Examples of dominantly inherited HCS

include retinoblastoma, Wilm’s tumor, neuroblastoma, nevoid basal cell carcinoma, familial poly -

posis coli, von Hippel-Lindau tumors, neurofibromatosis, and familial cancer syndrome. Syndromes

inherited in an autosomal recessive fashion include

Fanconi’s anemia and xeroderma pigmentosum.

Predisposition to Mental and Addictive

Disorders

New research has shown some mental and behavioral disorders to be, in part, genetically deter-mined.

The exact nature of genetic influence, however,

remains in dispute for most disorders. Nonetheless,

it is widely believed that there is likely a genetic

component to manic depression, schizophrenia,

autism, hyperactivity, some compulsive disorders,

and alcoholism (6,63,67). There is even evidence

that addiction to narcotics is influenced by physiological differences determined, in part, by our genes.

Scientists have identified a gene in rats involved in

the activation of dopamine, an important neurotransmitter (12). Abnormal dopamine function has been

linked to schizophrenia, manic depression, Parkinson’s disease, and chemical addiction (105).

Currently, disputes center not so much on

whether these disorders are genetic, but rather

on where their predisposing genes are found.

Most recently, two different research teams linked

two different markers to schizophrenia (53,93).

While it has long been known that schizophrenia

shows a tendency to cluster in families, the exact

nature of genetic influence has been unclear. Although it might appear that the identification of two

distinct markers for the disorder is contradictory,

most geneticists view the discrepancy as confirmatory that schizophrenia is a heterogeneous disorder

subject to unknown environmental influences

(30,63).

Similarly, a research group claimed to have

located the gene predisposing individuals to manic

depression. Subsequent studies revealed that conclusions drawn from the earlier study were premature

and the linkage association was greatly diminished

(24,56).

Recent studies of Alzheimer’s disease show that

at least 10 percent of the cases have a family history

with an autosomal dominant pattern and the gene for

the inherited form of the disease has been reported

to be on chromosome 21 (84). Other studies failed to

confirm that finding (104). The majority of cases

may be sporadic, with the clinical features identical

to the inherited form. The primary cause of Alzheimer’s disease remains unknown. Both environmental and genetic factors have been implicated. It

is clearly a heterogeneous disorder with an unknown

environmental component in at least 85 percent of

the cases (91,97).

More conclusive is the evidence for a genetic

predisposition to alcoholism. Researchers studying

the children of alcoholics have detected specific

biochemical and behavioral differences in their

responses to alcohol. Specifically, alcoholics have a

greater ability to synthesize a unique derivative of

alcohol known as phosphatidylethanol. While the

contribution of that trait to a predisposition is not

clear, it is feasible that testing for levels of phosphatidylethanol could serve as a biological marker for

alcoholism (8).

The one neuropsychiatric disorder for which a

definitive test has been developed is Huntington’s

disease, a progressive disease of the central nervous

system with no treatment and certain death an

average 15 to 17 years after onset some time in

mid-adulthood. Huntington’s disease is inherited as

an autosomal dominant trait with complete lifetime

penetrance. In 1983, Gusella and co-workers discov-
Chapter 5-The State-of-the-Art in Genetic Screening . 93

ered a RFLP on the short arm of chromosome 4 that

is linked to the Huntington’s disease locus (39).

Linkage analysis is 95 percent accurate. That is, 5

percent of those with the gene for the disease will be

missed because of the genetic distance of the marker

to the Huntington’s disease gene. As more markers

have been found, linkage studies have gained an

accuracy of approximately 99 percent (9,38). As

with other linkage tests, individuals whose test

results are uninformative will have to wait until a

second family member develops symptoms, or until

other polymorphisms are identified, before they can

receive definitive results. When the Huntington’s

disease gene and the mutations producing the

disease are discovered, the uncertainty may disappear. Linkage analysis will be unnecessary, only the

at-risk person will have to be tested.

The Huntington's disease case is the exception

in understanding the genetics of neuropsychiatric illness. Researchers are beginning to appreciate

the difficulties in examining the genetics of complex

mental illnesses. Scientists are often unable to

replicate linkage work performed by others

because of the multiple causes of what appears to

be the same disorder, the lack of large family

pedigrees and large numbers of pedigrees, misdiagnoses of affected relatives, and the sheer

complexity of mental illness (6). This has led some

to propose that the statistical scores conventionally

used to establish linkage be made more stringent for

mental disorders. Currently, a logarithmic ratio of 3

is taken as minimum evidence for linkage, meaning

that the likelihood is 1,000 to 1 that the marker and

Photo credit: Studios

Huntington’s patient being rowed across Lake Maracaibo,

Venezuela.

gene are linked rather than randomly distributed (6).

Raising that ratio to 6 would raise the requirement

for linkage and would take into consideration

genetic heterogeneity and variable expressivity of

the disorder (84). This, and improving clinical

diagnostic criteria, can protect against misleading

results until the genes for these disorders are actually

found.

Predisposition to Atherosclerosis

The associations between coronary artery disease,

or atherosclerosis, and cholesterol have been wellestablished. High-density lipoprotein (HDL) cholesterol promotes efflux of cholesterol from arterial

walls, thus earning the reputation of ‘good cholesterol.” Low-density lipoprotein (LDL) cholesterol

causes cholesterol deposition in arterial walls,

thereby earning the reputation of ‘bad cholesterol.”

Apolipoprotein A-I is the principal protein constituent of HDL. Decreased plasma concentrations of

both HDL and A-I have been associated with

premature coronary artery disease (80).

Early coronary artery disease and atherosclerosis

exhibit definite familial aggregation. Several different HDL-deficiency states have been reported. The

recent cloning of the apolipoprotein A-I gene

provides the necessary molecular probe for RFLP

analysis of normal and HDL-deficient states. Mutations of the A-I gene are found in 32 percent of

people who had severe coronary artery disease

before age 60, but only in 3 percent of people with

healthy heart arteries (80).

In addition, a single-gene defect at the LDL

receptor locus binds apolipoprotein B (apoB) and

accounts for the clinical entity known as familial

hypercholesterolemia (11). The heterozygote form

occurs in 1 out of every 500 individuals. The more

lethal homozygous form occurs 1 in 1 million births.

Genetic variation affecting LDL levels influences

atherosclerosis susceptibility (33).

Significant genetic variation in both the A-I and

apoB gene might explain variations in the onset and

severity of coronary artery disease among individuals. Biochemical screening for HDL and LDL will

continue to be the most reliable predictors of

predisposition to disease. The most obvious advantage of genetic screening over current methods is

that RFLP marker tests need only be conducted

once. Understanding the significance of the muta-
94 ● Genetic Monitoring and Screening in the Workplace

tions at the A-I and apoB loci will lead to more

effective and earlier therapy (41).

Predisposition to Diabetes

Diabetes is a disorder in which the body does not

produce or properly use insulin, a hormone needed

to convert sugars and starches into energy sources

for the body. One million of the Nation’s 11 million

diabetics are insulin-dependent (called type 1 or

insulin-dependent diabetes mellitus (IDDM)). Individuals with IDDM exhibit an immunological dysfunction, resulting in the destruction of the islets of

Langerhans, groups of cells in the pancreas where

beta cells reside to produce insulin is produced.

Recent studies reveal an inherited susceptibility in

95 percent of individuals with IDDM (108). Millions

of Americans, possibly 50 percent of the entire

population, possess the DR3 and DR4 markers

(107,108). Despite the prevalence of these susceptibility markers, relatively few people develop the

disease, leading to the conclusion that other genes,

or some viral or toxic insult, might be necessary to

trigger the disease. In addition, geographic variation

in rates supports the concept of an environmental

role.

COMMERCIAL DEVELOPMENT

OF GENETIC TESTS

With accelerating interest in tests to detect abroad

range of genetic disorders and increasing investment

in biotechnology industries, the market demand for

tests, especially DNA-probe tests, is expected to

expand. In addition to academic research centers,

several biotechnology companies are developing a

range of genetic tests (table 5-3), with projections of

market value in the millions. While the population

affected by genetic conditions for which there is a

test available is still somewhat small, the potential

future test population for multifactorial diseases is

enormous (see table 5-4).

In a 1987 OTA survey of biotechnology companies, it was found that biotechnology companies

developing DNA-based tests expected their products to be used by 1990 in: genetic and health

department clinics, health department screening

programs, prepaid health groups, private primary

care practices, reference and DNA labs, insurance

companies, the military, places of employment,

private nongenetic specialty practices, correctional

institutions, public schools, and homes (110).

Table 5-3-Some Companies Offering

DNA-Based Diagnostic Tests

Company Test

California Biotechnology, Inc.

Mountain View, CA . . . . . . . . .

Cetus Corp.

Emeryville, CA . . . . . . . . . . . .

Collaborative Research

Bedford, MA.. . . . . . . . . . . . . .

Genescreen

Dallas, TX . . . . . . . . . . . . . . . .

Genetrix

Alameda, CA . . . . . . . . . . . . . .

Integrated Genetics

Framingham, MA. . . . . . . . . . .

Lifecodes Corp.

Valhalla, NY . . . . . . . . . . . . . .

Nichols Institute

San Juan Capistrano, CA. . . .

Oncogene Science

Mineola, NY. . . . . . . . . . . . . . .

susceptibility to atherosclerosis

and hypertension

sickle cell anemia

adult polycystic kidney disease

cystic fibrosis

Iymphomas

insulin-dependent diabetes

sickle cell anemia

hemophilia

familial hypercholesterolemia

Ieukemias

adult polycystic kidney disease

Duchenne muscular dystrophy

Huntington’s disease

cystic fibrosis

sickle cell anemia

hemophilia B

alpha and beta thalassemia

non-Hodgkin’s Iymphoma

Iymphocytic leukemia

breast cancer oncogenes

sickle cell anemia

cystic fibrosis

cystic fibrosis

Duchenne muscular dystrophy

sickle cell anemia

hematologic malignancies

chronic myeloid leukemia

SOURCE: Office of Technology Assessment, 1990.

Although biotechnology firms developing genetic

tests did not overall rank places of employment as

important sites for testing in 1990, 5 of 12 thought

it likely that employers would be using genetic tests

to screen job applicants by the year 2000. Seven of

twelve agreed that health risks identified by genetic

screening could be used appropriately to exclude

susceptible workers from hazardous jobs; 9 of 12

thought this use likely by the year 2000. Other

sources predict that by then, most people will have

genetic profiles, possibly obtained through their

place of employment. Some companies are interested in employee “wellness” programs that include family histories and susceptibility to disease

(22,71,1 10). Five of the twelve companies thought

it likely by the turn of the century that insurance
Chapter 5—The State-of-the-Art in Genetic Screening . 95

Table 5-4-Genetic Tests Available and Total

Americans Affected

Genetic condition Total cases

Currently available:

Adult polycystic kidney disease . . . . . . .

Fragile X syndrome . . . . . . . . . . . . . . . . .

Sickle cell anemia . . . . . . . . . . . . . . . . . .

Duchenne muscular dystrophy . . . . . . . .

Cystic fibrosis . . . . . . . . . . . . . . . . . . . . .

Huntington’s disease . . . . . . . . . . . . . . . .

Hemophilia . . . . . . . . . . . . . . . . . . . . . . . .

Phenylketonuria . . . . . . . . . . . . . . . . . . . .

Retinoblastoma . . . . . . . . . . . . . . . . . . . .

Total . . . . . . . . . . . . . . . . . . . . . . . . . . .

Potential future tests:

Hypertension . . . . . . . . . . . . . . . . . . . . . .

Dyslexia . . . . . . . . . . . . . . . . . . . . . . . . . .

Atherosclerosis. . . . . . . . . . . . . . . . . . . . .

Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . .

Manic-depressive illness . . . . . . . . . . . . .

Schizophrenia . . . . . . . . . . . . . . . . . . . . . .

Type 1 diabetes . . . . . . . . . . . . . . . . . . . .

Familial Alzheimer’s . . . . . . . . . . . . . . . . .

Multiple sclerosis . . . . . . . . . . . . . . . . . . .

Myotonic muscular dystrophy . . . . . . . . .

Total . . . . . . . . . . . . . . . . . . . . . . . . . . .

500,000

100,000

65,000

32,000

30,000

25,000

20,000

16,000

10.000

798,000

58,000,000

15,000,000

6,700,000

5,000,000

2,000,000

1,500,000

1,000,000

250,000

250,000

100,000

89,800,000

SOURCE: hfedMW’or/dNews, p.58.Apr.11,1988.

companies would be using genetic tests on applicants (110).

Table 5-4 lists some of the tests currently available from commercial interests. Biotechnology cornpanies developing tests for genetic disease or

predispositions are generally employing one of three

strategies: l) linkage-based tests for family-centered

testing programs; 2) tests for single-gene disorders

or predictive tests for common polygenic disorders;

and 3)development of test processes or instrumentation(110). Tests generally range in price from $200

to $980 per individual. The test for Huntington’s

disease offered by Integrated Genetics (Framingham, MA) costs $450 per sample (48). Several tests,

specifically oncogene-based tests, are awaiting U.S.

Food and Drug Administration approval.

SUMMARY AND CONCLUSIONS

There are two categories of genetic characteristics

that are relevant to the occupational setting: those

that predispose the individual to adverse health

effects because of environmental exposure and those

that predispose the individual to adverse health

effects regardless of job, thereby having an impact

on employee ‘‘wellness’ and possible job performance. In both cases, identification of predisposed

individuals remains problematic because not all

people carrying predisposing genes develop disease.

Variable expressivity, heterogeneity, and reduced

penetrance confound the certainty of diagnoses,

lowering both the sensitivity and specificity of many

current tests.

Most DNA-based tests are indirect, relying on

linkage studies to identify those at risk. But even

direct tests for mutant genes can be ambiguous

without affected family members.

The obstacles to certainty, however, are slowly

being removed as the use of synthetic probes, PCR,

and automated DNA-sequencing machines increase

the efficiency and lower the cost of mass screening.

These advances are providing insights into the

genetic predisposition to adverse health effects from

drugs and environmental agents, cancers, diabetes,

atherosclerosis, and mental illness. Fifty human

genetic traits have been identified as having the

potential to enhance an individual’s susceptibility to

toxic or carcinogenic agents.

Yet, the environmental agents that trigger the

predisposition often remain the wild card. Even

though science has shown that cancer is often the

result of the activation of oncogenes or inactivation

of tumor suppressor genes, the agents that cause

these changes are hardly known, and speculated on

at best. It may be that as the associations between

mutation, carcinogenesis, and genetics become more

clear, the boundaries between occupational and

genetic disease will become more blurred.

1.

2.

3.

4.

5.

6.

7.

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Chapter 6

Legal Considerations
CONTENTS

Page

FEDERAL RESPONSIBILITY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103

Occupational Safety and Health Administration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103

National Institute for Occupational Safety and Health . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 109

Environmental Protection Agency . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ,...,... . . . . . . . .109

Title VII of the Civil Rights Act of 1964 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 110

Workers’ Compensation Programs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .....**. . . . . . . . 111

Rehabilitation Act of 1973 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113

The Americans With Disabilities Act of 1990 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 114

CONFIDENTIALITY AND PRIVACY ISSUES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116

Right To Confidentiality . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ..*..,.. . . . . . . . .116

Duties of the Occupational Health Physician. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 120

COLLECTIVE BARGAINING CONCERNS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 122

The Duty To Bargain Over Genetic Monitoring and Screening programs . . . . . . . . . . 123

Genetic Monitoring and Screening Refusals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 125

Arbitral Review . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 126

NLRA Preemption of Common Law Torts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 126

USE OF GENETIC MONITORING AND SCREENING RESULTS IN

EMPLOYMENT DECISIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 126

Right of Employer To Use Monitoring and Screening Data in Terminating

Employment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . 126

Uses of Genetic Monitoring and Screening Data in Other Employment Actions . . . . 127

Common Law Right to a Safe Workplace . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 128

Right of Employee To Know Monitoring and Screening Results . . . . . . . . . . . . . . . . . . 129

Right of Employee To Refuse Genetic Monitoring and Screening . . . . . . . . . . . . . . . . . 129

Liability of Employer for Inaccurate Monitoring and Screening Results . . . . . . . . . . . . 131

JUDICIAL USES OF GENETIC MONITORING AND SCREENING DATA . . . . . . . . 131

Use of Genetic Monitoring and Screening Data in Civil Liability Proceedings:

Nature of Civil Suits for Workplace Injury . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 131

Genetic Monitoring and Screening Data as Evidence in Occupational Disease Suits . 131

New Kinds of Claims Based on Genetic Monitoring and Screening Data . . . . . . . . . . . 132

SUMMARY AND CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 133

CHAPTER 6 REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . 134

Boxes

Box Page

6-A. Occupational Disease Throughout the Ages . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 104

6-B. The Lead Standard

. . . . .

. . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 106

6-C. Liability Issues . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 132
Chapter 6

Legal Considerations

Only a limited body of law exists dealing directly

with genetic monitoring and screening in the

workplace, because the technologies are so new.

However, a substantial body of law has developed in

dealing with the broad subject of medical testing.

Most likely, the body of law governing genetic

monitoring and screening in the workplace will

grow out of the rules dealing with this related

practice. As disputes arise, courts can look to

analogies with medical technologies that share

common features. An analysis of the law of genetic

monitoring and screening in the workplace, therefore, is largely an examination of ways that legal

disputes governing other kinds of medical testing of

workers have been handled. This chapter will

examine this broader area of medical testing law,

noting where genetic monitoring and screening

arguably differ from medical testing in general, and

where special rules regarding genetic monitoring

and screening have developed.

Whether workplace or clinical applications are in

question, techniques for analyzing an individual’s

genetic makeup present unique concerns. A person

generally has little control over his or her genetic

traits. When lifestyle issues such as drug use or

alcoholism are in question, it can be argued that there

is at least some element of individual choice. An

individual’s genetic composition, however, is acquired with no choice, but, it can be influenced to

some degree with prenatal diagnosis and eventually

with gene therapy (41). Analyzing these personal

characteristics raises legal questions of the most

sensitive sort. Among the fundamental legal issues

raised by genetic monitoring and screening are

privacy from unwanted testing, confidentiality of

the intimate information obtained, discrimination in employment opportunities, and ultimately, the health of the testing subject (see chs.

4,5, and 7).

Genetic monitoring and screening in the

workplace are governed by both statutory and

common (judge-made) law. Statutes governing genetic monitoring and screening include the Occupational Safety and Health Act (OSH Act) (29

U.S.C. 651 et seq.), which establishes a framework

for regulating workplace injury and disease hazards

by the Occupational Safety and Health Administration (OSHA). The work of other Federal agencies,

including the National Institute for Occupational

Safety and Health (NIOSH), is also important in this

regard. Common law applicable to genetic monitoring and screening includes employee relations,

medical malpractice, negligence, and the right to

privacy. There are also discrimination issues addressed by workers’ compensation statutes, Title VII

of the Civil Rights Act of 1964 (42 U.S.C. 2000e),

and the Rehabilitation Act of 1973 (29 U.S.C. 791 et

seq.). Issues governed by collective bargaining are

covered by the National Labor Relations Act

(NLRA) (29 U.S.C. 151 et seq.).

FEDERAL RESPONSIBILITY

A relationship between health hazards in the

workplace and disease has been recognized since the

early 1700s, when Bernardino Ramazzini penned A

Treatise of the Diseases of Tradesmen (see box 6-A)

(69). He wrote:

When you come to a sick Person says Hippocrates, it behoves [sic] you to ask what Uneasiness he

is under, what was the Cause of it, how many Days

he has been ill, how his Belly stands, and what Food

he eats: To which I’d presume to add one Interrogation more: namely, what Trade he is of (69).

In modern times, the U.S. Government has assumed

some responsibility for safeguarding worker health

by establishing various agencies to oversee

workplace safety. Several of these agencies are

discussed below.

Occupational Safety and Health

Administration

OSHA has regulated some employer practices

that could have a bearing on genetic monitoring and

screening, including employee access to medical

records and communications about hazards by

employers to employees. The limited experience

with genetic technologies will be addressed first,

followed by a more thorough discussion of experience involving related techniques.

Direct Experience With Genetic Monitoring

and Screening

In 1980, OSHA found itself embroiled in a

controversy concerning several of its carcinogen

–103–
104 ● Genetic Monitoring and Screening in the Workplace

Box 6-A--Occupational Disease Throughout the Ages

Occupational disease is not a recent phenomena. As long as men and women have work@ they have suffered

disease, illness, and injury as a result of their workplace environments. The following examples illustrate

occupational diseases prevalent in 17th and 18th century Europe:

. Miners--Individuals who work in the mines suffer from ‘‘difficulty of breathing, swellings of the feet,

falling of the teeth, ulcers in the gums, pains and tremblings in the joints. They especially fall prey to the

‘‘mineral spirits which the lungs suck in along with the air, and corrupt and taint the natural temperament

of the brain and the nervous juice, from whence spring the tremblings and stupidity. ”

● Brewers— “The servants employed in the brewing of ale and beer, undergo all the symptoms and

inconveniences of drunkenness merely from their being constantly employed in pouring out wine and taking

the grapes out of the press. In a word, those who do this sort of work for several months together and spend

most of the winter in such laboratories, grow lethargic and dejected with little or no appetite. ”

● Tobacco workers—“Those who make snuff find that their lungs do gradually become dry and withered. The

powder they work with pricks and dries the tender coat of the lungs and windpipe, and with their foul steams

not only cloud the Animal Spirits in the brain, but at the same time corrupt the ferment of the stomach by

enervating the acid of that part. ”

. Gilders-Gilders become asthmatic and their complexion assumes a dangerous ghostly aspect. Their neck

and hands tremble, their teeth fall out, their legs are weak and mauled with the Scurvy’ due to their exposure

to mercury in the air.

● Bakers--" Bakers, in sifting flower, in kneading it into dough, and in baking that in the oven, are exposed

to infinite fatigue and toil. The inspiration of the flying particles of the meal stuff up not only the throat, but

the stomach and the lungs with a tough paste; by which means they become liable to coughs, shortness of

breath, hoarseness and at last to asthma. Sometimes the hands of bakers are swelled and pained. Kneading

dough squeezes the nutritious juices out of the arteries of the hands. Last, both millers and bakers are

generally troubled with lice. ”

● Fishermen— ‘‘Fishermen and mariners have a skin as hard as an elephants and suffer from ulcers that are

dry and sordid, as if they were pickled with salt. And indeed sailors are forced to feed upon gross food, salt

meat, half rotten water, and bread half worm-eaten, we cannot but conclude that their bodies are crowded

with bad juices and disposed to malignant fevers. ’

● Field Workers—"Sifters of corn work with a grain powder that I am tempted to suspect has worms in it

imperceivable to the senses; and that these worms being put into motion, and dispersed through the air, in

the sifting and measuring of corn; some of them stick to the skin and mouth and cause the burning heat and

itching that is observed both in the throat and all over the body.

. Academics--" All Men of Letters in the Learned World do not escape from disease. ‘Tis a known saying

that a man grows wise by sitting, and is not aware of the inconveniences accruing to his body, All the Men

of Learning complain of a weakness of the stomach. For while the brain is employed in digesting, what the

itch of knowledge and the love of learning throws in, the stomach can’t but make an imperfect digestion of

the ailment, by reason that the Animal Spirits are diverted and taken up in the intellectual service. ”

SOURCE: B. Ramazzini, A Treasure oj the Diseases of Tradesmen (London, England: Publisher Unknown, 1705).

standards (56). Thirteen of the standards required a While it may have chosen in 1980 not to recognize

preassignment examination by a physician before an

employee could be assigned to a regulated area. The

standards specified that the examination include the

personal history of the employee, family and occupational background, including genetic and environmental factors (29 CFR 1910.1003(g)(l)(i)).

Subsequent to publicity surrounding this language,

OSHA later clarified that these words do not require

genetic screening or the exclusion of qualified

employees based on genetic findings (64).

a genetic screening requirement, OSHA still may

include such a rule in its standards in the future. The

OSH Act is silent on genetic monitoring and

screening. In the absence of a clear prohibition,

nothing in the Act appears to prevent OSHA from

requiring genetic monitoring and screening as it

does other kinds of medical tests.

OSHA actively considered using this authority on

one occasion. During 1983, as part of the standard-
Chapter 6--Legal Considerations ● 105

setting process for ethylene oxide, OSHA explored

the use of genetic monitoring for possible inclusion

in the standard’s medical surveillance requirements

(48 FR 17,284, 17,285). The monitoring merely

would have been recommended, though, since

OSHA felt that it lacked sufficient information on

which to base mandatory requirements (48 FR

17,305). In the final rule a set of mandatory tests not

including genetic measures was required to ensure

uniformity, and a proposed nonmandatory test for

chromosomal damage was dropped (49 FR 25,784).

Thus, OSHA considers genetic monitoring a

permissible medical surveillance procedure but has

not yet required it. This leaves open the possibility

that such tests could be mandated as part of a future

standard. They could also be recommended for use

subject to employer discretion. Whether an employer could require them is unresolved.

Requirements for Conventional Medical Testing

While leaving genetic monitoring and screening

to future proceedings, OSHA has addressed the use

of more conventional medical tests on several

occasions. Medical surveillance, encompassing both

the use of specific biological exposure measures and

routine clinical examinations, is required in over 20

OSHA standards governing workplace exposure to

hazardous substances. Under the OSH Act, OSHA

must ensure for each chemical controlled by a

standard that no employee suffers material impairment of health even if exposed throughout his or her

working life (6(b)(5) OSH Act).

Further authority is contained in a number of other

provisions of the OSH Act. Most notable among

these is the section which says that a standard shall

prescribe the type and frequency of medical examinations or other tests to be made available by the

employer (or at his or her cost) in order to most

effectively determine exposure risks (6(b)(7) OSH

Act).

Medical surveillance in one form or another is

also mandated in OSHA standards dealing with

noise and the occupation of diving. While these

standards prescribe certain tests that must be offered

to employees, they do not prevent employers from

supplementing them with other tests of their own

choosing. Therefore, even though OSHA does not

require the use of genetic monitoring and screening

measures, the exposure standards would not prevent

employers from choosing to use them.

The OSHA lead standard (29 CFR 1910.1025) has

generated considerable legal controversy. This is the

only OSHA standard calling for actual biological

monitoring rather than more general medical surveillance (see box 6-B).

Role of the General Duty Clause

Another section of the OSH Act provides OSHA

a more general authority that could be used to require

genetic monitoring and screening. Known as the

general duty clause, this section requires employers

covered by the Act to maintain a workplace free

from recognized hazards that are causing or likely to

cause death or serious physical harm to employees

(5(a)(1) OSH Act). A vigorous OSHA could interpret a workplace “free from recognized hazards’ to

be one in which workers have been genetically

tested for susceptibility to environmental exposures

capable of inducing toxic harm.

It can be argued that the clause requires employers

to use genetic monitoring tests if these measures can

provide a safer workplace or to use screening to

identify individuals with specific susceptibilities.

Failure to use them could demonstrate that an

employer had not taken all necessary precautions

before placing an employee in a high-risk job (99).

Further, absent the availability of other technologies, an employer wishing to use the tests could

argue that monitoring and screening tests provide

the only means to ensure a safe and healthy

workplace (99). Arguments against the use of

genetic monitoring and screening, however, are the

availability of other means to achieve safety, the lack

of established efficacy for most newly proposed

tests, and the adverse risks to employees when tests

are used inappropriately or the results are misinterpreted (18). On balance, it seems unlikely that an

employer could successfully contend that the

general duty clause requires genetic monitoring

and screening, absent a directive on their use

from OSHA.

Protections Against Genetic Monitoring and

Screening and Their Consequences

Considerations discussed so far involve sources

of authority in the OSH Act for mandating the use of

genetic monitoring and screening tests. On the other

side of the issue are the protections the Act provides

for employees who refuse testing, or who wish to

limit the negative consequences of unfavorable test
106 . Genetic Monitoring and Screening in the Workplace

Box 6-B—The Lead Standard

The history of the lead standard provides insight into the factors that could influence OSHA to adopt genetic

monitoring or screening requirements in the future. Before genetic monitoring or screening could be required, there

should be a readily available measure of exposure that is reasonably inexpensive and diagnostically reliable, similar

to that used in blood lead testing. The measure must also be a valid predictor of a disease process. Analysis of sister

chromatid exchanges, for example, provides a general indicator of cellular harm but not a predictor of a specific

illness (see ch. 4). In addition, there must be a medical benefit to be gained from early diagnostic information.A

chance must exist that absorption of a toxin can be reversed or that a disease process can be halted. Further, if the

experience of the lead standard is a guide, OSHA will probably only require genetic monitoring if ambient exposure

controls are not available as a reasonable alternative. Another solution is removal of the worker from the workplace

site.

The lead standard, which calls for periodic blood tests of workers exposed to lead, requires medical removal

protection (MRP) for workers found to have high blood lead levels. Under this procedure, the employee must be

removed from the job and placed in another involving no lead exposure with existing pay and benefits for up to 18

months. If no alternative job can be found, the employee still must be removed from the job while retaining full pay

and benefits, These requirements were upheld by the Circuit Court of Appeals for the District of Columbia citing

the provisions of the OSH Act.

Another aspect of the debate over the lead standard has interesting implications for the use of genetic

monitoring. The lead industry had argued that compliance with exposure standards be measured through biological

monitoring of individual workers to determine whether workplace lead levels were having measurable health

effects. Organized labor, however, contended that ambient air measurements were appropriate indicators of

workplace health effects. It feared that use of biological monitoring for this purpose would create an incentive for

employers to discharge workers who were sensitive to lead rather than to reduce exposure levels. The final OSHA

standard called for ambient lead levels to be used to measure workplace exposure and for biological monitoring to

be used to assess the health of individual workers. This resolution could be a model for the use of genetic monitoring

in exposure standards.

In addition to such health benefits of monitoring, reduction of ambient lead levels involves tremendous

engineering costs that may be beyond the means of many smaller companies. Biological monitoring and MRP may

be less expensive when weighed against the costs of these alternative measures. Of course, requirements that full

pay be given for 18 months means MRP creates an incentive to reduce ambient levels and maintain worker

productivity, While biological monitoring involves both indirect (e.g., anemia) and direct (e.g., elevated blood and

urine lead concentrations) indicators of excessive lead intake, medical surveillance follows symptoms (e.g.,

weakness, impaired mental function, disorders of peripheral nerves). Biological monitoring makes it possible to

identify effects or symptoms before toxins produce disease.

SOURCES: office of Technology Assessmcnt, 1990, based on R.I. Field, “The Federal Role in Biological Monitoring,” unpublished

manuscript, Boston University Center for Law and Health Sciences; United Steelworkers v. Marshall, 647 F.2d 1189 (D.C. Cir.

1981).

results. Such protections are limited, however, and ever, appears to be limited to instances of OSHAapply to only certain situations.

The OSH Act contains a protection for workers

having religious objections to OSHA practices

(20(a)(5) OSH Act). OSHA has granted a limited

number of exceptions to its safety standards for such

workers (76). It seems unlikely that many workers

would take advantage of this provision. An explicit

antidis crimination clause of the OSH Act prohibits

employers from firing or otherwise discriminating

against employees who have exercised any right

under or related to the Act (29 U.S.C. 660(c)).

Applying this language to discrimination resulting from genetic monitoring and screening, howmandated monitoring and screening programs, of

which there are none (39). If the employer instituted

genetic monitoring or screening on its own, the

worker would be protected only if some aspect of the

program violated the OSH Act unless, of course, the

worker refused to participate in the monitoring or

screening program.

Access to Medical and Exposure Records

The OSH Act also governs employee access to

medical and exposure records kept by employers (29

CFR 1910.20). Such standards seek to prevent

abuses that could result from the availability of these

data (56). These records can serve a number of
Chapter 6--Legal Considerations ● 107

purposes. By using them, OSHA can monitor

compliance, NIOSH can conduct research with

patient-identifying information removed, unions can

learn about workplace exposure levels, and employees can obtain information of possible value in

treatment or counseling by a private physician (34).

Such records can also be transferred to subsequent

employers.

The definition of ‘employee medical records’ in

the standard is fairly broad (29 CFR 1910.20

(c)(6)(i)) and would clearly cover results from

genetic monitoring and screening. Records include,

among other things, results of medical examinations, whether preemployment, preassignment, periodic, or episodic, and laboratory tests, including all

biological monitoring results (29 CFR 1910.20(C)).

Workers also have access to their ‘‘employee

exposure record’ which includes environmental

monitoring or measuring, biological monitoring

results, and material safety data sheets or ‘any other

record which reveals the identity . . . of a toxic

substance or harmful physical agent. ” The regulations also grant employees access to various types of

analyses that use these records.

#

The extent of the protection afforded workers by

these rules, however, is limited, since mere access

neither aids an employee unable to interpret the data

nor allows for the correction of erroneous information (74). The antidiscrimination provision of the

OSH Act protects employees from retaliation for

exercising their rights to see their medical records

(11(c)(1) OSH Act). This would also apply to

genetic monitoring and screening records. When test

results are wrong, unreliable, or invalid measures of

the traits they are purported to reflect, employees

would most likely have to rely on other legal

protections, such as a common law right of action for

defamation or for medical malpractice.

Finally, the regulations require employers to

provide medical information to employees only on

request. Once a request is made, all medical and

exposure records, including analyses based on them,

must be provided. These regulations apply only

where the employee has been exposed to certain

hazardous substances. Employees could fail to gain

access, however, if they are unaware the information exists.

Recordkeeping Requirements

Another OSHA regulation of potential relevance

is the requirement for recordkeeping involving

occupational injuries or illnesses (29 CFR 1904.2).

According to the regulation’s definition, occupational illness of an employee is any abnormal

condition or disorder, other than one resulting from

an occupational injury, caused by exposure to

environmental factors associated with employment.

It includes acute and chronic illnesses or diseases

that may be caused by inhalation, absorption,

ingestion, or direct contact.

Thus, genetic damage could be viewed as an

occupational illness provided the link between the

genetic defect and the subsequent disease were

clearly demonstrated. If OSHA were to adopt this

interpretation, then employers would have to include

in their logs any positive results of genetic monitoring tests.

The scope of this rule has been the subject of

conflicting interpretations by the Occupational

Safety and Health Review Commission (OSHRC),

which reviews OSHA enforcement actions. In one

case, OSHRC found congressional intent favoring a

broad interpretation of the reporting regulations to

provide information “for future scientific use” (36).

The employer argued that it did not have to record

the illnesses of three workers because the illnesses

had not resulted from occupational exposures.

OSHRC held that the requirement to record

illnesses is not limited to those directly caused by

occupational exposures and includes conditions

for which these exposures were either a contributing factor or aggravated a preexisting condition.

In another case, OSHRC deferred to the employer’s judgment as to what is reportable and ruled

that the standard does not require the employer “to

do more than make a reasonable judgment based on

the information and expertise available to it” (7).

The employer failed to record the illnesses of eight

employees with asbestosis. The occupational health

physician initially had not given this as the diagnosis, but did diagnose asbestosis in light of additional

information after the company received a citation.

OSHRC found that the medical evidence initially

had been unclear, so that no duty to provide the

correct occupationally related diagnosis existed.

Some argue that this decision signals a view by

OSHRC that all doubts about recordability
108 ● Genetic Monitoring and Screening in the Workplace

should no longer be resolved in favor of recording

(78).

Hazard Communication Standard

OSHA has issued a regulation mandating that

certain information on hazardous workplace substances be communicated to employees (29 CFR

1910.1200). Essentially, this rule amounts to a

workplace right-to-know law. Employers must keep

records of hazardous substances and provide labels,

data sheets, and written communications to employees.

The Hazard Communication Standard deals with

information on substances and not on individual

workers, so its effect on worker test data is likely to

be indirect. Genetic monitoring and screening tests

could, however, influence the scope of the rule. The

regulation very broadly describes the kind of data

needed to indicate a health hazard (sec. (d)(2)). For

health hazards, evidence which is statistically significant and which is based on at least one positive

study conducted in accordance with established

scientific principles is considered to be sufficient to

establish a hazardous effect if the study results meet

the health hazard definitions. Health hazards are

defined as hazards that may cause measurable

changes in body function such as decreased pulmonary function. Employees exposed to such hazards

must be apprised of both the change in body function

and the signs and symptoms that signal change.

Employers have considerable leeway in construing this language. Chemical manufacturers, importers, and employers evaluating chemicals are not

required to follow any specific methods for determining hazards, but they must be able to demonstrate that they have adequately ascertained the

hazards of the chemicals produced or imported in

accordance with established criteria.

This language is also significant because it

appears to relieve employers of any obligation to use

genetic monitoring procedures to evaluate toxicity.

Such a freedom to ignore genetic tests, however,

applies only in the context of communicating

hazards and would not preclude the inclusion of

genetic monitoring and screening requirements in

exposure standards.

The hazard communication regulation could have

one other effect on genetic monitoring. Genetic

monitoring tests, when developed, could be extremely sensitive measures of toxic effects that

Photo Kathy 

Epidemiological research at the National Institute for

occupational Safety and Health, Cincinnati, OH.

could detect early preclinical biological effects not

revealed by conventional techniques. To the extent

that genetic monitoring indicates health effects

before other measures, it could trigger a finding

of a health hazard and an obligation to provide

employee information. Such an obligation could

serve to discourage the use of genetic monitoring

in cases dealing with toxic substances covered by

the hazard communication standard. However,

some believe the evidence to date does not establish

clearly the potential of genetic monitoring tests to

predict future disease (18).

High Risk Occupational Disease Notification Act

Because of its possible relevance to future genetic

monitoring and screening, the High Risk Occupational Disease Notification and Prevention Act

deserves attention. If passed by Congress, the

legislation will establish a scheme to identify and

notify all current and former workers exposed to

hazardous chemicals during the last 30 years who are

determined to be at an increased risk of occupational

disease. The purpose is to enable them to seek early

medical screening and treatment for any toxic

effects.

Given the intent of early notification, identification of the most vulnerable workers could be an

issue. This legislative scheme could thereby become
Chapter 6--Legal Considerations ● 109

an impetus for application and evaluation of genetic

screening to locate susceptible workers. There is the

opposing view that this would have been resolved at

the risk assessment stage (73).

National Institute for Occupational Safety

and Health

NIOSH is charged with conducting research to

support OSHA’s regulatory activities, even though

it has no regulatory authority of its own (29 U.S.C.

671). As one of the foremost research organizations

in the field of occupational safety and health,

NIOSH, however, can have considerable influence

with OSHA and the occupational health community.

Based on its expertise and express statutory

authority, NIOSH is probably the most appropriate

Federal agency to conduct extensive research on

workplace medical screening (76). Seven areas

where NIOSH has authority to develop recommendations with relevance to genetic monitoring and

screening have been identified:

●

●

●

●

●

●

●

research on substances likely to affect sensitive

employees,

research to identify individuals most likely to

be sensitive,

certification of monitoring and screening procedures,

development of guidelines for evaluating test

results,

development of medical criteria for using tests,

investigation of protective policies needed for

high-risk workers, and

development of guidelines for personnel actions based on test results (74).

At the time OSHA’s medical surveillance and

biological monitoring requirements for hazardous

substances were being developed, NIOSH played an

active role. In particular, it aided in creating the lead

standard and provided support in developing testing

standards, certifying laboratories performing tests,

and establishing medical removal and wage retention protections.

NIOSH is an appropriate agency to conduct

research into the medical consequences of

workplace genetic monitoring and screening, but has

yet to undertake substantial work in this area due to

budget limitations. An additional role of NIOSH in

such genetic monitoring and screening should be

mentioned. Because medical monitoring programs

provide considerable sources of data for occupational health research, if genetic monitoring and

screening results were to become available and

accessible to NIOSH under OSHA access to medical

records rules (29 CFR 1904), tremendous opportunities for research would ensue. Nevertheless, the

sensitive nature of this information could require

special confidentiality and anonymity protections

for workers. More importantly, research is needed to

determine the validity and predictive value of

genetic monitoring and screening tests in the working population (18).

Environmental Protection Agency

While its mission is not directly related to worker

health, the Environmental Protection Agency (EPA)

administers a number of programs that could have

relevance for genetic monitoring and screening.

EPA’s mission of protecting the general population

from toxic pollution often intersects with the responsibilities of OSHA. Several programs of interest

have possible implications for workplace monitoring and screening.

The Toxic Substances Control Act (TSCA) (15

U.S.C. 2610 et seq.), the primary statute regulating

the chemical industry, requires testing and labeling

of hazardous chemicals. These procedures could

provide important information to genetically susceptible workers. Although the right to information

on specific chemicals under this Act is limited,

TSCA requires that toxic substance manufacturers

develop adequate data with respect to the substances’ effects on public health and the environment.

Two programs administered by EPA as part of the

Superfund program could also have implications for

genetic monitoring and screening. The original

Superfund law, the Comprehensive Environmental

Response, Compensation, and Liability Act (42

U.S.C. 9601 et seq.), established the Agency for

Toxic Substances and Disease Registry (ATSDR),

whose responsibilities include assessing health effects of toxic substances found at hazardous waste

dump sites and creating registries of individuals

living near these sites who might have been exposed

to these substances. The Superfund Amendments

and Reauthorization Act of 1986 (SARA) (Public

Law 99-499) substantially increased the responsibilities of ATSDR and established timetables for its

work. ATSDR has met those timetables by issuing
110 . Genetic Monitoring and Screening in the Workplace

toxicological profiles for high priority chemicals,

health assessments for all the National Priorities List

Superfund sites, and procedures for developing

exposure and disease registries.

Genetic monitoring could provide a useful measure of the exposures experienced by people on the

registries. Genetic screening could help to identify

those most at risk. While ATSDR’s mission is to

protect members of the general population living

near hazardous waste dump sites, its procedures

would be applicable to the protection of workers at

these sites, as well, either directly through EPA

guidelines or indirectly through adoption by OSHA.

In fact, ATSDR has worked with NIOSH, the

Centers for Disease Control, and unions with hazardous waste site workers.

SARA also included an extensive right-to-know

provision, Title III, requiring manufacturers and

others that regularly emit hazardous waste into the

environment to report the substances used and

regularly emitted to State and local authorities.

Genetic monitoring of populations exposed to chemicals as the result of leaks, whether workers or

members of the local community, may be one way

of dealing with such emergencies. Genetic screening

results could help to identify those in most need of

assistance in these circumstances.

Title VII of the Civil Rights Act of 1964

Title VII of the Civil Rights Act of 1964, as

amended (42 U.S.C. 2000e), prohibits discrimination in hiring, discharge, compensation, or other

terms, conditions or privileges of employment

because of an individual’s race, color, religion, sex,

or national origin. All forms of employment and

preemployment bias are forbidden, including discrimination in hiring, discharge, promotion, layoff

and recall, compensation and fringe benefits, classification, training, apprenticeship, referrals for employment, union membership, and all other ‘‘terms,

conditions, or privileges of employment. ”

The Act applies to employers, labor unions, and

employment agencies. Private firms with 15 or more

employees and engaged in an ‘‘industry affecting

commerce" are covered. While State and local

governments are subject to Title VII, the Federal

Government is specifically exempted along with

Indian tribes, departments and agencies of the

District of Columbia, and bona fide private membership clubs.

The Supreme Court has found as a central purpose

to Title VII “to make persons whole for injuries

suffered on account of unlawful employment discrimination’ (l). Although the term “discrimination” is not defined in Title VII, it has been defined

by one court as ‘‘a failure to treat all persons equally

where no reasonable distinction can be found

between those favored and those not favored” (10).

The Supreme Court has recognized two main forms

of employment discrimination, “disparate treatment’ and “disparate impact. ” Disparate treatment

occurs when an employer simply treats some people

less favorably than others because of their race,

color, religion, sex, or national origin. Proof of

discriminatory motive is required. Disparate impact

involves employment practices that appear to be

neutral in their treatment of different groups but in

fact affect one group more severely and cannot be

justified by the requirements of the job or business.

Proof of discriminatory motive is not required.

The disparate impact concept was established by

the Supreme Court in Griggs v. Duke Power Co. (37)

when it unanimously held that an employer’s use of

certain standardized tests violated Title VII because

they disqualified Black applicants at a substantially

higher rate and were not shown to predict job

performance.

In another case (l), the Court clarified Griggs and

held that a plaintiff may establish a prima facie case

of disparate impact by showing that the tests at issue

select applicants for employment or promotion in a

racial pattern significantly different from that of the

pool of applicants. The burden was then on the

employer to show that any given requirement has a

distinct relationship to the employment in question.

The plaintiff could still rebut this evidence, however, by demonstrating that other tests or selection

procedures, without a similarly undesirable racial

effect, would also serve the employer’s legitimate

interest in efficient and trustworthy workmanship

(l).

The recent Supreme Court decision in Wards

Cove Packing v. Atonio imposes more stringent

standards on workers attempting to use statistics to

prove discriminatory employment practices (96).

Some critics of the decision claim that it overrules

the Court’s ruling in Griggs. According to Griggs,

once an employee presented sufficient statistical

evidence that certain employment practices had a

discriminatory effect on women or Blacks, the
Chapter 6--Legal Considerations . 111

employer had the burden of proving that the

challenged practices were a justified business necessity.

It has been argued that the Wards Cove decision

is a victory for employers and forces employees to

bear the burden of disproving employers’ business

justifications for discriminatory practices. Employers, using genetic monitoring and screening to

identify workers or applicants susceptible to certain

illnesses, could discharge, fail to promote or hire, or

in other ways discriminate against such individuals

and claim business justification. Employees would

then be placed in the more difficult position of

disproving the need for that claim. This could mean

that certain minorities that are susceptible to certain

diseases (e.g., sickle cell disease, Tay-Sachs, hypertension) could face disproportionate discrimination

in job situations where genetic screening is used.

Many genetic screening procedures have a disparate

impact (e.g., sickle cell disease, glucose-6-phosphate dehyrogenase (G-6-PD) deficiency that could

implicate Title VII.

Workers’ Compensation Programs

Workers’ compensation programs were devised

in the early part of the 20th century to provide

no-fault compensation to workers suffering harm as

a result of their employment. There are also two

Federal workers’ compensation programs: the Federal Employees Compensation Act for Federal

Government workers and the Longshore and Harbor

Workers’ Compensation Act for shipyard and maritime workers. In addition, the Federal Employers’

Liability Act provides compensation for railroad

employees, and the Jones Act provides the same for

sailors. All of these programs seek to provide speedy

recoveries without the need to adjudicate fault, but

they require that the harm have a work-related cause.

Initially, workers’ compensation programs dealt

with traumatic injuries and not with work-related

diseases. As the workplace origin of many forms of

illness became apparent, workers’ compensation

systems responded either through statutory change

or judicial construction. A particular challenge is

posed, though, by diseases with long latency periods

between exposure to a causative agent and onset of

illness. It is the compensation of such long latency

conditions that presents the most likely opportunity

for the application of genetic monitoring and screening.

Photo credit: Earl Dotter

The use of protective clothing can help prevent

occupational illness and injury.

With a lapse of up to 40 years between exposure

to a toxic substance and manifestation of illness, the

task of determiningg which exposure caused the

disease and whether it is work related can become

problematic. When the disease is one that is generally caused by workplace substances, such as

asbestosis or silicosis, it is easier to establish the

work-relatedness of the worker’s claim. When it is

one that can be caused or aggravated by outside

factors, such as many forms of cancer, the long

interval can make evidence of work-relatedness

harder to establish.

According to one legal expert (48) genetic monitoring and screening obviously have many advantages for employers, not the least of which is the

reduction of the cost of workers’ compensation

claims. Workers’ compensation claims have escalated substantially in recent years, and employers are

finding the cost to obtain and maintain this insurance

extremely high. Compensation claims are becoming

more expensive because most cases require that the

compensation board determine whether the injury is

a work-related injury. In some cases, this is a

particularly difficult factual question. For responsible employers, determiningg this question early is

cost-saving because it reduces the need to legally

challenge an employee’s claim for compensation

(48).
112 . Genetic Monitoring and Screening in the Workplace

Role of Genetic Test Data as Evidence

Genetic monitoring and screening data may help

claimants with the evidentiary task of proving the

workplace etiology of occupational diseases. Generally, proof of a workers’ compensation claim for

occupational disease involves three primary elements (30). First, there is the hazardous nature of the

substance that is the suspected causative agent. This

can be based on OSHA or NIOSH reports and

standards, as well as on general scientific findings.

Second, there is the nature of the claimant’s illness

and resulting disability. This is usually based on the

testimony of an examining physician. Third, the

worker must establish the link between the hazardous exposure and the disease. This can be a difficult

step, especially when the disease is one that is

common outside of the workplace. An often-cited

example is lung cancer, which can result from

workplace asbestos exposure but also from smoking

outside of the workplace.

To prove this third element in the chain, monitoring and screening data obtained in the workplace can

be extremely helpful. Most studies linking occupational diseases to toxic agents are based on studies

of large populations or on animal responses. Extrapolating from these data to individual instances of a

disease gives questionable results. Genetic monitoring and screening data can support causality claims

in two ways. First, they can serve the same function

as conventional medical tests. Screening produces a

baseline to demonstrate a worker’s level of genetic

composition before employment has begun. Monitoring shows the worker’s response to the agent as

exposure progresses. The link between workplace

exposure and illness is thereby revealed. Genetic

screening can serve a second role of showing

whether the worker had a special susceptibility to the

substance involved. If the claimant did, it will be

easier for the claimant to assert that the disease is

work-related.

Monitoring and screening data are particularly

relevant to the issue of multiple causation. States

vary in their treatment of diseases that have both

work-related and outside causes. In some States,

such as California, workers are fully compensated

even when outside factors are involved (54).

In other States, such as Arkansas, workers can

only be compensated for the portion of their disease

caused by workplace factors (Arkansas Labor Code

sec. 14(a)(3)). In these States, genetic screening may

help workers show to which agents they are particularly sensitive and are most likely to contribute to

their illness. Monitoring may help them demonstrate

a pattern of progressive biological harm corresponding to a workplace exposure. At the same time,

employers may be able to show that nonworkplace

factors were the ones most likely to have harmed the

claimant and that workplace exposure did not

contribute to harm. In either case, genetic test data

may be able to improve the accuracy of compensation decisions.

Workers’ Compensation of

the Susceptible Employee

In most States, a claimant’s right to workers>

compensation is not affected by a preexisting

condition. The general rule is that an employer

takes the worker as the employer finds the

worker, with no allowance for a disability that

developed before employment that predisposes

the worker to occupational illness. Presumably,

this rule would extend to a preexisting genetic

vulnerability to workplace toxins.

Once an employer has hired a genetically susceptible individual, an employer faces an increased

likelihood of paying compensation which may

discourage hiring susceptible applicants. Many

States have tried to mitigate this possible effect in

one of a number of ways.

The frost approach is the use of second injury

funds. These are State-run funds that contribute to

the compensation of a worker whose work-related

injury or disease also has a preemployment cause

(49). The existence of such a fired, if applicable,

would reduce the risk to an employer who hires a

genetically susceptible worker. The availability of

screening, moreover, would make it easier to use this

mechanism, since the role of preemployment factors

would be more clearly revealed.

The second approach allows workers to waive

their right to file an occupational disease claim, once

a vulnerability is found. There are 5 States that

permit such waivers and another 15 that allow

waivers for claims involving aggravation of a

preexisting condition (76). Massachusetts, however,

expressly forbids such waivers (Mass. Ann. Laws,

ch. 152, sec. 46).

The availability of waivers could present a serious

dilemma for workers’ compensation. If genetic

screening were available, employers could screen all
Chapter 6-Legal Considerations ● 113

workers and ask the susceptible ones to waive their

right to bring claims. This could eliminate virtually

all liability for occupational disease while leaving

workers who develop work-related illnesses with no

available compensation. The issue of waivers is an

area that may require further examination if

workplace genetic screening becomes available.

The final approach apportions liability between

the employer and other responsible parties, including the worker, when a preexisting, nonemployment

cause is involved. The issue still arises, however, of

the amount of responsibility to attribute to each

cause. In the case of a genetic predisposition, the

question of liability maybe more one of ethics or of

public policy than of law. Another complicating

factor is the general rule that a prior nondisabling

condition is not a disability for purposes of apportionment (49). A latent genetic trait would appear to

fall under this category. Thus apportionment as

presently structured might not apply to susceptibilities found in genetic screening.

Admissibility of Genetic Monitoring

and Screening Data

In the spirit of granting compensation to workers

as quickly and efficiently as possible, compensation

proceedings are held informally, generally without

formal rules of evidence (49). In addition, most

States presume that the worker’s condition is compensable in the absence of evidence to the contrary

(49). Genetic monitoring and screening are likely to

remain controversial for some time after their initial

use, and there will likely be questions of reliability

and appropriateness of such tests. It is possible that

hearing officers, unaccustomed to novel forms of

medical evidence, will look on genetic data with

suspicion or give it more credence than it deserves.

They may tend to ignore any doubt that the data cast

on the compensability of claims. Employers may

face a heavy burden in seeking to rely on genetic

monitoring and screening to reduce occupational

disease liability.

Rehabilitation Act of 1973

The Rehabilitation Act of 1973 (29 U.S.C. 701-

796) enacted a comprehensive ban on discrimination

against handicapped individuals in a broad range of

areas. The principal provisions of the Act regarding

employment rights are found in section 501, which

requires affirmative action in Federal Government

employment (29 U.S.C. 791); section 503, which

regulates the practices of employers who have

service, supply, or construction contracts with the

Federal Government (29 U.S.C. 633a(c)); and section 504, which applies to practices of entities that

operate programs receiving Federal financial assistance (29 U.S.C. 794). The Act was amended in 1978

to add enforcement procedures for Federal applicants and employees claiming a violation of section

501 (29 U.S.C. 794a(a)(l)) and to adopt the rights

and remedies prescribed by Title VI of the 1964

Civil Rights Act for enforcement of section 504 (29

U.S.C. 794a(a)(2)).

The Act targets discrimination and deeds which

adversely “limit, segregate, or classify” handicapped applicants or employees. Among the practices specifically forbidden by interpretive regulations are discriminatory recruitment, transfers, job

assignments, leaves of absence, hinge benefits, and

“any other term, condition, or privilege of employment” (28 CFR 41.52; 34 CFR 104.11).

Sections 503 and 504 prohibit discrimination

against otherwise qualified individuals with handicaps in employment and other areas. The term

“individuals with handicaps” is defined for this

purpose as “any person who (i) has a physical or

mental impairment which substantially limits one or

more of such person’s major life activities, (ii) has a

record of such impairment, or (iii) is regarded as

having such impairment” (29 U.S.C. 706(6)(B)).

Under section 503, all Federal contracts and

subcontracts in excess of $2,500 must include

clauses obliging the contractor to refrain from

discrimination and take affirmative action to promote employment opportunities for the handicapped. By regulation, an employer with a contract

exceeding $50,000 and having more than 50 employees must prepare a written affirmative action

plan outlining the contractor’s practices and procedures for increasing opportunities for the handicapped (41 CFR 60-741-4 to 60-741-6). Absent a

waiver (41 CFR 60-741.3), contractors are subject to

the affirmative action obligation in all of their

activities so long as they are performing the government contract. Contracts with State and local governments, however, require affirmative action only

in the agencies performing work on the contract (91).

Section 504 prohibits discrimination against otherwise qualified individuals with handicaps regardless of ethnicity or other similar characteristics, by

entities that receive or administer Federal financial
114 ● Genetic Monitoring and Screening in the Workplace

assistance. This section tracks Title VI of the 1964

Civil Rights Act except that section 504, unlike the

latter, includes employment coverage and covers

programs conducted by the Federal Government.

The Civil Rights Restoration Act of 1987 was passed

in response to a 1983 Supreme Court decision that

had the effect of narrowing the applicability of

section 504 (and other civil rights statutes) to apply

only to the particular “program or activity’ receiving Federal financial assistance, and not to the

institution as a whole (38). In response to the Court

decision, the Restoration Act specified that section

504 (and other civil rights statutes) apply to all

operations of the entity receiving Federal financial

assistance, and not only to the particular activity

receiving such assistance.

In order to fall under the protection of the

Rehabilitation Act, an employee must prove that his

or her genetic trait is an impairment, or is regarded

as an impairment. Although the statute does not

define the term impairment, Department of Health

and Human Services regulation implementing section 504 defines physical impairment as:

. . . any physiological disorder or condition, cosmetic disfigurement, or anatomical loss affecting

one or more of the following body systems: neurological; musculoskeletal; special sense organs; respiratory, including speech organs; cardiovascular;

reproductive; digestive; genito-urinary; heroic and

lymphatic; skin; and endocrine (45 CFR

84.3(j)(2)(i)(A) (1983)).

Under the guidelines and model regulations

promulgated to implement section 504, an employer receiving Federal financial assistance may

not make preemployment inquiry about whether

the applicant is handicapped or about the nature

and severity of an existing handicap unless a

preemployment medical examination is required

of all applicants and the information obtained

from the examination is relevant to the applicant’s ability to perform job-related functions.

The basic purpose of section 504 is to ensure that

handicapped individuals are not denied jobs or other

benefits because of the prejudiced attitudes or the

ignorance of others (79). The Supreme Court,

applying a balancing test to section 504, has

observed a balance between the statutory rights of

the handicapped to be integrated into society and the

legitimate interests of Federal grantees in preserving

the integrity of their programs (2). While a grantee

need not be required to make fundamental or

substantial modifications to accommodate the handicapped, it maybe required to make reasonable ones.

In addition, to be covered under section 504, a

handicapped individual must be otherwise qualified.

This term has been defined judicially as meaning a

person who is able to meet all of a program’s

requirements in spite of his or her handicap (81).

Accordingly, an individual with a genetic predisposition for a disease or illness may not be eliminated

from consideration for employment or promotion

simply because of the predisposition so long as the

individual is otherwise qualified for the position. In

such a case, the employer would have to make

reasonable accommodation for the person.

The Americans with Disabilities Act of 1990

The Americans with Disabilities Act of 1990

(ADA) (Public Law 101-336) is a recently enacted

civil rights bill that extends a clear and comprehensive prohibition of discrimination on the basis of

disability to the private sector. Title I bans discrimination against individuals with disabilities in hiring,

discharge, compensation, or any term, condition, or

privilege of employment by an employer engaged in

an industry affecting commerce. In July 1992, Title

I will apply to employers with 25 or more employees

and, in July 1994, to employers with 15 or more

employees.

According to ADA some 43 million Americans

have one or more physical or mental disabilities, and

this number will increase as the population ages. The

Act defines disability as:

(A)

(B)

(c)

a physical or mental impairment that substantially limits one or more of the major life

activities of such individual;

a record of such an impairment; or

being regarded as having such an impairment.

However, questions have been raised concerning

the use of the word “impairment” in the ADA

definition of disability (29). For example, is it an

impairment when:

. an employee is at risk of developing cancer 20

years in the future from present-day workplace

exposure to a hazardous substance;

. an employer is at risk because the employee

may become disoriented from exposure to a

workplace toxin and damage some equipment;

or
Chapter 6--Legal Considerations ● 115

. the public is at risk because a pilot with a

genetic marker for heart disease suffers a heart

attack and crashes the plane?

Isa “fictional impairment” such as limb deformity,

epilepsy, or deafness the same as an increased risk of

possibly becoming ill in the future? An increased

risk of developing cancer at some future point is an

injury that courts have recognized. However, increased risk of future disease or illness does not

relate to present job performance in the same way

that present fictional impairment does. The possibility of developing cancer or asbestosis 20 years in

the future would not presently impair a worker so

that it substantially limits one or more of the major

life activities nor would it prevent the worker from

currently performing the job (29).

When applied to genetic monitoring and screening the definition of disability does not expressly

address the question of increased risk of disease

based on genetic factors. The emphasis in the

definition of “impairment” suggests that some

increased risk of disease without actually having the

disease (if the disease is considered an impairment)

would not be a disability. Moreover, the definition

addresses individuals presently having an impairment or being so regarded or having a record of such

an impairment in the past. It does not address

“future” impairments. On the other hand, if an

employer ‘regards’ any individual with a marker or

trait for a genetic condition as impaired, then

perhaps the individual would come under the

protection of the Act. This has not yet been tested in

court.

The exclusion from the scope of some protection

under ADA of individuals who have contagious

diseases or infections (so long as the disease about

which there is a genetically based increased risk is

only potentially a hazard, not currently contagious or

infectious, or is not a contagious or infectious

disease at all, i.e., genetically transmitted conditions), argues strongly that such increased risk

diseases could be considered a disability if the other

requirements are met (11). Thus, would such an

increased risk limit one or more of an individual’s

major life activities? If yes, that person is disabled

and probably protected by ADA.

An employer may have a defense to a charge of

discrimination under the Act if the employer can

demonstrate that qualification standards, tests, or

selection criteria that screen out or tend to screen out

or otherwise deny a job or benefit to an individual

with a disability are job-related and consistent with

business necessity, and no reasonable accommodation is possible. Under the Act reasonable accommodation -

 - - -

(A)

(B)

is defined as:

making existing facilities used by employees

readily accessible to and usable by individuals with disabilities; and

job restructuring, part-time or modified work

schedules, reassignment to a vacant position,

acquisition or modification of equipment or

devices, appropriate adjustment or modifications of examinations, training materials or

policies, the provision of qualified readers or

interpreters, and other similar accommodations for individuals with disabilities.

Accordingly, an employer could possibly deny a

transportation or public safety job (e.g., airline pilot,

bus driver) to a worker with a genetic marker for

heart disease. The genetic screening that would

identify the marker for heart disease could take place

only after a job offer has been made and before

employment duties begin. The job offer may be

conditioned on the results of such an examination

provided that all new employees are subjected to the

same examination and the confidentiality requirements of the Act are observed. If a genetic problem

is discovered, the employer may have to offer

reasonable accommodation in the form of a desk job

or other assignment where the possible heart problem would not affect public safety.

As to whether ADA permits or prohibits genetic

monitoring and screening, Title I section 102

subsection (c)(2) prohibits preemployment medical

examinations or inquiries designed to uncover

information about disabilities unless the inquiry is

designed to reveal the applicant’s ability to perform

the job-related tasks. Strict interpretation of this

language means that a covered entity may not

require a medical examination unless that examination is job-related and consistent with business

necessity. An employer’s attempt to lower costs by

reducing its contribution to group health insurance

premiums by detecting increased risk of experiencing diseases or conditions based on genetic factors

would appear not to be ‘job-related’ or a‘ ‘business

necessity, ’ no matter how advantageous such actions might be for the employer. The job-relatedness

of the medical examination or inquiry and consistency with business necessity requirements would
116 w Genetic Monitoring and Screening in the Workplace

●

seem to preclude remote cost-cutting measures

aimed at weeding out genetically costly employees

(11).

Employment safety and health issues are perhaps

in a different class to the extent to which a disabled

individual under ADA poses a threat to the

workplace and co-workers or to the general public.

Threats caused by that individual’s disability may

not be afforded protection under ADA. Increased

risk of disease--even if contagious—would have to

present a clear and present danger rather than a

simply statistically greater likelihood of ultimate

disease contraction (11). ADA appears to prohibit

genetic screening as a part of prohibited medical

examinations and genetic information obtained by

means of a prohibited inquiry.

CONFIDENTIALITY AND

PRIVACY ISSUES

Beyond the role of occupational health and safety

regulation, common law rules regarding confidentiality and privacy are relevant to genetic monitoring

and screening in the workplace. These include the

right to:

●

●

●

●

●

●

confidentiality of test results;

have information forwarded to other health care

personnel;

have information regarding implications for

immediate family;

know test results, the right to have a copy of test

results;

accuracy of test results; and

refuse testing.

Right To Confidentiality

There are four elements of the common law cause

of action for public disclosure of private facts:

the facts must be disclosed to the public;

the facts disclosed must be private;

the facts made public must be highly offensive

and objectionable to a reasonable person of

ordinary sensibilities; and

the public must not have a legitimate interest in

the information.

It can be argued that employers who learn of

their employees’ genetic defects and susceptibilities through genetic screening in the workplace

could have a duty to keep this information

confidential and not disclose it to anyone absent

express consent of the employee. Failure to do so

could result in a charge of invasion of privacy

brought by an employee against an employer.

There is also the argument that genetic information

may not be considered highly offensive and objectionable as would, for example, some diseases.

Under this line of reasoning, genetic information

may not be subject to the same constraints with

respect to privacy and confidentiality as some other

conditions.

The existence of a right to confidentiality depends

on the relationship between the test subject and test

administrator. When a patient and physician are

involved, an obligation of confidentiality can generally be found to flow from physician to patient. Since

physicians must necessarily be entrusted with communications of the most personal and private nature

in order to effectuate proper diagnoses and cures

(70), the confidentiality obligation has been part of

ethical codes for physicians since Hippocrates. In

1984, the American Medical Association’s (AMA)

Judicial Council reaffirmed the Hippocratic Oath in

publishing its most recent statement on confidentiality which says that the information disclosed to a

physician during the course of the relationship

between physician and patient is confidential to the

greatest possible degree. The patient should feel free

to make a full disclosure of information to the

physician in order that the physician may most

effectively provide needed services. The patient

should be able to make this disclosure with the

knowledge that the physician will respect the

confidential nature of the communication. The

physician should not reveal confidential communications or information without the express consent

of the patient, unless required to do so by law (5).

Ethical standards of the medical profession did

not have legal counterparts in common law. Early

English law indicated that neither a voluntary vow

of secrecy nor the privacy of the relationship alone

were sufficient to establish a privileged communication (98). Under common law, a physician could

disclose in court and elsewhere a patient communication. In jurisdictions, such as Georgia, that still

follow the common law approach, the result is a

harsh one for patients.

Evolving case law in most States, however, has

come to recognize a right of patients to sue when a

physician has made a disclosure of medical informa-
Chapter 6--Legal Considerations ● 117

BERRY’S WORLD JIM BERRY

“Pity! You, yourself, tested out well. Your

GENES didn’t make it. ”

Photo credit: United Media

tion about the patient without the patient’s consent.

The route taken toward recognizing the physician’s

duty to maintain confidentiality has varied. In some

States, courts have pointed to the Hippocratic Oath

and AMA’s statement to support the common law

requirement of confidentiality between doctor and

patient. Other States point to such a policy by

referring to statutory enactments such as the testimonial privilege statutes or the confidentiality provisions of the physician licensure and discipline

statutes.

Under the testimonial privilege statutes in virtually every State, physicians may not testify in court

about a patient’s condition unless the patient has

either consented to the testimony or waived the right

to consent. Only eight States lack testimonial

privilege statutes regarding physicians and patients

(Alabama, Connecticut, Florida, Kentucky, Maryland, Massachusetts, New Mexico, and South Carolina). Numerous cases have based a duty not to

disclose on the State testimonial privilege statute.

Twenty States protect the relationship between a

patient and his or her physician by providing that the

disclosure of confidential information by the physician is a ground for revocation of the medical license

or other disciplinary action. In an Ohio case, for

example, the plaintiff sued an insurance company

for fraudulently inducing his physician to divulge

confidential information obtained from the plaintiff

in the course of the doctor-patient relationship (40).

The court used three indications of public policy—

the medical profession’s code of ethics, the statutory

discipline provisions subjecting physicians to discipline for breach of confidentiality, and the testimonial privilege statute-to hold that a patient can

recover damages from a physician for unauthorized

disclosure concerning the patient.

Several grounds on which testimonial privilege

can be based have been described (74). Many States

recognize a testimonial privilege that permits a

patient to prevent a physician from divulging

medical information in court. State medical licensing statutes may also create a cause of action. In

California, there is statutory protection in the form

of the Confidentiality of Medical Information Act

(Cal. Civ. Code sec. 56) which provides for recovery

of compensatory damages, punitive damages up to

$3,000, attorney fees up to $1,000, litigation costs,

and criminal penalties for unauthorized disclosure of

medical information.

There may also be a cause of action for unauthorized disclosure of medical data based on the breach

of a contractual relationship. The obligation of the

physician to maintain confidentiality of medical

information can be seen as part of a contractual

obligation to the patient. Physicians also have a

responsibility to maintain confidentiality as part of

the generally accepted standards of professional

conduct in medicine.

A problem may arise, however, for subjects of

genetic monitoring or screening in employment

situations. In these cases it could be argued that the

physician is acting as an agent of the employer and

not as the patient’s representative. Moreover, in

many instances, the testing may be done by a nurse

or medical technician, with no physician involved at

all. The legal obligations of a medical professional

in these circumstances are not clear, but many courts

have held that there is no physician-patient relationship (74). In a Michigan case (7 1), the court held that

a physician who examines a patient for a purpose
118 ● Genetic Monitoring and Screening in the Workplace

other than diagnosis or treatment for the benefit of

someone other than the patient does not owe a duty

of care that would subject him to liability for

malpractice.

Even more problematic is the status of a genetic

screening subject who is a job applicant. In this case,

the subject lacks even the responsibilities created by

the employer-employee relationship to rely on for

legal support. Other sources of law must be looked

to for protection and will be discussed later.

One formidable obstacle that employees will face

is the right of their employer to see their test results.

When the employer has provided the physician and

paid for the procedure, there is little legal basis for

asserting that it should be denied access to the

results. The physician’s primary duty in this situation is to the employer who hired him. There are few

legal restrictions on employer access to workplace

records and, in many instances, workers are unaware

of the disclosures (74). The OSHA standard for

access to medical records does not limit an

employer’s access but merely guarantees employee access.

One source of limited protection for employees is

contained in the Code of Ethics for Physicians

Providing Occupational Medical Services (6,74).

The confidentiality obligations of physicians are

described in strong terms, limiting disclosure of

information to requirements of law or overriding

public policy. The code also prohibits disclosure to

other physicians unless requested by the subject

“according to traditional medical ethical practice. ’

The information that can be provided to the employer is limited to ‘‘counsel about the medical

fitness of individuals in relation to work.’ Employers may not be given “diagnosis or details of a

specific nature. ’

While the code lacks legal authority, it does

establish the accepted standard for medical practice

in this field, lending possible support to a claim for

malpractice for unauthorized disclosure of confidential medical information. The effectiveness of this

provision, though, would depend on the circumstances. Genetic screening results indicating susceptibility to the effects of a workplace toxin would,

presumably, be reported to the employer as a lack of

fitness for a particular job because of medical

sensitivity.

An employee or a job applicant who is subjected

to genetic monitoring or screening must assume that

there will be at least some employer access to the

results. The question then becomes protection

against disclosure beyond the immediate employment setting. In that context, the worker can rely on

two sources of law. For release of accurate information, a worker can look to professional and contractual obligations of the physician and employer. For

disclosure of false or unreliable information, a

worker may look to a claim for defamation.

Protection against release of information to the

general public is, for the most part, provided. Some

States, however, require reporting of individuals

with certain serious communicable diseases, such as

AIDS, but a genetic defect is not a communicable

disease and is unlikely to fall in this category.

There is an exception in California to the confidentiality rule for psychotherapists, who have a duty

to warn persons in immediate danger of harm from

a psychotherapy patient (87), but genetic monitoring

and screening results are not likely to reveal an

immediate risk to others. It is, of course, likely that

a genetic defect is shared by other family members

and that it can be passed onto offspring. Disclosure

in these circumstances, however, is generally a

matter of patient discretion and not a matter of legal

obligation of the physician. Unlike the case of a

communicable disease, there is no immediate threat

of harm to others.

The obligations of an employer who releases

employee medical records without authorization are

less clear. In California, such disclosure triggers

statutory civil and criminal penalties, as discussed.

Furthermore, the California Constitution explicitly

guarantees a right to privacy (Cal. Const. art. I, sec.

1). In other States, a worker could rely on a common

law claim for invasion of privacy.

Disclosure of inaccurate genetic monitoring or

screening information can be seen as a form of libel.

The key element of a libel claim is that the

information divulged is untrue, so such a claim

would be invalid when accurate test results are

released. If test data are incorrect, though, libel can

be found.

A question arises as to the libelous nature of test

results that are accurate but subject to possible

misinterpretation. This is an important issue for

genetic monitoring and screening information,
Chapter 6--Legal Considerations . 119

which is new and could be misunderstood by those

receiving it. A direct analysis of a subject’s chromosomes is likely to be reliable in terms of the presence

or absence of a particular gene. Whether the gene

always expresses itself through a particular trait,

however, may be subject to considerable individual

variation. A test result, for example, may reveal that

a worker has an undesirable gene that may predispose the worker to susceptibility to toxic harm.

Environmental or countervailing genetic factors,

though, may negate this susceptibility. A medical

report that includes the test result will be accurate in

terms of whether the subject has the gene, but might

bean unreliable predictor of whether the worker will

develop the disease in question.

It is unclear whether disclosure of such technically accurate information could constitute libel.

There may be an analogy to other kinds of tests

whose validity is subject to question (e.g., intelligence tests). In general, it is unlikely that an

employer or physician would commit libel for

simply reporting the test result. Any conclusions

based on it that are communicated to others, though,

might be suspect if careful qualifications are missing.

Another means of legal relief for patients whose

medical information has been disclosed is a suit for

tortious public disclosure of private facts. Such a

cause of action is part of the 20th century common

law protection of privacy. Common law privacy

action protects medical records because such records

involve intensely personal facts, which when disclosed are generally disclosed to an individual (a

health care professional) and not to the public. In an

Alabama case, the court recognized such an action,

stating that unauthorized disclosure of intimate

details of a patient’s health may amount to unwarranted publicization of one’s private affairs (42).

Neither the public nor the employer has a legitimate

interest in knowing each and every detail of an

employee’s health. Certainly, there are many ailments about which a patient might consult a private

physician, but which have no bearing or effect on

one’s employment.

The Supreme Court in Whalen v. Roe (97)

recognized that the physician-patient relationship

falls within a constitutionally protected zone of

privacy. Plaintiffs in Whalen challenged a New York

law that required physicians prescribing certain

drugs to report the drug name, dosage, pharmacy,

and patient’s name, address, and age to the State

Department of Health. The law was enacted to

address a concern that prescription narcotic drugs

were being diverted into unlawful channels either by

stolen or multiple prescriptions, unauthorized refilling of prescriptions, or over-prescribed medications.

While the Court recognized the need to protect the

privacy of the physician-patient relationship, it held

that the particular disclosure requirement did not

violate a patient’s constitutionally protected privacy

right because the information was securely stored,

the information was not publicly disclosed, and an

individual was not deprived of the right to acquire

and use the medication. The Court recognized “the

individual’s interests in avoiding disclosure of

personal matters.” However, the Court distinguished between an individual’s interest in autonomy and an individual’s interest in nondisclosure:

the former clearly being protected by the Constitution (97).

Finally, at least five States--California, Montana,

Rhode Island, Utah, and Wisconsin-maintain a

more direct means of protecting the patient from

unauthorized disclosures of medical information by

adoption of statutes that specifically protect such

information (Cal. Civ. Code 56.10- 56.16; Mont.

Code Ann. 50.16-525- 50.16-553; R.I. Gen. Laws

5-37.3-1 to 5-37.3-11; Utah Code Ann. 63-2-88;

Wise. Stat. Ann. 146.82).

At least three States have specific legislation

addressing genetic health care information. In

Maryland, genetic information is targeted as warranting protection. Under a Maryland statute, information collected in hereditary disorder programs

must be kept confidential (Md. Health-Gen. Code

Ann. 13-109(c)). Rhode Island and Utah laws

protecting privacy of genetic or general health care

information have special provisions providing for

compensation of patients when confidentiality is

breached. Rhode Island law provides that a patient

can collect actual and exemplary damages and, at the

discretion of the court, attorney fees maybe awarded

when a health care professional breaches the confidentiality act. Under the Utah Information Practices

Act, if State officials improperly and intentionally

disclose health care information, the patient can

receive exemplary damages of $100 to $1,000 (Utah

Code Ann. 63-2-88). Even if State law does not

specifically mention compensation for the patient,

the existence of statutes could serve as basis for a

private lawsuit claiming breach of confidentiality.
120 ● Genetic Monitoring and Screening in the Workplace

There is concern about whether doctor-patient

confidentiality extends to other types of health

professionals. Some States have enacted confidentiality statutes that apply to communications between

patients and any health care provider or officer,

employee or agent of a health care provider or

facility (R.I. Gen. Laws 5-37.3-.3(a)). Such would be

the case if paramedical health care providers did

genetic monitoring and screening in the workplace.

In other jurisdictions, courts have noted that the

rationale for creating physician-patient privilege to

protect the patient’s right of privacy justifies extending the privilege to cover people assisting physicians, even in the absence of a specific statute so

providing (101). The trend seems to be to extend the

duty of confidentiality to include other health care

professionals, which would mean that providers of

genetic services who were not physicians would

nevertheless be required to maintain confidentiality.

One could argue that no physician-patient relationship exists in the occupational health setting

when the company-hired physician has not been

chosen by the employee. When health examinations

are a condition of employment, submitting to an

examination by this physician maybe something an

employee cannot refuse. Further, if no treatment is

given, only health monitoring or screening, this, too,

supports the lack of a physician-patient relationship.

When, for example, a physician employed by an

insurance company examines an individual for the

purpose of insurance qualification, the physician

owes no duty to the individual to treat or to disclose

problems discovered during the examination (27).

Physicians in these circumstances would still be

expected to adhere to the standard of care for any

health care rendered but may not be held to the

traditional fiduciary duty that a traditional physician has to a traditional patient. The difficult

question arises when the condition or disease

discovered in the examination is one caused or

exacerbated by conditions in the workplace

environment. In that instance, it can be argued

that a company physician does have an ethical

and moral duty, if not a legal duty, to inform the

employee-patient of any findings.

Duties of the Occupational Health Physician

Occupational health physicians evaluate the medical fitness of applicants and employees in the

workplace. Occupational health physicians are different from private physicians in training, loyalties,

and legal and ethical duties (75). When an occupational health physician undertakes genetic monitoring or screening of an employee or job applicant,

there can be some question whether legal precedents

protecting confidentiality in the physician-patient

relationship apply. If the occupational health physician is hired by the employer, either on a contract

basis or as a salaried employee, to do genetic

monitoring or screening of other employees, it could

be argued that the occupational health physician’s

first duty is to the employer and not to the test

subject. If the employer is paying for the tests this,

too, could support the argument that the employer is

entitled to receive any test results. However, other

legal precedents based not on fiduciary or contractual aspects of the physician/employer-patient/

employee relationship, but on specific ethics codes

or statutes applying to occupational health physicians, as well as more general precedents regarding

tortious public disclosure of private facts or violation of a constitutional right to privacy provide a

basis for holding occupational health physicians

liable for unauthorized disclosure of medical information about a job applicant or employee. Occupational health physicians are left then to balance

patient privacy and confidentiality on the one hand

with employer need-to-know on the other.

Occupational health physicians do not practice

medicine in an ethics vacuum. The American

College of Occupational Medicine Code of Ethical Conduct (formerly American Occupational

Medical Association (AOMA)) specifies that occupational health physicians should maintain

confidentiality. Even with respect to disclosures to

employers, it cautions that occupational health

physicians should provide bottom-line information,

not specific details. The relevant provision states

that: “Physicians should treat as confidential

whatever is learned about individuals served,

releasing information only when required by law

or by overriding public health considerations, or

to other physicians at the request of the individual according to traditional medical ethical practice, and should recognize that employers are

entitled to counsel about the medical fitness of

individuals in relation to work, but are not

entitled to diagnoses or details of a specific

nature” (6). This code may provide the policy basis

for recognition of a legal duty of occupational health

physicians to maintain confidentiality, just as the

Hippocratic Oath and the AMA statement have
Chapter 6--Legal Considerations . 121

General:

●

●

●

●

●

●

●

●

●

●

Care of work-related illnesses and injuries

Follow-up treatment coordinated with your

personal physician

Occupational Rehabilitation Therapy

Respirator fit testing

X-rays

Medical laboratory testing (eg. cholesterol risk

factor analysis, throat cultures)

immunizations

● Allergy shots

● influenza vaccine injections

● Immunizations required for company travel

Blood pressure screening (walk-in)

Non-prescription cold medications (walk-m)

Percent body fat measurements

Tests/Exams

●

●

●

Chemical Specific Periodic Medical Exams

(offered to certain groups of employees with

potential exposures to regulated chemicals or

physical agents)

Health Exam (offered every two years as

a supplement to your personal physician’s

physical exam)

Included:

Health history

Blood pressure

Height and weight

Blood and urine analysis (drug testing

is NOT included in these exams)

Hearing test

Eye pressure testing for glaucoma

(employees over 40 years)

Tests for lung capacity

Stool exam for blood (ernployees over

40 years)

Vision testing

Chest X-ray

Electrocardiogram

All non-emergency tests and examinations

should be by appointment

Health Education

● Health promotion program

which includes presentations on a variety of

topics including:

● CPR Training ● Cancer Prevention

● Nutrition (Breast Self

● Stress Examination

● First Aid ● Ergonomic

● Hypertension Evaluation

● Shift Work

* Eyes Conservation

● Poisons ● Sports Injuries

● Coronary Risk * Back Injury

Factors Prevention

* AIDS ● Substance Abuse

* Basic First Aid Intervention

● Computer ● Hypothermia

Terminals ● Hyperthermia

* Exercise Classes

● Brochures on a Variety of Topics

● Assistance for lifestyle changes such as drinking, weight loss and smoking cessation

● Employee Assistance Program

. Medical consultations

● Pre-placement counseling

● Pregnancy in the workplace counseling

Photo credit: The Dow Chemical Co., Michigan Division

A pamphlet describing a medical department’s programs.
122 ● Genetic Monitoring and Screening in the Workplace

provided a basis in some States for judicial recognition of a duty on behalf of private physicians not to

disclose. On the other hand one commentator has

pointed out that the AOMA use of the word

‘‘individual’ in the code rather than ‘patient’ is an

attempt to make the occupational health physicianpatient relationship not a traditional doctor-patient

relationship (73).

The need for protection of health care records in

the hands of employers has been recognized by

legislatures. Statutes in Connecticut and California

specifically protect confidentiality of medical records obtained in the course of employment (Corn.

Gen. Stat. Ann. 31-128f; Cal. Civ. Code 56.20

(a)(c)). Public employers in Wisconsin have an

obligation to maintain confidential records of workrelated injuries and illnesses (Wise. Stat. Ann.

101.055(7)(a)). A Montana health care confidentiality statute could also be read to include occupational

health physicians. It covers even those health care

professionals who merely diagnose (Mont. Code

Ann. 50-16-101 et seq.). The preamble to the statute

states that persons other than health care providers

obtain, use, and disclose health record information

in many different contexts and for many different

purposes. It is the public policy of this State that a

patient’s interest in the proper use and disclosure of

his or her health care information survives even

when the information is held by persons other than

health care providers (Mont. Code Ann. 50-16-101-

502(4)).

Rhode Island law protects confidentiality of

health care information about a “patient,” even

when that information is in the hands of third-parties

such as employers. However, information obtained

outside of a doctor-patient relationship through

genetic monitoring or screening “arguably” would

not be considered information about a ‘‘patient”

(R.I. Gen. Laws 5-37.3-4(a)). Accordingly, Rhode

Island protections would only cover more traditional

health care information (e.g., information from an

employee’s personal physician about the employee’s genetic status) that makes its way to an

employer’s files.

In Florida, employees of the school systems are

guaranteed confidentiality of their medical records

except that a hearing officer or panel can have access

to the records at a hearing on the competency of the

employee (Fla. Stat. Ann. 231.291(3)(a)(5)).

In Connecticut, the law protecting the confidentiality of employee medical records has an exception

allowing dissemination of information pursuant to

terms of a collective bargaining agreement. Thus,

employees or unions may be able to obtain information about health care risks to the employee population as a whole in order to bargain for better health

and safety standards (Corn. Gen. Stat. Ann. 31-

128f’).

Various statutes protecting confidentiality of

health care records in the workplace might be used

as the basis for a private suit against an occupational

health physician or employer for breach of confidentiality. There have been no such cases brought so far.

The occupational health physician’s or employer’s

duty to an employee who is a union member may

also be created by terms of the collective bargaining

agreement. Thus, an employee might bring a claim

for violation of privacy under the bargained labor

agreement. Also, as is the case with physicians

generally, occupational physicians or employers

could be held liable for tortious or unconstitutional

invasion of privacy in disclosing confidential information.

COLLECTIVE BARGAINING

CONCERNS

NLRA sets forth a relatively complex scheme

governing relationships of employees, labor organizations (unions), and employers engaged in businesses affecting interstate commerce (29 U.S.C. 151

et seq.). Implementation of workplace genetic monitoring and screening programs implicate NLRA

provisions from several perspectives.

The Act allows employees to organize unions and

negotiate with employers over so-called “mandatory subjects of bargaining’ ’-i.e., wages, hours,

and other terms and conditions of employment (sec.

8(d) of the NLRA). NLRA also governs the relationship between individual employees and their unions

by stating that unions must “make an honest effort

to serve the interests of all. . . members [of an

appropriate collective bargaining unit], without

hostility to any.” Such efforts do not preclude

unions from entering into agreements with employers that have unfavorable impacts on some employees in the appropriate collective bargaining unit (3 1).
Chapter 6--Legal Considerations ● 123

The Duty To Bargain Over Genetic

Monitoring and Screening Programs

As employment conditions, safety and health

matters have long been recognized as mandatory

subjects of bargaining (61). The National Labor

Relations Board (Board or NLRB) has ruled that

mandatory subjects of bargaining include fitnessfor-duty physical examinations including medical

testing (51) and thus, has set the precedent for the

inclusion of genetic monitoring and screening of

current employees as mandatory subjects of collective bargaining.

Matters germane to the working environment are

considered mandatory subjects unless they affect an

employer’s ability to exercise entrepreneurial control. To the extent genetic monitoring and screening

programs are designed to assess either an employee’s continued fitness to safely perform the

work or an employee’s ability to safely perform

different work without affecting health, they are

material changes in the employment relationship. As

such, they are subject to bargaining insofar as they

implicate both job security and disciplinary consequences in the event the employee refuses to submit

to them (50,51,72). Such tests cannot be fairly

construed as cutting to the core of an employer’s

ability to exercise entrepreneurial control of its

business.

It now seems clear, however, that preemployment

genetic screening of job applicants will not be

considered a mandatory subject of bargaining. The

seminal case on this issue is Allied Chemical &

Alkali Workers of American Local No. 1 v. Pittsburgh Plate Glass Co. (4). In this case, the Supreme

Court held that conditions applicable to retirees, as

nonemployees, are subject to union bargaining if

they “vitally affect” current employees. The Court,

however, ruled that in this case the retirement

benefits at issue lacked a sufficiently vital effect on

existing employees. Thus, the contours of effects

sufficiently ‘‘vital” to current employees are unclear. Undoubtedly, resolution of the preemployment drug testing questions by NLRB and the courts

will have a heavy bearing on the issue of genetic

screening of applicants.

Relying on Allied Chemical, NLRB has ruled that

drug testing of applicants for employment is not a

mandatory subject of bargaining (83). Although the

courts have not reviewed this ruling, it can be

Photo 

Headquarters of the American Federation of Labor and

Congress of Industrial Organizations, Washington, DC.

expected to stand. The analysis used by the Board

would suggest that it would not regard genetic

testing differently than drug testing as applied to

applicants (89).

If NLRB and the courts ultimately decide that

unions have a right to negotiate preemployment

conditions, it might logically follow that this right

carries with it the corresponding duty to fairly

represent the interests of applicants. This question,

however, has yet to be addressed.

The duty to bargain in good faith recognized in

sections 8(b)(3) and 8(a)(5) of NLRA also includes

corresponding duties of unions and employers,

respectively, to provide on request information

relevant to the subject of negotiations (23,63). For

example, if an employer seeks to negotiate a change,

the union must be given access to information in the

employer’s possession supporting its proposals. In

terms of proposed implementation of genetic monitoring and screening requirements, the union would

have the right to receive information such as the

scientific literature the employer used in developing

a testing proposal and data on known workplace

exposures to chemicals that may be implicated by

that testing proposal (63). It is important to note that

this duty to supply information on request extends

beyond the conclusion of negotiations. On request,

employers must provide unions with information

32-799 - 90 - 5 : QL 3
124 ● Genetic Monitoring and Screening in the Workplace

that is necessary to police the employer’s compliance with a specific term of employment such as

genetic monitoring or screening as well as the

collective bargaining agreement as a whole (60).

Scope of the Duty To Bargain Over Genetic

Monitoring and Screening Programs

A threshold determination that genetic monitoring and screening are mandatory subjects of bargaining under section 8(d) of NLRA leads to a duty to

bargain initial implementation and subsequent

changes only if the union has not otherwise waived

its right to bargain. Employers may implement a

change affecting an area subject to bargaining if they

have negotiated the provision in good faith and those

negotiations resulted in an impasse (62,86). At that

point, the union is free to use its economic weapons—including the strike. On the other hand,

employers may not implement a proposal if such a

change represents a modification of an existing

collective bargaining agreement. Section 8(d) of

NLRA squarely prohibits such unilateral midterm

modifications. Hence, a collective bargaining agreement that defines the contents of permissible physical examinations and does not include genetic

monitoring or screening, or permits such testing with

limitations, would probably serve as a bar to an

employer’s ability unilaterally to implement such

testing or modify it during the term of the collective

bargaining agreement.

Collective bargaining agreements may, however,

contain waivers by the union of its statutory rights to

bargain over mandatory subjects during the term of

the agreements so long as such waivers are “clear

and unequivocal. ’ Such waivers are not to be

inferred lightly. The contract language relied on

must be specific or the bargaining history of that

language must be such that it can be concluded that

the union “consciously yielded.” Broad, so-called

management rights clauses have been regarded by

NLRB’s General Counsel as not permitting unilateral imposition of drug testing (55). A similar

position could be anticipated with respect to genetic

monitoring and screening.

While such waivers turn on the totality of

circumstances, including bargaining history and

wording of the clause at issue, it is fair to assume that

imposition of genetic monitoring or screening of

current employees may well be regarded by NLRB

as a significant change requiring a particularly clear

and unequivocal waiver even in the face of a history

of more “routine” forms of workplace medical

surveillance. The very controversial nature of genetic monitoring and screening, like that of drug

testing, may well dictate a heightened standard of

waiver by contract or by past practices regarding

medical surveillance.

Union inaction is considered another form of

waiver. An employer meets its duties under section

8(a)(5) of NLRA by giving the union notice of its

intended changes and thereby giving the union an

opportunity to negotiate. If it is otherwise permissible to implement the change, the employer may

institute it if the union fails to request negotiations

in a timely fashion (20,44). Hence, an employer

would not violate NLRA if it announced its intention

to use either genetic monitoring or genetic screening

of either current employees or applicants, and the

union, by its silence, acquiesced in the change. This,

of course, assumes that the intended change was not

presented to the union as a fait accompli over which

bargaining would be fruitless (19,66,82).

Once it is assumed that a duty to bargain genetic

monitoring and screening exists, absent waiver, that

duty encompasses an obligation to meet and discuss

all aspects of the monitoring and screening process

itself as well as its effects, including the uses to

which it can be put and protections for affected

employees.

While either party could insist to the point of

impasse on the use or abandonment of a specific test,

it is fair to assume that impasse would be far more

likely in situations where screening is used to predict

tendencies towards disease that bear little or no

relationship to occupational exposures. The lack of

immediate relationship to present ability to perform

or to possible deleterious effects of workplace

exposure could be regarded by the union as strong

reason to adamantly oppose the screening. On the

other hand, resistance by the union might be less in

the case of tests that predict susceptibility to

occupational agents such as dusts or fumes. This

would include screening for homozygous serum

alpha antitrypsin deficiency to assess increased risk

of emphysema in workers exposed to dusts. In all

probability, discussions of such screening would

focus on the accuracy of the tests and the employer’s

responses thereto.

Virtually all aspects of a mandatory genetic

monitoring and screening proposal would be subject

to negotiation. Regardless of whether proposed tests
.

Chapter 6--Legal Considerations ● 125

were to be used for applicant screening, employee

screening, or employee monitoring, the parties

would be required to discuss test selection. In this

context, the union would be free, and indeed duty

bound to explore with the employer the validity of

the test as applied to the workplace. The employer

would then be required to demonstrate why, in its

opinion, the proposed test furthers its interests in

maintaining employee health and safety.

Another area of negotiations that could apply to

genetic screening of job applicants, and genetic

monitoring or screening of current employees would

be the weight accorded test results. In this context,

the predictive and diagnostic value of tests would be

significant. If the test detected genetic changes or

abnormalities that bore on an employee’s or applicant’s present ability to work, such workplace

relevance would support hard bargaining by employers and acquiescence by unions without fear of

violating a duty of fair representation. On the other

hand, if such a test bore little relevance to present job

fitness and was, at best, an unspecific predictor of

potential, future ill effects, both the employer and

the union would be effectively constrained from

agreeing to monitoring and screening that violated

State or Federal handicap antidiscrimination laws.

Within these two extremes, unions and employers

could use their economic powers (strike and lockout,

respectively) to “convince’ each other of the

workplace relevance, or lack thereof, of a particular

test as well as to determine the weight it would be

given in other job-related matters.

Even if a particular genetic screening program

could be said to have sufficient workplace relevance,

unions could be placed in a difficult position with

respect to their duty of fair representation if organspecific genetic conditions disclosed by the screening occurred significantly more frequently in identifiable ethnic groups. Such is the case with screening

for sickle cell disease, G-6-PD deficiency, and

thalassemia (76). If responses to such testing would

have a disparate impact on a particular ethnic group,

a union’s duty to fairly represent all bargaining unit

members would be heightened (31,88). Absent a

cogent showing of business necessity, it could not

safely agree to such genetic screening.

Another bargainable element of a proposal regarding genetic monitoring and screening would be

access to test results. A variety of existing laws and

regulations already provide strict rules governing

the release of medical records. However, in order to

carry out their obligations to protect the safety and

health of bargaining unit members, unions could

(under section 8(a)(5) of NLRA) insist on receiving

summary data regarding genetic monitoring and

screening that did not disclose individual employee

results (29 CFR 1910.1001; 20 CFR 1910.1017).

Perhaps the most sensitive aspects of negotiations

regarding genetic monitoring and screening would

be those focusing on effects of a test result that

would disqualify employees from their existing jobs

or preclude them from moving to a different, and

perhaps, higher paying job. Both forms of disqualification would implicate existing wage and seniority

provisions in collective bargaining agreements.

Unions would, therefore, be obligated to explore in

depth effects of genetic monitoring and screening

with employers.

Presumably, genetic monitoring or screening of

employees in connection with their current jobs

could result in discovery of changes or traits,

respectively, that would require removal from the

presumed deleterious workplace exposure. If this

could be accomplished, unions could insist in

bargaining that those changes be implemented

before the job status of an employee is adversely

affected. Employers may insist, or the circumstances

may dictate, that the only ‘‘safe” alternative is

removal of an employee to a job free from the

deleterious exposure. If such a job existed, questions

would have to be resolved as to whether an employee

so disqualified could use seniority to displace

(bump) a junior employee or whether an employee

could only use seniority to claim available open

jobs. In either case, one result could be no available

job which an employee could safely perform. Hence,

the parties would have to address the issue of

benefits available for medical discontinuance (termination). Another result could be movement to a

lower paying job. In such circumstances, the parties

would have to explore the possibility of maintaining

an employee’s former rate of pay for some fixed

period of time or perhaps permanently (so-called red

circling).

Genetic Monitoring and Screening Refusals

Employee refusals to submit to employerrequired genetic monitoring and screening fall into

two categories, namely ‘‘concerted” refusals of one

or more employees and individual refusals. Explora-
126 . Genetic Monitoring and Screening in the Workplace

tion of any “rights” to refuse genetic monitoring

and screening under NLRA requires separate analyses of these two types of refusals with the assumption that the employer has otherwise complied with

its bargaining obligations.

Section 7 of NLRA gives employees the right to

engage in ‘‘concerted activities for the purpose of

collective bargaining or other mutual aid and protection” (e.g., the strike). This right to strike is not,

however, unfettered. Otherwise lawful strikes may

lose the protection of NLRA under certain circumstances.

An individual’s refusal to be tested at a unionized

or nonunionized workplace, however, may not be

protected by NLRA unless the action is an integral

part of group activity-past or present. Even then,

such refusals may be regarded as concerted, yet

unprotected, if they violate an express or implied

no-strike obligation.

Arbitral Review

Genetic monitoring and screening requirements

would, at some point, typically be subject to review

by arbitrators under arbitration provisions in collective bargaining agreements. This is the preferred

method for dispute resolution in organized

workplaces to avoid strikes and lockouts. In the

wake of presumptions favoring the arbitrability of

labor disputes flowing from the so-called “Steelworker Trilogy,’ it is fair to assume that many

disputes surrounding workplace genetic monitoring

and screening would be resolved by arbitrators

(93,94,95).

Genetic monitoring and screening requirements

implemented under broad provisions permitting

employers to take ‘‘reasonable measures’ to protect

health and safety can be challenged as to their

reasonableness (9,100). Indeed, even absent such

express management rights, arbitrators would typically infer a reserved management right to promulgate rules and regulations to ensure employee safety

and health and would review such rules and regulations under a standard of reasonableness (26).

NLRA Preemption of Common Law Torts

Drawing from recent experience involving

workplace drug testing programs, it is fair to assume

that employees covered by collective bargaining

agreements may seek to bypass contractual grievance and arbitration procedures by filing suits

against their employers in State or Federal courts

alleging violations of tort laws. Torts such as

intrusion on seclusion, invasion of privacy, defamation, and intentional (or negligent) infliction of

emotional distress could be alleged (34,77). Such

suits may, however, be preempted under the strong

Federal policy favoring arbitral resolution of

workplace disputes implicit in section 301 of the

Labor Management Relations Act. OSHA’s development of medical records access requirements

inspired controversy on several points, including

trade secret protections, the use of unreasonable

searches and seizures, and the right to access for

representatives of employees (56).

USE OF GENETIC MONITORING

AND SCREENING RESULTS IN

EMPLOYMENT DECISIONS

Right of Employer To Use Monitoring and

Screening Data in Terminating Employment

As in the case of the employer’s right to medical

examinations of employees, the right to use the

results of medical tests in employment decisions is

limited primarily by Title VII of the Civil Rights Act

of 1964 and by the Rehabilitation Act of 1973.

Common law rights in this area grow out of the

doctrine of employment-at-will. This rule formed

the basis for most employment relationships, absent

an explicit contract between the parties, and gave the

employer virtually unlimited authority to terminate

the employment relationship at any time (76).

The doctrine of employment-at-will includes the

right to refuse to hire an individual because of a

perceived physical inability to perform the job (24)

and the right to terminate employment because of a

belief that the employee is no longer able to perform

adequately (67). With respect to genetic monitoring

and screening, this would mean that an employer

could use either in any way, including personnel

decisions. Even if test results were inaccurate or

unreliable, the employer would be protected in

basing employment actions on them.

In recent years courts have begun to erode the

scope of the at-will doctrine by creating exceptions.

While some courts have found contractual obligations that override the doctrine, the more commonly

used exception is based on a tort of wrongful

discharge founded on public policy considerations

(59).
Chapter 6--Legal Considerations . 127

One such case that relied on a public policy

exception to the employment-at-will doctrine has

some relevance for genetic screening (68). The court

held that an employee had a cause of action for

wrongful discharge after he had been terminated for

refusing to take a polygraph test, even though the

State he was employed in, Pennsylvania, has a

statute prohibiting such a requirement. In the absence of a remedy for the employee in the statute, the

court ruled that he could sue under the common law

public policy exception to employment-at-will. It

was found that “Pennsylvania’s anti-polygraph

statute embodies a recognized facet of public

policy” that would give rise to a cause of action for

tortious discharge under Pennsylvania law, if refusal

to take a polygraph test was the basis for the

discharge (68). Under this holding, in a State with a

statute prohibiting the use of genetic monitoring and

screening, an employer would be constrained from

terminating an employee based on refusal to take

such a test. Had a statute on the subject not existed,

however, it is not clear whether the court would have

reached the same decision.

A New Jersey law based on atypical genetic traits,

may create an even broader exception to the at-will

doctrine for personnel actions based on genetic test

results (NJ Stat. Ann. sec. 10:5-5(y)). This law

appears to limit employers in taking any action

including dismissal, based on genetic screening

results that might have a discriminatory impact. A

question might arise, though, concerning the use of

monitoring. Chromosomal damage reflects harm to

genetic material, but is this harm a genetic trait? An

argument can be made that it is not, since the damage

is likely to affect specific cells and not a change in

the individual’s genetic makeup. An inherited trait

would not be at issue. Under this analysis, the New

Jersey statute would not apply to genetic monitoring

results.

Courts may react differently when genetic monitoring and screening results indicate occupational

susceptibilities than when they suggest a higher risk

for a nonoccupational condition. For example,

employees genetically at risk for manic-depressive

illness may never develop the condition. Whether

they do or not may depend on nonoccupational

exposures. In this case, the employer would be

taking a personnel action based on a purely nonwork-related factor. On the other hand, some employers are now excluding smokers on similar

grounds. The ultimate effect on the employee may

be speculative, since the expression of many

genetic traits depends on environmental influences, and their ultimate expression may also be

beyond the employee’s control. This may appear

to some judges to present a more compelling

violation of public policy principles than a personnel action based on work-related health effects.

Even when a nonoccupational medical condition

is present, however, a court may still decline to find

a public policy exception to the at-will doctrine. In

one case (17), a Federal appeals court upheld an

employer’s decision to discharge an employee with

diabetes based on an adverse medical report. It is

possible that many courts will find that employers

have broad discretion to make medical judgments of

the fitness of employees and that reliance on genetic

monitoring and screening for this purpose does not

violate public policy.

The weight of public policy arguments in favor of

exceptions to the at-will doctrine for genetic monitoring and screening findings may also depend on

whether a trait is more common in a specific racial

or ethnic group. Exclusion based on such a trait

raises issues under Title VII, since it could amount,

in practice, to racial or ethnic discrimination. If a

public employer were involved, this kind of exclusion could directly raise issues of equal protection

under the Constitution. Because of the constitutional

issues and profound public policy concerns raised by

racial or ethnic discrimination, courts may be more

likely to find a public policy exception to the at-will

doctrine when genetic monitoring and screening

touches on questions of discrimination.

Uses of Genetic Monitoring and Screening

Data in Other Employment Actions

While exceptions to employment-at-will have

grown to cover different grounds for dismissal, they

have not been applied to other kinds of employment

actions. Employers have few common law constraints in taking other actions, such as hiring,

promotion, and placement. It has been observed that

in the absence of a statutory protection, ‘monumental changes in the at-will doctrine will be required

before anything even approaching a good-cause

standard can be applied to an employer hiring

decision or promotion, transfer, work assignment, or

other related matters’ (76). In these other areas,

OSHA regulations--e.g., the medical removal and
128 ● Genetic Monitoring and Screening in the Workplace

rate retention rules for various hazardous substances, and statutes, including Title VII and the

Rehabilitation Act—provide the only existing constraints on employer use of genetic monitoring and

screening for personnel decisions.

It should be noted that Title VII may provide

substantial limits on employer actions. In one case

(103), the court considered the defendant’s practice

of excluding fertile women from certain jobs involving exposure to hazardous chemicals. The plaintiff

claimed that this violated Title VII as discriminatory, and the defendant asserted that it was necessary

to protect future offspring. The court placed a heavy

burden on the defendant to justify the practice and

ruled that it must demonstrate a business necessity

for the practice by showing that within the scientific

community there is sufficient opinion that female

workers face a significant risk. Moreover, plaintiffs

can rebut this defense by demonstrating that there

are alternative employment practices available that

would accomplish the same protection with a lesser

differential impact. While a further discussion of the

role of this case in extending Title VII protection to

nontermination employment actions is beyond the

scope of this chapter, it can be observed that Title

VII can place significant constraints on health and

safety employment practices that have a discriminatory impact (8). In a recent case (90), the Ninth

Circuit upheld the employer’s fetal protection policy. The case is pending before the Supreme Court.

Common Law Right to a Safe Workplace

As discussed earlier, employees have a right to a

safe workplace under common law, as well as under

the OSH Act. The obligation to provide such a

workplace may be affected by the availability of

genetic monitoring and screening data. It might be

argued that the obligation to provide a safe

workplace has been met if the workplace contains

only employees who have met reasonable genetic

standards. An employer might contend that a safe

workplace has been provided, if, absent other

safeguards, all of the workers have been screened

and found not to be susceptible to workplace

chemicals. It may be impossible, however, to show

that no risk remains for the workers who are not

susceptible to workplace chemicals. As one commentator points out, even if the most susceptible

workers are removed from the workplace, the

remaining workers may also face a serious risk (85).

According to one employer, perhaps the best

approach is to improve the OSHA requirements for

disclosure of workplace hazards to give current

employees the opportunity to receive regular voluntary monitoring, to provide the information only to

employees, and to allow the employees to make an

informed decision about whether to accept new

employment or continue working in an area where

principles of assumption of the risk would reduce

employer liability (assuming knowing and intelligent waivers are made by employees who have

access to the information needed to make a responsible decision). Since employers are currently obligated to provide a workplace free from recognized

hazards, employer liability should not be diminished

by genetic monitoring, nor should employer responsibility be reduced merely because the employer’s

workforce has been monitored, and those individu-
Chapter 6-Legal Considerations . 129

als with genetic susceptibility eliminated from the

workforce population (48).

The effects of genetic test data on the duty to

provide a safe workplace are subject to considerable

speculation, but a few observations can be made. As

discussed, there appear to be few common law limits

on an employer’s right to use preemployment

screening and to make hiring decisions at will. Even

under the Rehabilitation Act or ADA, an employer

can refuse to hire a handicapped individual when a

legitimate business qualification is involved. If

genetically susceptible job applicants can be

screened out, employers may have an easier task of

creating a safe workplace.

With regard to monitoring, though, the duty may

be increased. If sophisticated new tests become

available to detect preclinical harm, then unsafe

workplaces could become easier to identify. Furthermore, employers may have a duty to use any

reasonable test to ensure workplace safety. However, one commentator has pointed out that even if

a common law duty existed, employees may not

have any remedy (73). As with other legal issues

discussed, workers, unlike job applicants, have legal

protections and may see benefits from genetic

monitoring and screening.

Right of Employee To Know Monitoring and

Screening Results

Whether or not genetic monitoring and screening

results are communicated to employers or to others,

employees have an interest in knowing what they

are. An employee, for example, may wish to take

personal health precautions based on the results or

may choose to decline employment that is revealed

to be hazardous. An employee may use the results as

the basis for a legal action, or may have a general

interest in knowing information that may have

personal significance. There are several sources of

law available to compel such access.

First, there is the OSHA access to medical records

rule, discussed above. This regulation is broad in

scope, going beyond records maintained under

specific OSHA toxic exposure standards, but only

when exposure to certain substances occurs. Employees are also protected by common law obligations of physicians and employers concerning

known hazards. Physicians have a duty to inform

patients (but not necessarily applicants or employees) of diseases that are discovered (74). Massachusetts has a statute that requires an employee to be

provided a copy of the medical report for employerrequired exams (Mass. Ann. Laws ch. 149, sec. 19A

(1976)). Several cases have found company physicians liable for failing to detect or to inform

employees of illnesses such as lung cancer (12),

Hodgkins disease (13), and tuberculosis (102).

Beyond medical information on an individual

basis, employers have obligations to inform workers

about workplace hazards. The obligation created by

the OSHA hazard communication standard has

already been discussed. Employers also have a

common law obligation to provide safe working

conditions (32). This includes a duty to warn about

hidden dangers. In a California case, the court held

that while an employer does not have a duty to

discover whether an employee is fit for work, if the

employer assumes this task, the employer is liable if

it is performed negligently (21). This case could

have clear implications for genetic screening.

Should an employer decide to use a screening

program, whether through the use of genetic or

conventional tests, the employer must meet a

reasonable standard of care. It may be the case that

if the employer assigns an employee to a job for

which the employee is genetically unfit, liability

could ensue especially if the employee is never

informed of the screening results.

The duty of physicians to inform patients of

medical findings applies to job applicants as well as

employees. The physician’s professional responsibility in this regard is to protect the patient’s health,

regardless of employment considerations. The duty

of employers to warn of workplace hazards, however, would not protect job applicants. If not hired,

the screening subject cannot claim a need to know

about hazards in the workplace. Subjects might want

to know their test results, but absent a clear

contractual understanding, they would have no

rights in this regard.

Right of Employee To Refuse Genetic

Monitoring and Screening

If monitoring and screening are performed in

response to an OSHA standard, the employee is free

to decline the test. The OSH Act does not give

OSHA the authority to require employees to submit

to medical examinations (OSH Act 6(b)(7); 29

U.S.C. 656(b)(7) (1976)). OSHA's regulations do

not require employees to be tested against their will
130 . Genetic Monitoring and Screening in the Workplace

or provide sanctions against employees who refuse

testing. The rights of workers in relation to their

employers regarding employer-instigated genetic

monitoring or screening programs, however, are less

clear. Several arbitrators have held that employers

can require employees to take medical examinations

as a condition of employment to enable the employers to meet safe and healthful workplace maintenance obligations (15).

If they wish to be hired, job applicants probably

have few, if any, rights to decline. Their primary

legal rights would be based either on Title VII of the

Civil Rights Act of 1964 (42 U.S.C. 200e) (53) by

asserting that the tests were discriminatory or on the

Rehabilitation Act of 1973 or ADA by asserting that

the tests were not job-related. Beyond that, there is

no common law right to be considered for employment after refusing to submit to a preemployment

qualification.

Applicants for public employment, as well as

public employees, may have a remedy in the

protection of the Fourth Amendment to the Constitution against unreasonable searches and seizures (58).

While not every medical test is necessarily a search

and seizure, the Supreme Court has held that taking

a blood sample can constitute an unreasonable

search (80). A number of cases limiting employer

testing rights have relied on the obligation of

government bodies to provide this protection (84).

The reasoning in this case could be extended to

tests for markers of genetic diseases since the

analysis of blood for genetic conditions could easily

be analogous to the analysis of urine for traces of

specific substances. This analysis could be upheld,

if a government employer had a compelling need for

the information, if the testing were done only once

and with warning, and if the employee knowingly

submitted to the testing in order to be transferred to

a new job. A key question would clearly be what

constitutes a compelling need for the information.

An agency might argue, for example, that it needs to

know whether an applicant for a job involving

access to sensitive or secret information might

develop a psychological condition, e.g., schizophrenia or manic-depressive illness, that would compromise the applicant’s trustworthiness. It might also

claim that knowing an employee’s susceptibility to

toxic exposures was needed to ensure protection

from a job involving such exposures. Given the

apparent willingness of many courts to permit

government drug testing in the face of acknowledged constitutional concerns, it may be possible

that these arguments could prevail for a genetic

monitoring or screening program that involved a

government job found to be sensitive enough.

A medical test to which the employee does not

consent, then, can be a search if it is performed by the

government. As a result, medical tests by public

employers can only be performed on reasonable

grounds and only with the subject’s consent.

There are at least two situations in which this

protection may extend to private employers (52).

The first is when an employer’s activities are closely

intertwined with the government so that a government entity reserves the right to hire, promote,

terminate, or reinstate employees. The second is

when testing is government-mandated. It seems

unlikely that an indirect government connection of

a private employer (e.g., conducting governmentmandated medical tests or receiving government

funds) would be sufficient to establish government

involvement in a genetic monitoring or screening

program that would trigger constitutional protections against unreasonable searches and seizures.

An employee’s only reliable recourse in asserting

a right to refuse genetic monitoring or screening

would be found in statutes that specifically prohibit

use of such tests or related information for employment purposes. Three States—Florida, Louisiana,

and North Carolina-have laws prohibiting discrimination based on sickle cell trait. A refusal to submit

to a test for this trait would likely be upheld on public

policy grounds.

Of particular interest is the New Jersey law

discussed earlier banning discrimination based on

any “atypical heredity, cellular or blood trait” (NJ

Stat. Ann. sec. 10:5-5(y)). Such traits include sickle

cell and Tay-Sachs. An employee could argue that

this legislation forbids use of the results of genetic

screening for employment decisions, so an employer

may not require that genetic tests be administered as

a condition of employment. In States without such

laws, employees refusing to take genetic screening

tests must look to other legal authorities for protection against dismissal.
Chapter 6--Legal Considerations . 131

Liability of Employer for Inaccurate

Monitoring and Screening Results

As discussed, physicians may face malpractice

liability for producing inaccurate genetic monitoring

and screening results. Physicians may also face

actions for libel if they disclose incorrect information about testing subjects. Another form of liability

may exist if employers use inaccurate test results in

making employment decisions.

It is unclear whether such a claim would succeed,

unless the use of genetic information was already

established to be against a State’s public policy.

With respect to other employment decisions, the

common law offers little recourse. Job applicants

would have even less in the way of legal protection.

The employee’s primary recourse would appear to

be against the physician or other health professional

administering the test for malpractice or libel.

The accuracy of test results is an area that may

need further legal attention. Most discussions of

genetic monitoring and screening have focused on

the individual who is found to be genetically

vulnerable. Different problems may arise for the

individual who is incorrectly thought to be vulnerable but who is, in fact, not. Box 6-C illustrates some

specific claims that might be available to employees.

Of equal concern are the false negatives, the

individuals for whom genetic tests show an ability to

withstand exposure to a toxic substance but who are

actually susceptible to it. Based on genetic test

results, these workers may be placed in contact with

hazardous chemicals with which they would not

otherwise wish to work. Their legal remedy would

most likely be against the test administrator for

malpractice and against the employer for negligent

supervision of the test administration. These workers would, of course, be able to collect workers’

compensation for their harm, but in some States this

might not be a substantial recovery.

Workers with false negative test results are not

directly protected by other sources of law. They

would have access to their medical records under the

OSHA rules, but they would likely have no reason

to examine them for errors. The employer, moreover, may have fully complied with applicable

OSHA testing standards. All medical tests leave

some chance for mistaken results, even when

properly administered. If there is a regular practice

of producing incorrect test results, the employer

might face liability for malpractice constituting

gross negligence or for failure to provide a safe

workplace. Isolated instances of inaccuracy, though,

might be well within accepted testing standards.

Additional legal remedies in this area may be needed

(92).

JUDICIAL USES OF GENETIC

MONITORING AND

SCREENING DATA

Use of Genetic Monitoring and Screening

Data in Civil Liability Proceedings: Nature of

Civil Suits for Workplace Injury

One kind of civil suit related to genetic monitoring and screening has already been discussed. These

are suits against physicians and others administering

tests for inaccurate test results. These actions may be

based on claims of malpractice or libel. The most

profound effect of genetic monitoring and screening

on civil liability, however, is likely to be on suits for

harm from occupational diseases.

Direct tort actions against employers for

workplace injuries are barred in every State by

provisions in workers’ compensation laws making

them the exclusive remedy for workplace harm (49).

In return for the right to this simpler form of

compensation, workers’ compensation laws prohibit

employees from bringing actions for civil claims

directly against their employers. Two routes around

this ban are available. The frost is to use one of the

limited exceptions to the prohibition that are available inmost States, as will be discussed. The second

is to sue a third-party, such as a manufacturer who

supplied a product that caused or contributed to the

harm.

Third-party suits for toxic workplace harm have

often relied on a claim that a defendant failed to warn

of its product’s hazardous properties. A court

permitted such a suit against an asbestos manufacturer based on the defendant’s knowledge and

concealment of the dangers of asbestos (16). The

lack of an adequate warning was seen in this case to

make the product unreasonably dangerous.

Genetic Monitoring and Screening Data as

Evidence in Occupational Disease Suits

Genetic monitoring and screening data may serve

much the same role in tort suits for occupational
132 ● Genetic Monitoring and Screening in the Workplace

I

Box 6-C-Liability Issues

Inaccurate genetic monitoring and screening can lead to a variety of claims for injury beyond those for adverse

employment actions:

● Emotional Distress—If an employee tests positive for a genetic defect, but the test result is incorrect, the

resulting mental distress may be compensable. Such distress may be considered to be foreseeable to a

physician and an employer. A physician in a New York case was held liable for erroneously informing a

patient that she had tuberculosis, resulting in tuberculosis phobia In a New Jersey case, a court awarded

damages for emotional distress in the context of exposure t o toxic substances. A false or erroneous test result

may trigger anxiety or phobic reactions with debilitating effects on a patient, rendering the employer liable.

The primary issue here is whether the exclusivity provisions of workers’ compensation laws will bar such

suits.

● Failure to Counsel--If a monitoring or screening result is accurate and the employee-patient is positive for

a genetic ailment, and the employee-patient is notified a cause of action may still exist for the distress caused

by the news. A duty may exist to provide both pretest and posttest counseling, since otherwise the

employee-patient is not prepared to handle the news of positivity. Such a failure is likely to be viewed as

intentional, so that a worker may be able to sue in spite of worker’s compensation.

● Failure to Diagnose-If the monitoring or screening is positive but the employee is not fully notified of

either the results or their full implications, then a diagnosis may be missed that could have led to positive

medical intervention. The courts’ reactions in such a situation have been quite consistent: compensation has

been awarded for any mental distress and psychic injury suffered by the patient, and also for the “loss of

a chance’ of treatment because of the missed diagnosis.

SOURCES: Office of Technology Assessment, 1990, based on Barry R. Furrow, Widener University, Wilmington, DE, personal

comm unication March 1990; Ayers v. Township of Jackson, 106 NJ. 557, 525 A.2d 287 (1987); Kraus v. Spielberg, 37 Mis. 2d

29,236 N.Y.S.2d 143 (1%2); R.L. Willmore, “In Fear of Cancerphobia” Toxics Law Reporter 3(18):559-565, 1988.

diseases as in workers’ compensation claims. The studies, the plaintiff would have a much easier time

data can provide a crucial link in the causal chain

between exposure to a harmful substance and

manifestation of illness (30). Screening data can

show that the worker was susceptible to the substance before exposure began. Monitoring data can

show that biological harm developed as exposure

progressed.

The issue of scientific uncertainty on causation

has been an important one in much toxic tort

litigation (14). In the litigation over the health

effects of Agent Orange on Vietnam veterans, for

example, the court considered the lack of scientific

certainty concerning the consequences of exposure

to this substance in approving the settlement of a

product liability class action case (43). Similarly,

another court (3) struggled with the issue of probability of causation in awarding compensation to

some plaintiffs exposed to radiation from a nuclear

test. Similar issues have arisen in many other cases

involving allegations of toxic harm (14,22,35). If a

plaintiff in such a case were able to document a link

between individual injury and a toxic exposure,

rather than relying on epidemiologica1 or animal

demonstrating causation.

Genetic monitoring and screening data might also

help workers to use the two exceptions to the

exclusivity of the workers’ compensation remedy

described above. If an employer compiles test data

showing that injury has resulted, the employer may

have an obligation to reveal it to the worker (46).

Failure to do so may result in liability to direct suit

for intentionally concealing a hazard.

If the employer conducts the tests, the employer

may be functioning in a dual capacity (76). Any

negligence in test administration could then subject

the employer to direct suit. This could include

liability for harm from administration of the test

itself, for negligently obtaining and using incorrect

results, or for misusing correct results. Such suits

could include those for malpractice (25) and libel

described earlier.

New Kinds of Claims Based on Genetic

Monitoring and Screening Data

It is possible that the act of conducting genetic

monitoring and screening will create new responsi-
Chapter 6--Legal Considerations ● 133

bilities for employers that result in new liabilities

(65). Specifically, employers may be held to have a

duty to take protective measures when medical harm

is found. Failure to disclose positive medical results

was one basis for finding intentional concealment of

a workplace hazard (46). In an earlier case (45), a

court found a specific duty of an employer to

disclose to an employee a disease condition found in

the course of a medical examination and to refrain

from assigning him work that would aggravate the

condition.

Employers performing genetic monitoring and

screening may have an obligation to use the results

for worker protection. By gaining information that

creates the option of excluding susceptible workers

through genetic screening, they may also take on a

duty to exclude them. Similarly, by using genetic

monitoring, employers may create a duty as well as

an option to remove workers who show signs of

toxic harm.

This could put employers who use genetic monitoring and screening in a double bind. They face

constraints in using test results for hiring, firing, and

other personnel decisions based on civil rights

legislation, handicapped protection legislation, and

exceptions to the at-will doctrine. At the same time,

they also face constraints in not using the results

when risks to individual workers are found. Additionally, genetic monitoring and screening results, as

discussed, could make it easier for employees to file

suits against employers for occupational diseases.

The threat of these new liabilities could deter many

employers from using the tests.

SUMMARY AND CONCLUSIONS

The real dilemma posed by emerging technologies for genetic monitoring and screening lies in

their dual nature. They may prove to be invaluable

tools for preventive medicine, keeping vulnerable

workers from jobs that are almost certain to cause

them harm, and identifying those in need of medical

attention before serious illnesses develop. On the

other hand, they may present a means for discrimination against workers who, through no fault of their

own, are susceptible to the toxic effects of workplace

chemicals. The likely role of the legal system in

regulating these technologies, therefore, will not be

straightforward.

The legal system will also face a challenge in

making decisions in light of scientific uncertainty.

No medical test is perfectly accurate, and genetic

monitoring and screening are unlikely to be exceptions. Some healthy workers will undoubtedly be

screened out of jobs that would cause them no harm,

and some susceptible workers will likely gain

inaccurate reassurance. Who should bear responsibility for such uncertainty no one can control?

The contribution that will be made by several

important sources of law have been discussed. The

exact role of each will depend on the nature of the

tests that are developed and their application. While

it is clear that many legal tools presently exist, it is

probable that new ones will be needed as unexpected

challenges arise.

Over the past several years, changes directly

affecting the law in this area have been modest,

perhaps because genetic monitoring and screening

technologies have yet to see wide application. Two

changes, however, stand out. The most important

has been the statutes passed in a few States limiting

the use of genetic information in employment

decisions. In three of these States—Florida,

Louisiana, and North Carolina-the laws are specific to testing for sickle cell trait. In New Jersey,

though, a fairly broad measure was passed banning

employment discrimination based on genetic traits.

If this measure becomes a model for other jurisdictions, the adverse impact of genetic monitoring and

screening results on employees and perhaps benefits, too, could be severely curtailed. The New Jersey

experience will be interesting to observe as more

genetic monitoring and screening tests become

available.

The second important change is the proliferation

of right-to-know laws at both the State and Federal

levels. Primary among these in terms of its likely

effect on genetic monitoring and screening is the

OSHA hazard communication standard. This rule

requires that employees be given access to considerable information on the toxic chemicals with which

they work. It also gives employers broad discretion

in deciding whether or not to use genetic data in

determining the extent of a hazard. The degree to

which genetic findings are used by employers to

define hazards and by employees to make requests

for information may provide an early indication of

the role that genetic data will play in workplace

safety activities.

Other workplace right-to-know provisions include the OSHA access to medical records rule, the
134 . Genetic Monitoring and Screening in the Workplace

chemical labeling provisions of TSCA and Title III

of SARA. Congress recently gave consideration to

the High Risk Occupational Disease Notification

and Prevention Act of 1987, which would have

required access to information, including mandatory

notification, for large numbers of workers exposed

to toxic chemicals.

The recently enacted ADA—which extends a

clear and comprehensive prohibition of discrimination on the basis of disabilities to the private

sector-could potentially have considerable impact

on the use of genetic monitoring and screening in the

workplace. While the law protects individuals considered to have certain physical or mental impairments, it is unclear whether individuals having a

marker or trait for a genetic condition would also be

covered. As to whether it permits or prohibits

genetic monitoring and screening, ADA prohibits

preemployment medical examinations or inquiries

designed to uncover information about disabilities

unless they are intended to reveal the applicant’s

ability to perform job-related tasks. Thus, such a

requirement would seem to preclude measures

aimed at weeding out individuals having certain

genetic characteristics.

Changes in the common law relating to workplace

genetic monitoring and screening have been incremental over recent years. An increasing body of case

law is developing, however, over employer screening for drug use and AIDS. It is likely that

developments regarding privacy, confidentiality,

and the right of employers to make employment

decisions based on test results will continue to be

rapid in these areas and will form the basis for court

cases regarding genetic monitoring and screening.

Of particular interest in terms of common law

developments is the apparent continuing expansion

of the public policy exception to the at-will doctrine.

This trend may also play an important role in

forming judicial attitudes toward employment decisions based on genetic monitoring and screening test

results.

On the whole, it appears that Federal regulatory

law as administered by OSHA is likely to have the

most immediate impact on the use of workplace

genetic monitoring and screening. OSHA has already addressed this area to a very limited and

unspecific extent. It has also dealt extensively with

related practices of biological monitoring and

screening that will form a ready source of rules for

genetic monitoring and screening. OSHA’s rules on

access to medical records and hazard communication are among the most directly applicable sources

of existing law.

There is a need, however, to better anticipate the

impact that genetic monitoring and screening technologies will have on occupational safety and health

practices. As the primary authority in this area,

OSHA would seem to be the most appropriate

candidate for this role. In facing this issue, moreover, OSHA can draw upon the resources of NIOSH.

NIOSH is charged with providing research and

recommendations for OSHA regulatory development, and it is a well-respected source of these

clinical and legal issues that workplace genetic

monitoring and screening will present. Guidance

from these agencies as technologies develop can

serve a needed role in steering other sources of law,

both judicial and legislative, through the challenges

that

1.

2.

3.

4.

5.

6.

7.

8.

9.

10.

11.

12.

13.

14.

genetic monitoring and screening will present.

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85. Sweltz, E.L., “Genetic Testing in the Workplace:

An Analysis of the hgal Implications,” Forum

19:323-332, 1984.

86. Taft Broadcasting Co., 163 NLRB 475 (1967),

enforced 395 F.2d 622 (D.C. Cir. 1968).

87. Tarasoffv. Regents of the University of California,

17 Cal.3d 425,551 P,2d 334 (1976).

88. Teamsters, Local 692 (Great Western Unifreight

System), 209 NLRB 446,447448 (1974).

89. Trigg, H. S., E.I. du Pent de Nemours & Co.,

Wilmington, DE, personal communication, March

1990.

90. UnitedAuto Workersv. Johnson Controls, Inc., 886

F.2d 871 (7th Cti. 1989).

91. U.S. Congress, Library of Congress, Congressional

Research Service, Comparative Analysis of Title VII

of the 1964 Civil Rights Act, the Age Discrimination

in Employment Act, and the Rehabilitation Act of

1973, Dale, C.V., 89-240A (Washington, DC: Apr.

11, 1989).

92. U.S. Congress, OffIce of Technology Assessment,

Medical Testing and Health Insurance, OTA-H384 (Washington, DC: U.S. Government Printing

Office, August 1988).

93. United Steel Workers v. American Manufacturing

Co., 363 U.S. 564 (1960).

94. United Steel Workers v. Enterprise Wheel & Car

Corp., 363 U.S. 593 (1%0).

95. United Steel Workersv. Warrior & GulfNavigation

Co., 363 U.S. 574 (1960).

96. Wards Cove Packing v. Atonio, 109 S. Ct. 2115

(1989).

97. Whalen v. Roe, 429 U.S. 589,589-600 (1977).

98. Wigmore, Evidence, section 2380 at 818-819 (McNaughton rev. 1%1).

99. Williams, J.F., “Regulatory Model for Genetic

Testing in Employment,” Oklahoma Law Review

40:181-208, 1987.

100. Williams Pipe Line Co., 78 L.A. 617 (Moore 1982).

101. Williams v. State, 65 Okla. Crim. 336, 86P.2d 1015

(1939).

102. Wojcik v. Aluminum Co. of America, 18 M.isc.2d

183, 183 N. YS.2d 351 (1959).

103. Wrightv. Olin Corp.,697F.2d 1172(4th Cir. 1982).
Ethical

Chapter 7

Issues
CONTENTS

Page

ETHICAL DIFFERENCES BETWEEN GENETIC MONITORING AND

SCREENING . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 140

MORAL CONSIDERATIONS FOR WORKERS AND EMPLOYERS . . . . . . . . . . . . . . 141

The Decision To undergo Genetic Monitoring or Screening . . . . . . . . . . . . . . . . . . . . . . . 142

Access to Information Gained From Genetic Monitoring and Screening . . . . . . . . . . 143

The Communication and Interpretation of Test Results . . . . . , . . . . , . . . . . . . . . . . ‘. . . . . 143

ADDITIONAL CONSIDERATIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 145

Reducing the Incidence of Occupational Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 145

Protecting Privacy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 146

Fair Treatment of Individuals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 147

Economic Efficiency and Competitiveness . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 147

CRITERIA FOR WORKPLACE GENETIC MONITORING AND

SCREENING PROGRAMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 147

HOW MAY GENETIC MONITORING AND SCREENING RESULTS BE

USED TO PROTECT WORKER HEALTH? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 151

SUMMARY AND CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 153

CHAPTER PREFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 154

r

Boxes

Box Page

7-A. The Social Value of Work . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . 142

7-B. An International Survey of Attitudes of Medical Geneticists Toward

Workplace Genetic Screening and Access to Results . . . . . . . . . . . . . . . . . . . . . . . . . . 144

7-C. Sex Discrimination and Fetal Protection Policies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 148

7-D. Using Workplace Genetic Screening as Power . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 149

7-E. Protection of Others: A Case for Workplace Screening? . . . . . . . . . . . . . . . . . . . . . . . 152
Chapter 7

Ethical Issues

The benefits of genetic monitoring and screening

in the workplace lie in their potential to provide

reliable, long-range predictions about the health

risks that employees and job applicants face. These

predictions could benefit employees, job applicants,

and employers by allowing workers to avoid situations likely to cause illness, thereby maintaining

their productivity and defraying health care costs.

However, the workplace acquisition and use of this

predictive knowledge raise important ethical questions. Under what circumstances, if any, could

genetic monitoring and screening programs be

required of employees or job applicants? Who

should have access to test results? To what purposes

may such knowledge be applied?

The rights and responsibilities of individual

employees, job applicants, employers, and society in

such programs are not clearly defined. Several

values embedded in U.S. culture conflict with each

other as a result of genetic monitoring and screening:

autonomy of employees, job applicants, and employers; privacy and confidentiality of medical

information; rights to a safe workplace; fairness and

equality of opportunity; and efficiency in the

workplace and industrial competition.

Ethical and legal issues surrounding genetic

monitoring and screening in the workplace share

common ground. Legal and ethical arguments often

express common concerns and in some instances use

common language. Several laws discussed in chapter 6 confer rights or responsibilities to various

parties or identify and promote moral values shared

by society. For example, the Occupational Safety

and Health Act (OSH Act) (Public Law 91-596)

protects workers from exposure to toxic substances,

ensures they are provided with information about

occupational health risks, and guarantees employees

access to the results of any medical tests performed

in the workplace. This law could therefore be

interpreted as legal enforcement of a moral obligation to provide a safe work environment and a legal

‘‘right to know’ that reflects the moral value of

respect for autonomy. Similarly, the Americans with

Disabilities Act (ADA) (Public Law 101-336) may

prevent workplace discrimination based on genetic

factors.

The overlap between law and ethics, however, is

limited. Law does not reflect all moral values held by

members of society, nor can it necessarily be used to

resolve ethical dilemmas. Ethical arguments about

the use of genetic monitoring and screening in the

workplace often address obligations, rights or values

not explicitly covered by law, and are used to

express incumbency the law does not acknowledge.

Currently, employers might not be constrained by

existing statutes to always use genetic monitoring

and screening in ways that reinforce human values

or for purposes that are directly related to worker

health protection. Employers could find that performing certain genetic screening tests on workers

provides information useful in limiting workers’

compensation claims or decreasing insurance premiums. These same tests, however, may be a way to

fulfill legal obligations if they provide the only

effective protection for the sensitive worker against

irremedial damage. In this case, ethical and legal

concerns will come into conflict.

The relationship between law and ethics is dynamic. Awareness of the ethical issues surrounding

new technology is essential for formulating and

implementing policies that reflect the greatest possible regard for human values. The formulation of new

public policies often reflects ethical concerns, and

new ethical issues often arise from the implementation or interpretation of law.

Although the ethical issues have not changed

considerably since the Office of Technology Assessment (OTA) studied them in 1983 (17), the emphasis

placed on some concerns about genetic monitoring

and screening has shifted. Increased pessimism is

being expressed in public debate about the risks

genetic screening could have for employees’ autonomy and privacy. Attention has shifted from the

uncertain technical efficacy of genetic monitoring

and screening in predicting or identifying illness to

the potential abuses of genetic monitoring and

screening in the workplace. In 1983, genetic monitoring and screening were perceived to be ethically

justified to the extent they would enhance worker

health in a reamer consistent with established moral

principles. Considerable concern that these principles cannot be upheld has developed since that time.

–139–
140 . Genetic Monitoring and Screening in the Workplace

Because current U.S. law does not address these

ethical considerations, they are discussed in this

chapter.

For the most part, the ethical issues surrounding

genetic monitoring and screening involve concerns

about the social rules for and the implications of

their use, not the intrinsic properties of the technologies themselves. Two kinds of ethical concerns are

discussed in this chapter: problems that arise as

testing procedures create moral dilemmas for one or

another party, and possible problems that could stem

from the misuse of test results (3). The former type

of concern stems from the uncertain roles of the

various parties involved in testing programs, and

from the fact that not all current genetic monitoring

or screening tests developed are indisputably valid

means of determiningg either genetically determined

traits for illness or chromosomal damage (see chs. 4

and 5).

This chapter presents ethical issues raised by

genetic monitoring and screening based on the

perspectives of employees, job applicants, employers, and society. These perspectives describe possible considerations from each point of view, and will

address the overall questions: Should genetic monitoring and screening be performed in the workplace?

Should the tests be used in employment decisions?

May these tests be used to deny access to jobs? How

might potential policies affect employees, job applicants, employers, or society?

In discussing the interests of job applicants,

workers and employers, three principal issues exist:

the implementation of genetic monitoring and

screening tests in the workplace and the use of

the information they generate,

the dissemination and storage of information

gained from genetic monitoring and screening,

and

the role of genetic counseling for both employers and employees in genetic monitoring and

screening programs.

Some ethical issues presented by genetic monitoring and screening in the workplace go beyond the

interests of individual workers and employers to

affect society as a whole. Not all the social issues

discussed in this chapter are strictly ethical: some

have moral significance because they create conflict

among widely held values. For example, both the

health of the workforce and economic competitiveness can be regarded as valued goods that should be

protected, although neither has moral value in itself.

If employers are held responsible for conducting

genetic monitoring or screening to protect the health

of the workforce, some sacrifice could be involved

for both employers and society. Employers could

bear the expense of monitoring and screening and

taking necessary action to protect employees, and

society may sacrifice some economic advantage.

Values such as economic competitiveness will be

included in this discussion because they often affect

decisionmaking and weigh against ethical concerns.

ETHICAL DIFFERENCES

BETWEEN GENETIC

MONITORING AND SCREENING

The ethical issues associated with genetic monitoring and screening in the workplace vary according to whether the test performed is genetic monitoring for chromosomal damage, genetic screening’ for

susceptibilities to occupational illness, or genetic

screening for inherited conditions or traits unrelated

to the workplace.

Genetic monitoring can be effective to the extent

that it detects previously unrecognized hazardous

environments or identifies incipient damage in

exposed workers. This form of surveillance, however, differs from traditional environmental or biological monitoring, as it is intended to detect indirect

evidence of an adverse health effect that could occur

in the future rather than present levels or pathological effects of the hazardous substance itself. Indirect

evidence often limits the utility of genetic monitoring tests, making it unclear how to use the information gained from these tests if its predictive value is

uncertain.

Genetic screening can be used for two purposes in

the workplace. First, as indicated previously, it can

identify genetic susceptibilities to workplace exposures. The same conditions that make genetic

screening effective, however, make these tests

potential threats to workers’ privacy. Information

obtained from genetic screening is likely to be seen

by employees as extremely private, sensitive information. Because genes provide much of the basis of

human individuality, information about a person’s

genes is likely to be seen as intensely private. Since

genetic screening is meant to detect “defects” in

genetic makeup, genetic disease may also carry a

stigma. Genetic screening for workplace susceptibil-
Chapter 7--Ethical Issues ● 141

ities is more controversial than genetic monitoring,

but it maybe ethically justified in some situations.

Genetic screening can also be used by employers

to identify genetic traits or susceptibilities unrelated

to the workplace, but which indicate likelihood of

future disease. Because genetic disease can affect a

company’s productivity or profit in terms of sick

leave taken, workers’ compensation, disability,

early retirement, health and life insurance expenses

(if these are provided by the employer), and liability

for illness and injury, employers might want to know

as much as possible about workers’ genetic makeup.

Genetic screening for traits unrelated to the

workplace is controversial and many find it ethically

inappropriate to conduct these tests in an employment setting.

MORAL CONSIDERATIONS FOR

WORKERS AND EMPLOYERS

To the extent that genetic tests are able to detect

and prevent genetic disease, both workers and

employers could find genetic monitoring or screening in the workplace desirable. From the points of

view of both workers and employers, however,

genetic monitoring and screening raise several moral

considerations.

A worker’s motivation for participating in a

genetic monitoring or screening program would

most likely be self-benefit. While a mandatory

genetic monitoring or screening program might

benefit employees by preventing occupational disease, such a program could also deprive them of fair

treatment or the ability to make free choices.

Workers are likely to want to judge for themselves

what actions serve their benefit and act freely toward

this end. In many cases, workers want to work and

do not want their employment opportunities to be

curtailed (see box 7-A). Workers therefore have an

interest in maximizing their autonomy and thus their

freedom.

For the purposes of this chapter, “autonomy”

refers to the freedom and ability to make choices

concerning one’s own welfare. From the employee’s

perspective, autonomy consists in the liberty to

make free choices about the work he or she performs,

but autonomy also requires information about occupational health and safety risks so that informed

decisions can be made. Autonomy depends on being

able to plan and act deliberately, based on one’s

Photo credit: Dotter

A worker wearing protective clothing.

judgment about the consequences of certain behaviors and their value or utility to oneself or others.

This leads to the notion that individuals should be

free to act as they wish, regardless of how their

actions appear to others and without interference by

others, so long as their actions do not harm or

interfere with the liberty of others. In this light, an

employee might see genetic monitoring or screening

as a way to obtain information necessary to make

informed choices about accepting or remaining in a

job.

At the same time, employers want the freedom to

protect the interests of the company, and genetic

monitoring and screening might benefit employers

by reducing costs. A balance must be struck between

promoting one party’s autonomy and compromising

that of the other. If employers are free to implement

and enforce genetic monitoring or screening policies, the autonomy of employees will be limited.

Conversely, giving the employee complete freedom

to protect his or her own interests would restrict the

freedom of the employer and in some instances

present risk to co-workers or family. Employer and
142 . Genetic Monitoring and Screening in the Workplace

Box 7-A—The Social Value of Work

Most persons find it is in their best interest to work. In most American social, economic, and political thought,

labor tends to be regarded exclusively as an economic activity. Work has many dimensions, however, since it has

always been connected to moral and ethical, as well as economic values. For example, work ties into religious

perspectives, such as Puritanism which is based on a concept of work and faith in continuous tension with each

other. Secular and religious meanings of work are often inseparable.

While the range of feelings about the role and meaning of work in human life is broad, work is typically viewed

as a matter of practical necessity. Work is expected of those who participate in society, and adults who do not work

are often regarded with some suspicion. In the Marxist view, labor determines economic value. On a more personal

level, employment gives an individual dignity which is often reflected in the esteem of professional peers. Whatever

the reason for employment, a number of reasons exist for why a person needs employment: to survive, to fulfill

social expectations, or to maintain self-esteem.

Despite workers’ compelling reasons for obtaining and retaining jobs, in the United States, decisions about

beginning and terminating employment are usually left to employers. Although U.S. laws and moral codes do not

specifically recognize a right to work they do acknowledge strong protectable interests in fair work opportunities

and freedom from occupational injury and illness which might prevent a person from working. Genetic monitoring

and screening present a moral dilemma in that these tests could meet one aim, but violate the other: they could

protect workers from occupational illness but also be used to deny them employment. Different opinions are held

about how to resolve this conflict.

SOURCES: Office of Technology Assessment, 1990, based on F. Battaglia, ‘ ‘Work” Dictionary of the History of Ideas (New York NY: Charles

Scribner’s Sons, 1973); and A.J. Vidich, ‘‘The Morel, Economic, and Political Status of Labor in American Society,’ The

Environment of the Workplace and Human Values, S.W. Samuels (cd.) (New York, NY: Alan R. Liss, Inc., 1986).

employee interests can conflict at three points in the working at a job or take a job in spite of health

processes of genetic monitoring and screening:

● the decision to undergo genetic monitoring or

screening;

. the access to information gained from genetic

monitoring or screening; and

. the communication and interpretation of genetic monitoring or screening results.

The Decision To Undergo Genetic

Monitoring or Screening

Who decides whether an employee or job

applicant undergoes genetic monitoring or

screening?

Given employers’ legal obligations to prevent

harmful workplace exposures and workers’ interests

in acting autonomously, there may be disagreement

about whether employers should be able to require

workers to undergo genetic monitoring or screening.

Some workers will want to undergo genetic monitoring or screening to make informed decisions about

the benefits of any current or potential job (e.g., the

income from having that job) against risks of that job

(e.g., any heightened risk of developing occupational illness). Based on genetic monitoring or

screening results, they could decide to continue

hazards because they feel it is the best option

available to them. Alternatively, they might decide

against working in a hazardous environment, and

seek transfer to another job. Other workers, however, will prefer not to be tested. They might not

want to know psychologically burdensome information, or might choose to work in a job regardless of

health hazards. Any of these choices could be seen

as maximizing autonomy because the worker has

made the decision.

Employers, however, might want to be free to

conduct monitoring or screening programs and

establish the conditions for employee participation

and consequences for those who refuse to participate. Such practice would be consistent with current

preemployment medical testing practices. Employers weigh the benefits (e.g., minimizing the costs of

or liability for occupational disease) against the

costs (e.g., the cost of the monitoring and screening

program).

The degree of conflict between worker and

employer interests varies according to whether a

genetic monitoring or a genetic screening program is

implemented.
Chapter 7--Ethical Issues ● 143

Access to Information Gained From

Genetic Monitoring and Screening

Who should have access to the information

obtained from genetic monitoring or screening?

Are workers entitled to test results? Are employers? Are others?

Because information from genetic monitoring or

screening could provide the first indication that an

individual is at risk for genetic disease, workers need

to know test results in order to take action to protect

their health. Withholding test results deprives the

worker of autonomy by making it impossible for him

or her to make informed choices. Thus an employee

will likely find no reason to undergo genetic

monitoring or screening unless test results are shared

with him or her.

When patients have requested the test, medical

test results are usually given to patients by their

doctors. This tradition should not be taken for

granted, however, if genetic monitoring or screening

are performed in the workplace, especially if tests

are done at the employer’s expense. Unless the

genetic monitoring and screening programs are

established by the employer as part of an employee

wellness program, employers may find no reason to

provide genetic monitoring and screening results to

workers.

Rather than notifying workers, employers might

choose to protect employee interests paternalistically by preventing them from working in unhealthy

environments. While this approach fulfills a responsibility to provide a safe workplace, such action

denies the worker autonomy. Although there may be

no legal compulsion to provide workers with genetic

monitoring or screening results, a moral reason for

doing so probably exists based on a right to

information about one’s own medical condition, an

obligation to respect the autonomy of persons, and

the social benefit of open communication between

persons tested and those who conduct medical tests.

Whatever the explanation, compelling ethical reasons are present to ensure that workers who undergo

genetic monitoring or screening receive test results.

Whether an employer chooses to receive worker

test results depends on the motivations for implementing genetic monitoring or screening programs.

If genetic monitoring or screening is offered as a

health promotion service (e.g., a voluntary sickle

cell screening program), the employer might sponsor such programs without expecting to see the

results. If genetic monitoring or screening is offered

for economic or legal reasons, however, the employer will most likely want to see the results and

may want to retain the information. Indeed, the OSH

Act requires employers to keep medical records on

their employees.

The OSH Act, however, has no specific language

requiring occupational health professionals to protect the confidentiality of those records. Employers

have unrestricted access to them and may, in certain

circumstances, distribute genetic information to

third-parties (10). Thus, employees might not want

genetic monitoring and screening results from voluntary wellness programs to be disseminated to

employers. Employees could feel that all genetic

information should remain confidential under any

circumstance, especially if it might be used to

deprive them of a job, health insurance, or other

benefit (see box 7-B).

The Communication and Interpretation of

Test Results

How should test results be communicated to

workers and employers?

Even if workers receive genetic monitoring and

screening results, using them to make informed

choices could be problematic unless the communication of genetic information is accompanied by

appropriate interpretation. Results from genetic

monitoring and screening need to be placed in

context—unless their significance is properly communicated, there is much room for misunderstanding. Results delivered without adequate or accurate

interpretation could harm workers by causing them

extreme and, in some cases, undue concern about

their health. In other situations, some workers who

are found to be susceptible to workplace exposures

may continue to work in an unhealthy environment

unknowingly if the implications of the test results

are misunderstood. While it is impossible to ensure

that all workers make truly informed decisions,

failure to communicate the results of genetic monitoring and screening tests in a clear, thorough, and

responsible manner curtails employee autonomy by

not enabling workers to make informed choices.

Thus genetic counseling appears necessary for

employees to fully understand the results of genetic

monitoring or screening and to use this knowledge

appropriately. Currently, however, employers are
144 . Genetic Monitoring and Screening in the Workplace

Box 7-B—An International Survey of Attitudes of Medical Geneticists Toward

Workplace Genetic Screening and Access to Results

A survey on mass genetic screening was sent to 1,053 medical geneticists in 18 nations, of

whom 677 responded Geneticists strongly preferred voluntary over mandatory workplace

screening, by a 72 percent majority. In the United States, there was consensus (>75 percent) that

screening should be voluntary. Geneticists who thought screening should be voluntary cited the

worker’s autonomy or right to decide (74 percent), and the danger of stigmatization,

discrimination in employment, or misuse of information by institutional third-parties

(41 percent). Advocates of mandatory screening cited protecting the individual worker’s health

(64 percent), protecting public health (51 percent), and efficiency or cost-benefit arguments

(22 percent). Nine percent of those who advocated voluntary screening and 12 percent of those

who advocated mandatory screening based their responses in part on concern for economic

interests of employers.

In advocating voluntary versus mandatory screening, a clear difference of opinion on whose

welfare the respondent placed foremost was reported. Ninety-sewn percent who advocated

voluntary screening and 58 percent who advocated mandatory screening placed the worker’s

welfare as most important. Three percent who advocated voluntary screening and 37 percent who

believed in mandatory screening placed societal interests first. Only 1 percent placed the

employer’s welfare first.

Advocates of voluntary screening were more likely than supporters of mandatory screening

to describe a conflict of interest between worker and employer; 34 percent described such

conflicts, as opposed to 13 percent who advocated mandatory screening. A majority of both

groups, however, described no conflicts.

Ninety-eight percent of respondents said the worker should have access to test results,

including 86 percent who said the worker should be told the results even if he or she did not ask

for them. When asked whether the employer should have access to genetic screening results, 81

percent said employers should have no access without the worker’s consent, including 22 percent

who believed that employers should have no access at all.

Thirty percent of respondents who gave reasons for their choices about access believed it

would be to the worker’s benefit if the employer had some form of access, e.g., employers could

shift susceptible workers to less dangerous jobs. Only 6 percent of respondents, however, thought

that working conditions in general would be improved. Nineteen percent described potential

economic discrimination, stigmatization, or other misuse of test results by employers. Ten percent

based their responses on the economic interests of the employer.

when asked whether government health departments should have access, 68 percent said

there should be no access without worker consent. There was a strong consensus on this issue in

six nations, including the United States.

These differences in perception indicate that geneticists-those in a position to conduct

genetic screening tests--share concerns about how genetic screening might be used in the

workplace. A large majority of geneticists ranked the interests of workers and society above those

of employers in importance, but they disagree about how these interests can be best protected.

Many geneticists believe that workplace screening should be voluntary and that workers should

make autonomous decisions about whether to undergo genetic screening. Almost all geneticists

believed workers should receive genetic screening results, but that employers’ access should be

restricted. They expressed concern that genetic screening results may be used to justify personnel

actions that may stigmatize or discriminate against some workers.

SOURCE: D.C. Wertz and J.C. Fletcher, “An International Survey of Attitudes of Medical Genetics Toward Mass

Screening and Access to Results,” Public Health Reports 104(1 ):35-44, 1989.
Chapter 7--Ethical Issues ● 145

toring and screening results appears to be of both

moral and economic value to employers.

Photo credit: University of South Carolina School of 

A genetic counselor discussing results with clients.

under no legal obligation to have genetic monitoring

or screening results interpreted for workers by a

qualified genetic counselor. If test results are shared

with employees, the employer might suggest the

worker have them interpreted by a genetic counselor, but is not required to provide one. (See ch. 8

for further discussion of genetic counseling.)

Employers, too, would likely benefit from professional interpretation of genetic monitoring and

screening results, but might see no reason to obtain

a genetic counselor’s interpretation of test results.

An employer might not want or need to know the

exact levels of sensitivity or predictiveness for

individual workers before taking personnel actions

based on genetic tests. The employer could find it

sufficient to rely on aggregate or imprecise data in

making employment decisions without regard for

false positive or false negative results. Although

genetic monitoring and screening are not sensitive or

predictive enough to identify every worker at risk of

genetic disease, employers might still find the

procedures beneficial on a population basis.

Without qualified interpretation of test results,

however, employers might deny individuals jobs

that would never cause them disease. This denial

would then constitute unfair treatment of employees,

and could reduce the efficiency of the workplace--

thereby failing to serve the interests of the employer.

Having a genetic counselor interpret genetic moniADDITIONAL CONSIDERATIONS

A number of factors either promote or violate the

autonomy of workers and employers when ethical

considerations of genetic monitoring and screening

are analyzed. In some cases, genetic monitoring and

screening programs appear to benefit both workers

and employers; other programs likely function to the

detriment of one or both. But genetic monitoring and

screening in the workplace can affect societal

interests as well. Because genetic monitoring and

screening are likely to have impact beyond the

workplace, societal interests must also be balanced

against the interests of various parties.

Reducing the Incidence of

Occupational Disease

Occupational disease might be prevented in three

ways: increasing the safety of the work environment;

identifying workplace-induced genetic changes

early so as to minimize future damage; or removing

susceptible employees from a hazardous environment. Genetic monitoring is intended to address the

second goal; genetic screening the third. Some argue

that the first goal, providing a safe workplace, is the

employer’s responsibility and that the use of genetic

monitoring and screening to remove employees

from high-risk jobs does not release employers from

their obligation to improve the safety of working

conditions.

Under the OSH Act, the employer is responsible

for minimizing the potential for disease or physical

harm in the workplace by providing the safest

possible environment. When removing all risks is

not possible, engineering protections may be required. If employers use genetic screening to identify individuals most likely to be affected by

workplace conditions, they might consider it more

expedient to relocate those workers rather than

remove the hazards. Although ADA precludes

excluding workers from jobs based on genetic

characteristics, its coverage of genetic traits, susceptibilities, or disease is unclear. To minimize the costs

of occupational illness, the most effective prevention could result from a safe workplace, either alone

or in combination with genetic monitoring or

screening.
146 Genetic Monitoring and Screening in the Workplace

Photo Philosophical 

Eugenic and Health Exhibit, Kansas Free Fair, 1929.

Protecting Privacy

Protecting the privacy of workers undergoing

genetic monitoring and screening is important not

only to individuals, but to society as well. By

protecting the privacy of workers and the confidentiality of genetic information, workers who otherwise

would be unwilling to undergo genetic monitoring

or screening in the workplace (even if such tests can

protect their health) might choose to be tested. The

value placed on the confidentiality of medical

information is seen as early as the Hippocratic oath,

and is confirmed in the Patient’s Bill of Rights

adopted by the American Hospital Association in

1973 and other principles and codes of medical

ethics (2). The value society places on confidentiality is also seen in other contexts, such as the careful

protection traditionally given to the records of

adopted children.

Although a number of medical organizations have

dealt with the issue of protecting patients’ confidentiality in their codes of medical ethics (e.g., American Medical Association, World Medical Association), different views exist about whether medical

procedures performed in the workplace are subject

to the same constraints. Occupational health professionals might not consider the worker as a patient

and thus not see obligations to workers being ‘‘as

comprehensive or as stringent as the responsibilities

that apply in a typical physician-patient relationship” (2). While law does not prevent workplace
Chapter 7-Ethical Issues ● 147

physicians from notifying employers of employees’

medical conditions, the American College of Occupational Medicine’s Code of Medical Ethics emphasizes the importance of confidentiality of employees’ medical information (see ch. 6). Similar viewpoints have been expressed by other groups (5),

indicating a general interest in protecting the privacy

of individuals and the confidentiality of medical

information regardless of where it is obtained.

Society probably also has an interest in allowing

employers access to genetic monitoring and screening results. If employers are prevented from examining results, they may unknowingly hire or retain

workers who have genetic susceptibilities to

workplace risk, which could eventually increase the

costs of occupational illness to society. It could be

argued that, if all medical testing results must remain

confidential, genetic monitoring and screening in the

workplace should not be considered medical testing

or that these results should be considered an

exception to the confidentiality rule.

No clear answer exists to whether a privacy right

overrides the risk that might be presented to society

in maintaining confidentiality of workplace test

results. Currently, the matter is often resolved

according to who requests or pays for the tests: when

the employer pays for the test, the employer receives

the results.

Fair Treatment of Individuals

Certain legislation expresses the societal belief

that nondiscrimination promotes general well-being

(see ch. 6). Title VII of the Civil Rights Act, for

instance, states that denying jobs to qualified individuals for race, sex, or disability is prohibited (see

box 7-C). Since a person’s genetic endowment,

whether or not it causes an obvious disability, is also

beyond individual control, it might be unfair,

although not expressly illegal, to use the results of

genetic monitoring or screening as the basis for

hiring and firing decisions. Some believe existing

law does not protect workers from discrimination on

the basis of genetic endowment. It might be appropriate to explicitly include genetic susceptibilities

and traits among the conditions listed in Title VII or

ADA (see ch. 6) if it is found that employers use the

results of genetic monitoring or screening to stigmatize certain workers for genetic traits.

Some question whether the results of genetic

monitoring and screening tests should be used as a

basis for hiring or retention decisions if they show

that members of certain racial, ethnic, or gender

groups are more likely to be susceptible or potentially susceptible. It is not clear whether genetic

monitoring or screening would be a socially acceptable means of reducing occupational illness regardless of its impact on such groups, or whether such

testing would provide a means of justifying discrimination against such groups. Decisions to hire or fire

members of racial, ethnic, or gender groups that

already struggle for equality in the workplace, on the

basis of the results of genetic monitoring and

screening might be interpreted as discrimination

(See box 7-D).

Economic Efficiency and Competitiveness

Capitalist economy depends on competition. One

of the variables that determines successor failure for

a business is management style, including hiring and

firing policies and overall treatment of employees.

Apart from preventing blatant discrimination in

hiring practices, the law has largely left employers

free to make decisions in this regard. This freedom

is generally viewed as serving a societal interest by

promoting economic efficiency and productivity

within companies and competitive markets (9).

CRITERIA FOR WORKPLACE

GENETIC MONITORING AND

SCREENING PROGRAMS

Under ideal circumstances, genetic monitoring

and screening could benefit workers, employers, and

society by improving the health of the workforce.

Workers would gain maximal information about

risks of mutagenicity through genetic monitoring

and screening and would be provided with protective measures or reasonable work alternatives when

test results indicate such action is necessary. Employers would benefit by reducing the costs of

occupational illness and increasing productivity.

To protect the interests of all parties two factors

are necessary: a mechanism for deciding when it is

appropriate to use genetic monitoring and screening

in the workplace, and guidelines for how these

results are to be applied. No guarantee exists that

genetic monitoring or screening will be used to

reduce occupational illness or that such testing will

be conducted in an ethical manner. Therefore,

guidelines for the use of genetic monitoring and

screening in the workplace have been proposed.
148 . Genetic Monitoring and Screening in the Workplace

Box 7-C-Sex Discrimination and Fetal Protection Policies

Some companies have fetal protection policies (FPPs) that deny women of childbearing age jobs to prevent

harmful exposures to developing or future fetuses. Recently, several of these policies have been challenged, and

courts have found that an FPP that applies only to women constitutes sex discrimination.

Because battery production involves exposure to lead (a known hazard to fetal development), Johnson

Controls, Inc. has an FPP. Its policy denies all battery production jobs to women of childbearing age who lack

medical evidence of infertility except those fertile women who prove they can keep their blood lead level below

a specific minimum level.

Until 1982, Johnson Controls had a voluntary FPP that informed workers of the potential risks of lead exposure

to fetal health during pregnancy and encouraged female workers to consult their doctors. The company based its

voluntary policy on its view that fetal protection ‘‘is the immediate and direct responsibility of the prospective

parents . . . [it would] appear to be illegal discrimination ” to have an FPP that treated all fertile female employees

‘‘as though they will become pregnant.’ The company found that the voluntary policy was ineffective because

women refused to leave jobs which threatened exposure to hazadous amounts of lead.

Several court cases have been brought against Johnson Controls--one by a female employee m Johnson

Controls’ Globe Battery Co. plant in San Francisco, CA, who was denied a battery assembly job m 1983, although

she was not pregnant or planning to be. A lower court ruled that Johnson Controls’ FPP constitutes “overt

gender-based discrimination‘‘ founded in “unscientific stereotypic notions about women. ” The decision was based

in part on the facts that exposure to lead can affect fertile male workers as well as fertile women, and that Federal

and State work safety agencies ban both male and female workers from job sites if their blood lead levels rise.

Johnson Controls disputed the claim’s scientific basis but in May 1990, the California Supreme Court upheld the

ruling.

Another case has been brought against a Johnson Controls plant in Minnesota by the Auto Workers Union and

eight Johnson Controls employees. The plaintiffs include a woman who was sterilized to remain in a job she

considered desirable, several women who had been transferred to lower-paying jobs, and a man who desired a leave

of absence to lower his blood lead level before he became a father. The workers and union argued Johnson Controls’

FPP is explicit sex dismiminat ion because it singles out women for less favorable treatment on the basis of a factor

that has nothing to do with their ability to do the job. Johnson Controls’ FPP was upheld by the Circuit Court which

said the plaintiffs failed to prove the FPP was discriminatory. The case is now before the U.S. Supreme Court, and

a ruling is expected m 1991.

Other companies’ FPPs have been challenge& General Motors (GM) has one “intended to protect fetuses that

women may be carrying knowingly or unknowingly” and “to protect [GM] from possible lawsuits alleging that

workplace lead exposures caused birth defects. ” This policy Was challenged by a female iron pourer at GM’s

Defiance foundry in Cincinnati m a case currently under consideration by the U.S. Court of Appeals, sixth Circuit.

Neither case is new or unique, but both illustrate the ongoing problem with job discrimination and the

confusion that can result in job bias litigation from introducing risk assessment technologies to the workplace.

Scientific progress in identifying risks associated with exposure to hazardous workplace agents has been the basis

for these policies, yet the teratogenic effects of exposures seem to be poorly understood by employers.

Whether employers would use genetic monitoring or screening results to justify FPPs is unclear, since exposure

to lead and the detection of genetic sensitivities are not completely analogous. There is a crucial conceptual

difference between Meeting intrinsic genetic traits that might confer risk and measuring the effects of external

workplace agents on fetal development Detecting a susceptibility to worlplace explosures in a female worker does

not necessarily idcntify risk to a future fetus because offspring would not be adversely affected unless the

susceptibility was inherited from both parents, the trait was expressed, and workplace exposure could affect the fetus

in utero. While genetic monitoring that identified genetic changes might better indicate actual risk to a future fetus,

the gametes of both male and female workers would have to be affected, thus an FPP aimed at women would be

clearly discriminatory.

SOURCES: Office of Technology Assessment, 1990; based on L. Denniston, “High Court To Consider Fetal Safety:Workers' Choice at Center

of Case,” Baltimore Sun, p. 1, Feb. 18, 1990; B. Egelko, “California Court Rebuffs Ban on Women From Jobs That Could Harm

Fetuses," Associated Press, May 18, 1990; J. Nolan, Associated Press, Mar. 16, 1990; U.S. Congress, Office of Technology

Assessment, Reproductive Health Hazards in the Workplace OTA-BA-266 (Washington, DC: US. Government Printing Office

December 1985).

I
Chapter 7--Ethical Issues . 149

Box 7-D-Using Workplace Genetic Screening as Power

Some persons believe political power and social status influence employers’ uses of genetic screening. To

illustrate this claim, two authors present a scenario in which the roles of employers (the party the authors believe

are most likely to advocate occupational genetic screening programs) and workers are reversed.

‘‘Imagine that an administrative committee, composed of some of the least powerful members of a population

of workers--racial minorities, non-English-speaking immigrants, poorly educated youth-have suddenly been

granted full authority to impose a genetic screening program on their more highly paid employers. The goal: to

design and implement a test that will weed out ‘genetically defective’ business executives and mid-level managers.

These genetic misfits are then to be efficiently eliminated from corporate payrolls in an effort to improve the

company’s lagging profits.

First this powerful committee might decide to provide corporate research funds to spur studies into human

genetic variation in areas that might affect the job performance of managers. The search might encompass genes

thought to influence the development of a wide range of diseases that are approaching epidemic levels in the ranks

of executives, including alcoholism, drug abuse, heart disease, sexual dysfunction and mental illness, to name a few.

In time, it is likely that ambitious genetics researchers in both private and public laboratories, flushed by the sudden

influx of research grants, would find such DNA sequences or at least identify genetic markers that could be used

to signal their presence m genetic screening tests.

Later, other researchers might suggest techniques to carry out low-cost screening programs on the

chromosomes of these harried executives, who by now would almost certainly find themselves growing increasingly

uneasy over rumors of the committee’s benevolent plans to improve their genetic hygiene. As soon as these

experimental genetic tests began to promise a degree of predictive value for the target occupational diseases, the

committee, emboldened by the new scientific findings, might brashly demand that all managers submit to a series

of genetic tests designed to ferret out their ‘bad’ genes. Those managers whose genetic profiles revealed any

‘undesirable’ DNA sequences might then be asked-for their own good health, of course, as well as for the

economic health of the corporation--“ either to transfer to a less stressful position in the company or to seek more

‘genetically suitable’ employment elsewhere.

The pool of genetic information on these unfortunate would then be freely shared with other workers’

committees controlling other firms, in the hope that epidemics of alcohol and drug addiction, heart disease and

emotional disturbances could finally be controlled. No effort would be made to modify environmental factors that

might be contributing to the deterioration of these ‘executive diseases’—excessive work loads, social stresses,

dietary practices and so forth, The diligent genetic screening task force would singlcmindedly devote its efforts to

identifying what they perceived as disease-prone managers and plucking them unceremoniously from the

workplace.

The utter improbability of this imaginary role reversal underscores the imbalance of power that traditionally

exists between employers and employees in our society. But this thought experiment also reveals the potential for

the abuse of genetic knowledge by any special-interest group, regardless of its ideology, whenever information is

used to dictate important decisions to individuals, rather than to enlighten their own personal decisiomaking

processes. ”

SOURCE: D. Suzuki and P. Knudtson, "Genetic Screening” Genethics (Cambridge, MA: Harvard University Press 1989).

These guidelines call for the development of . Purposes for conducting genetic monitoring

workplace genetic monitoring and screening pro- or screening in the workplace should be

grams that produce maximal benefits to all parties by attainable and clearly articulated before

minimizing occupational illness without threatening implemention. The purpose of any workplace

. 

privacy and confidentiality, denying equality of genetic monitoring or screening program

opportunity, or stigmatizing workers: should be to protect employee health and

reduce the burdens of occupational illness to

● Employers should demonstrate the need for workers, employers, and society (7,10). This

a genetic monitoring or screening program zeal should be communicated to workers be-

(14). Employers should be able to prove a high fore testing to avoid misunderstanding and

prevalence of genetic disease among the work- heightened expectations for intervention that

force and an increased risk of morbidity (12). could be neither intended nor feasible. Only
150 . Genetic Monitoring and Screening in the Workplace

●

●

●

scientifically valid tests should be used, and the

ability of genetic monitoring or screening tests

to meet these ends should be determined before

implementing programs. Tests chosen should

be subject to minimal misinterpretation and

provide maximal, medically relevant information for protecting employee health (10).

Participation of both individual workers and

the workforce in general should be voluntary. For ethical reasons as well as purposes of

efficacy, maximal involvement of the

workforce in designing and implementing

workplace genetic monitoring or screening

programs is desirable (8,10,18). Voluntary

participation requires that workers who choose

not to undergo genetic monitoring or screening

do not jeopardize employment opportunities

(7). If possible, alternative protective measures

should be provided for workers who do not

wish to participate in diagnostic genetic monitoring or screening. Workers should be free to

discontinue participation in monitoring. Voluntary participation recognizes the autonomy

of workers: it provides opportunity for workers

to gain information about job risks if they so

choose, but does not compel participation.

Any program of genetic monitoring and

screening in the workplace should apply

equally to all workers. Providing equal access

to monitoring or screening lessens the possibility of such programs being used or perceived as

devices to discriminate against certain workers

(10). Particular attention should be given to

ensuring that screening for genetic conditions

normally concentrated in specific ethnic groups

(e.g., glucose-6-phosphate dehydrogenase deficiency or sickle cell anemia) be made available

to other members of the workforce on an equal

basis and that consistent action be taken for all

persons who test positive for a trait in order to

avoid disparate impact of workplace testing

policies.

Informed consent should be obtained from

any worker undergoing genetic monitoring

or screening for any reason. Meaningful

informed consent for genetic monitoring or

screening should be solicited whether genetic

monitoring or screening is performed at the

worker’s request, for research, or for diagnostic

●

●

●

purposes. Informed consent forms should

enumerate the purposes of the test, including a

description of any ambiguities inherent in the

test design, all projected uses of the results, and

plans for disclosure of resulting data.

Any worker undergoing genetic monitoring

and screening in the workplace should have

access to results. All results should be made

available to workers who participate in genetic

monitoring or screening programs, including

those who are involved in preemployment

testing (10). Since genetic monitoring does not

clearly indicate risk to individuals, denying

access might not limit employee autonomy, but

the restricted access to results should be made

clear to the employee before tests are performed, and employees should receive genetic

monitoring results if they still want them.

Genetic screening results should always be

provided to workers.

Professional interpretation of genetic

monitoring and screening results should be

provided for both workers and employers so

that genetic monitoring and screening can be

used in accordance with their intended ends.

Genetic monitoring results should be interpreted by a genetic counselor so that statistical

evidence of workplace hazards are completely

understood. Genetic counseling should be provided for all workers who undergo genetic

screening, especially when genetic screening

indicates increased risk of genetic disease.

Genetic screening results should also be conveyed to employers by a professional counselor, and “special care should be taken not to

perpetuate past instances of misinformation

and stigmatization of particular groups” (8).

Genetic monitoring and screening results

should be confidential. Workers should have

the ability to restrict access to genetic monitoring and screening results. Ideally, the results of

genetic monitoring and screening would be

provided only to tested employees, and could

only be provided to employers with the

worker’s explicit consent or without identifying individual subjects (8). In this regard,

genetic monitoring and screening would be like

any other form of medical testing service that

individuals receive from their own physicians.
Chapter 7--Ethical Issues ● 151

HOW MAY GENETIC

MONITORING AND SCREENING

RESULTS BE USED TO PROTECT

WORKER HEALTH?

Once genetic monitoring or screening has been

performed, what actions should be taken to protect

worker health? If genetic screening identifies a

susceptible individual, do employers have a responsibility to reduce the hazards in the workplace, or do

they have a right to remove workers at risk? How can

worker, employer, and societal interests be promoted equally in making these decisions?

This chapter and chapter 6 describe ethical and

legal duties for employers to provide a safe work

environment, but this obligation could be impossible

to fulfill for persons genetically susceptible to

workplace exposures. If engineering protections

cannot provide adequate protection for these workers, removing them from sites of dangerous exposure

could be the only recourse (16). Some workers are

likely to view this preventive measure to their

benefit; others, however, will take issue with what

they perceive as restriction of their free choice and

autonomous action.

Current employees who experience genetic

changes or who are found genetically susceptible to

occupational illness might be eligible for medical

removal protection, which requires employers to

transfer an at-risk employee to a safer job without

loss of pay or benefits. Job applicants, however,

might only be protected from genetic susceptibilities

if employers install only genetically “safe” workers

in hazardous environments: if genetically susceptible persons are denied employment in hazardous

jobs altogether they will certainly be protected from

exposure. An employment policy that excludes

some workers from job opportunities based on

genetic monitoring or screening results could be

considered discrimination against handicap, where

the disability is genetic susceptibility.

Some employees and job applicants might be

willing to risk adverse health effects despite genetic

monitoring and screening results. If freedom to

make informed decisions about acceptable personal

risks is a condition of autonomy, should autonomy

ever by limited by preventing individuals from

taking risks? The answer depends on whether other

persons are affected. People are generally free to

take risks in our society. Many people who engage

in dangerous hobbies, for example, risk their health

by doing so. When those risks affect others, however, there is usually cause to prevent them.

Workers who agree to work in hazardous conditions, or employers who hire workers with genetic

susceptibilities, might be assuming risks not only for

themselves but for others. Society might be responsible for medical care for workers if they become ill,

and for disability payments if they cannot work.

Family members can also suffer financially or

emotionally if the worker is injured or becomes ill.

There could be health or safety risks involved for

others as well. If a worker’s decision to risk genetic

disease threatens the well-being of other persons,

there may be reason to curtail his or her autonomy in

choosing to take chances. The safety of co-workers

or consumers of a company’s products or services

could be threatened if genetic disease impairs an

individual’s job performance.

A similar dilemma about whether to deny jobs on

the basis of predictive screening tests was a recent

source of controversy in the passage of ADA. Both

houses of Congress initially agreed the protections

of ADA should not be extended to food service

workers who have acquired immunodeficiency syndrome (AIDS). This decision was endorsed by the

restaurant and food service industry, which shared

congressional concern that restaurants would lose

customers if patrons learned a chef or other employee had AIDS (1,6). The exclusive language was

later removed from the bill as it became clear there

is no scientific evidence that the handling of food by

persons with AIDS presents a public health risk (1)

(see box 7-E).

Since employees are free to take other risks, such

as dangerous hobbies, despite the effects on others,

should employees known to be genetically susceptible to workplace exposures be allowed to acceptor

remain in jobs that increase the risk of disease? The

answer depends on several conditions, including

whether it is technically possible to reduce

workplace hazards so that workers with predisposing traits can work safely, and whether alternative,

acceptable forms of employment are readily available for those with a specific genetic predisposition

(11). In other words, it might only be justifiable to

prevent a worker from taking risks if the employer

has already done everything possible to make the

workplace safe and protect employees from harm.
152 . Genetic Monitoring and Screening in the Workplace

Box 7-E—Protection of Others: A Case for Workplace Screening?

Workplace screening for HIV infection and genetic susceptibilities to occupational illness are somewhat

analogous situations. Both types of screening tests are predictive rather than diagnostic tests intended to detect

possible future health problems that do not affect a worker’s job performance at the time the test is performed

Employers might want to avoid hiring workers with HIV infection for similar reasons they might not want to hire

a person with a genetic susceptibility to occupational illness: economic effect, stigma attached to the disease, or

perceived risk to co-workers or the public. Like genetic screening, HIV screening provides personal information

most workers want to be kept confidential.

Because HIV can only be transmitted through intimate contact or infected blood, it is generally acknowledged

that protection of public safety cannot be used to justify mandatory AIDS screening in the workplace. In some cases,

however, genetic susceptibilities may in fact present risk to others. If such is the case, would infringements of

autonomy and privacy inherent in mandatory workplace genetic screening ever be justified by protecting public

safety?

Some persons argue that the protection of others might just@ workplace genetic screening fo r

nonoccupational illness. A common example used to illustrate this possibility is an airline pilot who develops

Alzheimer’s disease. As the early symptoms of the disease incrementally affect his or her judgment and memory,

aircraft passengers could be endangered by the pilot’s behavior. A gene for a disease, however, is not the disease

itself, and should not be treated as one, since other factors can influence the gene’s expression. If the development

of a genetic disease, especially one that takes effect rapidly, can affect co-workers or the public, the potential for

genetic disease could justify exclusion from job opportunities.

Significant risk to others must be ascertained before workplace genetic screening can be used for the protection

of others. Employers should consider the predictive value of the test, how far in the future a detected trait would

likely take effect, and the consequences of a trait becoming rnanifest. Identification of a genetic susceptibility to

sudden heart failure might justify workplace genetic screening if expression of that trait could injure others and if

no other ways of identifying the risk exist. For other illnesses, however, especially those that develop gradually and

can be detected through other means, genetic screening might not be warranted Further discussion is needed to

identify the conditions that should exist for genetic screening in the workplace to be justified by public safety

considerations.

SOURCES: Office of Technology Assessment, 1990, based on AS. Leonard, “AIDS in the Workplace,” H.L. Dalton, S. Burris, and the Yale

AIDS Law Project (eds.),AIDS and the Law:A Guide for the Public (New Haven,CT: Yale University Press, 1987); M.A. Rothstein,

Medical Screening and the Employee Health Cost Crisis (Washington, DC: Bureau of National Affairs, Inc., 1989); M.A. Rothstein,

“Screening Workers for AIDS,” H.L. Dalton, S. Burris, and the Yale AIDS Law Project (eds.), AIDS and the Law: A Guide for

the Public (New Haven, CT: Yale University Press, 1987),

Many jobs present risks of illness or injury, and the induced predisposition to occupational illness,

possible impact on others has seldom been accepted

as reason to deny employment. It is impossible to

organize society so that the individuals who make

the decisions bear all of the risks themselves (15).

Should genetic screening be used in hiring decisions if they have a disparate impact on groups

politically protected against workplace discrimination? Some maintain that such impact might be

justified if it is generally accepted that it is necessary

for the safety of the worker and there are no equally

protective alternatives. Others argue that since “the

law has traditionally viewed with disfavor any

differentiation in treatment based on immutable

characteristics like race, sex, alienage, and legitimacy . . . a person’s genetic or environmentallywhich does not affect ‘present ability’ to perform the

job, should not be permitted to result automatically

in an adverse employment decision’ (13). The

tension between protecting the health of workers and

avoiding discrimination illustrates the need for

values to be balanced.

If the risk of occupational illness only affects the

individual worker there may be no ethical reason to

prevent employment on that basis. As long as

co-workers and family cannot be harmed directly or

indirectly, many argue that individual autonomy

should not be limited. Some argue that genetically

susceptible workers are responsible for their own

health as long as they are informed of risks, even if

alternative employment is available (4).
Chapter 7--Ethical Issues . 153

Employers could ask workers to sign waivers

indicating they are aware of possible health risks and

will not hold the employer liable. It has been argued,

however, that this practice limits employee autonomy by limiting the range of options available to

employees: forcing workers to relinquish benefits

and protections normally provided by employers

constitutes coercion (13). For many workers, a job is

primarily a source of income and other benefits that

provides security for themselves and their families

and is essential to their well-being. Workers might

be willing to risk their health in order to ensure

continued income. Thus, a worker might feel pressure to keep a job even if it requires assuming health

risks. On the other hand, waivers could provide a

means for employers and employees to learn about

possible health risks without employers being held

liable for workers’ autonomous decisions to accept

health risks.

SUMMARY AND CONCLUSIONS

The interests of workers, employers, and society

need to be addressed and balanced with respect to

each other. Employees and employers will strive to

maximize their autonomy and reduce their economic

or personal costs, while certain social values might

need to be protected. There is no consensus about

how ethical issues related to genetic monitoring and

screening in the workplace should be decided or

whether any group’s particular interests override

another ’s. Ethical arguments can be made for and

against a number of different options.

Since genetic monitoring and screening in the

workplace might, depending on circumstances,

identify workplace hazards and function to benefit

all the parties involved, the ideal solution would be

to develop programs that minimize occupational

illnesses while avoiding potentially harmful consequences from such testing, including the threat to

privacy, confidentiality, and equality of opportunity,

and the unfair stigmatization of employees. Striking

balance among different interests poses a considerable challenge, since it is difficult to give equal

emphasis to all the personal and social benefits and

hazards that may derive from genetic monitoring and

screening.

Some of the interests of different parties overlap

considerably. Genetic monitoring can be ethically

justified to the extent that it provides a verifiable and

useful index of workplace risks and employers are

willing to take action to improve the safety of the

workforce based on the results. Genetic monitoring

in the workplace currently might not be perceived as

a threat to employee privacy. Although it indicates

genetic damage in individuals, genetic monitoring

cannot accurately predict specific health effects. If

the proper conditions are fulfilled, genetic monitoring could mutually benefit employers, employees,

and society by reducing the burden of occupational disease.

Issues related to genetic screening are less easily

resolved, since genetic screening in the workplace is

more controversial than genetic monitoring. On one

hand, it can provide the most accurate and sensitive

detection of risks to individuals. On the other hand,

genetic screening results can be easily misused by

employers. Employers could implement workplace

genetic screening to protect their own interests

without regard for the interests of job applicants and

employees.

An additional problem with genetic screening in

the workplace perceived as most serious is that

employers can test for traits unrelated to workplace

exposures, i.e., traits that have no medical relevance

for the workplace. While identifying genetic

susceptibility to occupational illness might motivate

the employer to improve workplace conditions,

genetic samples collected for that purpose could be

put to other uses. Genetic screening for nonoccupational disease in the workplace does not protect

workers against occupational illness, could violate the privacy and autonomy of job applicants

and employees, and will not lower occupational

health costs for society although it may lower

health-related costs for employers.

Many of the standards suggested for an ideal

workplace testing program are likely to be difficult

to uphold while allowing the interests of workers,

employers, and society to be met. It is not clear how

conflicts of interest should be resolved, and there is

little agreement about whether workplace hazard

removal should be accomplished by denying employment to genetically susceptible individuals. For

now, ethical questions surrounding genetic monitoring and screening in the workplace can only be

answered on a case-by-case basis.
154 ● Genetic Monitoring and Screening in the Workplace

1.

2.

3.

4.

50

6.

7.

8.

9.

10,

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Susceptibility to Occupational Illness,” Michigan

Law Review 81:1379-1496, 1983.

Russell-Einhorn, M. L., and Rowe, M.P., “Employer

Screening for Genetic Disease: Current Legal Problems,’ Current Issues in Strategic Human Resources

Management, F. Foulkes (cd.) (New York, NY:

Prentice Hall Inc., 1989).

Sen, A., “The Right To Take Personal Risks,”

Values at Risk, D. Mclean (ecL) (Totowa, NJ:

Rowrnan & Allanheld, 1986).

Stokinger, H.E., and Scheel, L.D., “Hypersusceptibility and Genetic Problems in Occupational Medicine: A Consensus Report,’ Journal of Occupational

Medicine 20:319-322, 1978.

U.S. Congress, Office of Technology Assessment,

The Role of Genetic Testing in the Prevention of

Occupational Disease, OTA-BA-194 (Washington,

DC: U.S. Government Printing Office, April 1983).

Zola, M.L., “Genetic Tests Creating a Deluge of

Dilemmas,” Medical World News 27:48, 1986.
Chapter 8

The Worker as a Person:

Individual Uses of

Genetic Information
CONTENTS

Page

MONITORING V. SCREENING: ISSUES FOR THE INDIVIDUAL,, . . . . . . . . . . ,... 157

THE NEED FOR SUFFICIENT AND APPROPRIATE COUNSELING . . . . . . . . . . . . . 158

Pretest Counseling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 159

Posttest Counseling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . 160

THE ROLE OF GENETIC INFORMATION IN FAMILY MANAGEMENT

AND PERSONAL HEALTH . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 160

When Intervention Is Available . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 161

When Intervention Is Unavailable . . . . . . . . . . . . . . .

. . . . . . . . . .

. . . . . . . . . . . . . . . . . . . . . . . . . . . 161

When the Test Results Are Inconclusive . . . . . . .

. . . .

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 161

When the Results Affect Reproductive Futures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 162

When the Results Affect Other Family Members . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 164

AVAILABILITY OF AND ACCESS TO GENETIC SERVICES . . . . . . . . . . . . . . . . . . . . 165

Cost of Counseling and Additional Tests . . . . . . . . . . . . . . . . . . . . . . . . . 166

Use of Genetic Counseling: Survey Results . . . . . . . . . . . .

. . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . . . . . . . . . 166

SUMMARY AND CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 167

CHAPTER 8 REFERENCES . . . . . . .

. . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . 167

Boxes

Box Page

8-A. Screening for Coronary Artery Disease ● . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 162

8-B. Huntington’s Disease . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 163

\

Tables

Table Page

8-1. Genetic Counseling Referrals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . 167

8-2. Company Employment of Genetic Counselors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 167
The Worker

Individual Uses of Genetic

Chapter 8

as a Person:

Information

Our genetic identity is more than DNA sequences.

Our genes carry much that is relevant to our past and

our future. They also carry secrets. Everyone possesses a minimal number of deleterious genes, that

may or may not be expressed, depending on their

location, their phenotypic expression, the environment to which they are exposed, and the life choices

of those who bear them.

Most often, individuals learn about their genetic

identity in the context of family planning. Prospective parents may choose to undergo diagnostic tests

so they can increase their reproductive choices. In

other cases, individuals learn about their genetic

identity because they, or a relative, are diagnosed

with a genetic disease or syndrome. But in both

cases, the individual requests to participate in testing

and subsequent counseling, and understands, even if

in rudimentary terms, why the tests are being done.

At the least, the fact that tests are conducted in a

medical setting provides a context in which certain

assumptions and expectations can reasonably be

held by the person being tested. These factors might

be different if the workplace becomes the background for receiving genetic information.

New technical capabilities to diagnose and predict

genetically based disease have opened new pathways for informed decisionmaking about ourselves

and our family’s health. But they have also created

moral, ethical, and psychological dilemmas for

which there are no easy solutions. In addition,

genetic monitoring and screening tests often convey

a probability, but not a certainty, that disease will

appear, introducing difficult uncertainties into the

lives of those tested. Other chapters in this report

address the issues surrounding the application and

use of tests (both monitoring and screening) in the

employment setting. This chapter will address issues

faced by the individual who undergoes testing-not

as a worker—but as a person and a family member.

It discusses the role of genetic information in family

life and personal health and the need for sufficient

and appropriate counseling for those who find

themselves, or their families, at risk.

MONITORING V. SCREENING:

ISSUES FOR THE INDIVIDUAL

Three approaches have been proposed to consider

the various issues in genetic monitoring and screening (19). The frost is fatalistic, where the existence of

a particular genetic vulnerability is recognized as a

quirk of fate which could affect anyone and for

which society cannot be held responsible. This

approach most closely resembles the state of public

. . thinking until recently. As a society, we are quickly

moving away from this perspective.

The second approach is individualistic; i.e., society assists the individual to better understand the

problem and find the best means of dealing with it.

The burden, however, is on the individual to act or

be acted on. Screening an individual for genetic

traits and diseases, and removing the individual from

an allegedly hazardous environment on the basis of

test results reflects the individualistic approach. But,

as discussed in chapter 5, there are technical and

practical constraints to this way of thought because

of the limits of the tests themselves and the

uncertainty of cause and effect. Despite the technical

constraints of testing, the individualistic approach is

currently taken in the clinical genetics setting, the

routine environment for genetic tests.

The last approach is social welfare activism. It

applies the societal principles of justice and equity

to the genetically afflicted individuals. This view

holds that where conditions are found to be unequal,

or natural differences contribute to inequalities, they

should be rectified to benefit the least well-off

person. The use of genetic monitoring to identify

areas of potential risk for all individuals reflects the

concept of social welfare activism. In this scenario,

actions taken on the basis of test results are taken on

the group, not the individual. No one is singled out.

The difference between the individualistic and

social activism approaches lies in the locus of

burden and the implications for action. In the

individualistic approach, which involves screening,

the burden of dealing with the test results is placed

on the individual as a worker and a patient. In the

social welfare approach, which also includes moni-

–157-
158 . Genetic Monitoring and Screening in the Workplace

toring, the burden rests on the company to take

action by lowering or removing risks. Testing

becomes a source of surveillance data.

Whatever avenues society takes in applying

genetic monitoring and screening tests to workplace

decisions, it can never be overlooked that the focus

of the tests—the person—is being provided with

information which may have a significant impact on

decisions unrelated to employment; these include

marriage, procreation, and lifestyle. While positive

test results could be the end of the story for the

employer (having decided not to hire, to relocate, or

to fire the individual), they are likely to be the

beginning of the scenario for the individual, who

must now decide what the findings mean in his or her

private life.

THE NEED FOR SUFFICIENT AND

APPROPRIATE COUNSELING

For many individuals, even considering whether

to undergo genetic monitoring or screening constitutes a life crisis because of the possible outcomes.

If the results are positive (for the trait, disease, or

genetic change), the crisis obviously is exacerbated.

How the results will affect the individual has much

to do with the individual’s own frame of reference,

but also with the implications of the condition and its

prognosis.

Psychological issues permeate every aspect of

genetic consultation. Information received can be

ego-threatening or even life-threatening, as individuals find that they are ‘‘flawed, ‘‘imperfect, ’

‘‘defective, ‘‘ “inadequate,’ or ‘‘abnormal, ’ and

may have the potential of transmitting these

“flaws’ to their progeny (16,17). How the information is obtained, communicated, retained, and eventually used by the person being tested involves a

‘‘series of complex, multidimensional processes

with major rational and nonrational components”

(17). In addition to the intrapsychic consequences of

receiving genetic information, there are potential

impacts on family. Genetic information affects not

only the individual, but also the spouse, parents,

grandparents, siblings, and children. Social and

psychological stress, as well as future financial and

emotional burdens, can strain family functioning

(29).

In addition, genetic conditions found through

screening are permanent and chronic and may evoke

Photo credit: Diane 

A genetic counselor showing a chromosome chart to a

client. Genetic counseling may assist individuals and

families cope with positive test results.

labeling. The continuous, ever present diagnosis of

genetic disease or potential for disease may elicit

‘‘chronic sorrow” (24) in those affected. In addition

to coping with their own uncertain future, individuals may experience guilt or grief if they find they

have unknowingly passed a deleterious trait to their

offspring.

Obviously, the psychological impact of a positive

diagnosis varies with its severity and treatability,

and the fact that different families will react

uniquely to similar situations. Support, counseling,

and followup are likely to assist individuals and their

families in coping with positive test results. The

knowledge and skills of a properly trained counselor

can help the individual understand the diagnosis,

recurrence risk, prognosis, relevant preventive and

therapeutic measures, and also aid in communicating important information to other family members.

When these goals are accomplished, genetic counseling is usually perceived as a valuable experience

by the counselee and the counselor (22).

When it is not possible to make a specific

diagnosis, or to give an accurate recurrence risk or

more than a very general prognosis, as will be the

case in many predictive tests, interactions between

the testee and the tester are even more complex.

Until research progresses, it is likely that non-
Chapter 8--The Worker as a Person: Individual Uses of Genetic Information ● 159

specificity of diagnosis and prognosis will predominate in workplace genetic monitoring. Employers undertaking such programs should anticipate the complexity of interpretation and communication of test results.

Pretest Counseling

Professionals in the fields of health and education

are usually the first to see families who are seeking

information about genetics. Helping a client to cope

with the question “why is this happening to me?” is

one of the objectives of pretest counseling. Another

objective is helping a client understand the test—

what it is and is not, as well as why it is being done.

When employees are tested at the workplace by

someone insensitive to counseling objectives, the

workers may be confused throughout the entire

process.

In routine genetic counseling, the client discusses

why he or she chooses to be tested and discusses

with the counselor the implications of the possible

outcomes. The counselor prepares the individual for

both positive and negative test results. It is also the

time to discuss risk reduction strategies, if relevant.

Understanding Risk

One of the genetic counselor’s tasks is to communicate risk to the client-a job not easily performed

(13). A decision to be tested will be influenced by a

person’s perception of the chance that the test will be

positive. The interpretation of numerical risk varies

depending on: prior perception of the magnitude of

the risk; anxiety state of the client at the time of the

test; familiarity with the outcome (whether there is

an affected relative); how treatable the condition is;

and belief that the outcome with which the individual is familiar is representative of all such outcomes

(15).

The perception of risk may be a more important determinant of decisionmaking than the

actual risk. The way risks are posed by the

counselor may, in fact, influence the client’s

choices. When confronted with the risk of genetic

disease in their offspring and when making reproductive decisions, people tend to place greater

weight on their ability to cope with a disabled or

fatally ill child than on precise numerical risks. For

example, for some couples, a risk of 10 percent could

be perceived no differently than a risk of 50 percent

if they believe that they cannot cope with the

situation. In prenatal counseling, regardless of actual

risk, parents overwhelmingly perceive the chance of

recurrence as either O or 100 percent-it either will

or will not happen. By processing rates in this way,

individuals simplify probabilistic information and

shift their focus to the implications of being at risk,

and the potential impact of what could occur (20).

In addition to the subjective factors that influence

the interpretation of risk already discussed, the

understanding of risk in arithmetic terms is usually

deficient. Comprehension of the concepts of probability and risk will influence the client’s understanding of the genetic information provided by testing

(16). In a Maryland study of 190 predominantly

White, middle-class women, over one-fifth thought

that “1 out of 1,000” meant 10 percent, and 6

percent thought it meant greater than 10 percent (5).

The way risks are framed also influences choices

(21). The decision to have a genetic screening test

can be different if the risk is presented as a 25 percent

chance of having an affected child rather than a 75

percent chance of having a normal child. Presenting

risks in personal terms may improve the chance that

action will be taken (13).

Most studies of counseling have focused on cases

where the patient already has an affected child or

relative and is familiar with the disorder. Little is

known about the effect of counseling prior to genetic

screening in people with no previous family history

of the condition for which they are being tested. It is

likely that their misperceptions could be great.

Pretest counseling is all the more imperative in these

cases, as is the need for informed consent.

Obtaining Informed Consent

The following text presents the routine consent

process in contrast to that which we will find in the

workplace. (See ch. 6 for further discussion of

informed consent.) In the routine clinical genetics

setting, very few situations arise in which genetic

monitoring or screening can be performed by a

health care provider without informed consent.

Before any invasive procedure (including the taking

of samples such as blood, urine, or saliva) the

individual should be informed of the following:

● purpose of the test,

. risk of the test itself,

. validity of the test (the possibilities of false

results),
160 ● Genetic Monitoring and Screening in the Workplace

implications of a positive result (medical and

social),

nature of the condition for which the test is

being conducted,

options available to reduce the burden of

disease in the event of a confined positive test

result, and

alternatives if the individual decides not to have

the test.

Most of these, or analogous elements, are specified in the informed consent statutes of 21 States (l).

Informed consent is not obtained when a disclosure

is incomplete, constructed to prejudice the subject

toward a particular action, or obtained under pressure.

The process of obtaining informed consent in the

medical sense may not be practiced in the workplace. Consent may be obtained for using the results

to make hiring and employment decisions but the

future or current employee may not receive the

information needed to obtain explicit consent for

medical intervention.

Posttest Counseling

When attending a genetics clinic for reasons other

than prenatal genetic screening, people have historically come because they have had an affected

relative, usually a child. They tend to be familiar

with the disorder. The affected relative, rather than

a test, served as the indicator of potential disease for

others. As an increasing number of genetic screening

tests are administered to healthy individuals with no

apparent family history of genetic disease, counselors will have to spend more time describing the

disorder to those with positive test results.

Studies have shown that test results should be

reported in person, by the same person who provided

the pretest counseling (9). If the test results are

positive, prior contact may have alerted the counselor as to whom else should be informed, whose

help might be needed on behalf of the client (i.e.,

financial or emotional support), and important

information about the client’s lifestyle and family

(as well as financial and insurance information).

Followup counseling and support is also strongly

advised. News of a positive result impedes a

person’s ability to accept advice on both emotional

and practical levels. Faced with positive results,

most individuals are unable to take advice until they

overcome the shock and possible denial that their

fate or their children’s fate could suddenly shift in a

negative direction. Information about treatments

and the importance of changing lifestyle is best

assimilated several days after the test results are

communicated. Focusing on medical facts at this

stage could convey to the individual that the

psychological issues he or she is dealing with are

unimportant or irrelevant (38).

Even in the best of all worlds, where consistent

counseling has been provided all through the process, the effectiveness of counseling is sometimes

questionable. An analysis of nine studies on counseling published since 1970, concluded, “many

parents of children with a genetic disorder have an

inadequate understanding of the genetic implications of the disease, even after one or more genetic

counseling sessions” (10). One survey found that

more than half of the 87 percent of people who came

to a genetic counseling center with inaccurate

knowledge of risk were still misinformed after

counseling (13).

The task of communicating genetic information is

formidable. Counseling programs are continually

trying to educate counselors to improve the process

(35). A major impediment to satisfactory counseling

has been a profound lack of understanding of basic

genetics. Anyone administering tests necessarily

takes on the role of educator as well as practitioner

and examiner.

THE ROLE OF GENETIC

INFORMATION IN FAMILY

MANAGEMENT AND PERSONAL

HEALTH

A person’s genetic constitution (genotype) determines the broad limits of his or her potential,

whereas the expression of that potential (phenotype)

is dependent in an important way on the environment with which the genes interact. The assumption

that there is always a one-gene-disease relationship

is fallacious. There are numerous variables such as

general health, diet, medication, and stress that

contribute to or interact with the genetic trait, in

addition to workplace exposures, to produce a

disease state.

The harmful manifestations of some genetic

diseases can be prevented or ameliorated by the

administration of drugs or special diets, or by the
Chapter &The Worker as a Person: Individual Uses of Genetic Information ● 161

elimination of harmful environmental agents. To be

optimally effective, intervention must take place

early, frequently before symptoms of the disease

appear. Predictive tests have been unavailable for

most single-gene diseases, but with the use of

recombinant DNA technology many are being

developed (see ch. 5).

For most genetic diseases, the basic defect is not

known and effective interventions are not yet

feasible. Although linkage studies or direct DNA

analysis will eventually reveal the defect, there will

be long delays between the time the gene is located

and the time when effective interventions are

available. In the meantime, predictive tests for those

at risk could be developed and widely disseminated.

Healthy individuals could learn of their fate as

potential patients and face several options, depending on the prognosis for the disease and the

availability of effective intervention.

When Intervention Is Available

A considerable amount is known about the

pathogenesis of some multifactorial conditions,

such as diabetes mellitus, coronary artery disease,

and lung cancer. If it were possible to identify

individuals with genetic susceptibilities to these

conditions, the pathogenic process might be interrupted (if the person at risk adopts risk-reducing

behaviors). In contrast to highly penetrant singlegene disorders, however, it is doubtful that all

persons found to have a susceptibility-conferring

genotype would eventually manifest the disease,

even if they possessed other predisposing alleles or

were exposed to harmful environmental agents.

Unless one can be certain that disease will appear,

potentially harmful interventions should not be used

on those who may never become sick in the first

place. Avoidance of dispensable habits, however,

such as smoking or a high fat diet, would be safe

plans of action (see box 8-A).

Individuals found to be at risk for non-insulin

dependent diabetes could be counseled about the

importance of weight control. Counseling people

found to be at risk for colon cancer to increase fiber

intake, or to have periodic colonoscopic testing

could ensure early treatment. Those at risk for

melanoma could be advised to protect themselves

from sunlight.

In all these cases, individuals can be informed of

the likelihood that specific actions they can take,

could modify the prognosis delivered with the test

results. When positive test results are based on

monitoring, rather than screening, the individual’s

choices are not as clear (see ch. 4). At that point, the

patient as a person may wish to be removed from the

potentially hazardous exposure, but the patient as a

worker may have no choices.

When Intervention Is Unavailable

For many disorders, neither drugs nor diets nor

lifestyle changes have yet been found that markedly

improve the outcome. This greatly complicates the

personal burdens of threatening medical information. Examples of such disorders with a late onset are

Huntington’s disease and Alzheimer’s disease (see

box 8-B). Other disorders can be treated with some

benefit, but the outcome is not always good and the

management of the disease may be costly. Maple

syrup urine disease, hemophilia, bipolar affective

disorder, and schizophrenia fall into this category.

The psychological sequelae of facing the uncertainties of untreatable illness are devastating. There

is a growing body of literature related to coping

behaviors associated with testing positive for HIV

antibodies. One of the most psychologically unacceptable notions which confronts the individual at

risk is to be the passive victim of a totally random

event (36). Another aspect of detecting a late onset

disorder is the possibility of self and social stigmatization, and the increased opportunity for discrimination (16).

When the Test Results Are Inconclusive

In the case of screening for genetic disease, most

tests are fallible. Some of the problems are specific

to the method employed and some to the laboratory

performing the test. Others result from genetic

heterogeneity and incomplete penetrance. Failure to

correctly interpret monitoring and screening test

results poses a significant problem for the patient.

In the case of genetic monitoring, the uncertainty

is probably even more pronounced. Because of the

lack of causal linkages between exposures and

clinical prognosis, the clinician is left with little on

which to base a prognosis. If the results reveal

chromosomal damage, there is little reliable and

valid information available that would allow individuals to make informed choices. For example, they

can be told that there appear to be causal linkages

between cancer and their condition, but that there is
162 ● Genetic Monitoring and Screening in the Workplace

Box 8-A—Screening for Coronary Artery Disease

Coronary artery disease (CAD) is a major public health problem. Myocardial infarction, secondary to CAD,

causes 30 to 35 percent of all deaths in men between ages 35 and 50 and is responsible for more than half a million

deaths per year in the United States. CAD results from atherosclerosis, a slow, progressive disease of the arteries

that begins early in life and may go undetected until the first heart attack which maybe fatal.

A strong association between hyperlipidemia and the risk to develop CAD has been demonstrated. There is

evidence for the existence of three monogenic forms, as well as of polygenic and nongenetic forms, of

hyperlipidemia. Familial hypercholesterolemia, familial hypertriglyceridemia and familial combined hyperlipidemia are transmitted as autosomal dominant traits and are well-established entities. In most cases of autosomal

dominant transmission of CAD, the individual has symptoms that lead to the diagnosis.

Several different genetic factors have been associated with CAD. Only 1 percent of those classified as

hyperlipidemic have a clear-cut monogenic cause. Nongenetic factors, e.g., cigarette smoking, high cholesterol

diets, obesity, physical inactivity, stress, and diabetes mellitus, may also contribute to the disease state. Most cases,

therefore, are heterogeneous or multifactorial and would be prime candidates for some type of predictive tests.

Intervention could be started well before the appearance of heart disease.

Research using restriction fragment length polymorphisms has demonstrated an association between a 3.3

kilobase band and inherited apolipoprotein abnormalities that could predispose an individual to CAD. Tests at the

DNA level may ultimately prove better predictors of CAD than lipid or apofipoprotein measurements. These tests

may provide risk information prior to elevated lipid levels. When such tests become widely available, persons at

risk could begin a prevention program including lowering dietary levels of cholesterol or taking drugs that bind

cholesterol-like compounds in the intestine or inhibit cholesterol biosynthesis.

SOURCES: R.T. Acton, R. Bamberg, R.C.P. Go, et al., ‘‘Utilization of Genetic and Other Laboratory Test Results To Predict and Reduce the

Risk of Disease,” Proceedings of the Society of Prospective Medicine, 1988; J.L. Goldstein, W.R Hazzard, H.G. Schrott, et al.,

“Hyperlipidemia in Coronary Heart Disease,” Journal of Clinical Investigation 52:1544, 1973; A.G. Motulsky and H. Boman,

‘‘Screening for the Hyperlipidemias,’ Genetic Counseling, H.A. Lubs and F. de la Cruz (eds.) (New York, NY: Raven Press, 1977);

J.M. Ordovas, E.J. Schaefer, D. Salem, et al., ‘‘Apolipoprotein A-I Gene Polymorphisms Associated With Premature Coronary

Artery Disease and Familial Hypoalphalipoproteinemia’ ‘ New England Journal of Medicine 314:671-677, 1986; J. Stamler,

“Epidemiology of Coronary Heart Disease,” Medical Clinics of North America 57:5, 1973; G.L. Vega and S.M. Grundy,

“Treatment of Primary Moderate Hypercholesterolemia With Lovastatin (Mevinolin) and Colestipol,” Journal of the American

Medical Association 257:33-38, 19S7.

no certainty that they are going to develop cancer. alteration to stop children from inheriting nonfatal

For individuals trying to cope with uncertain medical prognoses “(e.g., cancer, multiple sclerosis, or

Hodgkin’s disease) the loss of certainty in one’s

future (having a family, children, grandchildren,

retirement, etc.) is often just as destructive to mental

well-being as the certainty of death from a definitive

prognosis.

When the Results Affect Reproductive Futures

In the past 15 years, genetic screening tests have

most frequently been used for prenatal diagnosis and

family planning. Tests intended to detect disorders

in offspring appear to be viewed differently than

tests undertaken to identify personal risk. A 1986

Office of Technology Assessment (OTA) poll found

that a majority of Americans who think human gene

manipulation is morally wrong in the abstract

approve of its use to save lives and heal sick

children. In addition, a large majority of those polled

(77 percent) say they approve of human genetic

birth defects or to reduce the risk of developing a

fatal disease later in life (32).

Those identified as being carriers of autosomal

recessive disorders (e.g., Tay-Sachs disease, thalassemia, and sickle cell anemia) currently have several

options in family planning. They can proceed with

an unmonitored pregnancy knowing that they have

a 25 percent chance of having an affected child; if a

prenatal diagnostic test is available, they can avail

themselves of amniocentesis or chorionic villus

sampling to determine whether the fetus is affected,

at which point they can decide whether to continue

or terminate the pregnancy; they can choose to

become pregnant by alternative methods, or not to

become pregnant at all.

Adequate and timely information is a key factor in

helping families make their choices. Prospective

parents need to understand the prognosis for an

affected child before making a decision. For exam-
Chapter &The Worker as a Person: Individual Uses of Genetic Information ● 163

Box 8-B—Huntington’s Disease

Huntington’s disease is a chronic, progressive, degenerative disorder, beginning usually between the ages of

30 and 50 years. It is characterized by uncontrollable, spasmodic movements in the face and extremities, as well

as gradual loss of mental faculties, ending in dementia. The disease is lethal and incurable; death usually occurs on

average 15 to 17 years after disease onset. The disease is transmitted as an autosomal dominant trait; offspring of

an affected individual have a 50 percent chance of developing the disease. The test for the Huntington’s gene is most

often performed on an asymptomatic individual. If someone has the gene, that person will definitely develop the

disease. Symptoms for the disease usually begin past the typical childbearing years, between ages 35 to 45.

The test provokes considerable anxiety among those at risk who elect to take it. Not all of those at risk elect

to be tested, even though there is a 50 percent chance that they will receive good news. Prior to the availability of

a predictive test for Huntington’s disease, surveys indicated that between 56 and 85 percent of those at risk would

avail themselves of the test. In a survey conducted after the test became available, less than 14 percent of the sample

population at risk elected to take the test.

In another survey, 66 percent of the sample population at risk said they wanted the test. Of that group, 15

percent said they might commit suicide if the test were positive. Of the group that chose not to be tested, 30 percent

feared they might be suicidal and therefore did not want their fears confirmed. For some people, uncertainty appears

to be preferable to certainty.

A recent study on the psychological reaction of people being tested for the disease found no clear increase in

psychiatric illness among people who tested positive for the Huntington’s gene. People’s reactions to their test

results ranged from ‘‘extreme joy and relief to disappointment, sadness and demoralization. ” This study suggests

that people cope well with this type of information if they are carefully screened, counseled, and provided followup

care. In addition, those who test positive should be given appropriate long-term monitoring.

SOURCES: Office of Technology Assessment, 1990; based on C. Mastromauro,

Presymptomatic Testing in Huntington’s Disease,”

 R.H. Myers, and B. Berkman, “Attitudes Toward

American Journal of Medical Genetics 26:271-282, 1987; K.A. Quaid, J.

Brandt, and S.E. Folstein, “The Decision To Be Tested for Huntington’s Disease, ” Journa/ of the American Medical Association

257:3362 (letter), 1987; B. Teltscher and S. Polgar, “Objective Knowledge About Huntington’s Disease and Attitudes Toward

Predictive Tests of Persons at Risk,” Journal of Medica1 Genetics 18:31-39, 1981; A. Tyler and P.S. Harper, ‘‘Attitudes of Subjects

at Risk and Their Relatives Toward Genetic Counseling in Huntington's Chorea” Journal of Medical Genetics 20179-188, 1983.

pie, in one study, at least 89 percent of 333 couples

identified as at risk for having children with

Tay-Sachs disease used prenatal diagnosis (14).

Tay-Sachs is a progressive, fatal disorder that results

in death usually before a child’s fifth birthday. On

the other hand, couples at risk for sickle cell anemia

might not seek prenatal diagnosis, possibly because

the disease is partly manageable and, therefore,

many women would not abort an affected fetus (see

chs. 3 and 5).

In the case of a late onset autosomal dominant

disorder (e.g., Huntington’s disease, or adult polycystic kidney disease), adults at risk face a double

dilemma. Before the availability of predictive tests,

individuals at risk (who knew of their risk status)

could forego childbearing as the only way of

avoiding passing on the trait. Now that those at risk

can find out whether they will most likely develop

the disease, they are presented with new options. If

not at risk, they can freely reproduce without the

burden of passing the gene to their children. If found

Photo credit: Woody Guthrie Publications

Woody Guthrie: A famous American folksinger who died of

Huntington’s disease.
164 . Genetic Monitoring and Screening in the Workplace

Photo credit: Diane Baker

An employee’s genetic information can play an important

role in his or her family planning.

to be carriers of the gene, they can elect to have

prenatal diagnosis to determine whether their offspring will also inherit the fatal gene. However, this

is complicated by the fact that many do not know

they are at risk until they have already had children.

The availability of these genetic screening tests is

recent enough that very little is known about how

high risk people who are tested deal with the

psychological aftermath. Clearly, counseling and

other support services should be offered in conjunction with any test.

When the Results Affect Other

Family Members

In the case of genetic monitoring, it is unlikely

that positive results will directly affect other members of the existing family (with the exception of the

 unborn). Obviously, other family members can be

secondarily affected by any consequences of potential or real deteriorating health of a loved one.

In genetic screening, there is a real possibility that

test results will affect other family members. In the

usual genetic counseling setting, the person being

tested (the proband) is routinely advised of risks to

other family members. For example, if the client is

found to be a carrier for an autosomal recessive

disorder, e.g., Tay-Sachs or sickle cell disease, the

counselor informs the client that siblings each have

a 50 percent chance of also being carriers. In most

cases, the counselor suggests that the proband

contact his or her siblings and suggest that they

consult with their personal physician or come to the

same clinic. The counselor cannot confirm that the

proband has informed relevant family members.

Unauthorized disclosure of medical information

could result in legal action.

The issue of disclosure of medical information to

others, e.g., insurers and employers, is discussed in

chapter 6. Disclosure of medical information to

relatives raises different issues. Not all families are

emotionally and psychologically secure. Sibling

relationships could impede full disclosure. Sharing

highly personal medical information that involves

reproductive and health futures may cause personal

embarrassment or emotional stress for family members.

The question of duty to warn the proband’s spouse

also arises as a consequence of genetic screening.

For example, a woman informed that she is a carrier

of an X-linked condition might not wish to inform

her husband or prospective husband that their male

offspring will have a 50 percent chance of being at

risk.

The President’s Commission for the Study of

Ethical Problems in Medicine and Biomedical and

Behavioral Research took the position that physicians may release genetic information to relatives

without the patient’s or client’s consent provided

certain conditions are met. They are:

●

●

●

●

reasonable efforts to elicit voluntary consent to

disclosure have failed;

high probability exists both that harm will

occur if the information is withheld and that the

disclosed information will actually be used to

avert harm;

identifiable individuals will suffer serious

harm; and

appropriate precautions are taken to ensure that

only the genetic information needed for diagnosis and/or treatment of the disease in question

is disclosed (26).

A different view was taken by the Committee for

the Study of Inborn Errors of Metabolism of the

National Academy of Sciences. It held that “under

current law, genetic screeners would be ill advised

to contact relatives without the screenee’s explicit

consent” (8).
Chapter 8--The Worker as a Person: Individual Uses of Genetic Information ● 165

AVAILABILITY OF AND ACCESS

TO GENETIC SERVICES

Tests are already available for a multitude of

conditions with a genetic component. There are

numerous tests available to diagnose a preexisting

genetic condition in an individual or in utero.

Several States require genetic screening for certain

genetic conditions in the newborn period (e.g.,

phenylketonuria, sickle cell anemia) (30). In addition, tests are available to identify carriers of

autosomal recessive conditions such as Tay-Sachs

disease. Traditionally, these tests have been used

almost exclusively within the disciplines of pediatrics and obstetrics.

In the next decade, it is estimated that tests will be

available to identify genetic predispositions to

certain disease, such as cancer or heart disease (31).

In a 1987 survey of firms developing tests, half of the

respondents felt that within 5 years, demand for

genetic testing would outstrip current laboratory

capabilities (31).

Comprehensive diagnostic, treatment, and management services are offered to high risk or symptomatic individuals and their families at approximately 20 clinical genetic service centers throughout

the United States (33). Most (63 percent) are located

at university-affiliated medical centers, with some

centers operating satellite clinics in rural areas.

However, genetic counseling services are not readily

available to everyone, particularly those unable to

pay for the tests themselves.

In examining the ability of workplace monitoring

and screening programs to provide adequate followup services, the following should be considered.

Genetics consultations tend to require longer officevisit time than most other specialties because of the

need for detailed family histories and thorough

physical examinations. Considerable time may be

spent explaining the diagnosis for several family

members as well as providing counseling (2). In

addition, there are a number of other potential

barriers-geographic, financial, linguistic, cultural,

and educational-to the provision of followup

services. Perhaps the greatest barriers to be overcome are those related to language and cultural

differences (23). Bilingual genetic counselors will

be needed in increasing numbers as more immigrants come to the United States.

Photo credit: University of South Carolina of 

Genetics consultations can require longer office-visit time

because of the need for gathering detailed information

about the client. This genetic counselor is discussing the

client’s chromosome profile with her.

As tests become available to a growing number of

presumably healthy Americans, the administration

of diagnostic tests and subsequent treatment for an

increasing number of individuals will have to be

assumed by medical professionals in other areas of

primary care. There are doubts within the medical

community about the adequacy of medical genetics

education in medical schools for students not

pursuing pediatrics or obstetrics. At the very least,

primary care providers need to be equipped to

discuss tests results and make necessary referrals.

This requires a basic understanding of genetics. Yet,

in a 1985 survey, only 21 percent of U.S. medical

schools were considered to have good or excellent

instruction in human genetics. Forty-seven percent

of the schools responding were considered to have

either nonexistent or poor human genetics teaching

(27).

An OTA survey of companies developing predictive tests revealed that they had little confidence in

the ability of primary care physicians to inform their

patients about genetic screening, arrange for tests,

and interpret test results (31). There is ample

evidence that physicians have difficulty interpreting

results of laboratory tests more familiar to them and

less complicated than genetic tests (3,6,25).

Adequate genetic services are not always provided in the most likely setting-hospitals. In a

study of Huntington’s disease counseling in Veterans’ Administration Hospitals, less than 1 percent of
166 . Genetic Monitoring and Screening in the Workplace

the hospitals had a formal policy regarding the

provision of genetic counseling (18).

While physicians are likely to be required to

administer most genetic monitoring and screening

tests, they are not the only health care professionals

qualified to provide genetic services. Nurses, social

workers, and master’s level genetic counselors

frequently participate in counseling and followup

programs for individuals seeking genetic services.

There are currently 15 programs in the United States

and Canada offering a master’s in genetic counseling

(34). For many years, there has been some recognition that genetics is an important feature of the

nursing curriculum (4) and, yet, when nurses have

been surveyed about their genetic knowledge, important gaps have been noted (37). This has important implications for job site genetic monitoring and

screening, as occupational health nurses are likely to

be involved.

The American Board of Medical Genetics has

certified more than 1,000 providers of genetic

services, of which approximately half are clinical

geneticists (M.D., D. O., or D.D.S.) (28). However,

certification does not necessarily test one’s counseling ability. Nonphysician genetic counseling personnel have been trained since 1969 and play a

critical role in delivering services in an already

overburdened system. One of the rate-limiting

steps in the widespread use of genetic monitoring

and screening tests will be the availability of

adequately trained personnel to interpret results

and provide followup services.

Cost of Counseling and Additional Tests

If an employer proceeds with monitoring or

screening and then refers the worker to an outside

source for additional testing or followup, unless the

employer is willing to pay for those services, the

costs of further testing or followup may deter some

employees from proceeding. When tests are coupled

with prenatal diagnosis or when multiple family

members need to be evaluated for linkage studies,

the bill can be well over $1,000. For example, the

cost for predictive testing for Huntington’s disease

currently ranges from $2,800 to $4,000. This includes genetic and psychological counseling, a

neurological examination, as well as posttest counseling (7).

Presently, some Blue Cross/Blue Shield Plans

(BC/BS) and State Medicaid programs reimburse for

genetic services, although services covered and

amounts reimbursable vary. Reimbursement by

Medicaid is frequently less than the full charge. This

is particularly true for genetic counseling, which is

sometimes not reimbursed at all (12). Fewer than

half of BC/BS plans reimburse for carrier screening

tests, and genetic counseling is covered by less than

60 percent (11). Twenty-three of the thirty-five

health maintenance organization plans provide genetic counseling as a covered benefit.

Deficiencies in reimbursement for genetic counseling in both BC/BS and Medicaid programs are in

part due to the absence of an American Medical

Association code for genetic counseling (which is

used by insurers to guide payment) and the policy of

third-party insurers of not reimbursing nonphysician

genetic counselors. Nonphysician genetic counselors are likely to be a needed source for referral of

individuals identified through screening and monitoring programs. The fact that genetic consultations

are frequently excluded in part, or in full, from

insurance coverage is a disincentive for individuals

pursuing further interpretation of their test results.

As part of the OTA survey on genetic monitoring

and screening practices in the workplace, questions

concerning genetic counseling were asked. The

following section describes these results.

Use of Genetic Counseling: Survey Results

Corporate health officers in companies (Fortune

500 and non-Fortune 500 companies) that have

conducted any form of genetic monitoring or screening were asked:

Has an employee ever been referred for genetic

counseling by your company’s medical staff as a

result of any medical or genetic testing?

Health officers in 10 percent of those companies that

had ever done genetic monitoring or screening

reported that one or more employees in their

companies had been referred to genetic counseling

as a result of medical testing (table 8-l). Half of

these companies were currently conducting some

form of genetic monitoring or screening, and the

other half had only tested in the past. Nearly all of the

companies referring employees to genetic counselors (8 out of 9) had 10,000 or more employees.

OTA found that 6 percent of the companies that

had conducted genetic monitoring or screening

employed a genetic counselor. No companies re-
Chapter 8--The Worker as a Person: Individual Uses of Genetic Information ● 167

Table 8-l-Genetic Counseling Referrals

Q. 26. Has an employee ever been referred for genetic counseling by your company’s medical staff as a result of any

medical or genetic testing?

(Base: Health Officers in companies that have ever done genetic

monitoring or screening)

Total percent

Unweighed base (59)

Yes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10

NO . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 80

Don’t knowa . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5

No answer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5

a volunteered response.

SOURCE: Office of Technology Assessment, 1990.

ported contracting with a

8-2).

SUMMARY AND

genetic counselor (table

CONCLUSIONS

Individuals who have just learned about a genetic

condition through employment genetic monitoring

or screening face a double dilemma. Workers may

have found that they are unemployable in certain job

positions (including their current one) and that their

future health or that of family members may be in

jeopardy.

How individuals react depends on their own life

circumstances as well as the diagnosis and prognosis. Because a probability, but not a certainty, that

disease may result if difficult uncertainties are

introduced into the lives of those tested. The

information provided prior to administration of the

test can help to prepare individuals for the outcome.

In addition, a genetic counselor can help the person

being tested understand the concept of risk. When

the test results are positive, posttest counseling and

followup are essential.

An important aspect of human communication is

the context in which it occurs. Workplace testing is

an atypical setting for receiving information of such

personal importance. The absence of referrals to

trained professionals and reimbursement for the

costs of additional tests or counseling may be

prohibitive factors influencing an individual’s ability to obtain additional information. Current resources to provide counseling may be strained as

more tests are developed and made commercially

available.

Table 8-2 -Company Employment of

Genetic Counselors

Q. 25. Does your company employ or contract with a genetic

counselor?

(Base: Health Officers in companies that have ever done genetic

monitoring or screening)

Total percent

Unweighed base (59)

Employ . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

Contract with . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0

Neither . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89

No answer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5

SOURCE: Office of Technology Assessment, 1990.

1.

2.

3.

4.

5.

6.

7.

8.

9.

10.

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Berwick, D. M., Fineberg, H.V., and Weinstein,

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Brantl, V.M., and Esslinger, P.N., “Genetic Implications for the Nursing Curriculum,” Nursing Forum

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Chase, G.A., Faden, R.R., Holtzman, N.A., et al.,

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Biology 33:57-64, 1986.

Christianson-Szalanski, J.J., and Bushyhead, J.B.,

“Physician’s Use of Probabilistic Information in a

Reid Clinical Setting,” Journal of Experimental

Psychology: Human Perception and Pe#orrnance

7(4):928-935, 1981.

Cohen, P., Huntington’s Disease Society of America,

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Research (Washington, DC: National Academy of

Sciences, 1975).

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from the First Interdisciplinary Conference on

Human Inumumdeficiency Virus Antibody Testing

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College and Memo~

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Published Follow-Up

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168 ● Genetic Monitoring and Screening in the Workplace

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Gibbs, J.O., Henes, C., and Kaplan, G.N., Health

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Holtzman, N. A., Proceed With Caution: Predicting

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1989).

Holtzman, N.A., “Screening for Congenital Abnormalities,” International Journal of Technology Assessment in Health Care 1:805-819, 1985.

Kahneman, D., and Tversky, A., “The Psychology of

Preference,’ Scientific American 246:160-171,

1982.

Kenen, R. H., and Schmidt, R. M., “Stigmatization of

Carrier Status: Social Implications of Heterozygote

Genetic Screening Programs,’ American Journul of

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Kessler, Seymour (cd.), Genetic Counseling: Psychological Dimensions (New York, NY: Academic

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Spring-Summer 1988.
Chapter 9

Genetics in the Workplace:

Perceptions and Practice
CONTENTS

Page

WORKER PERCEPTIONS OF GENETIC

MONITORING AND SCREENING . . . . . . . . 171

STUDY DESIGN . . . . . . . . . . . . . . . . . . . . . . . . . . . 172

Definition of Genetic Monitoring and

Screening . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 172

The Questionnaire .. .. .. ... ... .+...... . . . . 173

GENETIC MONITORING AND SCREENING:

U.S. CORPORATIONS AND UNIONS ...+. 173

Current Use of Genetic Monitoring . . . . . . . . . 173

Current Use of Genetic Screening . . . . . . . . . . 174

Past Uses of Genetic Monitoring . . . . . . . . . . . 174

Past Uses of Genetic Screening +.. . . . . . . . . . 174

Combined Genetic Monitoring and

Screening: 1989 Survey Results . . . . . . . . . . 175

Overall Use of Genetic Monitoring and

Screening in 1989 and 1982 ..,..+.,.,.,.. 175

General Use of Genetic Monitoring and

Screening Tests,. . . . . . . . . . . . . . . . . . . . . . . . 176

Total Use of Genetic Monitoring or

Screening . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 177

Future Use of Genetic Monitoring and

Screening ● ?..+. . . . . . . . . . . . . . . . . . . . . . . ., 178

Genetic Monitoring for Other Reasons:

1989 Survey ResultS .. .. .. .,. ... ,.. +.-.. 178

Genetic Screening for Other Reasons:

1989 Survey Results . . . . . . . . . . . . . . . . . . . . 178

Specific Types of Cytogenetic Monitoring

Conducted in 1989 .. ............,.,..+., 179

Specific Types of Genetic Screening Tests

Conducted in 1989 . . . . . . . . . . . . . . . . . . . . . . 179

Reasons for Conducting Genetic Monitoring

and Screening . . . . . . . . . . . . . . . . . . . . . . . . . . 181

Actions Taken as a Result of Genetic

Monitoring or Screening .. .. ... ..+. ,...,. 182

Survey Results without Certain Tests

Included . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 183

Survey Results of the 1,000+ Companies:

Current Use . . . . . . . .,.,.,*. . . . . . . . . ....+ 184

Survey Results of the 1000+ Companies:

Past Use ..*.** . . . . . . . . . . . . . . . . . . .. . . . . . 184

UNIONS AND GENETIC MONITORING

AND SCREENING ......+. . . . . . . . . . . . . . . . 184

Genetic Monitoring and Screening

Conducted by Unions . . . . . . . . . . . . . . . . . . . 185

Genetic Monitoring or Screening

Conducted by Companies . . . . . . . . . . . . . . . . 186

Union Positions on Genetic Monitoring

and Screening . . . . . . . . ..,.,..,+.4....+.4 186

Unions and the Future of Genetic Monitoring

and Screening . . . . . . . . . . . . . . . . . . . . . . . . . . 188

CHAPTER 9 REFERENCES .. ... ... ..,...+. 188

Tables

Table Page

9-1. Availability of Genetic Test From

Physicians . . . . . . . . . . . . . . . . . . . . .. . . . . 171

Page

9-2. Using Genetic Tests for Personal -

Health . . . . . . . . . . . . . . . .,.....+ ,..,.., 172

9-3. Using Genetic Test Before Having

Children . . . . . . . . . . . . . . . . . . . . . . . . . . . . 172

9-4. Current Use of Genetic Monitoring by

Fortune 500 Companies . . . . . . . . . . . . . 174

9-5. Current Use of Genetic Screening by

Fortune 500 Companies . . .. ..,,+.... 174

9-6. Past Use of Genetic Monitoring Tests

by Fortune 500 Companies . . . . . . . . . . . 175

9-7. Past Use of Genetic Screening Test by

Fortune 500 Companies . . . . . . . . . . . . . 175

9-8. Combined Testing: Current v. Past

Monitoring and Screening by Fortune

500 Companies . . . . . . . . . . . . . . . . . . . . . . 176

9-9. Use of Genetic Monitoring or Screening:

1989 v. 1982 Survey Results......,.. 176

9-10. Summary Data on Use of Genetic

Monitoring and Screening: 1989 Results

Among Fortune 500 Companies . . . . . . 177

9-11. Total Prevalence of Genetic

Monitoring or Screening: 1989 Survey

Results Among Fortune 500

Companies +*+..*. . . . . . . . . . . . . . . . . . . . 177

9-12. Consideration To Conduct Genetic

Monitoring and Screening in the Next

Five Years: Health Officers . . . . . . . . . . 179

9-13. Prevalence of Genetic

Monitoring for Voluntary Wellness

Programs at Employee Request and for

Diagnosis: Fortune 500 Companies . . . 179

9-14. Prevalence of Genetic Screening for

Voluntary Wellness Programs, at

Employee Request and for Diagnosis:

Fortune 50() Companies . . . . . . . . . . . . . 180

9-15. Types of Cytogenetic Monitoring

Conducted in 1989 by Fortune 500

Companies .**+**- ● *.*.... .*...**. ,.* 180

9-16. Types of Biochemical Genetic Screening

Conducted by Fortune 500 Companies, 181

9-17. Specific Biochemical Genetic Screening

Tests Reported by Companies Reporting

No Genetic Monitoring or Screening

Among Fortune 500 Companies . . . . . . 182

9-18. Factors in the Decision To Conduct

Genetic Monitoring or Screening of

Employees Among Fortune 500

Companies . . . . . . . . . . . . . . ., +, .,,.,.”. 183

9-19. Current Use of Genetic Monitoring

or Screening Tests Among Companies

With 1,000 or Mom Employees . . . . . . 185
Chapter 9

Genetics in the Workplace: Perceptions and Practice

The use of genetic monitoring and screening in

the workplace is a multifaceted issue that has drawn

scientists, ethicists, lawyers, genetic counselors, and

occupational health care providers into an ongoing

debate. Yet what is the extent of actual use of genetic

monitoring and screening by U.S. employers and

unions? Except for a 1982 Office of Technology

Assessment (OTA) survey, evidence about past,

present, and future genetic monitoring and screening

of workers by U.S. companies and unions is

anecdotal (5).

To assess the current practice of genetic monitoring and screening by U.S. employers, OTA commissioned Schulman, Ronca, & Bucuvalas, Inc. to

conduct a followup survey in 1989 of current

Fortune 500 companies, the 33 largest unions, and

the 50 largest utilities. The comparable population

surveyed by OTA in 1982 was included in this

population to provide trend data. (See app. C for a

discussion of the 1982 survey.) The 1989 survey was

designed to include a representative sample of all

other companies with 1,000 or more employees so

that broader estimates of the use and pattern of

genetic monitoring and screening in the workplace

could be made. This chapter discusses Americans’

perceptions toward genetic tests in general, examines employer practices, and reports how genetic

monitoring and screening in the workplace have

changed since the 1982 OTA survey.

WORKER PERCEPTIONS OF

GENETIC MONITORING AND

SCREENING

Assessing worker attitudes, about genetic monitoring and screening was not possible for this report.

Other recent studies, however, have examined attitudes (e.g., regarding risk v. benefit) and understanding of the general American public toward science

and technology (2,3,4). Specifically, the results of a

1986 OTA nationwide survey on public perceptions

of human genetics could shed light on the general

attitude of Americans toward genetic tests (4). For

example, in response to the question:

If there were genetic tests that would tell a person

whether they or their children would be likely to

have serious or fatal genetic diseases, would you

approve or disapprove of making those tests available through a physician?

Eighty-nine percent of the American populace said

they approved, while 9 percent said they disapproved of having such tests available through

physicians (table 9-l).

The 1986 OTA survey did not probe American

attitudes toward genetic tests and their availability

through employers, but approval likely would be

lower than tests through private physicians. In fact,

a November 1985 Business Week-Lou Harris nationwide survey posed the question:

Even though they might not be able to cure a

genetic disease, scientists will be able to test people

to find out if they are likely to come down with

one-as much as 20 years before it happens. Do you

feel that an employer should have the right to make

[sic] such tests before hiring someone, or not?

Eighty-nine percent of adult Americans answered

that employers should not have the right to use such

tests for hiring decisions. Furthermore, 82 percent of

respondents felt an employer’s knowledge of a job

applicant’s potential to have a serious disease in the

future was not acceptable grounds for that candidate

to be denied work. The survey also asked:

Using the same kind of [genetic] testing, an

employer may soon be able to tell how vulnerable an

employee is to having a heart attack or stroke as a

result of being put in a stressful work situation. Do

you feel an employer should be able or not to bar

people who do poorly on such tests from certain

kinds of jobs?

Table 9-l—Availability of Genetic Tests From

Physiciansa

Question: If there were genetic tests that would tell a person

whether they or their children would be likely to have

serious or fatal genetic diseases, would you approve

or disapprove of making those tests available through

a physician?

Percent

Approve . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89

Disapprove . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

Not sure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2

a percentages are presented as weighted sample estimates. The unweighed base from which the sampling variance can be calculated is

1,273.

SOURCE: Office of Technology Assessment, 1987.

–171–
172 . Genetic Monitoring and Screening in the Workplace

Thirty-five percent of Americans felt employers

should be able to exclude individuals from certain

jobs based on the results of such a test. And 21

percent of respondents felt that insurance companies

would be justified in using genetic tests to refuse life

or health insurance coverage. The Business WeekLou Harris poll found that if genetic testing was not

linked to employment or insurance decisions, about

50 percent of respondents were willing to be tested

for incurable and fatal diseases they would develop

later in life (l).

Similarly, the 1986 OTA survey explored the

kinds of genetic tests Americans would be inclined

to use, if available. Two-thirds of the public said

they would take a test to determine whether they are

likely to develop a fatal disease later in life, if such

a test becomes widely available (table 9-2). Greater

than 8 of 10 Americans (83 percent) reported they

would use a genetic test before having children, if

such a test would tell them whether their children

would probably inherit a fatal genetic disease (table

9-3). And, perhaps in a measure of how workers

would accept genetic monitoring and screening to

benefit their own health outlook, the 1986 OTA

survey found members of the general public said

they were less likely to take tests to determine their

own proclivity to a fatal genetic disease than to

prevent heritable diseases in their offspring.

In general, the overall rate of acceptance by

Americans of biotechnology, including human genetic applications, increases with the likelihood of

personal benefit (4). Thus, worker attitudes toward

genetic monitoring and screening to benefit personal

health could be higher, if the testing were perceived

to be in the individual’s self-interest, not linked to

corporate interests and employment decisions.

Table 9-2—Using Genetic Tests for Personal Healtha

Question: If genetic tests become available that would indicate

whether or not a person was likely to develop a fatal

disease later in life, would you personally take such a

test or not?

Percent

Would take test . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66

Would not take test . . . . . . . . . . . . . . . . . . . . . . . . . . 29

Not sure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4

a percentages are presented as weighted sample estimates. The unweighed base from which the sampling variance can be calculated is

1,273.

SOURCE: Office of Technology Assessment, 1987.

Table 9-3—Using Genetic Tests Before Having

Childrena

Question: If genetic tests become available that would indicate

whether or not it was likely that your children would

inherit a fatal genetic disease, would you personally

take such a test before having children or not?

Percent

Would take test . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83

Would not take test . . . . . . . . . . . . . . . . . . . . . . . . . . 15

Not sure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3

a percentages are presented as weighted sample estimates. The unweighed base from which the sampling variance can be calculated is

1,273.

SOURGE: Office of Technology Assessment, 1987.

STUDY DESIGN

The 1989 OTA survey was designed to provide

comparability to the 1982 survey in terms of the

populations sampled and the questionnaire content.

At the same time, the survey was designed to go

beyond the 1982 survey by sampling additional

populations (non-Fortune 500 companies with 1,000

or more employees) and expanding the questionnaire content. (See app. B for a discussion of the

survey methodology.)

Definition of Genetic Monitoring

and Screening

For purposes of the 1989 survey, genetic monitoring and screening were defined for respondents as

follows:

By genetic monitoring, we mean periodically

examining employees to evaluate modifications of

their genetic material via tests such as cytogenetic or

direct-DNA tests. By genetic screening, we mean

screening job applicants or employees for certain

inherited characteristics. Screening tests may be

biochemical tests or direct-DNA tests. They can be

used to indicate a predisposition to an occupational

illness if exposed to a specific environmental agent,

or they could be used to detect any inherited

characteristic such as Huntington’s disease. In contrast to periodic monitoring, screening tests are

generally performed one time per characteristic.

In addition, the series of questions on genetic

monitoring and screening practices were preceded

by this explanation:

The following questions concern cytogenetic

monitoring and/or biochemical genetic screening

that may have been conducted by your company on

one or more employees or job applicants. By
Chapter %-Genetics in the Workplace: Perceptions and Practice ● 173

conduct, we mean perform, contract for, or arrange

for the test as part of a routine or ongoing program.

The 1982 survey defined genetic monitoring and

screening in a similar but less detailed fashion.

Unlike the 1989 survey, the 1982 survey had no item

covering the use of genetic monitoring or screening

for diagnosis. The 1982 survey defined biochemical

genetic screening as tests that screen “healthy,

asymptomatic individuals. ” The 1989 survey contained no such requirement. Other differences in

question wording are described in the following

section.

The Questionnaire

The scope of the 1982 survey questionnaire was

limited to measures of the frequency of past, present,

and anticipated genetic monitoring and screening;

which tests were used and under what circumstances; how the results were used; and the criteria

against which tests have been measured to determine

acceptability for use. Nearly all of these questions

were repeated in the 1989 survey to measure change

in corporate practice over time.

In order to flesh out the details of the survey data,

OTA added questions that explored the use of

genetic monitoring and screening in more depth. The

additional questions not covered by the 1982 survey

specifically asked about genetic monitoring and

screening tests that may have been conducted as part

of a voluntary wellness program, at the request of the

employee, or for diagnosis. These questions were

not part of the 1982 survey. Including the results of

the new questions produced a broader definition

of genetic monitoring and screening. Questions

were also added to cover current use of direct-DNA

monitoring and direct-DNA screening tests.

The wording of the trend questions on the 1989

survey instrument concerning current and past use of

genetic monitoring and screening tests was changed

slightly from 1982 to make the language more

specific. For example, the survey asked whether

genetic monitoring or screening tests were conducted “for research or any other reason,” a phrase

not present in the 1982 survey. Questions on genetic

monitoring and screening practices were changed

from asking about monitoring and screening of

“employees or potential employees” to monitoring

and screening of “any employees or job applicants. OTA believes the increased specificity

attained an accurate measure of genetic monitoring and screening in 1989, established a firm base

for future comparisons, and preserved general

comparability to the 1982 survey.

The 1989 questionnaire was also modified to

provide increased details on the use of specific

genetic monitoring and screening tests. The 1982

survey asked about current or past use of four

general types of biochemical genetic screening tests.

In comparison, the 1989 survey asked about current

use of 16 specific biochemical genetic screening

tests. Similarly, the 1982 survey asked about current

or past use of five types of cytogenetic monitoring

tests, while the 1989 survey asked about current use

of seven types of cytogenetic monitoring tests.

Health officers in companies that had conducted

any genetic monitoring or screening tests were asked

which specific tests their companies had conducted.

It should be noted that some health officers who

reported that their companies had never used genetic

monitoring or screening, including testing as part of

a voluntary wellness program, at employee request

or for diagnosis, did report that their companies had

conducted a specific genetic screening test. For

example, some health officers who reported no

corporate experience with genetic monitoring or

screening also reported that their companies were

testing for sickle cell trait. Thus, counting affirmative answers to specific genetic screening tests

further expanded the number of companies reporting

any use of genetic monitoring or screening.

GENETIC MONITORING AND

SCREENING: U.S. CORPORATIONS

AND UNIONS

Before presenting the trend data from 1982 to

1989, there will first be a discussion of current, past,

and combined use of genetic monitoring and screening. Following those sections, the overall and future

use of genetic monitoring and screening in 1989 and

1982 will be discussed.

Current Use of Genetic Monitoring

The one company reporting current use of cytogenetic monitoring in 1989 was a petroleum firm

with more than 10,000 employees (table 9-4). No

health officer from Fortune 500 companies surveyed

in 1989 reported conducting direct-DNA monitoring, either at the time of the survey or in the past.
174 ● Genetic Monitoring and Screening in the Workplace

Table 9-4-Current Use of Genetic Monitoring by

Fortune 500 Companies

Q.15. Is your company currently conducting cytogenetic monitoring of any employees or job applicants, for research or any

other reason?

Q.18. Is your company currently conducting direct-DNA monitoring of any employees or job applicants, for research or any

other reason?

(Base: Health officers)

Table 9-5-Current Use of Genetic Screening by

Q.13.

Q.17.

Fortune 500 Companies - -

Is your company currently conducting biochemical genetic

screening of any employees or job applicants, for research

or any other reason?

Is your company currently conducting direct-DNA screening of any employees or job applicants, for research or any

other reason?

(Base: Health officers)

Number of companies

currently conducting

Number of companies

currently conducting

Cytogenetic Direct-DNA

monitoring monitoring

Total . . . . . . . . . . . . . . . . . . . . . . . . 1

Type of business

Electrical utility . . . . . . . . . . . . . . . . 0

Pharmaceutical . . . . . . . . . . . . . . . . 0

Other chemical . . . . . . . . . . . . . . . . 0

Petroleum . . . . . . . . . . . . . . . . . . . . 1

Electronic . . . . . . . . . . . . . . . . . . . . O

Other manufacturing . . . . . . . . . . . 0

Nonmanufacturing . . . . . . . . . . . . . 0

Number of employees

Less than 5,000 . . . . . . . . . . . . . . . O

5,000-9,999 . . . . . . . . . . . . . . . . . . 0

10.000 or more . . . . . . . . . . . . . . . . 1

0

0

0

0

0

0

0

0

0

0

0

SOURCE: Office of Technology Assessment, 1990.

Questions relating to direct-DNA monitoring were

not asked in 1982.

Current Use of Genetic Screening

The OTA survey found that in 1989, 12 companies reported current biochemical genetic screening.

Of these 12 companies, 4 represented the chemical

industry, 1 represented the petroleum industry, 2

represented other types of manufacturers, and 5

represented other nonmanufacturing companies.

None of the 12 companies was an electric utility,

pharmaceuticals firm, or electronics firm (table 9-5).

Companies conducting genetic screening were disproportionately large fins, including 9 with 10,000

or more employees, 2 with 5,000 to 9,999 employees, and 1 with less than 5,000 employees. No health

officers reported current use of direct-DNA screening by their companies. Questions relating to directDNA screening were not asked in 1982.

Past Uses of Genetic Monitoring

The 1989 survey asked health officers whether

their companies had conducted genetic monitoring

tests in the past 19 years, for research or any other

reason. Five health officers in Fortune 500 companies reported that their companies had conducted

cytogenetic monitoring in the past 19 years of any

Biochemical

genetic Direct-DNA

screening screening

Total . . . . . . . . . . . . . . . . . . . . . . . . 12

Type of business

Electrical utility . . . . . . . . . . . . . . . . 0

Pharmaceutical . . . . . . . . . . . . . . . . 0

Other chemical . . . . . . . . . . . . . . . . 4

Petroleum . . . . . . . . . . . . . . . . . . . . 1

Electronic . . . . . . . . . . . . . . . . . . . . O

Other manufacturing . . . . . . . . . . . 2

Nonmanufacturing . . . . . . . . . . . . . 5

Number of employees

LeSS than 5,000 . . . . . . . . . . . . . . . 1

5,000-9,999 . . . . . . . . . . . . . . . . . . 2

10,000 or more . . . . . . . . . . . . . . . . 9

0

0

0

0

0

0

0

0

0

0

0

SOURCE: Office of T~nology Assessment, 1990.

employees or job applicants, for research or any

other reason (table 9-6). All 5 companies that

formerly conducted cytogenetic monitoring reported

no current use of genetic monitoring or screening,

and all 5 had 10,000 or more employees. One was a

chemical company, one was another type of manufacturer, and the other three were nonmanufacturing

fins. None of the five was an electric utility,

pharmaceutical company, petroleum company, or

electronics firm.

Past Uses of Genetic Screening

A total of eight health officers in the Fortune 500

companies reported that their companies had conducted biochemical genetic screening of any employees or job applicants in the past 19 years (table

9-7). This included four health officers in Fortune

500 companies that reported they were currently

conducting biochemical genetic screening.

The 8 health officers who reported that biochemical genetic screening was conducted by their companies in the past 19 years were disproportionately

from large companies, with 7 in companies with

10,000 or more employees, and 1 in a company with

5,000 to 9,999 employees. Four were in the chemical
Chapter 9-Genetics in the Workplace: Perceptions and Practice ● 175

Table 9-6—Past Use of Genetic Monitoring Tests by

Fortune 500 Companies

Q.16. Has your company conducted any cytogenetic monitoring

of any employees or job applicants, for research or any

other reason in the past 19 years?

(Base: Health officers)

Number of companies

conducted in past

Cytogenic monitoring

Total . . . . . . . . . . . . . . . . . . 5

Type of business

Electrical utility . . . . . . . . . . 0

Pharmaceutical . . . . . . . . . . 0

Other chemical . . . . . . . . . . 1

Petroleum . . . . . . . . . . . . . . 0

Electronic . . . . . . . . . . . . . . . 0

Other manufacturing. . . . . . 1

Nonmanufacturing . . . . . . . 3

Number of employees

Less than 5,000 . . . . . . . . . 0

5,000-9,999 . . . . . . . . . . . . . 0

10,000 or more . . . . . . . . . . 5

Table 9-7—Past Use of Genetic Screening Tests by

Fortune 500 Companies

Q.14. Has your company conducted any biochemical genetic

screening of any employees or job applicants, for research

or any other reason in the past 19 years?

(Base: Health officers)

Number of companies

conducted in past

Biochemical genetic screening’

Total . . . . . . . . . . . . . . . . . .

Type of business

Electrical utility . . . . . . . . . .

Pharmaceutical . . . . . . . . . .

Other chemical . . . . . . . . . .

Petroleum . . . . . . . . . . . . . .

Electronic . . . . . . . . . . . . . . .

Other manufacturing. . . . . .

Nonmanufacturing . . . . . . .

Number of employees

Less than 5,000 . . . . . . . . .

5,000-9,999 . . . . . . . . . . . . .

10,000 or more . . . . . . . . . .

8

0

0

4

0

0

2

2

0

1

7

SOURCE: Office of T~nology Assessment, 1990. ‘NOTE: Includes companies currently conducting genetic screening.

SOURCE: Office of Technology Assessment, 1990.

industry, two were in other manufacturing companies, and two were in nonmanufacturing firms.

Combined Genetic Monitoring and Screening:

1989 Survey Results

A total of 20 health officers reported that their

companies had conducted cytogenetic monitoring or

biochemical genetic screening, either currently or in

the past 19 years. This includes 12 health officers

who reported that genetic monitoring or screening

was currently conducted, and 8 who reported that

genetic monitoring or screening had been conducted

in the past 19 years, but not currently (table 9-8).

Six Fortune 500 health officers reported that their

companies had conducted cytogenetic monitoring,

either currently or in the past 19 years. One was in

a company currently conducting cytogenetic monitoring, while five were in companies that had

conducted cytogenetic monitoring in the past 19

years, but no longer conducted such monitoring.

Sixteen Fortune 500 health officers reported that

their companies had conducted biochemical genetic

screening, either currently or in the past 19 years.

Twelve health officers reported their companies

currently conducted genetic screening, while four

were in companies that conducted genetic screening

in the past 19 years, but not at the present time.

Overall Use of Genetic Monitoring and

Screening in 1989 and 1982

Trend data on the use of genetic monitoring or

screening can be obtained by tabulating comparable

questions in the 1989 and 1982 surveys. These are

general questions dealing with the use of genetic

monitoring or screening, and do not include items

added in 1989 on genetic monitoring or screening as

part of a voluntary wellness program, at the request

of an employee, or for diagnosis. Using this narrow

definition, the 1989 survey found a total of 20 health

officers in the Fortune 500 sample who reported that

their companies had conducted genetic monitoring

or screening, either currently or in the past 19 years.

In comparison, the 1982 survey found 18 health

officers in the Fortune 500 companies who reported

current or past use of genetic monitoring or screening (table 9-9). These figures suggest little change

between 1982 and 1989 in the number of companies

that had used genetic monitoring or screening in the

workplace.

In the 1982 survey, six health officers (1.6

percent) reported their companies currently conducted genetic monitoring or screening. In 1989, 12

health officers (5 percent) reported their companies

currently conducted genetic monitoring or screening. (These numbers do not directly correlate because of different sized survey populations in 1982
176 ● Genetic Monitoring and Screening in the Workplace

Table 9-8-Combined Testing: Current v. Past

Monitoring and Screening by Fortune 500 Companies

(Base: Health officers)

Number of

companies

Conducted genetic monitoring or screening for

research or any other reason, at present or

in past 19 years . . . . . . . . . . . . . . . . . . . . . . . . . 20

Currently conducting genetic monitoring or

screening . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12

Conducted monitoring or screening in past

only . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

Conducted genetic screening for research or any

other reason at present or in past 19 years . . 16

Currently conducting genetic screening . . . . . . . 12

Conducted genetic screening in past only . . . . . 4

Conducted cytogenetic monitoring for research or

any other reason at present or in past 19

years . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

Currently conducting cytogenetic monitoring . . . 1

Conducted cytogenetic monitoring in past

only . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5

Currently conducting direct-DNA screening for

research or any other reason . . . . . . . . . . . . . . . 0

Currently conducting direct-DNA monitoring for

research or any other reason . . . . . . . .: . . . . . . 0

SOURCE: Office of Technology Assessment, 1990.

and 1989.) The increase in the number of ‘‘current

users ‘‘ in 1989 could reflect slight differences in

question wording between the two surveys.

Of the six companies that reported current use of

genetic monitoring or screening in 1982, two were

in the chemical industry, two were electric utilities,

and two were in the electronics industry. In 1989, 12

companies reported current use of genetic monitoring or screening. Of those, all 12 conducted genetic

screening, while one also conducted cytogenetic

monitoring, Of the companies reporting current use

of genetic screening four were in the chemical

industry, one in the petroleum industry, two were

other types of manufacturers, and five were other

nonmanufacturing companies. None of the 12 companies was an electric utility or electronics firm. The

petroleum firm was the only company also reporting

current use of cytogenetic monitoring of any employees or job applicants in 1989.

No health officer from Fortune 500 companies

surveyed in 1989 reported conducting direct-DNA

monitoring or direct-DNA screening, either at the

time of the surveyor in the past. No question related

to direct-DNA monitoring and direct-DNA screening was asked in 1982.

Table 9-9—Use of Genetic Monitoring or Screening:

1989 v. 1982 Survey Results

(Base: Health officers)

Number of companies

1989 1982

Conducted genetic monitoring or

screening for research or any

other reason, at present or in

the past* . . . . . . . . . . . . . . . . . . . 20 18

Currently conducting genetic

monitoring or screening . . . . . . . 12 6

Conducted monitoring or screening

in past only . . . . . . . . . . . . . . . . . 8 12

*Defined as past 19 years in 1989 survey and past 12 years in 1982 survey.

SOURCE: Office of Technology Assessment, 1990.

In summary, in the 1989 survey 12 companies

reported current use of genetic monitoring or screening, while 8 companies reported conducting genetic

monitoring or screening in the past but were no

longer conducting such tests. The ratio of current to

past monitoring and screening was reversed in 1982,

with 6 companies indicating current use of genetic

monitoring or screening and 12 companies indicating past but not current use of monitoring or

screening. overall, OTA found that 20 companies

had used genetic monitoring or screening in 1989, as

compared to 18 companies in 1982.

General Use of Genetic Monitoring and

Screening Tests

A total of 27 health officers in Fortune 500

companies reported current or past use of genetic

monitoring or screening tests of any employees or

job applicants, for any reason, including research, as

part of a voluntary wellness program, or for diagnosis (table 9-10). In addition, one personnel officer

from a company not represented by the health

officers who returned surveys reported use of

genetic monitoring or screening. Thus, a total of 28

companies in the 1989 Fortune 500 sample

reported current or past use of genetic monitoring or screening tests.

Health officers reporting any experience with

genetic monitoring or screening included 17 who

reported that their companies were currently conducting genetic monitoring or screening, and 10 who

reported that their companies had conducted genetic

monitoring or screening in the past, but were not

currently conducting either. (Of those 17 companies,

5 are currently testing.) None reported current or past
Chapter 9-Genetics in the Workplace: Perceptions and Practice ● 177

Table 9-10-Summary Data on Use of Genetic

Monitoring and Screening: 1989 Results Among

Fortune 500 Companies

(Base: Health officers)

Number of

companies

Conducted genetic monitoring or screening for

research or any other reason, at present or in

past 19 years, including as part of a voluntary

wellness program, at the request of the

employee, or for diagnosis . . . . . . . . . . . . . . . . 27

Currently conducting genetic monitoring or

screening . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17

Conducted monitoring or screening in past

only . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10

Conducted direct-DNA screening or direct-DNA

monitoring. currently or in the past . . . . . . . . . . . 0

SOURCE: Office of Technology Assessment, 1990.

use of either direct-DNA monitoring or direct-DNA

screening by his or her company.

However, a number of health officers who

reported no current or past use of genetic

monitoring or screening tests, including testing

for voluntary wellness programs, at employee

request, and for diagnosis, did report use of

specific genetic screening tests listed in the

survey. Thus, responses to general questions on

genetic monitoring and screening appeared to

somewhat understate the prevalence of these

tests. Total use of genetic monitoring and screening

is discussed in the next section.

Total Use of Genetic Monitoring or Screening

A total of 33 health officers from the Fortune 500

companies reported that their companies had used

any type of genetic monitoring or screening, either

currently or in the past (table 9-11). In other words,

13 percent of the health officers from Fortune 500

companies responding to the survey reported that

their companies had used some type of genetic

monitoring or screening, either currently or in the

past. This measure of genetic monitoring or screening included testing as part of a voluntary wellness

program, at the request of the employee, or for

diagnosis. It also included health officers who

reported that their companies conducted one or more

specific biochemical genetic screening tests or

cytogenetic monitoring tests.

Counting all health officers from Fortune 500

companies who reported that their companies had

conducted genetic monitoring or screening, in one

Table 9-1 I—Total Prevalence of Genetic Monitoring or

Screening: 1989 Survey Results Among

Fortune 500 Companies

(Base: Health officers)

Number of companies with any

current or past use of genetic

monitoring or screening

Total . . . . . . . . . . . . . . . . 33

Number of employees

Less than 5,000 . . . . . . . 3

5,000-9,999 . . . . . . . . . . 3

10,000 or more . . . . . . . 27

Type of business

Electrical utility . . . . . . . . 0

Pharmaceutical . . . . . . . 3

Other chemical . . . . . . . 11

Petroleum . . . . . . . . . . . 3

Electronic . . . . . . . . . . . . 0

Other manufacturing . . . 5

Nonmanufacturing . . . . . 11

SOURCE: Office of Technology Assessment, 1990.

form or another, produced the most accurate measure of the total- use of genetic monitoring or

screening in 1989. It appears likely that the 1982

survey probably understated the prevalence of genetic monitoring and screening at that time, because

that questionnaire included a more limited set of

items on the use of genetic monitoring and screening. As the results from the 1989 survey indicate, a

fuller battery of questions likely detected all forms

of genetic monitoring and screening.

Twenty-seven of the thirty-three health officers

surveyed in 1989 who reported that their companies

had conducted genetic monitoring or screening were

in large companies with 10,000 or more employees.

Of the 33, 11 were in chemical companies, 3 were in

pharmaceutical fins, 3 were in petroleum companies, 5 were in other manufacturing companies,

and 11 were in nonmanufacturing firms.

The findings of the 1989 survey suggest that the

1982 survey may have underestimated the actual

prevalence of workplace use of the technology at

that time. The 1989 survey asked about past and

present use of genetic monitoring and screening in a

number of different contexts—screening to identify

increased susceptibility to workplace risk, as part of

a voluntary wellness program, at the request of the

employee, and for diagnosis—in addition to the set

of questions used in 1982. When all reports of

genetic monitoring and screening were taken into

account, the number of companies that had used

genetic monitoring or screening increased to 33 from
178 . Genetic Monitoring and Screening in the Workplace

18 companies in 1982. The larger number of

companies identified as using genetic tests appeared

to be almost entirely the result of additional questions about the use of genetic monitoring or screening, rather than changes in industry practices. Using

the comparable measures, the number of companies

that had ever conducted genetic monitoring or

screening had only increased from 18 in 1982 to 20

in 1989.

Future Use of Genetic Monitoring

and Screening

If there has been little or no real growth in the

number of companies conducting genetic monitoring and screening in the workplace, what do

companies foresee for the future? The 1982 OTA

survey found that 4 companies (1.1 percent) anticipated using the tests in the next 5 years, and 55

companies (15 percent) stated they would ‘ ‘possibly” use the tests in the next 5 years. In order to

avoid classifying an indefinite response as a positive

response to future genetic monitoring or screening,

the 1989 survey provided the response categories

‘‘yes, “ “no,” and ‘‘not sure’ for the same questions.

OTA found one Fortune 500 company that

anticipated cytogenetic monitoring, one company

that anticipated direct-DNA monitoring, and four

companies that anticipated biochemical genetic

screening. No company anticipated using directDNA screening in the next 5 years. Twenty-seven

companies in 1989 indicated they were not sure

whether they anticipated cytogenetic monitoring,

and 27 were not sure whether they anticipated

direct-DNA monitoring. For biochemical genetic

screening, 25 companies were not sure whether they

anticipated using it, and 23 were not sure about

future direct-DNA screening (table 9-12).1 In 1982,

55 companies said they would possibly use such test

in the next 5 years. Although this number cannot be

directly compared to the current survey, the 1989

OTA survey appear-s to indicate fewer companies

anticipate using genetic monitoring or screening.

Intervening events offered another possible explanation for the absence of expected growth since 1982

in industry adoption of the technology of genetic

monitoring and screening in the workplace. Specifically, the experience of other employers with genetic

monitoring and screening-publicity, criticism, employee problems—might have dissuaded some prospective users from adopting the technology. However, the survey found fewer than 10 cases among

Fortune 500 companies that had never used genetic

monitoring or screening in the past, reporting that

they had chosen not to use such tests as a result of the

experiences of other companies.

Genetic Monitoring for Other Reasons:

1989 Survey Results

Questions added to the 1989 survey covered

applications of genetic monitoring that had not been

specifically covered in the 1982 survey. Some health

officers reporting that their companies conducted

genetic monitoring and screening for these purposes,

however, did not report that their companies conducted genetic monitoring or screening “of any

employees or job applicants, for research or any

other reason.

One health officer reported past use of cytogenetic

monitoring at employee request and one reported

past use of cytogenetic monitoring as part of a

voluntary wellness program. One health officer

reported current use of cytogenetic monitoring for

diagnosis and one reported past use of cytogenetic

monitoring for diagnosis (table 9-13).

Genetic Screening for Other Reasons:

1989 Survey Results

Questions added to the 1989 survey covered

applications of genetic screening that had not been

specifically covered in the 1982 survey. Current use

of genetic screening was reported by two companies

for voluntary wellness, eight companies at employee

request, and seven for diagnosis (table 9-14). These

figures may overlap, since health officers were asked

to report all types of genetic screening conducted by

their companies. Past use of genetic screening for

voluntary wellness was reported by four health

officers, while five health officers reported past use

of genetic screening at employee request, and three

health officers reported past use of genetic screening

for diagnosis.

l~ese numbers cannot be added because of cross counting; nor do they directly correlate to the 55 COmpties because Of question WOrdiLlg. m

retrospec~ those who chose ‘possibly’ in 1982 might not have meant to indicate that genetic monitoring or screening was anticipated, they simply could

not rule out the possibility they would use it in the future.
Chapter 9-Genetics in the Workplace: Perceptions and Practice ● 179

Table 9-1 2—Consideration To Conduct Genetic Monitoring and Screening in the Next Five Years: Health Officers

Q.33. Does your company anticipate conducting any biochemical genetic screening, for any reason, in the next 5 years?

Q.34. Does your company anticipate conducting any cytogenetic monitoring, for any reason, in the next 5 years?

Q.35. Does your company anticipate conducting any direct-DNA screening, for any reason, in the next 5 years?

Q.36. Does your company anticipate conducting any direct-DNA monitoring, for any reason, in the next 5 years?

(Base: Health officers)

Percent

Yes No Not sure No answer

Biochemical genetic screening . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 218 25 3

Cytogenetic monitoring . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 219 27 3

Direct-DNA screening . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 224 23 3

Direct-DNA monitoring . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 218 27 4

SOURCE: Office of Technology Assessment, 1990.

Table 9-13-Prevalence of Genetic Monitoring for

Voluntary Wellness Programs at Employee Request

Q.19.

and for Diagnosis: Fortune 500 Companies

Has your company conducted any of the foIlowing tests

Specific Types of Cytogenetic Monitoring

Conducted in 1989

As with genetic screening, the 1989 survey asked

health officers in companies that had conducted

cytogenetic monitoring to list which specific types

of monitoring were being conducted. The survey

covered seven categories of cytogenetic tests. For

each test conducted, health officers were asked to

give the reason their companies were conducting the

test. The only cytogenetic tests reported were those

testing for chromosomal aberrations and sister

chromatid exchanges. No health officer reported

testing for mutations by assaying the DNA, enzymes/proteins, hypoxanthine-guanine phosphoribosyltransferase (HPRT) mutation rate, DNA adduct

formation, or by using other cytogenetic tests (table

9-15).

Only two reasons were reported for cytogenetic

monitoring: 1) testing as part of a voluntary research

program, and 2) testing as part of followup diagnosis. No health officers reported conducting cytogenetic monitoring as part of routine health surveillance,

as part of a voluntary wellness program, or at

employee request. Moreover, only one health officer

reported conducting cytogenetic monitoring for

followup diagnosis. Genetic monitoring for a voluntary research program was reported by three health

officers in companies monitoring for chromosomal

aberrations and three in companies monitoring for

sister chromatid exchanges.

(biochemical genetic screening, cytogenetic monitoring,

direct-DNA screening, direct-DNA monitoring), as part of a

voluntary wellness program, at the request of an employee,

or for diagnosis? (MARK ALL THAT APPLY)

(Base: Health officers)

Number of companies

Cytogenetic Direct-DNA

monitoring monitoring

As part of voluntary wellness

program

Currently . . . . . . . . . . . . . . . . . . . . .

In past 19 years . . . . . . . . . . . . . . .

No . . . . . . . . . . . . . . . . . . . . . . . . . .

Not sure . . . . . . . . . . . . . . . . . . . . . .

No answer/not applicable . . . . . . .

At the request of the employee

Currently . . . . . . . . . . . . . . . . . . . . .

In past 19 years . . . . . . . . . . . . . . .

No . . . . . . . . . . . . . . . . . . . . . . . . . .

Not sure . . . . . . . . . . . . . . . . . . . . . .

No answer/not applicable . . . . . . .

For diagnosis

Currently . . . . . . . . . . . . . . . . . . . . .

In past 19 years . . . . . . . . . . . . . . .

No . . . . . . . . . . . . . . . . . . . . . . . . . .

Not sure . . . . . . . . . . . . . . . . . . . . . .

No answer/not applicable . . . . . . .

0

1

113

3

132

0

1

111

4

133

1

1

107

9

131

0

0

114

2

133

0

0

111

4

134

0

0

108

9

132

SOURCE: Office of Technology Assessment, 1990.

Specific Types of Genetic Screening Tests

Conducted in 1989

The 1989 survey asked health officers in companies that had ever done biochemical genetic screening tests to list which specific genetic screening tests

were being conducted, and for each, to indicate the
180 ● Genetic Monitoring and Screening in the Workplace

Table 9-14-Prevalence of Genetic Screening for

Voluntary Wellness Programs, at Employee Request

and for Diagnosis: Fortune 500 Companies

Q.19. Has your company conducted any of the following tests

(biochemical genetic screening, cytogenetic monitoring,

direct-DNA screening, direct-DNA monitoring), as part of a

voluntary wellness program, at the request of an employee,

or for diagnosis? (MARK ALL THAT APPLY)

(Base: Health officers)

Number of companies

Biochemical

genetic Direct-DNA

screening screening

As part of voluntary wellness

program

Currently . . . . . . . . . . . . . . . . . . . . .

In past 19 years . . . . . . . . . . . . . . .

No . . . . . . . . . . . . . . . . . . . . . . . . . .

Not sure . . . . . . . . . . . . . . . . . . . . . .

No answer/not applicable . . . . . . .

At the request of the employee

Currently . . . . . . . . . . . . . . . . . . . . .

In past 19 years . . . . . . . . . . . . . . .

No . . . . . . . . . . . . . . . . . . . . . . . . . .

Not sure . . . . . . . . . . . . . . . . . . . . . .

No answer/not applicable . . . . . . .

For diagnosis

Currently . . . . . . . . . . . . . . . . . . . . .

In past 19 years . . . . . . . . . . . . . . .

No . . . . . . . . . . . . . . . . . . . . . . . . . .

Not sure . . . . . . . . . . . . . . . . . . . . . .

No answer/not applicable . . . . . . .

2

4

127

3

113

8

5

116

6

114

7

3

116

12

111

0

0

113

3

133

0

0

111

4

134

0

0

108

9

. . 132

SOURCE: Office of Technology Assessment, 1990.

purpose of the test. A total of 16 specific biochemical genetic screening tests were covered by the 1989

survey.

Genetic screening tests cited most frequently as

being conducted by Fortune 500 companies included: contact dermatitis, sickle cell trait, allergic

respiratory disease, serum alpha-l-antitrypsin deficiency, alpha and beta thalassemias, and glucose-6-

phosphate dehydrogenase (G-6-PD) deficiency.

Other genetic screening tests cited by one or two

health officers included methemaglobin reductase

deficiency, aryl hydrocarbon hydroxylase inducibility, slow v. fast acetylation, histocompatibility

markers, other immune system markers, Bloom

syndrome, and xeroderma pigmentosum. None reported conducting biochemical screening tests for

Fanconi syndrome, ataxia-telangiectasia, or other

heterozygous chromosomal instabilities (table 9-

16).

The 1989 survey asked whether the specific

biochemical screening tests were being conducted

on a routine basis for health surveillance, as part of

a voluntary research program, as part of followup

diagnosis, as part of a voluntary wellness program,

or at the request of an employee. Obtaining a

followup diagnosis and responding to an employee

request were the two reasons given most often for

conducting biochemical genetic screening. Followup diagnosis was cited by 13 health officers in

companies testing for contact dermatitis, 11 in

companies testing for allergic respiratory disease, 7

in companies testing for serum alpha- 1-antitrypsin

deficiency, 6 in companies testing for sickle cell

trait, and 6 in companies testing for alpha and beta

thalassemias. Genetic screening at employee request

was listed by 12 health officers in companies testing

for sickle cell trait and 5 in companies testing for

allergic respiratory disease. In addition, testing as

part of routine health surveillance was reported by

six health officers in companies testing for allergic

Table 9-15—Types of Cytogenetic Monitoring Conducted in 1989 by Fortune 500 Companies

Q.21. Which of the following types of cytogenetic monitoring are being conducted by your company of any employees?

(Base: Health Officers in companies that have conducted cytogenetic monitoring)

Number of companies

Routine Voluntary Voluntary At

health research Followup wellness employee

surveillance program diagnosis program request

Chromosomal aberrations . . . . . . 0 3 1 0

Sister chromatid exchanges . . . . 0 3 0 0 :

Mutations by assaying the DNA . 0 0 0 0 0

Mutations by assaying the

enzyme/protein . . . . . . . . . . . . . 0 0 0 0 0

HPRT mutation rate . . . . . . . . . . . 0 0 0 0 0

DNA adduct formation . . . . . . . . . 0 0 0 0 0

Other (specify) . . . . . . . . . . . . . . . 0 0 0 0 0

SOURCE: Office of Technology Assessment, 1990.
Chapter 9-Genetics in the Workplace: Perceptions and Practice ● 181

Q.20.

Table 9-16-Types of Biochemical Genetic Screening Conducted by Fortune 500 Companies

Which of the following types of biochemical screening tests are being conducted by your company of any employees or job

applicants? For each test conducted, mark whether the testing is being done on a routine basis for health surveillance, as part of

a-voluntary research program, as part of followup diagnosis, or only at the request of an employee.

(Base: Health officers)

Number of companies

Routine Voluntary Voluntary At

health research Followup wellness employee

surveillance program diagnosis program request

Sickle cell trait . . . . . . . . . . . . . . . 1 0 6 3 12

Glucose-6-phosphate dehydrogenase (G-6-PD) deficiency . . . 0 1 3 2 3

Methemaglobin reductase

deficiency . . . . . . . . . . . . . . . . . 1 0 0 1 0

Serum alpha-1 -antitrypsin

deficiency . . . . . . . . . . . . . . . . . 1 0 7 2 4

Alpha and beta thalassemias . . . 0 0 6 2 4

Aryl hydrocarbon hydroxylase

(AHH) inducibility . . . . . . . . . . . 0 0 0 1 0

Slow v. fast acetylation . . . . . . . . . 0 0 0 1 0

Allergic respiratory disease . . . . . 6 11 1 5

Contact dermatitis . . . . . . . . . . . . . 5 ; 13 1 4

Histocompatibility markers (HLA). o 0 0 1 0

Other immune system markers . . 0 0 1 0 1

Bloom syndrome . . . . . . . . . . . . . 0 0 0 1 0

Fanconi syndrome . . . . . . . . . . . . 0 0 0 0 0

Ataxia-telangiectasia . . . . . . . . . . 0 0 0 0 0

Xeroderma pigmentosum . . . . . . 0 0 1 0 0

Other heterozygous chromosomal instabilities . . . . . . . . . . . 0 0 0 0 0

SOURCE: Office of Technology Assessment, 1990.

respiratory disease and five health officers in companies testing for contact dermatitis.

As previously noted, some health officers who

reported that their companies conducted specific

biochemical genetic screening tests did not report

that their companies had conducted genetic monitoring or screening, at present or in the past 19 years,

including testing for voluntary wellness programs, at

employee request, or for diagnosis. Each of the

following genetic screening tests was reported as

being currently conducted by more than one health

officer who reported no current or past genetic

monitoring or screening tests: sickle cell trait,

serum-1-antitrypsin deficiency, allergic respiratory

disease, and contact dermatitis (table 9-17). In

addition, each of the following tests was reported as

being currently conducted by one health officer who

had reported no current or past use of genetic

screening or monitoring: G-6-PD deficiency, alpha

and beta thalassemias, and xeroderma pigmentosum.

Reasons for Conducting Genetic Monitoring

and Screening

Personnel officers in the Fortune 500 companies

that conducted genetic monitoring or screening were

asked: “To the best of your knowledge, which of the

following were important factors in the decision to

conduct genetic monitoring or screening of employees in your company?” Six possible reasons for

conducting genetic monitoring or screening were

listed. Only six personnel officers responded to this

set of questions.

Four of the six personnel officers in companies

conducting genetic monitoring and screening reported that cost-benefit analysis was an important

factor in the decision by their companies to conduct

genetic monitoring or screening of employees (table

9-18). Four personnel officers also reported that the

evidence of a possible association between chemical

exposure and illness in epidemiological studies was

an important reason in the decision by their compa-
182 ● Genetic Monitoring and Screening in the Workplace

Table 9-17-Specific Biochemical Genetic Screening Tests Reported by Companies Reporting No Genetic

Monitoring or Screening Among Fortune 500 Companies

Q.20. Which of the following types of biochemical screening tests are being conducted by your company of any employees or job

applicants?

(Base: Health officers in companies reporting no monitoring or screening)

Number of companies

Routine Voluntary Voluntary At

health research Followup wellness employee

surveillance program diagnosis program request

Sickle cell trait . . . . . . . . . . . . . . . 0 0 1 1 2

Glucose-6-phosphate

dehydrogenase (G-6-PD)

deficiency . . . . . . . . . . . . . . . . . 0 0 0 1 0

Methemaglobin reductase

deficiency . . . . . . . . . . . . . . . . . 0 0 0 0 0

Serum alpha-1-antitrypsin

deficiency . . . . . . . . . . . . . . . . . 0 0 1 1 1

Alpha and beta thalassemias . . . 0 0 0 1 0

Aryl hydrocarbon hydroxylase

(AHH) inducibility . . . . . . . . . . . 0 o “ o 0 0

Slow v. fast acetylation . . . . . . . . . 0 0 0 0 0

Allergic respiratory disease . . . . . 0 0 4 0 1

Contact dermatitis. . . . . . . . . . . . . 0 0 4 0 1

Histocompatibility markers (HLA). o 0 0 0 0

Other immune system markers . . 0 0 0 0 0

Bloom syndrome . . . . . . . . . . . . . 0 0 0 0 0

Fanconi syndrome . . . . . . . . . . . . 0 0 0 0 0

Ataxia-telangiectasia . . . . . . . . . . 0 0 0 0 0

Xeroderma pigmentosum . . . . . . 0 0 1 0 0

Other heterozygous chromosomal instabilities . . . . . . . . . . . 0 0 0 0 0

SOURCE: Office of Technology Assessment, 1990.

nies to conduct genetic monitoring and screening of

employees.

In addition, three personnel officers reported that

the legal consequence of a failure to test was an

important reason in the decision to conduct genetic

monitoring or screening. One personnel officer

reported that evidence of a possible association

between chemical exposure and illness in animal

studies was an important factor, and one personnel

officer reported that union or employee initiative

was an important factor in the decision to conduct

genetic monitoring or screening. None of the six

personnel officers reported “something else” as an

important factor in the decision to conduct genetic

monitoring and screening.

Actions Taken as a Result of Genetic

Monitoring or Screening

The survey found relatively few instances of

negative personnel decisions as a result of genetic

monitoring or screening. Only one corporate personnel officer for the Fortune 500 companies reported

ever rejecting a job applicant, primarily or partly,

based on the results of a genetic screening test.

Similarly, a single corporate health officer reported

ever suggesting an employee seek a job elsewhere,

as a result of a genetic monitoring or screening

program. (In 1982, a comparable two companies

reported that they had suggested an employee seek

a job elsewhere.)

No instances were reported by personnel officers

from Fortune 500 companies in the 1989 survey of

cases in which employees were transferred or

terminated, primarily or partly, based on the results

of genetic monitoring or screening. Health officers

in three Fortune 500 companies, however, reported

that their companies, as a result of a genetic

monitoring or screening program, had transferred or

placed employees in different jobs within their

companies. This is comparable to the five companies

that reported transferring employees in the 1982

survey.

Although instances of genetic monitoring and

screening were rare, the health officers in Fortune

500 companies that had done it were at least as likely

to report that the genetic monitoring and screening
Chapter 9--Genetics in the Workplace: Perceptions and Practice ● 183

had resulted

Table 9-18-Factors in the Decision To Conduct Genetic Monitoring or Screening of

Employees Among Fortune 500 Companies

Q.13. To the best of your knowledge, which of the following were important factors in the decision to

conduct genetic monitoring or screening of employees in your company?

(Base: Personnel officers answering question)

Number of personnel officers

Unweighed Not

base Important important

Cost-benefit analysis . . . . . . . . . . . . . . . . (6) 4 2

Evidence of a possible association

between chemical exposure and

illness in animal studies . . . . . . . . . . . . (6) 1 5

Evidence of a possible association

between chemical exposure and

illness in epidemiological studies . . . . (6) 4 2

Legal consequence of failure to test . . . . (6) 3 3

Union/employee initiative. . . . . . . . . . . . . (6) 1 5

Something else (please specify) . . . . . . . (1) o 1

SOURCE: Office of Technology Assessment, 1990.

in changes in the workplace, as had

resulted in changes in workers. A number of health

officers reported that, as a result of genetic monitoring and screening programs, their companies had:

. recommended personal protection devices (five

in 1989, compared to three in 1982); 

● implemented engineering controls (four in

1989, compared to two in 1982);

. implemented a research program (four in 1989,

compared to one in 1982); or

. discontinued a product or changed materials in

a product (two in 1989, compared to one in

1982).

In Summary, only a small proportion of companies had conducted any form of genetic monitoring

or screening, and such monitoring and screening, in

most cases, had not generated personnel action

against employees or changes in the workplace. The

findings of the 1989 survey are virtually identical to

the 1982 survey in these areas.

The 1989 survey finds little evidence that

companies anticipate the use of any kind of

genetic monitoring or screening in the foreseeable future. Personnel officers in this representative, national sample of companies with 1,000 or

more employees were asked whether or not they

anticipated that their companies would conduct

biochemical genetic screening, DNA-based screening, cytogenetic monitoring, or DNA-based monitoring within the next 5 years, either on a mandatory

or voluntary basis. The survey found only 2 percent

of companies with 1,000 or more employees anticipated any form of mandatory genetic monitoring or

screening within the next 5 years, while another 3

percent said they anticipated conducting some form

of genetic monitoring or screening on a voluntary

basis.

Survey Results without Certain Tests Included

In the original 1982 survey, certain tests were

included in the basic definition of biochemical

genetic screening tests. The 1989 survey, however,

did not contain those specific tests in the definition

of biochemical genetic screening. Instead, they were

added to a later question that asked which types of

biochemical screening tests were conducted by the

company of employees or applicants. This means

that the proportion of the 1989 survey findings

concerning the prevalence of biochemical genetic

screening attributable to certain tests (the nongenetic

tests) can be identified. Two tests were identified in

the 1989 survey that were included in the 1982

survey as being nongenetic tests—allergic respiratory disease and contact dermatitis.

A variable from the responses to the question

asking which types of screening tests were conducted was constructed from the health officer’s

questionnaire. (Note: This could only be done for the

long survey forms returned by mail, not the short

forms conducted by telephone, which were identical

to the 1982 survey-but which yielded no genetic

testers.) If the respondent said yes to either allergic

respiratory disease or contact dermatitis in this

question, but no to other tests in this question, the

respondent was labeled “nongenetic only. ” Re-
184 ● Genetic Monitoring and Screening in the Workplace

spondents saying yes to either of these tests, in

addition to other tests in the question, were labeled

“both.” Those responding yes to other tests in this

section, but not to either of the two nongenetic tests,

were labeled “genetic only. ”

This constructed variable was run against the two

questions about biochemical genetic screening—

whether companies were currently screening and

what their past screening history was—as well as

against the general banner, which included all of the

definitions of genetic monitoring and screening.

There were a total of 10 cases (weighted) in which

genetic screening tests of allergic respiratory disease

or contact dermatitis were reported, but none of the

other biochemical genetic screening tests were

specified. This includes 5 (weighted) of the 18

(weighted) cases in which respondents are identified

as ‘‘current users’ of genetic monitoring and

screening. The other 5 cases were only picked up in

the ‘‘total test’ variable, which includes individuals

reporting any of the tests from the question, regardless of whether they reported that they were conducting ‘‘genetic tests. ’

If these are not genetic screening tests, then the

prevalence of genetic screening is even less (29

percent less for both the traditional definition and the

expanded definition) than previously estimated in

1982, when these tests were explicitly part of the

question. In 1989, there were five respondents that

said they were conducting biochemical genetic

screening, and apparently these were the only tests

they reported conducting (contact dermatitis and

allergic respiratory disease).

Survey Results of the 1,000+ Companies:

Current Use

Less than one-half of 1 percent of companies with

1,000 or more employees reported they were currently conducting cytogenetic monitoring of any

employees or job applicants, for research or any

other reason. Such cytogenetic monitoring was

currently conducted by no company with 1,000 to

4,999 employees, 2 percent of companies with 5,000

to 9,999, and 2 percent of companies with 10,000 or

more employees.

Three percent of health officers in companies with

1,000 or more employees reported that their companies were currently conducting biochemical genetic

screening of any employees or job applicants, for

research or any other reason. Seven percent of

companies with 10,000 or more employees reported

current genetic screening, compared with 4 percent

of those with 5,000 to 9,999 employees and less than

3 percent of companies with fewer than 5,000

employees (table 9-19).

No health officer in a company with 1,000 or more

employees reported currently conducting directDNA monitoring of any employees or job applicants, for research or any other reason. Similarly,

none reported currently conducting direct-DNA

screening of any employees or job applicants.

Survey Results of the 1,000+ Companies:

Past Use

OTA found that few companies have ever conducted genetic monitoring and screening of workers

and job applicants for any purpose. Six percent of

health officers in companies with 1,000 or more

employees reported that their companies had conducted genetic monitoring or screening tests within

the past 19 years, for research or any other reason.

This included companies that had conducted genetic

monitoring or screening as part of a voluntary

wellness program, for diagnosis, or at the request of

the employee. It also included reported use of

specific genetic screening tests listed in the survey.

Larger companies were most likely to have

conducted genetic monitoring or screening tests of

job applicants or employees. Seventeen percent of

health officers from companies with 10,000 or more

employees reported that their companies had used

genetic monitoring or screening tests, of some kind,

in the past. By contrast, use of genetic monitoring or

screening was reported by only 5 percent of health

officers from companies with 5,000 to 9,999 employees and 4 percent in companies with 1,000 to

4,999 employees.

UNIONS AND GENETIC

MONITORING AND SCREENING

A total of 10 unions responded to the OTA survey,

out of the 33 unions that were mailed the survey.

This response rate of 30.3 percent was close to the

36.4 percent response rate (4 out of 11) reported for

the 1982 survey. Unions responding to the 1989

survey represented workers in a wide variety of

occupations. The 10 unions ranged in size from 1

with less than 100,000 members to 2 with more than

1 million members each. A total of 5.1 million
Chapter 9-Genetics in the Workplace: Perceptions and Practice ● 185

Table 9-19—Current Use of Genetic Monitoring or Screening Tests Among Companies With

1,000 or More Employees

Q.13. Is your company currently conducting biochemical genetic screening of any employees or job applicants, for research or any other

reason?

Q.15. Is your company currently conducting cytogenetic monitoring of any employees or job applicants, for research or any other reason?

Q.17. Is your company currently conducting direct-DNA screening of any employees or job applicants, for research or any other reason?

Q.18. Is your company currently conducting direct-DNA monitoring of any employees or job applicants, for research or any other reason?

(Base: Health Officers)

Percent of companies currently conducting

Biochemical

genetic Cytogenetic Direct-DNA Direct-DNA

screening monitoring screening monitoring

Total . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (546) 3 ●o 0

Type of business

Electrical utility . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ( 39) 1 0 0 0

Pharmaceutical . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (22) 5 0 0 0

Other chemical . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (47) 7 0 0 0

Petroleum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (5) o 0 0 0

Electronic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (21) 2 0 0 0

Other manufacturing . . . . . . . . . . . . . . . . . . . . . . . . . (1 79) 4

●

o 0

Nonmanufacturing . . . . . . . . . . . . . . . . . . . . . . . . . . . (233) 3 1 0 0

Number of employees

Less than 5,000 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72;)3 o 0 0

5,000-9,999 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 2 0 0

10,000 or more . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (167) 7 2 0 0

less than 1%.

SOURCE: Office of Technology Assessment, 1990.

members were represented

spending to the survey.

Genetic Monitoring

by the 10 unions

and Screening

reconducted by Unions

None of the 10 unions responding to the survey

reported that it now conducted genetic screening,

cytogenetic monitoring, direct-DNA screening or

direct-DNA monitoring of members or potential

members, or had conducted such tests in the past.

However, one union did report that it conducted tests

for allergic respiratory disease and contact dermatitis as part of a voluntary research program. The same

union wrote under ‘‘other’ cytogenetic tests that it

does conduct a ‘‘review of ailments & material

safety data sheets. ” The respondent also reported

that the union had conducted genetic monitoring or

screening of its members based on job exposures.

Three reasons were given as important factors in the

union’s decision to conduct genetic screening:

evidence of a possible association between chemical

exposure and illness in epidemiological studies;

union-employee initiative; and “individual rights &

privacy.’ It should be noted that the respondent

wrote: “Union does not conduct any genetic monitoring or screening tests. ” On the other hand, the

respondent also indicated that the union had conducted genetic monitoring or screening of its members based on job exposures.

A second union reported arranging biochemical

genetic screening tests and cytogenetic monitoring

tests for a union member, at the request of the

member, in the past 19 years. These tests were for

allergic respiratory disease, contact dermatitis, histocompatibility markers, other immune system

markers, other heterozygous chromosomal instabilities, and chromosomal aberrations. The respondent

explained:

Our own medical staff consists of two physicians

on retainer, who also have faculty appointments at

university medical schools. So far as I know, they

have not conducted genetic monitoring and screening tests themselves. In rare cases, they have referred

patients for testing to assist in diagnosis.

A third union respondent reported no genetic

monitoring or screening but was ‘not sure’ whether

the union was currently conducting biochemical

genetic screening tests. Thus, a total of two unions

appeared to have some limited experience in conducting one or more genetic monitoring or screening

tests, or arranging these tests for their members. This
186 . Genetic Monitoring and Screening in the Workplace

limited experience in conducting genetic monitoring

and screening was consistent with the prevalence of

genetic monitoring and screening reported by large

companies, particularly since one union only arranged for genetic monitoring and screening without

conducting it itself. None of the unions responding

to the survey employed or contracted with a genetic

counselor.

Genetic Monitoring or Screening

Conducted by Companies

Three of the ten unions responding to the survey

reported that companies had conducted genetic

monitoring or screening tests of their members. All

three unions reported that such tests were based on

job exposures. One union reported that the company

conducted genetic monitoring of its members to

identify increased individual susceptibility to

workplace risk. A second union reported that company genetic monitoring or screening were also

based on family history and cofactors (e.g., smoking). A third union reported that company genetic

monitoring or screening were also based on ethnicracial background. (This was the same union that

had referred a few members to outside doctors for

genetic monitoring or screening.)

In addition, two union respondents reported that

they did not know whether companies had conducted genetic monitoring or screening of their

members. One respondent was unable to answer the

survey question on whether companies had conducted genetic monitoring or screening of its members, as well as many other questions, because

“there are 15,000 employers with enormous variations in size, practice and policy. No general

conclusions can be drawn.

None of the 10 unions reported that genetic

monitoring or screening were used by a company,

primarily or partly, to reject a union member

applying for a job. One union was not sure whether

a company had used genetic monitoring or screening

to reject a job applicant.

However, one union did report that a company

had transferred or terminated a union member based

on the results of genetic monitoring or screening.

This case took place 1 to 2 years ago. The job action

involved hypersensitivity to isocyanates. Consistent

with limited union experience in job terminations

involving genetic monitoring and screening, no

union reported that biochemical and cytogenetic

tests were used as rejection categories in statistical

data on the reasons for job terminations. However,

it should be noted that only one union reported

maintaining statistical data on the reasons for job

terminations, using medical but not genetic criteria

as rejection categories.

Union Positions on Genetic Monitoring

and Screening

Four unions reported having a formal policy

related to the use of genetic screening of employees

or job applicants. Two of these unions also had a

formal policy related to the use of genetic monitoring of employee health.

The only union to report making recommendations to companies as a result of genetic monitoring

and screening was one whose members reported

genetic monitoring or screening by companies and

which had also referred a few of its members to

outside doctors for genetic monitoring or screening.

Specifically, the union recommended that the company(ies) implement engineering controls, provide

personal protection devices, implement a research

program, and discontinue a product or change

materials in a product. The union also recommended

that a company change its workplace practice or

exposure level due to the results of genetic monitoring in establishments where the union is not

represented. No other union responding to the

survey reported having made recommendations for

company changes in the workplace as a result of

genetic monitoring or screening.

One union reported having engaged in contract

negotiations covering the topic of genetic monitoring and/or screening. It reported that companies had

conducted genetic monitoring of its members. The

union had a formal policy for the use of genetic

screening, but not monitoring. The union respondent

took the following position:

We assume that, as with many types of employer

surveillance of workers, genetic monitoring and

screening are going on without any formal notification to workers or the union, much less any request

for consent. Notification and consent (including

provision of payment for scientific peer review by

trade union medical consultant) should be mandated.

Furthermore, employer genetic testing should be

limited to monitoring, and screening prohibited.

Questions of suitability of an employee for continued work should be resolved by worker and private

physician, in a confidential manner, No individual’s
Chapter 9--Genetics in the Workplace: Perceptions and Practice . 187

results should be reported to employers directly—

only the collective results. In other words, employersponsored health research on workers should be

conducted according to the same rules as any

NIH-sponsored research, complete with Human

Subjects Review Board oversight and doctor/patient

confidentiality. Just because an employer pays for it

does not justify the abandonment of these fundamental concepts.

Answers to survey questions showed that for

some unions, the perceived acceptability of genetic

monitoring or screening depended on the circumstances. Unions were divided on the acceptability of

genetic monitoring or screening of employees or job

applicants by employers:

● to make a clinical diagnosis of a sick member—

five found it generally acceptable, four found it

generally unacceptable;

● to monitor chromosomal changes associated

with workplace exposures-five found it generally acceptable, four found it generally unacceptable; and

. to inform members of their increased susceptibility to workplace hazards-four found it

generally acceptable, five found it generally

unacceptable.

In contrast, genetic monitoring or screening was

viewed as generally unacceptable: to establish links

between genetic predisposition and workplace hazards (seven unions); to establish evidence of

preemployment health status for liability purposes

(eight unions); and to exclude members with increased susceptibility to workplace hazards (eight

unions). Consistent with union opposition to using

genetic monitoring and screening to exclude members with increased susceptibility to workplace

hazards, eight unions viewed health examinations to

identify job applicants with genetic susceptibility to

workplace exposures as unacceptable.

Unions took issue with the idea that employers

should have control over the use of genetic monitoring and screening tests. All nine unions expressing

an opinion disagreed with each of these three

statements:

. The employer should have the option of deciding how to use the information obtained

through genetic monitoring and screening.

. The decision to perform genetic screening of

job applicants and employees should be the

employers.

● The decision to perform genetic monitoring of

employees should be the employers.

One union qualified disagreement to the above

three items by explaining that employers and unions

should both have a say, but that the decision whether

to perform genetic monitoring and screening was the

employer’s.

Unions also showed a general consensus on two

other questions. Nine unions disagreed-with eight

expressing strong disagreement-that ‘ ‘it’s fair for

employers to use genetic screening to identify

individuals whose increased risk of occupational

disease poses a threat for greater costs to the

employer. ” Eight unions agreed strongly that “genetic screening in the workplace represents a potential threat to the rights of employees.” However,

there was no consensus among the unions on the

desired role of government concerning genetic

monitoring and screening. Five unions agreed

strongly or somewhat with the statement that “government agencies should provide guidelines for

genetic screening of job applicants and employees,’

but four disagreed strongly. Similarly, six unions

agreed that “government agencies should provide

guidelines for genetic monitoring of employees,”

but three disagreed strongly. The survey asked:

If an employer becomes aware that an employee

has a genetic susceptibility to serious illness if he or

she is exposed to substances in the workplace, do

you think the employer should exclude that employee from those jobs for which he/she is at

increased risk, or do you think the employer should

allow the employee to take those jobs, if he/she

waives corporate liability?

Three unions thought the employee should be

excluded, while two thought the employee should be

allowed to take the job. Another two unions said that

the employee should be allowed to take the job, but

there should be ‘no waiver of liability’ or no waiver

of liability ‘‘to the point of no coverage. ’ One union

said the decision depended on the nature of the

exposure, and the availability of work. Two union

respondents did not answer the question. One of

these respondents criticized the question as inherently biased because it did not offer the responses of

“preventing risks by ameliorating the conditions

and reducing exposure’ or ‘transferring susceptible
188 ● Genetic Monitoring and Screening in the Workplace

workers to other jobs with guarantees of pay and job

security. ’

Unions and the Future of Genetic Monitoring

and Screening

None of the 10 unions was currently considering

conducting, or anticipated conducting, biochemical

genetic screening, cytogenetic monitoring, directDNA screening or direct-DNA monitoring, for any

reason in the next 5 years.

One respondent was not sure whether the union

anticipated conducting cytogenetic monitoring in

the next 5 years, and was also not sure whether the

union anticipated conducting any direct-DNA monitoring over that period. This union was “not

opposed to genetic monitoring as research, or in

diagnosis, where the investigation focuses on the

relationship between workplace exposure and genetic damage. ” This union’s medical staff had

referred a few patients for genetic monitoring or

screening to assist in diagnosis.

Another union respondent did not answer the

question on whether the union anticipated conducting any biochemical genetic screening in the next 5

years. However, it should be noted that the respondent commented that “employer genetic testing

should be limited to monitoring, and screening

prohibited. Questions of suitability of an employee

for continued work should be resolved by worker

and private physician, in a confidential manner. ’

Many of these unions viewed genetic screening in

the workplace as a threat to the rights of employees

and were strongly opposed to employers having

control over the decision to perform genetic monitoring or screening of employees. Half of the unions

regarded genetic monitoring or screening as generally acceptable to diagnose sickness and monitor

chromosomal changes resulting from workplace

exposures. However, most were opposed to genetic

screening to link genetic predisposition to

workplace hazards, exclude members with increased

susceptibility from risk situations or establish evidence of preemployment health status for liability

purposes.

Given these views, unions may be expected to

object to large-scale use of genetic monitoring or

screening mandated by employers without union

involvement and consent. The survey suggests that

some unions might approve of genetic monitoring or

screening, but only for limited purposes, under

carefully controlled circumstances agreed on by

unions and management.

1.

2.

3.

4.

5,

CHAPTER 9 REFERENCES

Business Week-Lou Harris Poll, “It’s OK To ‘Play

God’ -Within Limits,” Business Week 2921:85,

1985.

National Science Board, National Science Foundation,

Science Indicators, 1980: An Analysis of the State of

U.S. Science and Engineering, and Technology

(Washington, DC: U.S. Government Printing Office,

1981).

National Science Board, National Science Foundation,

Science Indicators, 1984: An Analysis of the State of

U.S. Science and Engineering, and Technology

(Washington, DC: U.S. Government Printing Office,

1985).

U.S. Congress, Office of Technology Assessment,

New Developments in Biotechnology: Public Perceptions of Biotechnology, OTA-BP-BA45 (Washington, DC: U.S. Government Printing Office, May

1987).

U.S. Congress, Office of Technology Assessment, The

Role of Genetic Testing in the Prevention of Occupational Disease, OTA-BA-194 (Washington, DC: U.S.

Government Printing Office, April 1983).
Appendixes
Appendix A

Basic Tenets of Human Genetics

Basic Human Genetics

The chemical bearer of genetic information is DNA,

which takes the structural form of a double-stranded helix

(figure A-l). DNA is composed, in part, of four chemical

subunits called bases. These four bases—guanine (G),

adenine (A), thymine (T), and cytosine (C)-are the

coding units of genetic information. The bases normally

pair predictably-A with T, and G with C (figure

A-2)—to form the DNA double helix structure. The order

and organization of the base pairs determines all genetic

information. Genes, which are segments of DNA, come in

many different sizes ranging from 1,000 to 1 million base

pairs in length. A mutant gene results in an altered amino

acid sequence, which can alter the protein in such a way

that clinical symptoms arise.

Genes are organized in microscopically visible bundles

called chromosomes (figure A-3). The chromosomal

constitution of each individual is derived equally from

mother and father. In humans, 23 chromosomes are

contributed by each parent in the gamete (egg or sperm),

resulting in a total of 46 chromosomes-22 pairs of

autosomes and 1 pair of sex chromosomes (two X

chromosomes for females and an X and a Y for males).

The entire complement of genetic material in this set of

chromosomes, about 3.3 billion base pairs-50,000 to

100,000 structural genes—is called the human genome.

Only about 2 percent of the genes have been identified

along the chromosomes.

The physical location of a gene on a chromosome is

called its locus. Some genes have been mapped and

cloned and can be identified directly at their locus. But it

is the exception that the direct link between one gene, one

locus, and one disease can be made. Most diseases are

multifactorial and polygenic; i.e., several genes in combination with specific environmental factors act together to

produce the disease state.

Because chromosomes come in pairs, there are two

copies of a gene at each locus, one inherited from each

parent. Different “versions” of a gene at a particular

locus are called alleles. When two or more alleles of a

gene are found at a particular locus in the population, the

genetic variants are referred to as polymorphisms. Polymorphisms (i.e., common genetic differences between

people) play an important role in diagnosing genetic

diseases.

The term ‘mutation’ refers to a change in the sequence

or number of nucleotides in a gene. Mutations arise

through a number of mechanisms: through environmental

agents as mentioned previously, or through normal

cellular processes. Not all mutations cause disease,

although that is the reference in which the term is

commonly used. Mutations that form in germline cells

that produce eggs and sperm are inherited by offspring,

whereas those that occur in somatic cells remain only in

the descendants of those cells in the affected individual.

This distinction is critical in distinguishing between

monitoring and screening. Genetic screening can detect

traits that are caused by mutations in both somatic

and germ cells, whereas monitoring generally detects

mutations that have occurred in that population of

somatic cells being tested and cannot be extrapolated

to other tissues.

Genetics and Disease

The link between familial factors and certain health

conditions has long been recognized. A useful classification of the genetic basis of disease is disorders caused by:

. a single mutant gene (monogenic);

. chromosomal aberrations;

● genetic predisposition combined with environmental

interaction (multifactorial); and

● changes in the somatic cells (cancer, aging, autoimmune disease, and some congenital malformations).

Figure A-l—The Structure of DNA

SOURCE: of Technology Assessment, 1990.

–191–
192 ● Genetic Monitoring and Screening in the Workplace

Figure A-2—DNA Base Pairing

Phosphate Molecule

/

Deox 

Sugar Molecule

I Nitrogenous

o\

0,

0,

 o

‘CH

0 0

Weak Bonds Between

Base Pairs

/o-

‘ 0

,/o-

‘ 0

,/o-

‘ 0

which are referred to as alleles. Each individual carries

two sets of genes, one from each parent. If the two

members of a pair of genes are the same, the individual is

considered to be homozygous for that locus. If the two

members of the pair are different, the individual is said to

be heterozygous for the locus. Such an individual has the

trait, but not necessarily the disease. Heterozygotes for

certain traits, therefore, make two kinds of gene products

from their two genes. If only one functional gene is

needed to produce sufficient protein activity, the individual will be normal for that trait and the mutant allele will

be considered recessive. If, however, the one mutant

allele is sufficient to produce a defect in the individual, the

trait is considered dominant.

Most often, single gene mutations, whether transmitted

recessively or dominantly, cause a defect in enzymes that

may cause “inborn errors” of metabolism and transport.

These errors result from lack of a functional enzyme and

may

●

●

●

●

result in:

diseases resulting from absence of the end product;

diseases resulting from the accumulation of substrates or metabolizes;

diseases resulting from interference with regulatory

mechanisms; and

diseases where there is an inborn error of membrane

transport.

Single gene mutations can also cause amino acid

substitutions that produce “hemoglobinopathies’ (hemoglobins with abnormal functions). Sickle cell anemia

is a common form of hemoglobinopathy. The mutant gene

in this disease causes an abnormality in hemoglobin

which distorts the red blood cells, resulting in small blood

vessel blockage and subsequent oxygen deficit.

Some 400 gene products of the approximately 3,000

known single gene disorders have been identified (5).

The nature of the mutations involved, however, has

only been determined in 45 of these disorders (see table

A-l). Better understanding of the nature of the mutation

leads to increased capabilities for diagnosis, both prenatally and in children and adults and, in a few disorders, has

- 1 resulted in improved treatment for affected individuals.

 The Sugar-Phosphate 

Backbone

The four bases of DNA, guanine (G), adenine (A), thymine (T), and cytosine

(C) form the four letters of the genetic code. The pairing of the four bases

is A with T, and G with C, It is the sequence of bases along the strand of DNA

encodes the genetic information.

SOURCE: Office of Technology Assessment, 1990.

Single Gene Disorders

A gene can be altered by a “point” mutation (i.e., a

change in only a single base pair) resulting in an altered

protein or function for which it codes. Thus, a gene can

have several functional and dysfunctional variants, all of

Critical to diagnosis and treatment has been understanding the mode of inheritance of the mutant gene. The

three modes of inheritance are discussed below. Figure

A-4 illustrates the various modes of inheritance for single

gene disorders. The figure represents a pedigree or family

tree, the standard tool used by geneticists tracking the

history and mode of inheritance of genetic disease in

families.

Autosomal Dominant Inheritance

If the mutant gene is located on one of the autosomes

(not a sex chromosome) and it is dominant, every affected
Appendix A--Basic Tenets of Human Genetics ● 193

Figure A-3-Chromosome Complement of a Normal Human Female

SOURCE: The Genetics & Institute, Fairfax, VA.

individual has an affected parent, except for cases arising

from a fresh mutation. If that affected individual has an

unaffected spouse, each of their children will have a 50

percent chance of inheriting the mutant gene and having

the disease. Offspring of affected persons who have not

inherited the mutant gene will not have affected offspring.

Examples of genetic disease inherited in this manner

are Huntington’s disease, adult polycystic kidney disease,

and Marfan syndrome. Except for eases where the disease

has appeared as a fresh mutation in an individual, families

with dominantly inherited genetic disease are more likely

to know they are at risk because of the appearance of the

disease in preceding generations. More problematic are

those diseases with a late onset, such as Huntington’s,

because individuals might not know they are affected

until they already have children.

mutant allele until they either produce an affected

offspring or undergo testing for heterozygote or ‘carrier’

status. There is infrequently a family history of the disease

because of the small likelihood that two individuals

heterozygous for the same trait would meet and have

children. Recessive disorders are more common than

dominant disorders. Even if both parents are carriers of

the trait, each child has a 1 in 4 chance of inheriting the

mutant gene from both parents, producing the homozygous or disease state. Statistically, each child also has a 50

percent chance of inheriting one mutant gene from either

parent, thus, becoming a carrier. Each child also has a 25

percent chance of inheriting the normal gene from both

parents.

Examples of some common autosomal recessive disorders are cystic fibrosis, sickle cell anemia, phenylketonuria, and beta-thalassemia.

Autosomal Recessive Disorders

Sex Linkage Recessive deleterious genes produce disease only in the

homozygote, that is, persons- with two copies ‘of the Theoretically, if the mutant gene is on one of the sex

mutant gene. Affected individuals have received one chromosomes, the X or the Y, the pattern of inheritance

mutant gene from each parent. Most often both parents are differs. In reality, the Y chromosome is very small and

asymptomatic heterozygotes, unaware that they carry the contains few genes. There are no known diseases trans-
194 ● Genetic Monitoring and Screening in the Workplace

Table A-l-Some Known Hereditary Disorders for Which Gene Has Been Cloned

Acatalalasemia

Alpha 1 -Antitrypsin deficiency

Alpha-Thalassemia

Antithrombin Ill deficiency

Argininosuccinic aciduria

Atransferrinemia

Beta-thalassemia

C2 deficiency

C3 deficiency

C4 deficiency

Carbamylphosphate

Chronic granulomatous disease

Citrullinemia

Color blindness

Congenital adrenal hyperplasia

Diabetes mellitus due to abnormal insulins

Duchenne muscular dystrophy

Dysfibrinogenemias

Dyslipoproteinemia

Ehlers-Danlos syndrome type IV

Ehlers-Danlos syndrome Vll A2

Elliptocytosis-1

Elliptocytosis-2, spherocytosis

Fabry’s disease

Factor Vll deficiency

Factor X deficiency

Factor XIII deficiency

Familial hypercholesterolemia

Familial hypoparathyroidism (one form)

Fructose intolerance

Fucosidosis

Gaucher’s disease

Hereditary congenital hypothyroidism

Hers’ disease (glycogen storage disease VI)

Homocystinuria

Hypobetalipoproteinemia, premature

atherosclerosis

Isolated familial growth hormone deficiency

Lecithin-cholesterol acyltransferase disease

Lesch-Nyhan syndrome

Lipid adrenal hyperplasia deficiency

McArdle’s disease

Medium-chain acyl-CoA dehydrogenase deficiency

Mucopolysaccharidosis Vll

Ornithine transcarbamylase deficiency

Osteogenesis imperfecta

Phenylketonuria

Phosphoglycerate kinase deficiency

Porphyria cutanea tarda

Propionic acidemia type I

Propionic acidemia type II

Pyruvate carboxylase deficiency

Renal tubular acidosis with osteopetrosis

Retinoblastoma

Sandoff’s disease

Severe combined immuo-deficiency from

adenosine deaminase deficiency

Sickle cell anemia

Tay-Sachs disease

Thrombophilia from plasminogen activator

deficiency

Thrombophilia from plasminogen variant

Thrombophilia from protein C deficiency

Glucose-6-phosphate dehydrogenase deficiency Triosephosphate isomerase deficiencyGyrate atrophy Tyrosinemia type II

Hemophilia A X-linked icthyosis

Hemophilia B von Willebrand’s disease

SOURCE: S.E. Antonarakis, “Diagnosis of Genetic Disorders at the DNA Level,” New Eng/and Journal of Medicine

320:153-163, 1989.

mitted via the Y chromosome. The X chromosome,

however, is much larger and contains numerous genes,

many of which are known to cause disease when in the

mutant form. Genes on the X chromosome can also be

dominant or recessive, but the fact that females have two

X chromosomes, and males have only one X and one Y

leads to differences in the patterns of inheritance. Figure

A-4 illustrates the characteristic pedigree for X-linked

disease, usually being transmitted by an asymptomatic

female to each of her sons with a 50 percent probability.

Daughters of the unaffected carrier mother each have a 50

percent chance of also being unaffected carriers. Sons

who do not inherit the abnormal gene are unaffected and

cannot transmit the gene.

Examples of X-linked disorders are Duchenne muscular dystrophy and hemophilia.

Confounding Factors in Mendelian Patterns

Not all mutant genes display the regularity of transmission implied by the previous discussion. Several irregularities can complicate accurate genetic diagnoses and are

described in the following sections.

Mutation-As mentioned earlier, for two reasons,

family history does not usually forewarn individuals that

they are at risk for genetic disease. First, many diseases

are transmitted in an autosomal recessive manner, meaning the chances are very low that two carriers for the same

disease will meet, procreate, and have an affected child.

Second, naturally occurring mutation rates exist for all

diseases. For example, “Fragile X Syndrome and Duchenne muscular dystrophy have high mutation rates which

explains why these diseases persist despite the fact that

those who have them rarely procreate.

Variable Expressivity--Variable expressivity is the

term used for the variation in severity of effects produced

by the same genes in different people. The physical

presentation of effect of a gene is referred to as the

“phenotype.” Thus, one genotype often gives rise to a

range of phenotypes in different individuals. For example,

the neurofibromatosis gene may cause multiple disfiguring tumors in one patient but only skin discoloration and

a few insignificant tumors in another patient.
Appendix A--Basic Tenets of Human Genetics ● 195

Figure A-4-Modes of Inheritance of Single Gene Disorders

Autosomal dominant

X-linked

SOURCE: Office of Technology Assessment, 1990.

Heterogeneity-The same or similar physical characteristics can be produced by different genes or loci. Thus,

several different genotypes can produce similar phenotypes. In most genetic diseases, heterogeneity appears

to be the rule rather than the exception.

Penetrance—To further complicate matters, a gene

that expresses itself clinically in one person can produce

no detectable effect in another. The failure to reach the

“clinical surface’ in an individual is called ‘‘nonpenetrance.” The gene is silent. At the population level, the

gene is said to have reduced penetrance. Reduced

penetrance is most easily detected in the case of dominant

traits, when an individual who must carry the mutant

genes, based on pedigree or DNA analysis, does not have

the disease or trait.

Phenocopies--Sometimes the effect of a gene is

simulated by an environmental agent in an individual not

carrying the mutant gene. For example, congenital

deafness can be caused by a recessive gene or by the drug

streptomycin.

Multifactorial Inheritance

Combinations of genes encode complex aspects of the

human phenotype, such as the immune response and

cholesterol metabolism. Defects in one or more of these

genes can cause diseases that may be exacerbated by

environmental factors such as viruses, chemicals, and

Autosomal recessive

I

Key: Male

 Female

■ Affected male

● Affected female

 Carrier male

 Carrier female

radiation; thus the term ‘‘multifactorial disease. ” Multifactorial diseases are far more common than single gene

disorders. They include coronary artery disease, diabetes

mellitus, multiple sclerosis, schizophrenia, epilepsy, allergic rhinitis, asthma, some forms of arthritis, and some

forms of emphysema, to name a few (4).

Identification of the genes that make an individual

“susceptible” to disease state is especially compelling

because of the possibility of prevention. An individual

identified to be at risk can avoid known exogenous risk

factors such as diet or infectious agents, or watch for the

developments of symptoms for treatment at an early stage.

Chromosomal Disorders

Sometimes genetic disease is caused by structural

aberrations in the chromosomes. Chromosomal aberrations (CAs) are gross structural changes visible under the

light microscope that arise from errors in cell division.

During the two types of cell division in humans —mitosis

and meiosis—’ ‘mistakes” can occur resulting in too

much, too little, or rearranged chromosomal material in

the daughter cells. Errors in the number or structure of

chromosomes can result in maldevelopment of the fetus

and subsequent disorders in liveborn infants.

In some cases, CAs can be caused by environmental

agents such as radiation, chemicals, or viruses (2,3,6,8).

These environmental insults have been associated less
196 . Genetic Monitoring and Screening in the Workplace

with errors in number than with breakage of the chromosomes. Such breakage can interfere with the genetic

signals necessary for normal cell growth and repair (e.g.,

it is well-documented that large doses of ionizing

radiation cause chromosomal breakage correlated with

certain forms of cancer) (1,7).

Errors in chromosome number and structure can

present clinical disorders in a variety of forms, from

before conception to the advanced stages of disease. The

spontaneous frequency of CAs (both structural and

numerical) in newborns is about 6 per 1,000. Chromosomal analysis of human spontaneous abortuses shows that

about 50 percent are chromosomally abnormal. In addition, persons exposed to ionizing radiation and certain

chemicals have increased frequencies of CAs in their

lymphocytes. Many forms of cancer are associated with

increased frequencies of aberrations. And, several human

hereditary conditions, such as ataxia telangiectasia and

Fanconi’s anemia, are associated with increased frequencies of CAs as well as increased incidence of cancer.

Genetic evaluation at the chromosomal level, rather

than the biochemical or molecular level, is referred to as

‘‘cytogenetics. Cytogenetic approaches to genetic

screening are most reliably used in prenatal diagnosis for

women of advanced maternal age, and for the diagnosis

of certain forms of cancer and certain hereditary traits.

The use of cytogenetic tests for monitoring populations

exposed to genotoxic agents and ionizing radiation is

discussed in chapter 4.

1.

2.

3.

4.

5.

6.

7.

8.

Appendix A References

Bender, M.A., Awa, A.A., Brooks, A. L., et al., “Current

Status of Cytogenetic Procedures To Detect and Quantify

Previous Exposures to Radiation,” Mutation Research

196:103-159, 1988.

Bender, M.A., honard, R. C., White, O., et al., “Chromosomal Aberrations and Sister-Chromatid Exchanges in Lymphocytes From Coke Oven Workers,” Mutation Research

206:11-16, 1988.

Carrano, A.V., Thompson, L. H., Lindl, P.A., et al., “Sister

Chromatid Exchange as an Indicator of Mutagenesis,”

Nature 271:551-553, 1978.

Czeizel, A., %_nkaranarayanan, K., Imsonci, A., et al., “The

Load of Partially Genetic Diseases in Man II. Some Selected

Common Multifactorial Diseases: Estimates of Population

Prevalence and of Detriment in Terms of Years of Lost and

Impaired Life,’ Mutation Research 196:259-292, 1988.

McKusick,V.A., ‘The New Genetics and Clinical Medicine:

A Sumrning Up,” Hospital Practice, pp. 79-93, July 15,

1988.

National Research Council, Drinking Water and Health Vol.

9: Selected Issues in Risk Assessment (Washington, DC:

National Academy Press, 1989).

National Research Council, Health Eflects of Exposure to

Low Levels ofIonizing Radiation (Washington, DC: National

Academy Press, 1989).

Puck, T.T, and Waldren, C.A., “Mutation in Mammalian

Cells: Theoq and Implications,’ Somatic Cell and Molecular Genetics 13(4):405-409, 1987.
Appendix B

Survey Methodology

Study Design

The survey was conducted for the Office of Technology

Assessment (OTA) from March 24 to July 15, 1989, by

Schulman, Ronca, & Bucuvalas, Inc. (SRBI). The core of

the 1989 survey remained a national survey of the 500

largest U.S. industries, 50 largest utilities, and 33 major

unions. The 1989 survey contained comparable questions

to core survey items from the 1982 OTA survey. (See

table B-1 for a summary of the methodology of the 1989

and 1982 surveys.)

Sampling Design

The purpose of the sampling design was to provide

comparability with OTA’s 1982 survey, while expanding

the ability to generalize the results to a broader population. The 1989 survey results were based on four samples.

First, all Fortune 500 companies were selected to provide

information on genetic monitoring and screening at large

corporations in the United States. The procedure for

specifying this population was to use the Fortune 500

listing of manufacturers and utilities from the previous

year. This procedure, which was identical to the procedure

used in the 1982 survey, produced an independent census

of the current Fortune 500 population rather than a panel

of previously surveyed organizations.

Second, the 50 largest private utility companies in the

United States were surveyed to provide coverage of large

utilities. This sampling was based on the most recent

Fortune Magazine listing prior to the survey. As with the

Fortune 500 listing, this produced a current census of the

50 largest utilities.

Third, a sample of large unions was developed by OTA

to provide broad coverage of a wide variety of unions. The

1982 sample of unions was based on 11 unions with the

largest number of members working for Fortune 500

companies, identified from the 1979 Directory of National Unions and Employees Association published by

the U.S. Department of Labor. This publication was

discontinued in the early 1980s, so no comparable list was

available for the 1989 survey. A broader sample of unions

was desired, in any case, since the 1989 survey had been

expanded to include a cross-section of medium and large

companies with 1,000 or more employees. Therefore, a

sample of 33 large unions was identified by OTA for the

1989 survey.

Fourth, the 1989 survey added a stratified cross-section

sample of large- and medium-sized companies with at

least 1,000 employees that did not belong to the Fortune

500 group, to provide results projectable to the universe

of companies with 1,000 or more employees. Public

organizations, such as nonprofit groups and governmental

organizations, were excluded. The number of employees

in the company was defined as the total number of persons

employed company-wide in the United States, rather than

the number of employees at company headquarters or at

a particular establishment.

The sample of companies with 1,000 or more employees was stratified by company size. The sample was

divided into four size strata: companies with 10,000 or

more employees, companies with 5,000 to 9,999 employees, companies with 2,500 to 4,999 employees, and

companies with 1,000 to 2,499 employees. Companies

were randomly selected within each strata from Dun &

Bradstreet lists. The final sample consisted of 100

companies with 10,000 or more employees, 100 companies with 5,000 to 9,999 employees, 300 companies with

2,500 to 4,999 employees, and 350 companies with 1,000

to 2,499 employees. Such division by size allowed the

survey to oversample the largest companies and obtain a

relatively high sampling incidence of these firms.

Table B-l-Summary of Methodology

Samples

Fortune 500 companies . .

50 largest utilities . . . . . . .

Unions . . . . . . . . . . . . . . . .

Companies with 1,000+

employees . . . . . . . . . .

Designated respondent

Private companies:

Chief health officer . . .

Chief personnel officer.

Unions:

Union president . . . . . .

.

.

Followup methodology

Reminder letters . . . . . . . .

Remailing questionnaires

to nonresponders . . . . .

Telephone followup to

Sampled in 1989 and 1982.

Sampled in 1989 and 1982.

33 unions in 1989 and 11 unions in

1982.

1,000 sampled in 1989. Not sampled

in 1982.

Designated respondent in 1989 and

1982.

Received version of questionnaire

for health officers.

Designated respondent in 1989 only.

Received different questionnaire

version for personnel officers.

Designated respondent in 1989 and

1982.

Sent in 1989 and 1982.

Sent to all nonresponders in 1989

and 1982.

nonresponders . . . . . . . All Fortune 500 and utilities in 1989.

Only 200 largest companies in

1982.

Actual telephone interviews with nonresponders to mail

survey . . . . . . . . . . . . . . . Done as a last resort in 1989 and

1982.

SOURCE: Office of Technology Assessment, 1990.

–197–
198 . Genetic Monitoring and Screening in the Workplace

In addition, companies with certain standard industrial

code (SIC) groups were oversampled to obtain sufficient

numbers of oversampled companies and permit analysis

of certain types of SIC groups. The oversampled SIC

groups covered pharmaceuticals (SIC 2834), other chemical companies (rest of SIC group 28), petroleum (SIC

group 29), semiconductors (SIC 3674), other electronics

companies (SIC 3675-3679), and electric utilities other

than the 50 largest utilities (SIC 4911 and 4931). A target

subsample size of 50 companies was adopted for each of

the oversampled industry groups. In order to achieve this

subsample size, a sufficient number of companies with

1,000 or more employees in each oversampled group were

randomly selected to supplement the core cross-section

sample so that the final sample included 50 companies in

the oversampled group. In cases where there were 50 or

less U.S. companies in an oversampled group with 1,000

or more employees, all companies in that group with

1,000 or more employees were included in the final

sample.

Questionnaire Development

A survey questionnaire was developed by the contractor in concert with OTA according to the detailed research

objectives set forth by OTA. The OTA advisory panel

reviewed the questionnaire at the March 1989 panel

meeting after a pretest was conducted between February

17 and March 1, 1989. The findings of the pretest were

used to revise the questionnaire.

The 1989 survey contained comparable questions to

core survey items from the 1982 survey. This provided

OTA with the necessary comparability to the 1982 survey

so that changes in the workplace over time could be

assessed. However, the method was altered to increase the

usefulness of the information. The central components

were:

1. The content of the questionnaire was broadened to

include the use of genetic monitoring and screening in the

workplace in the context of other types of employee

testing. The survey was expanded to deal with attitudes of

employers toward the proper and improper uses of genetic

monitoring and screening in the workplace. The survey

also covered more areas related to the applications of

genetic monitoring and screening in personnel matters, as

well as applications for employee health.

2. As in 1982, the survey was directed to the chief

health officer, to answer questions dealing with the

medical applications of genetic monitoring and screening.

A different questionnaire was also directed to the chief

personnel officer focusing on personnel applications (e.g.,

recruitment, placement, advancement, and retention) of

genetic monitoring and screening.

3. The universe of Fortune 500 companies was supplemented by a sample of non-Fortune 500 large- and

medium-sized employers so that the extent of genetic

monitoring and screening in the workplace could be

examined more broadly.

4. Telephone recontact was attempted with all nonrespondents in the Fortune 500 and 50 largest utility

companies.

5. The identity of companies returning questionnaires

was anonymous in 1982. In order to improve tracking of

the sample and prevent duplicate responses, the 1989

survey used questionnaires with identification numbers

on peel-off labels. The respondent was encouraged to

leave the label on the questionnaire when it was returned,

but this was voluntary. All labels were removed after

receipt of the questionnaires,

anonymous and confidential.

Confidentiality

making the data both

The 1982 survey used a postcard system to verify

which companies had returned questionnaires. Each

questionnaire was sent to the company along with a

postcard. Substantially more questionnaires were returned (n=373) than postcards (n=307). This raised the

possibility that more than one survey was completed by

the same organization, since respondents are normally

more likely to return a postcard without a questionnaire,

so that he or she would not be subject to followup. In fact,

a few organizations returned more than one questionnaire

in 1989, i.e., the original questionnaire and a questionnaire sent in a followup mailing. These were identified

and removed from the 1989 sample.

Because there appeared to be a problem with the use of

a separate postcard to track anonymous questionnaire

returns, a respondent identification number was proposed

for the 1989 questionnaires. This permitted improved

sample tracking and allowed identification of duplicate

returns. Due to concerns about the anonymity of the

questionnaires, a compromise solution was to affix the

identification number to the 1989 questionnaires on a

peel-off label that could be removed by respondents who

wished to remain anonymous. Respondents were encouraged to leave the peel-off label on the survey, which

explained it would be removed after receipt. After SRBI

received the questionnaires, the peel-off labels were

removed, making the data both anonymous and confidential.

Nine out of ten survey participants left the peel-off

label on the questionnaire. The peel-off labels were

removed from 11 percent of the health officer questionnaires, and 10 percent of the personnel officer questionnaires returned to SRBI. Only 5 of 59 health officers

reporting any type of genetic monitoring and screening

removed the label before returning it.
Appendix B--Survey Methodology . 199

Table B-2—Sample Disposition for 1989 Survey:

Fortune 500 and 50 largest utilities

Sample mailing and eligibilitv Number

Drawn sample. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Companies ineligible before mailing: merged/out

of business/bought by other company in sample.

Companies mailed questionnaires . . . . . . . . . . . . . .

Companies ineligible to complete survey . . . . . . . .

Merged/out of business/bought by other

company in sample. . . . . . . . . . . . . . . . . . . . . .

Noncontactable by mail and telephone,

no forwarding address and nonlocatable . . . .

Companies eligible to complete survey. . . . . . . . . .

Participation in survey

Total questionnaires received during field period. .

Health questionnaires received. . . . . . . . . . . . . .

Personnel questionnaires received . . . . . . . . . . .

Companies returning at least one questionnaire

during field period . . . . . . . . . . . . . . . . . . . . . . . .

Companies returning both questionnaires . . . . .

Companies returning only health questionnaire .

Companies returning only personnel

questionnaire . . . . . . . . . . . . . . . . . . . . . . . . . . .

Companies returning questionnaires after close

of field period . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Total companies returning questionnaires . . . . . . .

Nonparticipation in survey

Companies refusing to participate . . . . . . . . . . . . . .

Too busy to complete survey . . . . . . . . . . . . . . . .

Participation against company policy . . . . . . . . .

Company too decentralized for someone to

do survey . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Other refusals. . . . . . . . . . . . . . . . . . . . . . . . . . . .

Companies in callback status: had been remailed

questionnaires . . . . . . . . . . . . . . . . . . . . . . . . . . .

Other companies not returning questionnaires. . . .

Completion rate

(Total companies returning questionnaires/

eligible companies). . . . . . . . . . . . . . . . . . . . . .

550

3

547

18

15

3

529

453

250

203

325

128

122

75

5

330

150

41

51

5

53

45

4

62.4%

SOURCE: Office of Technology Assessment, 1990.

Field Procedures

The field procedures used in this study included:

. an advance letter, produced on OTA stationery and

signed by OTA Director John H. Gibbons, sent to the

Chief Executive Officer (CEO) of each sampled

company and union Presidents prior to mailing the

questionnaire;

a first mailing of the questionnaire with a cover letter

to the CEO, asking that one questionnaire be directed

to the firm’s chief executive for health affairs and a

second one to the chief personnel officer;

a followup letter to individuals whose replies were

not received within 2 weeks of the first mailing;

a second questionnaire mailing approximately 3

weeks after the followup letter;

a telephone followup of all Fortune 500 companies

and the 50 largest ‘utility

return both questionnaires;

telephone interviews after

lowup and remails.

Sample Disposition

companies that did not

and

repeated telephone folA total of 330 organizations in the Fortune 500 and 50

largest utilities categories completed and returned at least

one questionnaire for the 1989 survey (see table B-2). An

additional 21 organizations in these groups were classified as ineligible for the survey because they had merged,

were no longer in business, or had been bought by another

Fortune 500 company or by one of the 50 largest utilities.

The overall response rate among the 529 eligible

organizations was 62.4 percent.

By comparison, the 1982 survey on genetic monitoring

and screening reported a 65.2 percent response rate

among the Fortune 500 companies, 50 largest utilities and

11 unions, based on 366 organizations returning questionnaires. One four-page questionnaire was mailed to CEO’s

and directed to chief health officers in 1982. In 1989, two

questionnaires totaling 20 pages were mailed to CEO’s,

including a 12-page instrument for chief health officers

and an 8-page questionnaire for chief personnel officers.

The 62.4 percent response rate was achieved after

repeated followup telephone calls and remails of the

questionnaires. A total of 150 companies refused to

participate in the 1989 survey, or 28 percent of the Fortune

500 companies and 50 largest utilities. These telephone

followup efforts were not conducted among the additional

sample of companies with 1,000 or more employees

because response rate comparability was not sought. A

somewhat lower response rate was obtained from this

group as a result (see table B-3).
200 . Genetic Monitoring and Screening in the Workplace

Table B-3-Sample Disposition for Survey:

Non-Fortune 500 Companies

Sample mailing and eligibility Number

Drawn sample ... , . . . . . . . . . . . . . . . . . . . . . . . . . .

Companies ineligible before mailing: merged/out of

business/bought by other company in sample. .

Companies mailed questionnaires. . . . . . . . . . . . . .

Companies ineligible to complete survey: merged/

out of business/bought by other company in

sample. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Companies eligible to complete survey. . . . . . . . . .

Participation in survey

Total questionnaires received during field period. .

Health questionnaires received. . . . . . . . . . . . . .

Personnel questionnaires received . . . . . . . . . . .

Companies returning at least one questionnaire

during field period . . . . . . . . . . . . . . . . . . . . . . . .

Companies returning both questionnaires . . . . .

Companies returning only health questionnaire.

Companies returning only personnel

questionnaire . . . . . . . . . . . . . . . . . . . . . . . . . . .

Companies returning questionnaires after

close of field period . . . . . . . . . . . . . . . . . . . . . . . .

Total companies returning questionnaires . . . . . . .

Nonparticipation in survey

Companies refusing to participate .,. . . . . . . . . . . .

Companies requesting mail to different address . .

No response after two mailings . . . . . . . . . . . . . . . .

Completion rate

(Total companies returning questionnaires/

eligible companies) . . . . . . . . . . . . . . . . . . . . . .

1,039

0

1,039

40

999

667

301

366

460

207

94

159

10

470

22

19

488

47.O%

SOURCE: Office of Technology Assessment, 1990.
Appendix C

1982 Survey of the Use of Genetic Testing in the Workplace

There have been conflicting accounts of the extent of genetic testing and the use of its results.

In testimony given before Congress in the fall of

1981, the corporate medical director of a large

chemical company stated that except for sickle

cell trait tests, his company” . . . is not conducting genetic screening of its employees, and I am

not aware of any other company which is” (2).

However, a series of articles in the New York

Times in February 1980 alleged a widespread corporate practice of such testing on American

workers (3). Furthermore, a May 1981 survey of

east coast industrial physicians indicated that

preemployment, preplacement, and periodic testing for sickle cell anemia, hemoglobin disease, and

glucose 6-phosphate dehydrogenase (G-6-PD) deficiency was being conducted in some large east

coast companies (l).

None of these or other accounts examined by

OTA has been based on a rigorous, scientifically

valid assessment of the use of genetic testing.

Therefore, in an attempt to dispel the confusion

and speculation and to provide necessary data for

policy analysis, OTA surveyed major U.S. industrial companies, utilities, and unions about their

use of this technology.

Purpose

The survey was designed to determine: ●

● the frequency of past, present, and an- ●

ticipated genetic screening and cytogenetic ●

monitoring* in the workplace and whether

they had been conducted on a routine,

special, or research basis;

“The questionnaire used the term biochemical genetic testing to

refer to genetic screening and the term cytogenetic testing to refer

to cytogenetic monitoring.

Study design

The survey was conducted for OTA from

February 25 to June 8, 1982, by the National Opinion Research Center (NORC), a nonprofit survey

research corporation affiliated with the University of Chicago. NORC sent confidential questionnaires to the chief executive officers of the 500

largest U.S. industrial companies, * the chief executive officers of the 50 largest private utility

——

“Identified by Fortune 500 listing of U.S. companies engaged in

manufacturing/mining; Fortune, vol. 103, No. 9, May 4, 1981,

which tests were used and under what

circumstances;

how the results of the tests were used; and

the criteria against which tests have been

measured to determine acceptability for use.

The survey did not attempt to establish the

number of workers involved in these tests; that

information would have required a much more

extensive effort.

companies, * * and the presidents of the 11 major unions that represent the largest numbers of

employees in those companies.** * For further information on the study design and other aspects

of survey methodology, see appendix A. The

NORC report to OTA on the survey is in appendix B.

“ “Identified by Fortune Magazine List C; Fortune, vol. 103, No.

9, May 4, 1981.

“ “ “identified in Directory of National Unions and Employees

Association (1979) by the U.S. Department of Labor.

–201–
202 . Genetic Monitoring and Screening in the Workplace

By the June 8, 1982, cutoff date, 366 organizations had answered the questionnaire, a 65.2 percent response rate, and 26 organizations had specifically declined to do so, a 4.6 percent refusal

rate. Those who declined generally gave either

no reason for refusal or the reason of corporate

policy not to respond to surveys. (See table 1.)

Results

Overall rates of testing

Of the 366 organizations responding, 6 (1.6 percent) were currently conducting genetic testing, *

17 (4.6 percent) used some of the tests in the past

12 years, 4 (1.1 percent) anticipated using the tests

in the next 5 years, and 55 (15 percent) stated they

would possibly use the tests in the next 5 years.

Most of these organizations are in manufacturing/mining (particularly chemicals) or are utility

companies. Of those organizations that have

tested in the past 12 years, five are currently

doing SO. (See table 2.) Because the questionnaire

instructed respondents to include any instance

of testing, positive responses can include isolated

instances of testing as well as long-term testing

programs. Among the six companies currently

testing, two are in the chemical industry, two are

utilities, and two are in the electronics industry.

Half of those that tested in the past are chemical

companies. Of the four organizations that anticipate the use of genetic testing, two are conduct -

ing testing at present, one has done so in the past,

and one has never had such a program. None of

the four responding unions reported any testing.

These results are set forth in more detail in tables

3, 4, and 5.

Types of testing genetic screening and

cytogenetic monitoring

Organizations that reported some genetic

screening were asked whether they had ever

tested employees for genetic traits associated

——

“Genetic screening and/or cytogenetic monitoring

Table 1 .—Frequency of Response to Survey by 6/8/82

By Type of Response (based on 561 organizations)

Type of response Number Percent

Participated . . . . . . . . . . . . . . . . . . . 366 65.20/o

Refused to participate: . . . . . . . . . 4.60/o

Policy not to reply to surveys . (:;

Not interested, no time. . . . . . . (3)

Object to methodology . . . . . . . (1)

Phone refusal—no reason . . . . (12)

Unknown . . . . . . . . . . . . . . . . . . . . . 169 30.1 %

Total . . . . . . . . . . . . . . . . . . . . . . . 561

SOURCE National Oplnlon Research Center, survey conducted for OTA, 1982,

Table 2.—2 x 2 Contingency Table for

Organizations Engaged in Genetic Testing

(past testers by current testers)

Past testers —

Yes No Total

Current Yes 5 1 6

testers No 12 348 360

Total 17 349 366

SOURCE Nat~onal Opinion Research Center, survey conducted for OTA, 1982.

with: (A) any red blood cell and serum disorders,

(B) liver detoxification systems, (C) immune system

markers, or (D) heterozygous chromosomal instabilities. For each of the four broad categories A

through D, the questionnaire listed several examples. Of those who have ever tested, 14 of the organizations had tested in category A, 3 in category

B, 5 in category C, and none in category D. Organizations that have used red blood cell and serum

disorder tests, category A, often used more than

one type of test. The most frequently used test

in this category was that for sickle cell trait, for

which 10) organizations have tested. The G-6-PD

and serum alpha-l antitrypsin deficiency tests

were the second most frequently used. (See table

6 for a summary of the frequency of individual

genetic screening tests.)

For each test, companies were asked about the

circumstances under which the tests were done

(that is, routinely, for research, or for other reasons) and the type of employee tested. Respondents generally said they tested routinely or for

unspecified reasons. (See table 6.) Employees most

often were selected on the basis of ethnicity and

race for sickle cell trait testing and on the basis
Appendix C—1982 Survey of the Use of Genetic Testing in the Workplace ● 203

Table 3.—Distribution of Organizations By Type, Indicating Current, Past, and/or Future Use of

Genetic Testing (based on 366 responses)

Testing

Current Past Future

Organization type (number of respondents) Yes No/NAa Yes No/NAa Yes/Poss. No/NAa

Manufacturing/mining companies (322) . . . . . . . . . 4 318 16 306 49 273

Private utility companies (31) . . . . . . . . . . . . . . . . . 2 29 1 30 9 22

Unions (5) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . O 5 0 5 0 5

Unknown (8) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 8 0 8 1 7

Total (366). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 360 349 307

(1.:%) (4:(A) (16%0)

SOURCE: National Opinion Research Center, survey conducted for OTA, 1982

Table 4.—Frequency of Current, Past, and/or Future Use of Genetic Testing, By Type (based on 366 responses)

Testing

Current Past Future

Type of test Yes No N/A Yes No N/A Yes Poss. No N/A

Genetic screening . . . . . . . . . . 5 350 11 12 342 12 1 53 292 20

Cytogenetic monitoring . . . . . . 2 354 10 6 348 12 3 49 294 20

SOURCE: National Opinion Research Center, survey conducted for OTA, 1982

Table 5.—Distribution of Companies by Classification,” Indicating Current, Past,

and/or Future Use of Genetic Testing (based on 366 responses)

Genetic testing

Current Past Future

Main industrial classification

(number of respondents) Yes No/NAb Yes No/NAb Yes/Poss. No/NAb

Chemical (37) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 35 8 29 11 26

Utilities (33) ‘... . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Petroleum (18) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Pharmaceuticals (9) . . . . . . . . . . . . . . . . . . . . . . . . .

Rubbers/plastics (4) . . . . . . . . . . . . . . . . . . . . . . . . .

Metals (16) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Others (249) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Total (366). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

2 31 1

0 18 0

0 9 0

0 4 0

0 16 0

2

C

247 8

6 360 17

32 10 23

18 4 14

9 3 6

4 3 1

16 2 14

241 26 223

349 59 307

(1.60/ii) (4.6%) (16.1 0

/0)

aMaln Industrial classification baaed on the first listed response of respondent to question concerning the major Industrial classificatlon of their company.

b A combination response. Further breakdown impossible since the category (current, past, future) is a summary of two questions: 1) genetic screening, 2) Cytogenetic

_monitorlng. In the case of No/NA, most responses were No; for Yes/Poss. most responses were possibly. See table 4 for further breakdown.

c Both of these companies report electronics as their main industrial classification

SOURCE: National Opinion Research Center, survey conducted for OTA, 1982.

of job category for other types of tests. No organization reported basing a genetic screening test

on an employee’s sex. (See table 7.)

Of the organizations that reported cytogenetic

monitoring, four had tested for chromosomal

aberrations and two for sister chromatid exchanges (SCE). None reported having tested for

mutations by assaying either deoxyribonucleic

acid (DNA) or enzymes. Most frequently, no

reason was given for chromosomal aberration

testing. The two companies that did SCE testing

said it was for research purposes. (See table 6.)

Job category was the only employee-related

characteristic used to determine who would be

tested. (See table 7.)
204 . Genetic Monitoring and Screening in the Workplace

Table 6.—Genetic Testing Evera Conducted By Purpose and Type of Test (based on 18 responses)

Genetic screening Cytogenetic monitoring

Unspecified Unspecified

red blood immune Sister

Methemoglobin cell/serum Unspecified system Chromosomal chromatid

Purpose Sickle cell G-6-PD SAT reductase disorder liver detox markers aberrations exchanges

Routine . . . 5 3 1 0 1 1 4 1 0

Research . . 1 0 2 1 2 1 0 1 2

Other . . . . . 6 2 2 1 2 1 3 3 0

Total

number of

respondents

utilizing

test b . . . . 10 4 4 1 3 3 5 4 2

a in the past 12 years.

b

since categories above are not mutually excluslve, total can be Iest/more than sum of categories.

SOURCE: National Opinion Research Center, survey conducted for OTA, 1982.

Table 7.—Genetic Testing Evera Conducted By Criteria and Type of Test (based on 18 responses)

Genetic screening Cytogenetic monitoring

Unspecified Unspecified

red blood immune Sister

Methemoglobin cell/serum Unspecified system Chromosomal chromatid

Criteria Sickle cell G-6-PD SAT reductase disorder liver detox markers aberrations exchanges

Job category 1 2 2 0 2 1 1 2 1

Ethnicity/race 7 0 0 0 0 0 0 0 0

Sex . . . . . . . . 0 0 0 0 0 0 0 0 0

Total

number of

respondents

utilizing

test b . . . . . 10 4 4 1 3 2 4 4 2

a ln the past 12 years.

b since categories above are not mutually excluslve, total can be less/more than sum of categories.

SOURCE National Opinion Research Center, survey conducted tor OTA, 1982,

Recipients were asked about the factors considered in the decision to implement testing and

the criteria employed in selecting specific tests.

Data from epidemiological studies, data from animal studies, and other reasons such as employee

protection were the highest ranked factors involved in decisions to implement genetic testing

for both genetic screening and cytogenetic monitoring. (See table 8.) The predictive value of a test,

its specificity, scientific consensus, and other factors such as research findings were the factors

cited most frequently as criteria for selecting a

specific genetic test. These responses were similar

for both genetic screening and cytogenetic monitoring. (See table 9.)

The types of testing carried out by current

testers were compared with those of past testers.

For genetic screening, current testers are using

Table 8.—Genetic Testing Evera Conducted

By Reasons for and Type of Testing

(based on 18 responses)

Type of testing

Reasons for deciding to Genetic Cytogenetic

implement testing screening monitoring

Data epidemiologic studies 6 2

Data animal studies . . . . . . 4 2

Legal consequences of not

testing . . . . . . . . . . . . . . . . 3 0

Union employee initiative . 3 0

Cost-benefit analysis . . . . . 2 0

Otherb . . . . . . . . . . . . . . . . . . . 4 3

a ln the past 12 years.

Includes reasons related to protecting employees, research findings.

SOURCE: Nationat Opinion Research Center, survey conducted for OTA, 1982,

a slightly greater variety of tests (tests for red

blood cell and serum disorders, liver detoxification systems, and immune system markers) than
Appendix C—1982 Survey of the Use of Genetic Testing in the Workplace .205

Table 9.—Genetic Testing Evera Conducted By

Criteria for Test Selection and Type of Testing

(based on 18 responses)

Type of testing

Genetic Cytogenetic

Criteria b

screening monitoring

Predictive value of testc . . . 5 1

Specificity of testd . . . . . . . 5 1

Scientific concensus . . . . . 4 2

Sensitivity of teste . . . . . . . 3 0

Cost of test . . . . . . . . . . . . . 2 0

Otherf . . . . . . . . . . . . . . . . . . 4 3

past testers and at a slightly higher proportion

of usage. Of the six current testers, five are testing

for red blood cell and serum disorders, three for

liver detoxification systems, and two for immune

systems markers. Eight of twelve past testers had

tested for red blood cell and serum disorders,

none had tested for liver detoxification systems,

and two had tested for immune system markers.

In fact, however, because of the small numbers

involved, the only notable difference between current and past testers may be the current use of

tests for liver detoxification systems. In any event,

testing for red blood cell and serum disorders

continues to be the most frequently used test. (See

table 10.)

A different pattern of use emerges for cytogenetic monitoring. Of the six current testers, one

is testing for chromosomal aberrations and one

is testing for sister chromatid exchanges. For the

12 past testers, 3 tested for chromosomal aberrations and I tested for sister chromatid exchanges.

This may reflect the change in the state of the

art concerning the science of sister chromatid exchanges. (See table 10.) In any event, the number

of tests remain small and caution is advised in

interpreting these data.

Actions taken as a result of testing

Responses concerning the way in which the results of genetic screening or cytogenetic monitoring were used varied greatly, ranging from actions involving an employee to changing or discontinuing a product. Of the 18 companies that reported taking some action, 8 reported that they

had informed an employee of a potential problem. Five respondents reported transferring the

“at-risk” employee. Two suggested that the employee seek another job as a result of testing. One

discontinued or changed a product. The complete

list of actions taken appears in table 11.

Generalizability of the survey

Can the results of this survey be generalized

to the population of Fortune 500 companies, large

utility companies, and major unions? An answer

to this involves two additional questions: Are the

responses equally distributed among the groups

Table 10.—Distribution of Type of Testing By Status of Tester (based on 18 responses)

Status of tester

Current N-6 Past N-12

Percent Percent

Type of testing Yes No/NA using Yes No/NA using Total

Genetic screening:

Red blood cell and serum disorders. . . . . . . . . . . . . . . . . . . . . . . . . . .

Liver detoxification systems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Immune system markers. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Heterozygous chromosomal instabilities . . . . . . . . . . . . . . . . . . . . . . .

Cytogenetic monitoring:

Chromosomal aberrations. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Sister chromatid exchange. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Mutations by assaying DNA. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Mutations by assaying enzymes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Other . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

5

3

2

0

1

1

0

0

1

1

3

4

6

5

5

6

6

5

830/o

50%

33 ”/0

0%

17 ”/0

17%

00/0

0%

17“/0

8

0

2

0

3

1

0

0

0

4 67% 18

12 O% 18

10 1O% 18

12 O

O

/o 18

9 25% 18

11 8% 18

12 O

O

/o 18

12 O% 18

12 O% 18

SOURCE: National Opinion Research Center, survey conducted for OTA, 1982.
206 . Genetic Monitoring and Screening in the Workplace

Table 11 .—Actions Taken by Respondents That Have

Evera Used Genetic Testing (based on 18 responses)

Number of

Type of actionb

companies

Informed employee of a potential problem 8

Transferred employee . . . . . . . . . . . . . . . . . . 5

Personal protection device . . . . . . . . . . . . . . 3

Other action . . . . . . . . . . . . . . . . . . . . . . . . . . 3

Suggested employee seek other job . . . . . 2

Installed engineering control . . . . . . . . . . . . 2

Implemented research program . . . . . . . . . . 1

Discontinued/changed product . . . . . . . . . . 1

a ln the past 12 years.

A respondent may have taken more than one action.

SOURCE National Opinion Research Center, survey conducted for OTA, 1982.

represented in the survey? Are characteristics of

the respondents different from the nonrespond -

ents? These two questions are discussed in turn.

By the close of the survey, a discrepancy in response rate among the groups represented in the

survey became apparent. The large corporations

had the highest response rates: 68 percent for

utilities and 61.5 percent for the top 200 companies in the Fortune 500 listing; the unions and

small corporations had the lowest response rates:

36.4 percent for unions and 44 percent among

the bottom 300 companies in the Fortune 500 listing. (See app. A.) The variation in response pattern was most probably due to the followup efforts that focused on the top 100 companies of

the Fortune 500 listing and organizations in selected industrial classifications such as utilities.

Thus, the results of this survey may be more applicable to the larger manufacturing/mining and

utility companies than to smaller manufacturing/mining companies and unions.

Analysis of selected characteristics of respondents compared with nonrespondents is limited to

the Fortune .500 companies. Respondents and

nonrespondents were compared on the following characteristics: geographic location, size of

organization, and type of industry. Rates of

response and nonresponse did not differ greatly

geographically. (See app. A.)

For size of company, however, the rate of nonresponses did differ widely from the rate of responses. For example, 53 percent of the nonrespondents were in the smallest companies, compared with 32 percent of the respondents. Again,

because larger companies were used in followup

efforts, the response rates may reflect these efforts. (See app. A.)

Rate of nonresponse did not vary greatly from

rate of response with respect to industry classification. Eleven industries had a slightly higher

rate of response than predicted. Of these industries, five (chemicals, petroleum refining, rubber

and plastic products, metal manufacturing, and

pharmaceuticals) were the key industries selected

for followup activities and the rates from the remaining six (glass/concrete, electronics, measuring equipment, motor vehicles, aerospace, and office equipment) may be explained by such factors

as the effect of followup based on size of company or chance. (See app. A.)

Thus, the results of the survey may be more

representative of the larger manufacturing/mining corporations and private utility companies as

identified in Fortune magazine listings; however,

the respondents do not appear to differ greatly

from the nonrespondents in geographic location

or type of company.

Comments on survey

Respondents were encouraged to write explanatory notes or other comments on the questionnaires and on the post cards. Thirty-one respondents did so. (See app. C for complete text of comments.) Three current testers sent in comments.

Two of these respondents said testing was being

done for reasons of health evaluation—preplacement and/or routine monitoring; one respondent

said that such testing should not be interpreted

to mean a large-scale testing program or a problem exists.

Comments were received from two companies

that had tested in the past. Both respondents referred to testing for sickle cell trait, one at the

request of the State health department, and the

other at the request of the employer for employees of child-bearing age as part of the company’s

preventive medical program.

Seven organizations that anticipate future testing but that have not conducted any testing to

date provided comments. The comments ranged
Appendix C—1982 Survey of the Use of Genetic Testing in the Workplace ● 207

from addressing animal research to questionnaire

improvement to any future testing being dependent on “practical utility. ”

Comments received from 19 organizations that

have never tested or that do not plan to test in

the future focused on three major points. The

first was the genetic testing was not relevant to

the products or processes to which their workers

were exposed. The second was that these tests

were not sufficiently developed for use. The third

point was that the organization was satisfied with

its current conventional industrial hygiene practice and standard medical surveillance of its

workers.

Caveats

In evaluating the results of the survey, several

caveats must be considered. First, since the

questionnaire instructed respondents to include

any instances of testing, positive responses can

include isolated cases as well as long-term testing

programs. Second, the questionnaire was not

structured to provide information on the number

Conclusions

of workers tested. Positive responses indicate only

the existence of testing, not its extent. Third, since

approximately one-third of the population did not

respond and the number of organizations testing

is very small, any generalizing of these results to

the study population as a whole is not warranted.

Fourth, the level of effort employed in completing

each questionnaire is unknown. For example,

holding companies which have autonomously operating subsidiaries may or may not have included

the activities of those subsidiaries in their responses. Fifth, a limitation of an anonymous questionnaire is that respondents cannot be contacted

about missing information or unclear responses.

Approximately 3 percent of the respondents failed

to answer every item in the core questions. Eight

returned questionnaires did not provide enough

information to allow the respondents to be classified as a Fortune 500 company or ‘as a utility.

Sixth, the use of post cards for followup has pitfalls: respondents may return post cards but not

questionnaires or vice versa; NORC received 293

post cards and 366 questionnaires. This may have

resulted in duplication of information or minimized the effect of followup.

The survey of major U.S. industrial companies,

utilities, and unions has shown that genetic testing

currently is being used by a few companies, that

its use has declined in the past 12 years, but that

it may be used by many more companies in the

future. The responses cannot be generalized to

the survey population or to all U.S. companies and

labor unions. However, it is clear that 17 organizations have used genetic testing in the past 12

years, 5 of the 17 and 1 other currently are doing so, and 59 organizations have expressed an

interest in using these tests. None of these organizations is a union. The extent of testing by these

organizations is unknown.

Further, of the 18 companies that have ever

conducted genetic testing in the past 12 years,

more companies have conducted genetic screening (17 companies) than cytogenetic monitoring

(8 companies). Tests for sickle cell trait were the

most frequently used type of genetic screening

and tests for chromosomal aberrations were the

most frequently used type of cytogenetic monitoring. Research was the least frequently mentioned

purpose for testing. Respondents generally tested

routinely or for other unspecified reasons. The

type of employee chosen for testing was based

most often on ethnicity and race for sickle cell

trait testing, and job category for other types of

tests. Sex was never stated as a criterion used in

determining the test of choice. Actions taken on

the results of the tests ranged from informing the

employee of a potential problem (eight companies)

to discontinuing or changing the product (one

company).

Data from epidemiological and animal studies

were the most frequently cited factors in the decision to implement testing of those companies that

tested. A cost-benefit analysis was the least impor-
208 ● Genetic Monitoring and Screening in the Workplace

tant factor. The predictive value and specificity while research findings were most important in

of a test were the most important criteria in the the selection of the specific cytogenetic monitorselection of the specific genetic screening test, ing test.

Chapter 3 references

1. Compton, A., “Company Practices in Protecting

Minority Workers)” paper presented at The National Conference on Occupational Health and

Issues Affecting Minority Workers, sponsored by

the National Institute of Occupational Safety and 3

Health, July 6-8, 1981.

2. Karrh, B. W., Corporate Medical Director, E. I. du

Pent de Nemours & Co., testimony before Subcommittee on Investigations and Oversight of the

House Committee on Science and Technology, Oct.

14 and 15, 1981.

Severe, R., “Screening of Blacks by DuPont

Sharpens Debate on Gene Tests,” The New York

Times, Feb. 4, 1980.
Appendix D

Federal Research in Genetic Monitoring and Screening

Both the public (State and Federal) and private research

funding sectors place a high priority on projects related to

human genetics. Part of these efforts include basic

research applicable to genetic monitoring and screening

in the workplace. Assessing State programs that could

involve applications was beyond the scope of this report.

However, State spending in biotechnology, including

some applications to human genetics was documented

recently in New Developments in Biotechnology: U.S.

Investment in Biotechnology (2). Similarly, surveying

private funding efforts in basic research on genetic

monitoring and screening was not possible, although the

Office of Technology Assessment (OTA) identified that

chief among private resources in this area is the Howard

Hughes Medical Institute (HHMI). In fiscal year 1989,

HHMI funded over 100 studies related to human genetics—many of which could be important to future applications of genetic monitoring and screening (l).

Several Federal agencies fund research applicable to

genetic monitoring and screening. This appendix describes federally funded projects underway as of early

1990. Because of the wide variation in both accounting

and definitions used by agencies that fund research related

to genetics (2), OTA did not attempt to determine the

funding levels for genetic research with potential use in

the workplace (2). Rather, OTA contacted Federal agencies and asked them to describe areas of basic research

they conducted intramurally, or funded extramurally, that

could have implications for genetic monitoring and

screening in the workplace (all of the data available from

the agencies by April 1990 is included here).

Department of Energy

Although the U.S. Department of Energy (DOE) does

not directly support a program in occupational safety and

genetics, DOE does conduct research into the effects of

energy-related agents on human health. DOE, through the

Office of Health and Environmental Research, supports

approximately 150 projects investigating the effects of

radiation and chemicals on living systems, including

human health effects. In addition, much of the $27 million

DOE is investing in the human genome project in fiscal

year 1990 will result in improved ability to carry out

genetic monitoring and screening.

As in the past, much of DOE’s current genetic research

focuses on the development of genetic monitoring tests.

A new test, the glycophorin assay, which measures

mutations in red blood cell surface proteins, is being

applied in the Hiroshima and Nagasaki studies, as well as

in studies related to the Chernobyl accident. Cytogenetic

tests comprise an important part of many DOE projects.

Research in genetic monitoring tests is still in early stages,

but includes assays for DNA repair, sister chromatid

exchange, and DNA adduct formation. DOE is also

working on a number of models for cellular response to

genetic damage in an attempt to elucidate the role of

genetic change per se and subsequent disease. A noteworthy feature of DOE-funded research is a focus on

health effects of radiation, including ultraviolet radiation.

A number of DOE projects are also investigating the

carcinogenic effects of different chemicals and different

radiation exposure levels.

Department of Health and Human Services

The U.S. Department of Health and Human Services

(DHHS) is the principal government department responsible for research funding in genetic monitoring and

screening. Through several different agencies, DHHS

funds three broad categories of basic research that could

be important to genetic monitoring and screening in the

workplace:

● pursuing new genetic screening tests for specific

diseases;

. developing general DNA assays for monitoring

genetic damage; and

● identifying substances that damage DNA.

DHHS agencies involved in genetic monitoring and

screening research include the Agency for Toxic Substances and Disease Registry (ATSDR), the Center for

Environmental Health and Injury Control (CEHIC), the

National Center for Toxicological Research (NCTR), the

National Institute for Occupational Safety and Health

(NIOSH), and the National Institutes of Health (NIH).

Agency for Toxic Substances and

Disease Registry

Established in 1983 within the U.S. Public Health

Service (PHS), ATSDR funds several activities designed

to protect public health and worker safety. Empowered

with health-related mandates under the Superfund Act,

ATSDR is charged with determining the health effects

associated with exposure to hazardous substances. Where

necessary, ATSDR is to develop scientific methods to

measure the linkages between human exposure to hazardous substances, with particular concern about substances

stored in sites covered by Superfund, and adverse health

effects. ATSDR funds several projects related to genetic

monitoring and screening in cooperation with both

CEHIC and the National Toxicology Program (NTP).

–209–
210 . Genetic Monitoring and Screening in the Workplace

Genetic monitoring tests are a component of work

funded by ATSDR. In supporting research through

CEHIC, ATSDR is investigating different DNA assays as

markers of genetic damage. In particular, one project

hopes to develop an assay of human leukocyte cells as an

indicator of potentially harmful effects of environmental

agents. ATSDR also is cooperating with NTP to test the

toxicological effects of chemicals and substances relevant

to the Superfund legislation. These studies occasionally

employ cytogenetic tests to evaluate DNA damage by

hazardous substances. Finally, studies underway also

include direct evaluation of chemically altered DNA.

Center for Environmental

Health and Injury Control

As the focal group for nonoccupational injury control

within the Centers for Disease Control (CDC), CEHIC

conducts research in several fields of environmental

health. Among CEHIC responsibilities are the prevention

of chronic diseases and their morbidity and mortality.

CEHIC research includes all aspects of chronic disease,

including diagnosis and treatment. Many of these diseases, such as cardiovascular disease, neoplasia, and

diabetes have distinct genetic components to be tested and

identified.

A second responsibility of CEHIC is cancer treatment

and control, including the genetic aspects of carcinogenesis. For example, for coronary heart disease (CHD),

CEHIC is developing methods of measuring bloodcholesterol and investigating genetic factors in CHD. In

addition to general research in chronic diseases, three

particular projects could have important implications for

genetic monitoring and screening in the workplace: the

role of genetic and oncogenic factors in leukemia and

other cancers; the identification of biological and genetic

markers associated with chemical effects; and the development of fluorescent assays to detect DNA adduct

formation or sister chromatid exchanges. CEHIC also

funds studies of radiation effects on human health and

chemical toxicology, both areas that could lead to

advances in genetic monitoring and screening in the

workplace.

National Center for Toxicological Research

Operated within the U.S. Food and Drug Administration, NCTR investigates the biological effects of potentially harmful chemical substances. As applied to genetic

monitoring and screening, much of NCTR’s efforts

emphasize genetic monitoring, e.g., the health effects of

prolonged, low-level exposure to and the biochemical

effects of chemical toxicants. Like the National Institute

of Environmental Health Sciences (NIEHS), NCTR also

participates in cooperative research with NTP.

Genetic monitoring research conducted by NCTR falls

into two different categories: studies to detector elucidate

the mechanism of genetic damage; and studies of specific,

chemical-caused damage. Projects cover DNA repair,

general effects of chemicals on replication-repair mechanisms, nuclear matrix markers of toxicology, sister

chromatid exchanges in mice, and the DNA repair system

as a test for genetic damage. NCTR also is measuring the

effects of known carcinogens on chromosomal damage,

and hopes to extrapolate the data to chemicals with

unknown genetic effects. NCTR investigations addressing specific chemicals focus on environmentally pervasive chemicals. During fiscal year 1988, NCTR projects

investigated over 25 different chemicals, as well as

studies on others supported through NTP.

National Institute for Occupational Safety

and Health

NIOSH is a research agency that is part of CDC. It is

the lead Federal agency for research into occupational

safety and health problems. NIOSH supports intramural

and extramural research in a variety of areas related to

genetic monitoring and screening. NIOSH participates in

cooperative projects with NTP, National Cancer Institute

(NCI), and the U.S. Environmental Protection Agency

(EPA).

Many of NIOSH’s projects investigate exposure and

disease surveillance of occupational cancers. Such projects include studies of environmental monitoring, biological monitoring methods, and medical screening (3).

Test mechanisms under review include the methodologies

to assess DNA adducts, assays as screening tests to

determine the carcinogenic potential of chemicals, monitoring methods for various chemicals, sister chromatid

exchanges, and chromosomal micronuclei. In addition,

extensive epidemiological research is conducted to assess

the association between work-related exposure to toxic

and hazardous substances and the risk of developing

disease (primarily cancer). An example is a study of

workers exposed to ethylene oxide and their risk of

developing leukemia.

National Institutes of Health

Under its general mission to promote the health of the

American people, NIH conducts intramural and supports

extramural biomedical research in many fields, including

disease prevention. Apart of PHS, NIH is composed of 20

major institutes and centers for public health research.

Research into the genetic basis of human disease is

conducted by many of the member institutes of NIH,

including NCI; the National Heart, Lung, and Blood

Institute; the National Institute of Diabetes and Digestive

and Kidney Diseases; and NIEHS.

For fiscal year 1990, NIH has awarded over $104

million in grants to support 627 projects that both directly

and indirectly relate to genetic monitoring and screening.

The majority of NIH research funds are directed to
Appendix D--Federal Research in Genetic Monitoring and Screening . 211

independent and university-sponsored research groups.

Current projects include investigations of: the possible

genetic predisposition to alcoholism; cellular DNA repair

processes; hazardous occupational and environmental

exposures; and chemical toxicity.

National Institute of Environmental Health Sciences—NIEHS supports research on the effects of chemical, biological, and physical factors on human health. A

particular research focus of NIEHS is the interaction

between these factors and human genetic material as

applied to genetic monitoring (e.g., adduct formation).

NIEHS conducts intramural research and contributes to

private and public projects, including work with NTP.

Intramural and extramural research supported by

NIEHS includes a wide array of genetic toxicology

experiments that provide new insight to the mechanisms

of genetic damage. One area of intensive NIEHS investigation is cancer risk from environmental exposure.

Researchers currently are studying human bladder cancer,

carcinogen-induced DNA damage, breast cancer, liver

tumors, and the role of mutation in cancerous cells.

NIEHS-funded projects are pursuing test procedures for

detecting genetic damage. Test mechanisms under review

at NIEHS include lymphocyte markers, DNA adduct

detection, and sister chromatid exchange. Other NIEHS

investigations include projects to elucidate the general

mechanisms of replication, DNA synthesis, and DNA

repair in order to gain an understanding of the role of

mutations and DNA repair in genetic disease.

National Toxicology Program

Primarily through contract funding, NTP conducts

experimental investigations into the toxicity of environmental substances. As a cooperative program within PHS,

NTP research projects are funded by several agencies,

including NIEHS, ATSDR, and NCTR. An important part

of NTP research involves its efforts in development,

standardization, validation, and field application of toxicology tests, including genetic toxicology. NTP projects

applicable to genetic monitoring and screening fall within

several programs, including cytogenetic testing, genetic

toxicology, and germ cell mutation. NTP’s cytogenetic

testing program includes efforts to develop highly reliable

assays with respect to certain mutagens and involving

sister chromatid exchange or other chromosomal aberrations.

Department of Veterans Affairs

The U.S. Department of Veterans Affairs (VA) does

not support work that directly applies to genetic monitoring and screening in the workplace. As with many Federal

research programs, the projects supported by VA include

several areas that could become applicable to both genetic

monitoring and screening. Cancer morbidity and mortality is a major area of concern in the VA patient population.

In particular, several VA facilities are involved in

investigating the role of genetics, if any, in carcinogenesis. Cancers of the bowel, bladder, and liver are of

particular concern. In the area of genetic monitoring,

some basic research to identify specific damage caused by

certain chemicals is being conducted by VA. Most

chemicals under review are those that veterans could have

been exposed to in the course of duty, including ethanol,

dioxin, and other Agent Orange components. VA also

funds some projects in radiation effects, especially effects

of low-level exposures. Finally, VA research includes

genotoxic effects of drug therapies for long-term treatment of certain physiological and psychological disorders.

Environmental Protection Agency

Since its establishment in 1970, EPA’s research efforts

have included, to some extent, research to assess the

effects of toxic substances on human populations. A

recent EPA report recommended expansion of its research

efforts to include investigation of the effects of chemicals

on the environment and on humans (4).

In the face of accelerating demands, extramural collaboration and coordination are becoming increasingly

important tools in advancing EPA’s research agenda.

EPA supports several research projects in the area of

genetic monitoring. Current EPA-sponsored studies are

addressing two main issues: associations between exposure, biological effects, and disease (e.g. the relationship

between chemical damage to DNA and chromosomal

damage); and the determination of the predictive value of

chemical, gene mutation, or chromosomal damage measured inhuman tissues and the risk of cancer in the affected

individual.

EPA projects applicable to genetic monitoring fall

within two divisions, the Genetic Toxicology Division

and the Health Effects Research Laboratory (HERL),

located in Research Triangle Park North Carolina. Much

of their research focuses on evaluating methods of

assessing human exposure to genotoxins. Related efforts

include research in DNA adduct formation, genetic

bioassays, biomonitoring, and biochemical epidemiology. Research at HERL should help define which

biological mechanisms identified in experimental studies

are relevant in the assessment of health effects from

specific exposures in humans.

National Science Foundation

The National Science Foundation (NSF) promotes the

progress of science through the funding of research and

education projects in many fields, including genetics.

While NSF does not sponsor research of a clinical nature,

it does support extramural basic research projects that

indirectly apply to genetic monitoring and screening.
212 ● Genetic Monitoring and Screening in the Workplace

Programs supported in fiscal year 1989 include research

on the spontaneous and mutagen-induced DNA deletions

responsible for many disease-related genetic events. NSF

is also currently investigating the potential use of a 3.

bacterial virus as an efficient, and rapid identification of

the mutational products of different types of DNA lesions.

Appendix D References

1. Howard Hughes Medical Institute, Research in Progress, q

1988 (Bethesda, MD: 1989).

2. U.S. Congress, OffIce of Technology Assessment, New

Developments in Biotechnology: U.S. Investment in Biotechnology, OTA-BA-360 (Washington, DC: U.S. Government

Printing Office, July 1988).

U.S. Department of Health and Human Services, Public

Health Service, Centers for Disease Control, National

Institute for Occupational Safety and Health, National

Institute for Occupational Safety and Health: Projects forFY

1989, DHHS (NIOSH) Pub. No. 89-112, May 1989.

U.S. Environmental Protection Agency, Future Risk: Research Strategies for the 1990’s (Washington, DC: September 1988).
Appendix E

Survey Instrument: Corporate Health Officers

SURVEY OF WORKPLACE HEALTH AND

GENETIC SCREENING AND MONITORING

CORPORATE HEALTH OFFICER VERSION

The Congressional Office of Technology Assessment is conducting a national survey of the opinions and experiences of employers related to the usc of genetic screening and monitoring in the workplace. This questionnaire has been directed to you as the person in your organization whose responsibilities include employee

health. We need your assistance in answering, as best you can, some questions about workplace testing and

employee health in your company.

For the purposes of this survey and the subsequent report, OTA has adopted the following definitions. By

genetic monitoring we mean periodically examining employees to evaluate modifications of their genetic material via tests such as cytogenetic or direct-DNA tests. By genetic screening we mean screening job applicants or

employees for certain inherited characteristics. Screening tests may be biochemical tests or direct-DNA tests.

They can be used to indicate a predisposition to an occupational illness if exposed to a specific environmental

agent, or they could be used to detect any inherited characteristic such as Huntington’s disease. In contrast to

periodic monitoring screening tests are generally performed only one time per characteristic

This is an important study, which has been requested by the Congress of the United States, designed to represent the opinion and experience of the employer. We need to know how employers view the technologies of

genetic screening and monitoring in terms of their current and future applications to the workplace. We also

want to know how these technologies are seen in the broader context of more common forms of employee

health screening and monitoring in the workplace.

Your responses are very important, regardless of whether you have had any experience with genetic screening

or monitoring. If your company has never explored the technology, the questionnaire will only take ten

minutes. If you have some experience with the technology, it may take a little longer to complete the questionnaire. In either case, your experiences and opinions will help to inform congressional, opinion about this area.

Please read each question and mark the box(es) that most nearly corresponds to your answer. After each

answer continue with the next question unless there is an instruction to skip to a particular question. Please

feel free to qualify your answers, if you feel it is necessary. Space has been provided at the end for comments

and opinions that you feel arc not adequately represented by the survey questions.

You arc free to decline to answer any questions that you consider inappropriate. The questionnaire and any

identifying information will be destroyed after data entry, so that all responses will be anonymous as well as

confidential.

1. In your company, are pre-employment health examinations required of all, most, some, few, or no

job applicants?

u ❑

All Host Few

❑

Nom ~SKIP to Q.6

–213–
214 . Genetic Monitoring and Screening in the Workplace

—

2. Would your company consider It acceptable or unacceptable to conduct a pre-employment health examination in order to:

Identify Job applicants

Identify job applicants

identify Job applicants

Identify job applicants

ldentify job applicants

Identify job applicants

ACCEPTABLE

who are physically unfit for employment. . . . . . . . . . . . . . .❑

who are emotionally or psychologically unstable . . . . . . . ❑

who are currently using drugs . . . . . . . . . . . . . . . . . . . . . . . . .• 1

who are at increased risk to workplace hazards . . . . . . . . ❑

with genetic susceptibility to workplace exposures....❑

who represent high insurance risks . . . . . . . . . . . . . . . . . . . . ❑

UNACCEPTABLE

❑

❑

❑

3.Whichofthe following are normally part of the pre-employment examination in your company for

non-administrative positions? (MARK ALL THAT APPLY)

Personal medical history . . . . . . . . . . . . . . ❑

Family medical history . . . . . . . . . . . . . . . . ❑

Simple physical examinations . . . . . . . . . . • 1

Standard blood chemistry tests . . . . . . . . ❑

EKG ● 0..0.... .*,....*,. ● ..,.,,... ● ****. a

Chest X-ray . . . . . . . . . . . . . . . . . . . . . . . . . . . ❑

Pulmonaryfunctlon test. . . . . . . . . . . . . . . ❑

Eye and hearing exam. . . . . . . . . . . . . . . . . .❑

Urinalyses for drug use. . . . . . . . . . . . . . . ❑

Lower back X-ray....................o. u

4. Which of the following types of results of pre-employment examinations would normally be releasedtojob

applicants?

Normal results (negative findings) . . . . . . . . ..*.***,.. . . . . . . . . . . . . . . u

Positive findings already indicated in medical history . . . . . . . . . . . .• 1

Positive findings not reflected in medical history . . . . . . . . . . . . . . . . ❑

Positive findings which disqualify them for employment. . . . . . . . . . . . ❑

Positive findings which affect position/site eligibility . . . . . . . . . .• l

All of the above . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .,.. ❑

None . . . . . . . . . . . . . . . . . . . . . . . . . . . ● . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ❑~SKIPTOQ.6

5. How would that information normally be released to job applicants?

❑

Letter Consultationwith Both

medical staff

❑

Other
Appendix E--Survey Instrument: Corporate Health Officers ● 215

-.— .

6. Are there any specific medical criteria, other than those mandated by regulation, that would exclude individuals from eligibility for certain positions, jobs or sites in your company (e.g., hypersensitivity to dust or

platinum, pregnancy)?

IJ

Yes No~ SKIP

6a. Which medical criteria would exclude employment in which jobs?

Medical Criteria Excluded Position/Job/Site

*

TO Q.7

A.

2.

3.

7. Are any employees in your company exposed to chemicals or ionizing radiation in the workplace setting?

❑ *

Yes Ho~SKIP TO (2.8

7a. Arc those employees who are exposed to chemicals or ionizing radiation

prolonged exposure?

routinely rotated to avoid

❑ o

Yes No

7b. Does your company conduct any form of medical surveillance of employees whose job may expose

them to environmental health risks, other than testing required by OSHA?

❑ n

Yes No

8. Are any employees in your company exposed to any known workplace condition where there is a greater risk

of negative health outcome, depending upon individual susceptibilities?

❑ ❑

Yes No ~SKIP TO Q.9

8a. Do you conduct any form of screening to identify employees or job applicants at increased risk for

these jobs? —

KI

Yes No~ SKIP TO (?.9

8b. Which, if any, of the following types of screening are conducted to identify increased individual susceptibility to workplace risk?

❑ c1 ❑ ❑

Medical History Non-genetic screening Genetic screening MM

(e.g., lower back X-ray,

allergy testing)
216 . Genetic Monitoring and Screening in the Workplace

9a. As part of ongoing worker health evaluation does the company require, as a condition of continued employment, all employees, only those in certain plants or jobs, only employees with certain medical conditions or histories, or no employees to have:

a. Routine physi

9b. Which of these tests (in Q.9a-g), if any, do you offer to employees

on a voluntary basis as part of a corporate wellness program?

-------- Q. !ka

ML PLANTS/

JOBS

cal examination ❑

b. Test for hypersensitivity . . . . . . . ❑ n

c. Hearing tests . . . . . . . . . . . . . . . . . . .❑ 0

d. Pulmonary function tests . . . . . . . . ❑ o

e. Vision tests . . . . . . . . . . . . . . . . . . . .❑ 0

f. Chest X-rays . . . . . . . . . . . . . . . . . . . .❑ n

g. Blood chemistry tests . . . . . . . . . . . ❑ o

REQUIRE --------

CONDITIONS/

HISTORIES NONE

❑

❑

❑

❑

❑

❑

❑

--- Q. % -----

OFFER V(XMITARY

YES NO

❑ n

❑ 0

❑ 0

ran

❑ o

10. Would your company consider the usc of genetic screening or monitoring of employees or job applicants as

generally acceptable or generally unacceptable to:

GENERALLY

ACCEPTABLE

Make a clinical diagnosis of a sick employee ● . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . n

Establish 1 inks between genetic predisposition and workplace hazards . . . . . . . . . . .• 1

Inform employees of their increased susceptibility to workplace hazards . . . . . . . . ❑

Exclude employees with Increased susceptibility from risk situations . . . . . . . . . . . ❑

Monitor chromosomal changes associated with workplace exposures . . . . . . . . . . . . . . . . ❑

Establish evidence of pre-employment health status for liability purposes . . . . . .• 1

GENERALLY

UNACCEPTABLE

c1

❑

11. Does your company have a formal policy related to the use of genetic tests in the screening of job applicants

or employees?

❑

Yes No

12. Does your company have a formal policy related to the use of genetic tests in the monitoring of employee

health?

❑ ❑

Yes No
Appendix E--Survey Instrument: Corporate Health Officers .217

13. Is your company currently conducting biochemical genetic screening of any employees or job applicants, for

research or any other reason?

❑

Yes No Not Sure

14. Has your company conducted any biochemical genetic screening of any employees or job applicants, for

research or any other reason in the past 19 yearn?

❑ ❑ R

Yes No Not Sure

15. Is your company currently conducting cytogenetic monitoring of any employees or job applicants, for research or any other reason?

n ❑ ❑

Yes No Not Sure

16. Has your company conducted any cytogenetic monitoring of any employees or job applicants, for research

or any other reason in the past 19 years?

❑ ❑

Yes No Not Sure

17. Is your company currently conducting direct-DNA screening of any employees or job applicants, for research or any other reason?

❑

• 1 ❑

Yes Ho Not Sure

18. Is your company currently conducting direct-DNA monitoring of any employees or job applicants, for

research or any other reason?

u El

Yes Ho Not Sure

19. Has your company conducted any of the following tests, either currently or in the past, as part of a voluntary wellness program, at the request of an employee, or for diagnosis? (MARK ALL THAT APPLY)

a. As part of a voluntary

wellness program

b. At the request of the

employee:

c. For diagnosis:

BIOCHEMICAL

GENETIC

SCREENING

Currently.. . . . . . . . . . . . . . .❑

In past 19 years . . . . . . . . .• 1

No. . . . . . . . . . . . . . . . . . . . ● . . ❑

Not sure. . . . . . . . . . . . . . . . . ❑

Currently.. . . . . . . . . . . . . . .• 1

In past 19 years . . . . . . . . . ❑

No. . . . . . . . . . . . . . . . . . . . . . . ❑

Not SUre. . . . . . . . . . . . . . . . . ❑

Currently.. . . . . . . . . . . . . . .• 1

In past 19 years . . . . . . . . . ❑

No. . . . . . . . . . . . . . . . . . . . . . . ❑

Not sure. . . . . . . . . . . . . . . . . c1

CYTOGENETIC

MONITORING

❑

c1

❑

❑

❑

c1

❑

a

❑

❑

n

DIRECT-DNA

SCREENING

❑

0

❑

❑

u

❑

❑

n

❑

DIRECT-DNA

MONITORING

c1

❑

❑

n

❑
218 . Genetic Monitoring and Screening in the Workplace

IF YOUR COMPANY HAS NEVER DONE BIOCHEMICAL GENETIC SCREENING, CYTOGENETIC

MONITORING, DIRECT-DNA SCREENING, OR DIRECT-DNA MONITORING, SKIP TO QUESTION 28

ON PAGE 8

IF YOUR COMPANY HAS DONE CYTOGENETIC MONITORING, DIRECT-DNA SCREENING, OR

DIRECT-DNA MONITORING OF EMPLOYEES, FOR ANY PURPOSE, BUT NOT BIOCHEMICAL

GENETIC SCREENING, SKIP TO QUESTION 21 ON PAGE 7

IF YOUR COMPANY HAS EVER DONE BIOCHEMICAL GENETIC SCREENING OF ANY EMPLOYEE,

FOR ANY PURPOSE, PLEASE CONTINUE WITH QUESTION 20

20. Which of the following types of biochemical screening tests are being conducted by your company of any

employees or job applicants? (MARK ALL THAT APPLY)

FOR EACH TEST CONDUCTED, MARK WHETHER THE TESTING IS BEING DONE ON A ROUTlNE BASIS FOR HEALTH

SURVEILLANCE. AS PART OF A VOLUNTARY RESEARCH PROGRAM. AS PART OF FOLLOW-UP DIAGNOSIS. OR AS

PART OF A VOLUNTARY WELLNESS PROGRAm,OR ONLY AT THE REQUEST OF An EMPLOYEE

NOT

DONE

Sickle cell trait . . . . . . . . . . . . . . . . . . . . . . . . . . . . ❑

Glucose-6-phosphate dehydrogenase

deficiency (G-6-PO) . . . . . . . . . . . . . . . . . . . . . . . . . . .• 1

Methemaglobin reductase deficiency . . . . . . . . . . . .• 1

Serum alpha-1-antitrypsin deficiency. . . . . . . . . .• 1

Alpha and beta thalassemias . . . . . . . . . . . . . . . . . . .• 1

Aryl hydrocarbon hydroxylase

inducibility (AHH) . . . . . . . . . . . . . . . . . . . . . . . . . . . . ❑

Slow vs. fast acetylatlon. . . . . . . . . . . . . . . . . . . . .• 1

Allergic respiratory disease . . . . . . . . . . . . . . . . . ❑

Contact dermatitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . ❑

Histocompatibility markers (HLA) . . . . . . . . . . . . . .❑

Other immune system markers . . . . . . . . . . . . . . . . . . . • 1

Bloom syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ❑

Fanconi syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ❑

Ataxia-telangiectasia . . . . . . . . . . . . . . . . . . . . . . . •. 1

Xeroderma pigmentosum . . . . . . . . . . . . . . . . . . . . . . . . ❑

Other heterozygous chromosome?

instabilities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ❑

ROUTINE

HEALTH

SURVEILLANCE

❑

❑

❑

❑

❑

El

❑

❑

VOLUNTARY

RESEARCH

PROGRAM

❑

❑

❑

❑

❑

❑

❑

FOLLOW-UP

DIAGNOSIS

❑

❑

❑

❑

❑

n

VOLUNTARY AT

WELLNESS ----- -----

PROGRAM

El

❑

❑

❑

❑

EMPLOYEE

REQUEST

❑

❑

❑

❑

❑

❑

❑

n

❑

❑

❑

❑
Appendix E--Survey Instrument: Corporate Health Officers ● 219

ROUTINE

NOT HEALTH

DONE SURVEILLANCE

Other (SPECIFY)

● ..0...0.. . . ..❑

22. Has genetic screening or monitoring ever been done in your company based on:

YES NO

Family history ● 0.0..... . . . . . . . . . . . . . . . . . ❑ ❑

Gander . . . . . . . . . . . . . . . . . ● .*...... . . . . . . . . n ❑

Ethnic or racial background . . . . . . . . . . . . .• 1 ❑

Co-factors (e.g., smoking). . . . . . . . . . . . . •. ❑ 1

Job exposures . . . . . . . . ● . . . . . . . . . . . . . . . . . .• 1 1

23.

24.

❑

❑

❑

❑

❑

❑

❑
220 ● Genetic Monitoring and Screening in the Workplace

25. Does your company employ or contract with a genetic counselor?

❑

Employ Contract with Neither

26. Has an employee ever been referred for genetic counseling by your company% medical staff as a result of

any medical or genetic testing?

Yes

❑

No

27. As a result of a genetic screening or monitoring program has your company ever..-?

YES

Suggested an emloyee seek job elsewhere . . . . . . . . . . ❑

Placed an employee or transferred an

employee to a different job in the company . . . . . . . . ❑

Implemented engineering control . . . . . . . . . . . . . . . . . . .K1

Recommended personal protection devices. . . . . . . . . . .• 1

Implemented a research program . . . . . . . . . . . . . . . . . . .• 1

Discontinued a product or changed

materials in a product . . . . . . . . . . . . . . . . . . . . . . . . . . . . ❑

NO

❑

El

❑

❑

❑

28. Has your company ever instituted or changed a workplace practice or exposure level due to the

results of:

29.

NO

❑

❑
Appendix E--Survey Instrument: Corporate Health Officers ● 221

Other (SPECIFY)

. . . . . . . . . .•❑ 1

❑ ❑ ❑

Yes No Not sure
222 . Genetic Monitoring and Screening in the Workplace

36. Does your company anticipate conducting any direct-DNA monitoring for any reason, in the next five

years?

Yes

❑

No Not Sure

37. Which office/division within the company is/will be responsible for administering genetic tests?

38. Which position/ofl’ice within the company Mill be responsible for interpreting genetic test results?

39. Which office in your company is responsible for employee health records?

tkdfcal/Occupational health. . . . . . . . . .• 1

Personnel . - . . . . . . . . . . . . . . . . . . . . . . . . .n

otti (SPECIFY)

40. Does your company permit access to employee medical records -- at company discretion, with employee

permission, or both, to:

AT COMPANY

DISCRETION

Personnel department . . . . . . . . . . . . . ❑

Health Insurance carriers . . . . . . . . ❑

Life insurance carriers . . . . . . . . . .• 1

Disability insurance carriers.... u

Unions . . . . . . . . . . . . . . . . . . . . . . . . . . .• 1

Other companies. . . . . . . . . . . . . . . . . .• 1

Employee . . . . . . . . . . . . . . . . . . . . . . . . . ❑

Employee’s spouse . . . . . . . . . . . . . . . . u

Other family.. . . . . . . . . . . . . . . . . . . . ❑

EMPLOYEE

PERMISSION

❑

❑

❑

❑

❑

❑

❑

❑

BOTH

❑

u

❑

❑

❑

❑
Appendix E--Survey Instrument: Corporate Health Officers ● 223

GENERAL ATTITUDES

41. How do you feel about the following general statements concerning genetic screening and monitoring in the

workplace? For each statement, please indicate whether you agree strongly, agree somewhat, disagree

somewhat, or disagree strongly.

AGREE AGREE DISAGREE DISAGEE

STRONGLY SOMEWHAT SOMEWHAT STRONGLY

It’s fair for employers to use

genetic screening to identify

individuals whose increased risk

of occupational disease poses the

potential for greater costs to the

employer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ❑ un

The employer should have the option

of deciding how to use the information

obtained through genetic screening

and monitoring . . . . . . . . . . . . . . . . . . . . . . . . ❑ 00

The decision to perform genetic

screening of job applicants and employees should be the employer’s... . . . ❑ 00

The decision to perform genetic

monitoring of employees should be

the employer’s. . . . . . . . . . . . . . . . . . . . . . . . ❑ ncl

Government agencies should provide

guidelines for genetic screening of

job applicants and employees. . . . . . . . . . ❑ 00

Government agencies should provide

guidelines for genetic monitoring of

employees ● 0....... . . . . . . . . . . . . . . . . . . . . ❑ 00

Genetic screening in the workplace

represents a potential threat to

the rights of employees. . . . . . . . . . . . . . . ❑ 00

❑

❑

❑

❑

❑

DEMOGRAPHICS

D1. What is the major industrial classification of your company (sue.haschemicals,fo@textil~etcJ ?

D2. Approximately how many persons are employed in the Unlted States by your company?

• ❑ 1 1 1

Less than 1,000 1,000-4,999 5,000-9,999 10,000 or more

D3. What proportion of the establishments in your company have occupational health care professionals on

premises?

❑ 00

All Host Few None

D4. Which of the following types of health professionals are employed, either full or part time, as part of the

occupational health staff of this company?

❑ ❑

Physicians Physician Nurse Registered

(MD/Do)

Industrial Other health

assistants practitioners nurses hygienists professionals
224 . Genetic Monitoring and Screening in the Workplace

D5 What is your job title?

D6. What are your main job responsibilities?

Thank you very much for your cooperation in answering our questions. We would also like to give you an

opportunity to give us any other opinions, concerns or suggestions related to genetic testing in the workplace

that you feel our questions did not address. These comments may be “incorporated in our report to Congress.

We would also appreciate your comments on any survey questions that you found confusing or difficult to

answer, to help us analyze the results. Please write these comments below.

We have attached a peel-off identification number on the questionnaire. This is the only link between the

companies who were sampled and the questionnaires returned. We would prefer that you leave the identification number on the questionnaire when you return it. Our staff will remove the label upon receipt, making the

questionnaire completely anonymous. No linkage between companies and questionnaires will be retained. The

label from the completed questionnaire will allow us to eliminate your company from those that we have to

recontact.

However, if you feel that you cannot complete the questionnaire if there is even temporary identification, then

peel off the label before returning the questionnaire. We appreciate your help and we want YOU to be Comfortable with doing the survey.

PEEL OFF LABEL

IDENTIFICATION

WITH SAMPLE

NUMBER HERE

PLEASE RETURN IN THE POSTAGE PAID RETURN ENVELOPE SENT WITH THE QUESTIONNAIRE.

IF THE RETURN ENVELOPE HAS BEEN LOST, THE RETURN ADDRESS IS:

Schulman, Ronca and Bucuvalas, Inc.

444 Park Avenue South

New York New York 10016

(212) 4814$200 Attn: Dr. Mark Schulman
Appendix F

Survey Instrument: Corporate Personnel Officers

SURVEY OF WORKPLACE HEALTH AND

GENETIC SCREENING AND MONITORING

CORPORATE PERSONNEL OFFICER VERSION

The Congressional Office of Technology Assessment is conducting a national survey of the opinions and experiences of employers related to the usc of genetic screening and monitoring in the workplace. This questionnaire has been directed to you as the person in your organization whose responsibilities include personnel

issues. We need your assistance in answering, as best you can, some questions about workplace testing and

employee health in your company.

For the purposes of this survey and the subsequent report, OTA has adopted the following definitions. By

genetic monitoring we mean periodically examining employees to evaluate modifications of their genetic material via tests such as cytogenetic or direct-DNA tests. By genetic screening wc mean screening job applicants or

employees for certain inherited characteristics. Screening tests may be biochemical tests or direct-DNA tests.

They can be used to indicate a predisposition to an occupational illness if exposed to a specific environmental

agent, or they could be used to detect any inherited characteristic such as Huntington’s disease. In contrast to

periodic monitoring screening tests arc generally performed only one time per characteristic.

This is an important study, which has been requested by the Congress of the United States, designed to represent the opinion and experience of the employer. We need to know how employers view the technologies of

genetic screening and monitoring in terms of their current and future applications to the workplace. We also

want to know how these technologies are seen in the broader context of more common forms of employee

health screening and monitoring in the workplace.

Your responses arc very important, regardless of whether you have had any experience with genetic screening

or monitoring. If your company has never explored the technology, the questionnaire will only take ten

minutes. If you have some experience with the technology, it may take a little longer to complete the questionnaire. In either case, your experiences and opinions will help to inform congressional opinion about this area.

Please read each question and mark the box(es) that most nearly corresponds to your answer. After each

answer continue with the next question unless there is an instruction to skip to a particular question. Please

feel free to qualify your answers, if you feel it is necessary. You arc free to decline to answer any questions that

you consider inappropriate. The questionnaire and any identifying information will be destroyed after data

entry, so that all responses will be anonymous as well as confidential. Space has been provided at the end for

comments and opinions that you feel arc not adequately represented by the survey questions.

We would like to begin with a few questions about your views on the appropriateness of employee testing in

certain workplace situations.

1. Do you think that it is generally appropriate or generally inappropriate for a company to require preemployment health examinations of job applicants in workplace settings where there are no known health

risks?

.——

Appropriate . . . . . . . . .• 1 Inappropriate . . . . . . . . . ❑

2. Do you think that it is generally appropriate or generally inappropriate for a company to require pre-employment health examinations of job applicants in workplace settings where there are known health risks? —.———

Appropriate .,...... ❑ Inappropriate . . . . . . . . . .❑

IF ‘lNAPPROPRIATE IN BOTH Q. 1 AND Q. 2, SKIP To Q. 4.

–225–
226 ● Genetic Monitoring and Screening in the Workplace

3. Would your company consider it acceptable or unacceptable to conduct a pm-employment health examination in order to:

Identify job applicants who are

Identify job applicants who are

Identify job applicants who are

Identify job applicants who are

ACCEPTABLE Unacceptable

physically unfit for employment. . . . . . . . . . . . . . . . . ❑ ❑

emotionally or psychologically unstable . . . . . . . . .• 1 1

currently using drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . ❑ ❑

at increased risk to workplace hazards . . . . . . . . . .❑ ❑

Identify job applicants with genetic susceptibility to workplace exposures . . . . . . ❑ ❑

Identify job applicants who represent high insurance risks . . . . . . . . . . . . . . . . . . . . . .•❑ 1

4. Do you think that it is generally appropriate or generally inappropriate for a company to require periodic

medical testing of employees in workplace settings where there are no known health risks? .—— —

Appropriate . . . . . . . . . ❑ Inappropriate . . . . . . . . .• 1

5. Do you think that it is generally appropriate or generally inappropriate for a company to require periodic

medical testing of employees in workplace settings where there ———— areknown health risks?

Appropriate . . . . . . . . ❑ Inappropriate . . . . . . . . .• 1

IF ”INAPPROPRIATE” IN BOTH Q.4 AND Q.5, SKlP TO Q.7.

6. Do you think that it is generally cost effective or not cost-effective for a company to conduct periodic medical

testing of employees foR:

NOT

COST EFFECTIVE COST EFFECTIVE

High blood pressure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . c1 ❑

Respiratory function . . . . . . . . . . . . . . . . . . . . . . . . . . . . .❑ ❑

Malignancies ● ....**.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . ❑ ❑

Hearing function . . . . . . . . . ● ....*.... . . . . . . . . . . . . . .• 1 1

Vision .*..*.., . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . •. ❑ 1

Chromosome abnormalities. . . . . . . . . . . . . . . . . . . . . . . .•u 1

Drug abuse ...**... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .❑ ❑

7. Do you think it is currently cost-effective or not cost-effective for a company like yours to:

COST NOT COST NOT

EFFECTIVE EFFECTIVE SURE

conduct biochemical genetic tests as part of pre-employment screening . . . . . . . . . . ❑ DO

Conduct direct-DNA tests as part of pre-employment screening . . . . . . . . . . . . . . . . . . . ❑ on

Conduct genetic monitoring of all workers exposed to workplace hazards . . . . . . . . .❑ on

Conduct genetic screening of workers to detect

genetic susceptibilities to workplace hazards . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ❑ 00
Appendix F--Survey Instrument: Corporate Personnel Officers ● 227

8. Would your company consider the use of genetic tests for employees or job applicants generally acceptable

or generally unacceptable to:

ACCEPTABLE

Hake a clinical diagnosis of a sick employee . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .❑

Establish links between genetic pre disposition and workplace hazards . . . . . . . . ❑

Inform employees of their increased susceptibility to workplace hazards . . . . . .• 1

Exclude employees with increased susceptibility from risk situations. . . . . . . . .• 1

Monitor chromosomal changes associated with workplace exposures . . . . . . . . . . . . . .• 1

Establish evidence of pre-employment health status for Inability purposes.... ❑

UNACCEPTABLE

❑

❑

❑

Should be excluded . . . . . . . .❑ Allowed to take. . . . . . . . . . . ❑

10. As part of your pre-employment hiring practices, do youcurrently require each of the following as a condition of employment for all applicants, only applicants for certain plants or job classifications, only applicants with certain medical conditions or histories, or for no applicants?

ALL

Routine physical “examination . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .❑

Biochemical genetic screening tests . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .❑

Cytogenetic monitoring tests . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .❑

Other medical criteria, e.g., lower back X-ray, allergy testing . . . . .• 1

PersonalitY/psychological testing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .❑

Drug testing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . • J

IF “NONE” TO ALL IN Q. IO, SKIP To Q.12

11. Is it company policy to inform applicants of positive test results?

Yes. . . . . . . . . .•1“() •1 . . . . . . . . . .

PLANTS/

JOBs

❑

❑

❑

❑

❑

CONDITIONS/

HISTORIES

❑

HONE

❑

❑

❑

ha. Is it company policy to refer applicants to appropriate health care providers if positive test results

are obtained?

Yes. . . . . . . . . . c1 No. . . . . . . . . .• 1
228 . Genetic Monitoring and Screening in the Workplace

12a. Does your company have a policy concerning hiringFOR EACH’’YESn IN Q. 12a

12b. Generally speaking, would you say it is against

company policy to hire... 1

0.12a

n n

Cigarette sinkers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . u u

Persons with criminal records . . . . . . . . . . . . . . . . . . . . . . . ❑ 0

Persons with pre-existing medical conditions. . . . . . . . ❑ cl

Persons with increased genetic

susceptibility to substances

or conditions in the workplace . . . . . . . . . . . . . . . . . . . .❑ 0

Q. i2b

~

AGAINST POLICY ~ HIRE

~DEP~

❑ a n

❑ o n

clan

❑ 0 0

IF YOUR COMPANY HAS NEVER DONE ANY BIOCHEMICAL GENETIC SCREENING, CYTOGENETIC MONITORING, DIRECT-DNA SCREENING, OR DIRECT-DNA

MONITORING, SKIP TO QUESTION 19.

1.3. To the best of your knowledge, which of the following were important factors in the decision to conduct

genetic screening or monitoring of employees in your company?

IMPORTANT NOT IMPORTANT

Cost benefit analysis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .❑ ❑

Evidence of a possible association between chemical exposure

and illness in animal studies • 1 1 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Evidence of a possible association between chemical exposure

and illness in epidemiological studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

•c1 1

Legal consequence of failure to test . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .❑ ❑

Union/employee initiative . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . o ❑

Something else (Please Specify)

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .❑ ❑

14. To the best of your knowledge, has your company ever rejected a job applicant, primarily or partly, based

on the results of genetic screening tests?

Yes. . . . . . . . . .•“o1 . . . . . . . . . .•~SKIjJ TO Q. 15

14a. When was the most recent time that occurred?

Within past month. . . . . . . . . . ❑

Within past year. . . . . . . . . . . ❑

1-2 years ago. . . . . . . . . . . . . .• 1

3 or more years ago. . . . . . . . ❑

14b. What was the condition(s)?

14c. Was the applicant informed of the reason for the rejection?

yes. . . . . . . . . . a “. ❑ . . . . . . . . . .
Appendix F--Survey Instrument: Corporate Personnel Officers . 229

14& Was alternative employment within your company offered?

Yes. . . . . . . . . . ❑ No. . . . . . . . . .❑

15. Have any medical or physical criteria been specified that would disqualify individuals from:

YES

work in the company . . . . . . . . . . . . . . . . . . . . . . . . . . . . .❑ ;

Work in specified plants or locations . . . . . . . . . . . ❑ o

Work in specified jobs . . . . . . . . . . . . . . . . . . . . . . . . . .❑ 0

16. Does your company maintain statistical data on job applications, outcomes, and reasons for rejection?

Yes. . . . . . . . .• 1 Ho. . . . . . . . . .•~st(lp TO (2. 18

17. Are biochemical or cytogenetic tests used as rejection categories in these data?

Yes. . . . . . . . . .❑ NOEJ. . . . . . . . . .

18. Has your company ever transferred or terminated an employee, primarily or partly, based on the results of

genetic screening or monitoring?

Yes. . . . . . . . . .❑ INO . . . . . . . . . .•~S/(IP TOQ. 19

18a. When was the mostrecent time that occurred?

Within past month. . . . . . . . . .❑

Within past year. . . . . . . . . . .• 1

1-2 years ago.. . . . . . . . . . . . .• 1

3 or more years ago. . . . . . . . ❑

18b. what was the condition?

l8c. Was the employee informed of the reason for the action?

Yes. . . . . . . . . .❑ l)iocl . . . . . . . . . ●

19. Is it your company’s policy to conduct periodic medical testing of persons in any risk categories?

Yes. . . . . . . . . .❑ No. . . . . . . . . .•~SK/P TO Q. 20

19a. Is it company policy to inform employees of positive test results?

Yes. . . . . . . . . .• 1 No. . . . . . . . . .❑

19b. Is it company policy to refer employees to appropriate health care providers if positive test results

are obtained?

Yes. . . . . . . . . .• 1 No. . . . . . . . . .n

19c. Is it company policy to release positive test results to anyone outside of the company, other than the

employee?

Yes. . . . . . . . . .❑ No . . . . . . . . . .❑ —wsKIP TO Q. 20

19d. Under what circumstances?
230 ● Genetic Monitoring and Screening in the Workplace

19e. Was alternative employment within your company offered?

Yes. . . . . . . . . .❑ . . . . . . . . . . .0

19f. Does your company have a set of guidelines for this type of situation or is it left to the discretion of the

particular establishment?

Yes. . . . . . . . . .•❑ . . . . . . . . . . ,01

20. Does your company maintain statistical data on the masons for job terminations?

Yes. . . . . . . . . .❑ no. . . . . . . . . . •~SKIP TO 0.21

20a. Are biochemical or cytogenetic tests used as rejection categories in these data?

Yes. . . . . . . . . .a “o . . . . . . . . . . ❑

20b. Are other medical criteria used as rejection categories in these data?

Yes. . . . . . . . . .•“.1 ❑ . . . . . . . . . .

21. Within the next five years, do you anticipate that your company will conduct:

Mandatory

Voluntary

Mandatory

Voluntary

Mandatory

Voluntary

Mandatory

Voluntary

YES

biochemical genetic screening. . . . . . . . . . . . ❑

biochemical genetic screening . . . . . . . . . . . . ❑

cytogenetic monitoring . . . . . . . . . . . . . . . . . . .• 1

cytogenetic monitoring.........., . . . . . . . . ❑

DNA-based genetic screening . . . . . . . . . . . . . . ❑

MA-based genetic screening,... . . . . . . . . . .• 1

DNA-based genetic monitoring. . . . . . . . . . . . . ❑

DNA-based genetic monitoring. . . . . . . . . . . . . • 1

NO

❑

❑

❑

❑

22. If you were asked, would you recommend to your company that genetic screening be done as part of preemployment screening?

Yes. . . . . . . ❑ ~ Based on what criteria?

No. . . . . . . .• 1

23. If you were asked, would you recommend to your company that periodic genetic monitoring of employees be

done?

Yes. . . . . . .•1 ~ Based on what criteria?

No. . . . . . . .•1

24. Approximately what proportion of your employees are covered by collective bargaining agreements?

Less than 10%. . . . . .• 1

10% to 49%. . . . . . . • ● . 1

50% to 75%. . . . . . . . .• 1

More than 75%. . . . . .• 1

25. Have union contract negotiations ever covered the topic of genetic screening and/or genetic monitoring?

Yes. . . . . . . . . . .❑ h• . . . . . . . . . . 1
Appendix F--Survey Instrument: Corporate Personnel Officers .231

26. What proportion of your company% employees are covered by health insurance offered by the company?

All . . . . . ❑ Host . . . . .❑ ~.o..oa Fw.,.o.n Noneo..o.~ SK/P TO(2. 2 7

26a. Is the company% current health insurance plan(s) purchased from a private carrier, self-insured

or both?

Private carrier . . . . . .❑ ~lf.fns”~...a.a Both....... n

27. If a job applicant is currently healthy and able to perform the job, but is considered to be a health insurance risk would that consideration reduce the likelihood of his/her being hired by your company - a lot

some or not at all?

A lot. . . . . . . . ❑ SCNIBB.........D Not at all...a

28. Does your company assess the health insurance risk of job applicants on a routine basis, sometimes or

never?

Routine. . . . . . ❑ htims...on Never........ D~ SKIP TOQ. D1

28a. Does the health insurance assessment of job applicants also consider the health of dependents?

Yes. ● ● .,. ● ❑ No........n

DEMOGRAPHIC CHARACTERISTICS

D1. What& the major industrial classification of your company (such as chemicals, food, textiles, etc.) ?

D2. Approximately how many persons are employed in the United States by your company?

Less than 1,000 . . . . . . . . ❑

1,000 - 4,999 . . . . . . . . . .❑

5,900- 9,999 . . . . . . . . . .• 1

10,000 or more. . . . . . . . . .• 1

D3. What is your job title?

D4. What are your main job responsibilities?
232 . Genetic Monitoring and Screening in the Workplace

Thank you very much for your cooperation in answering our questions. We would also like to give you an

opportunity to give us any other opinions, concerns or suggestions related to genetic testing in the workplace

that you feel our questions did not address. These comments maybe incorporated in our report to Congress.

We would also appreciate your comments on any survey questions that you found confusing or difficult to

answer, to help us analyze the results. Please write these comments below.

We have attached a peel-off identification number on the questionnaire. This is the only link between the

companies who were sampled and the questionnaires returned. We would prefer that you leave the identification number on the questionnaire when you return it. Our staff will remove the label upon receipt, making the

questionnaire completely anonymous. No linkage between companies and questionaires will be retained. The

label from the completed questionnaire will allow us to eliminate your company from those that wc have to

recontact.

However, if you feel that you cannot complete the questionnaire if there is even temporary identification, then

peel off the label before returning the questionnaire. We appreciate your help and wc want you to be comfortable doing the survey.

PEEL OFF LABEL WITH SAMPLE

IDENTIFICATION NUMBER HERE

PLEASE RETURN IN THE POSTAGE PAID RETURN ENVELOPE SENT WITH THE QUESTIONNAIRE.

IF THE RETURN ENVELOPE HAS BEEN LOST, THE RETURN ADDRESS IS:

Schulman, Ronca and Bucuvalas, Inc

444 Park Avenue South

New York New York 10016

(212) 481-6200 Attn: Dr. Mark Schulman
Appendix G

Survey Instrument: Union Presidents

SURVEY OF WORKPLACE HEALTH AND

GENETIC SCREENING AND MONITORING

LABOR UNION VERSION

The Congressional Office of Technology Assessment is conducting a national survey of the opinions and experiences of unions related to the use of genetic screening and monitoring in the workplace. We need your assistance in answering as best you can, some questions about workplace testing and member health in your union.

For the purposes of this survey and the subsequent report, OTA has adopted the following definitions. By

genetic monitoring wc mean periodically examining members to evaluate modifications of their genetic material via tests such as cytogenetic or direct-DNA tests. By genetic screening, wc mean screening members or

potential members for certain inherited characteristics. Screening tests may be biochemical tests or directDNA tests. They can be used to indicate a predisposition to an occupational illness if exposed to a specific

environmental agent, or they could be used to detect any inherited characteristic such as Huntington’s disease.

In contrast to periodic monitoring screening tests arc generally performed only one time per Characteristic

This is an important study, which has been requested by the Congress of the United States, designed to represent the opinion and experience of leading unions. We need to know how unions view the new technology of

genetic screening and monitoring in terms of its current and future applications to the workplace. We also

want to know how these technologies arc seen in the broader context of more common forms of employee

health screening and monitoring in the workplace.

Your responses arc very important, regardless of whether your union has had any experience with genetic

screening or monitoring. If your union has never explored the technology, the questionnaire will only take ten

rninutes. If you have some experience with the technology, it may take a little longer to complete the questionnaire. In either case, your experiences and opinions will help to inform congressional opinion about this area.

Please read each question and mark the box(es) that most nearly corresponds to your answer. After each

answer continue with the next question unless there is an instruction to skip to a particular question. Please

feel free to qualify your answers, if you feel it is necessary. Space has been provided at the end for comments

and opinions that you feel are not adequately represented by the survey questions.

You arc free to decline to answer any questions that you consider inappropriate. The questionnaire and any

identifying information will be destroyed after data entry, so that all responses will be anonymous as well as

confidential.

1. Are health examinations required by companies that employ members of your union of all, most, some, few

or no members?

a ❑ ❑ ❑

Al 1 Host Fen

❑

None ~SKiP to Q.3

–233–
234 . Genetic Monitoring and Screening in the Workplace

2. Which of the following are normally part of the examination that is given by companies for your union

members? (MARK AU THAT APPLY)

Personal medical history . . . . . . . . . . . . . . ❑ Chest X-ray . . . . . . . . . . . . . . . . . . . . . . . . . . .

• 1

family medical history. . . . . . . . . . . . . . . .• 1 Pulmonary function test. . . . . . . . . . . . . . . ❑

Simple physical examinations . . . . . . . . . .• 1 Eye and hearing exam. . . . . . . . . . . . . . . . . . ❑

Standard blood chemistry tests . . . . . . . .• 1 Urinalysis for drug use. . . . . . . . . . . . . . . ❑

EKG ❑ Lower back X-ray . . . . . . . . . . . . . . . . . . . . . . ● . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . • 1

3. Are any members of your union exposed to chemicals or ionizing radiation in the workplace setting?

❑ ❑

Yes No~ SKIPTOQ.4

3a. Are those members who are exposed to chemicals or ionizing radiation routinely rotated to avoid

prolonged exposure?

• 1 1

Yes no

3b. Does your union conduct any form of medical surveillance of employees whose job may expose them to

environmental health risks?

❑

Yes No

4. Are any members of your union exposed to any known workplace condition where there is a greater risk of

negative health outcome, depending upon individual susceptibilities?

❑ ❑

Yes No ~SKIP TO Q.5

4a. Is any form of screening conducted to identify members of your union at increased risk for these jobs?

❑ ❑

Yes, Yes, Yes, No ~SKIP TO Q.5

by union by company by union

and company
Appendix G-Survey Instrument: Union Presidents ● 235

4b. Which, if any, of the following types of screening are conducted to identify increased individual susceptibility to workplace risk?

CHECK ALL THAT APPLY

CONDUCTED CONDUCTED

BY UNION BY COMPANY

Medical History.... . . . . . . . .• 1 ❑

Non-genetic screening

(e.g.. lower back

X-ray, allergy testing).... ❑

Genetic screening . . . . . . . . . . ❑

Genetic Monitorlng. . . . . . . . . ❑

None. ● . . . ● . . . . . . . . . . . . . . . . .•1

❑

❑

❑

S. Does your union have a formal policy related to the use of genetic tests in the screening of employees or job

applicants?

❑

Yes No

6. Does your union have a formal policy related to the use of genetic tests in the monitoring of employee

health?

❑

Yes Ho

7. Has your union ever recommended to a company that it change a workplace practice or exposure level due to

the results of:

YES NO

Genetic monitoring in establishment(s) where your members work. . . . . . . . . . . . . .•❑ 1

Other non-genetic medical monitoring in

establishment(s) where your members work . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .❑ ❑

Genetic monitoring in establishments

where your union is not represented . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

•❑ 1

Other non-genetic medical monitoring In

establishments where your union is not represented . . . . . . . . . . . . . . . . . . . . . . . . . ❑ ❑

Information published by federal agencies, including NIOSH and OSHA. . . . . . . . . ❑ ❑

8. Have union contract negotiations ever covered the topic of genetic screening and/or genetic monitoring?

❑

Yes No

9. Has your union ever filed an employee grievance related to genetic screening or monitoring?

❑

Yes No ~ SKIP TO Q.1O
236 . Genetic Monitoring and Screening in the Workplace

9a. Did that grievance involve employee firing, transfer or something else?

❑ ❑

Firing Transfer Other

10. To the best of your knowledge, has a member of your union applying for a job been rejected, primarily or

partly, based on the results of genetic screening tests?

❑

Yes No~SKIP TOQ.11

10a. When was the most recent time that occurred?

Within past month.. . . . . . . . . . . . .• 1

Within past year. . . . . . . . . . . . . . .❑

1-2 years ago. . . . . . . . . ● .*... . . .❑

3 or more years ago. . . . . . . . . . . . ❑

10b. What was the condition(s)?

10c. Was alternative employment within the company offered?

❑

Yes No

11. To the best of your knowledge, has any member of your union been transferred or terminated by a company

based on the results of genetic screening or monitoring?

❑ El

Yes No ~ SKIP TO Q.12

ha. When was the most recent time that occurred?

Within past month. . . . . . . . . . . . . . ❑

Within past year. . . . . . . . . . . . . . . ❑

1-2 years ago. . . . . . . . . . . . . . . . . . ❑

3 or more years ago. . . . . . . . . . . . ❑
Appendix G--Survey Instrument: Union Presidents .237

12. Does your union maintain statistical data on the reasons for job terminations?

❑

Yes Ho~SKIP TO Q.13

12a. Are biochemical and cytogenetic tests used as rejection categories in these data?

❑

Yes No

12b. Are other medical criteria used as rejection categories in these data?

❑

Yes Ho

13. Would your union consider It acceptable or unacceptable for an employer to conduct a health examination

of job applicants In order to:

ACCEPTABLE UNACCEPTABLE

Identify job applicants who are physically unfit for employment . . . . . . . . . . . . . . . ❑ ❑

Identify job applicants who are emotionally or psychologically unstable . . . . . . .• 1 ❑

Identify job applicants who are currently using drugs . . . . . . . . . . . . . . . . . . . . . . . . .• 1 ❑

Identify job appl

Identify Job appl

Identify job appl

icants who are at increased risk to workplace hazards . . . . . . . . ❑ ❑

icants with genetic susceptibility to workplace exposures.... • 1 c 1

icants who represent high insurance risks. . . . . . . . . . . . . . . . . . . .• 1 ❑
238 . Genetic Monitoring and Screening in the Workplace

14. How do you feel about the following general statements concerning genetic screening and monitoring in the

workplace? For each statement, please indicate whether you agree strongly, agree somewhat, disagree

somewhat, or disagree strongly.

AGREE AGREE DISAGREE DISAGREE

STRONGLY SOMEWHAT SOMEWHAT STRONGLY

It’s fair for employers to use

genetic screening to identify

individuals whose increased risk

of occupational disease poses a

threat for greater costs to the

employer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .❑

The employer should have the option

of deciding how to use the information

obtained through genetic screening

and monitoring. . . . . . . . . . . . . . . . . . . . . . . . ❑

The decision to perform genetic

screening of Job applicants and employees should bethe employer’s. . . . . .• 1

The decision to perform genetic

monitoring of employees should be

the employer’s. . . . . . . . . . . . . . . . . . . . . . . .❑

Government agencies should provide

guidelines for genetic screening of

job applicants and employees . . . . . . . . . . ❑

Government agencies should provide

guidelines for genetic monitoring of

employees . 0000 . ., . 0 . . . . . . . . . . 00.,00... ❑

Genetic screening in the workplace

represents a potential threat to

the rights of employees. . . . . . . . . . . . . . . ❑

❑

❑

❑

El

❑

❑

❑

El

❑

❑

❑

❑

15. Would your union consider the use of genetic screening or monitoring of employees or job applicants by —

employers as generally acceptable or generally unacceptable to:

GENERALLY

ACCEPTABLE

Hake a clinical diagnosis of a sick member . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ❑

Establish links between genetic predisposition and workplace hazards.. . . . . . . . . . KI

Inform members of their increased susceptibility to workplace hazards . . . . . . . . . . ❑

Exclude members with increased susceptibility from risk situations . . . . . . . . . . . . .KI

Monitor chromosomal changes associated with workplace exposures . . . . . . . . . . . . . . . . ❑

Establish evidence of pre-employment health status for liability purposes . . . . . . ❑

GENERALLY

UNACCEPTABLE

❑

❑

❑
Appendix G--Survey Instrument: Union Presidents . 239

16. If an employer becomes aware that an employee has a genetic susceptibility to serious illness if he or she is

exposed to substances In the workplace, do you think the employer should exclude that employee from

those jobs for which he/she is at increased risk, or do you think the employer should allow the employee to

take those jobs, if he/she waives corporate liability?

Should be excluded . . . . . . . . . . . . . . . ❑ Allowed to take ................0

17. Is your union currently conducting biochemical genetic screening of any members or potential members,

for research or any other reason?

❑ • 1

Yes No Not Sure

18. Has your union conducted any biochemical genetic screening of any members or potential members, for

research or any other reason In the past 19 years?

❑ ❑

Yes No Not sure

19. IS your union currently conducting cytogenetic monitoring of any members or potential members, for

research or any other reason?

❑

• 1

❑

Yes No Not Sure

20. Has your union conducted any cytogenetic monitoring of any members or potential members, for research

or any other reason in the past 19 years?

Kl

Yes Ho Not Sure

21. Is your union currently conducting direct-DNA screening of any members or potential members, for research or any other reason?

❑ ❑

Yes No Not Sure

22. Is your union currently conducting direct-DNA monitoring of any members or potential members, for

research or any other reason?

❑ ❑

Yes No Not Sure
240 . Genetic Monitoring and Screening in the Workplace

23. Has your union conducted any of the following tests, either currently or in the past, as part of a voluntary

wellness program, at the request of a member, or for diagnosis? (MARK ALL THAT APPLY)

BIOCHEMICAL.

GENETIC

SCREENING

a. As part of a voluntary

wellness program Current ly.. . . . . . . . . . . . . . . ❑

In past 19 years . . . . . . . . ❑

No. . . . . . . . . . . . . . . . . . . . . . .• 1

Not sure. . . . . . . . . . . . . . . . . ❑

b. At the request of the

member: Currently.. . . . . . . . . . . . . . .• 1

In past 19 years . . . . . . . . .• 1

No .. ..0.00. . . . . . . . . . . . . . .• 1

Not sure. ● ● ● .0 . . . ● . ● . ● . . .

• 1

c. For diagnosis:

CYTOGENETIC

MONITORING

❑

El

❑

❑

❑

E!

❑

Currently . . . . . . . . . . . . . . . . ❑ ❑

In past 19 years . . . . . . . . .•❑ 1

No.. . . . . . . . . . . . . . . . . . . . . .❑ ❑

Not sure. . . . . . . . . . . . . . . . .•1 ❑

DIRECT-DNA

SCREENING

❑

❑

❑

❑

❑

DIRECT-DNA

MONITORING

❑

❑

❑

❑

❑

❑

❑

IF YOUR UNION HAS NEVER DONE BIOCHEMICAL GENETIC SCREENING, CYTOGENETIC MONiTORING, DIRECT-DNA SCREENING, OR DIRECT-DNA MONITORING, SKIP TO QUESTION 32 0N

PAGE 12

IF YOUR UNION HAS DONE CYTOGENETIC MONITORING, DIRECT-DNA SCREENING, OR DIRECTDNA MONITORING OF MEMBERS, FOR ANY PURPOSE, BUT NOT BIOCHEMICAL GENETIC

SCREENING, SKIP TO QUESTiON 25 0N PAGE 10

IF YOUR UNION HAS EVER DONE BIOCHEMICAL GENETIC SCREENING OF ANY MEMBER, FOR

ANY PURPOSE, PLEASE CONTINUE WlTH QUESTiON 24
Appendix G--Survey Instrument: Union Presidents ● 241

24. Which of the following types of biochemical screening tests are being conducted by your union of any

members or potential members? (MARK AU THAT APPLY)

NOT

DONE

Sickle cell trait . . . . . . . . . . . . . . . . . . . . . . . . . . . .• 1

Glucose-6-phosphate dehydrogenase

deficiency (G-6-PO) . . . . . . . . . . . . . . . . . . . . . . . . . . . ❑

Nethemaglobln reductase deficiency . . . . . . . . . . . . ❑

serum alpha-1 -antftrypsln def Iciency. . . . . . . . . . ❑

Alpha and beta thalassemlas. . . . . . . . . . . . . . . . . . .• 1

Aryl hydrocarbon hydroxylase

imducfbility (AHH) ● . . . . . . . . . . . . . . . . . . . . . . . . . . . ❑

Slw vs. fast acetylatfon....... o... . . . . . . . . . . ❑

Allergic respiratory disease . . . . . . . . . . . . . . . . . ❑

Contact dennatltls . . . . . . . . . . . . . . . . . . . . . . . . . . . .❑

Hfstocoupatlbillty mmkers (HIA). . . . . . . . . . . . . .• 1

Other hmune systeamrkers. . . . . . . . . . . . . . . . . . . ❑

Bloom syrxh-om . . . . . . . . . . . . . . . . . . . . . ● . . . . . . . . . . ❑

Fanconi syndrorm . . . . . . . . . . . . . . . . . . . . . . . . . . . . .• 1

Ataxia-telangiectasia . . . . . . . . . . . . . . . . . . . . . . . .❑

Xerodenm pigmmtosum . . . . . . . . . . . . . . . . . . . . . . . .❑

Other heterozygous chromosomsl

Instabil{tles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

• 1

ROUTINE VOLUNTARY

HEALTH RESEARCH

SURVEILLANCE PROGRAM

❑ ❑

❑

❑ 0

❑ u

El

❑

❑

❑

❑

❑

❑

❑

❑

❑

FOLLOW-UP

DIAGNOSIS

❑

❑

❑

❑

❑

❑

❑

❑

❑

❑

VOLUNTARY

WELLNESS

PROGRAM

❑

❑

❑

❑

❑

❑

❑

AT

MEMBER

REQUEST

❑

❑

❑

❑

❑

❑

❑

❑

❑

❑

❑

❑
242 . Genetic Monitoring and Screening in the Workplace

25. Which of the following types of cytogenetic monitoring are being conducted by your union of any members?

(MARK ALL THAT APPLY)

ROUTINE VOLUNTARY VOLUNTARY AT

NOT HEALTH RESEARCH FOLLOW-UP WELLNESS

DONE

MEMBER

SURVEILLANCE PROGRAM DIAGNOSIS PROGRAM REQUEST

Chromosome aberrations . . . . . . . . . . . . . . . . . . . .• 1

Sister chromatid exchanges . . . . . . . . . . . . . . . . .• 1

Mutations by assaying the DNA. . . . . . . . . . . . . .• 1

Mutatlons by assaying the enzyme/protein... ❑

HPRT mutation rate. . . . . . . . . . . . . . . . . . . . . . . . . ❑

DNA adduct formation. . . . . . . . . . . . . . . . . . . . . . .• 1

❑ ❑

❑

❑ ❑

❑

❑ ❑

❑ n

❑ n

❑ n

❑ n

❑

❑

❑

❑

❑

Other (SPECIFY)

. . . . . . . . . . ● ✎ ✎ ✎•❑ ❑ 1 ❑ o ❑

26. To the best of your knowledge, which of the following were important factors in the decision to conduct

genetic screening of your members?

IMPORTANT NOT IMPORTANT

Cost benefit analysis . . . . . . . . . ● .......0. ● ...*..... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ❑ ❑

Evidence of a possible association between chemical

exposure and illness In animal studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .❑ ❑

Evidence of a possible assocciation between chemical

exposure and Illness in epidemiological studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ❑ ❑

Legal consequence of failure to test . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .❑ ❑

Union/employee initiative . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . • 1 ❑

Something else. (PLEASE SPECIFY) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .•❑ 1

27. Are all members routinely informed of abnormal (positive) findings, normal (negative) findings, both or

neither from genetic screening and monitoring tests?

Abnormal (positive). . . . . . . . . . . . ❑

Normal (negative). . . . . . . . . . . . . . ❑

Both . . . . . . . . . . . . . . . . . . . . . . . . . . . ❑

Neither . . . . . . . . . . . . . . . . . . . . . . . . ❑
Appendix G--Survey Instrument: Union Presidents ● 243

28. Is counseling offered to all members with abnormal (positive) genetic test results by the union or are they

referred to their own physicians?

Union counseling. . . . . . . . . . . . . . . . ❑

Referred to own physicians... . . .• 1

29. Does your union employ or contract with a genetic counselor?

❑ ❑ ❑

Employ Contract with Neither

30. Has a member ever been referred for genetic counseling by your union’s medical staff as a result of any

medical or genetic testing?

❑

Yes No

31. As a result of a genetic screening or monitoring program has your union ever—?

YES

Suggested a member seek a job in another company.... . . . . . . ❑

Suggested a member seek a transfer to a

different job in the same company . . . . . . . . . . . . . . . . . . . . . . . . . ❑

Recommended company implement engineering control . . . . . . . . . ❑

Recommended company provide personal protection devices . . . K1

Recommended company implement a research program . . . . . . . . . ❑

Recommended company discontinue a product or change

materials in a product . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ❑

Some other action (PLEASE SPECIFY) . . . . . . . . . . . . . . . . . . . . . . . . ❑

NO

❑

❑

❑

K3
244 ● Genetic Monitoring and Screening in the Workplace

32. Is your union currently considering conducting direct-DNA screening of members or potential members for any

reason?

❑

33. Is your union currently

for any reason?

Yes No Not Sure

considering conducting direct-DNA monitoring of members or potential members

❑ ❑

Yes No Not Sure

34. Does your union anticipate conducting any biochemical genetic screening, for any reason, in the next five

years?

• 1 1 1

Yes No Not Sure

35. Does your union anticipate conducting any cytogenetic monitoring, for any reason, in the next five years?

❑ ❑ ❑

Yes No Not sure

36. Does your union anticipate conducting any direct-DNA screening, for any reason, in the next five years?

• ❑ ❑ 1

Yes No Not Sure
Appendix G--Survey Instrument: Union Presidents . 245

37. Does your union anticipate conducting any direct-DNA monitoring for any reason, in the next the years?

❑ ❑

Yes no Not sure

38. Which office/division within the union is/will be responsible for administering genetic tests?

39. Has genetic screening or monitoring ever been done of your union members based on:

CHECK ALL THAT APPLY

CONDUCTED CONDUCTED

BY UNION BY COMPANY

Family History. . . . . . . . . . . . . ❑

Gender . . . . . . . . . . . . . . . . . . . . .❑

Ethnic/racial background... c1

Co-factors (e.g. smoking).. • 1

Job exposures... . . . . . . . . . . . ❑

NO TEST CONDUCTED.... . . . . . .• 1

DEMOGRAPHICS

D1. What are the major industrial classifications (such as chemicals, food, textiles, etc.) of those companies in

companies in which your members work?

D2. Approximately how many members does your union have?

D3. What is your job title?

D4. What are your main job responsibilities?
246 ● Genetic Monitoring and Screening in the Workplace

Thank you very much for your cooperation in answering our questions. We would also like to give you an

opportunity to give us any other opinions, concerns or suggestions related to genetic testing in the workplace

that you feel our questions did not address. These comments may be incorporated in our report to Congress.

We would also appreciate your comments on any survey questions that you found confusing or difficult to

answer, to help us analyze the results. Please write these comments below.

We have attached a peel-off identification number on the questionnaire. This is the only link between the

unions who were sampled and the questionnaires returned. We would prefer that you leave the identification

number on the questionnaire when you return it. Our staff will remove the label upon receipt, making the

questionnaire completely anonymous. No linkage between unions and questionnaires will be retained. The

label from the completed questionnaire will allow us to eliminate your union from those that wc have to recontact.

However, if you feel that you cannot complete the questionnaire if there is even temporary identification, then

peel off the label before returning the questionnaire. We appreciate your help and we want you to be comfortable with doing the survey.

PEEL OFF LABEL WITH SAMPLE

IDENTIFICATION NUMBER HERE

PLEASE RETURN IN THE POSTAGE PAID RETURN ENVELOPE SENT WITH THE QUESTIONNAIRE.

IF THE RETURN ENVELOPE HAS BEEN LOST, THE RETURN ADDRESS IS:

Schulman, Ronca and Bucuvalas, Inc.

444 Park Avenue South

New York New York 10016

(212) 481-6200 Attn: Dr. Mark Schulman
Appendix H

Acknowledgments

OTA would like to thank the members of the advisory panel who commented on drafts of this report and the many

individuals and organizations that supplied information for the study. In addition, OTA acknowledges the following

individuals who reviewed drafts of this report:

Ronald T. Acton

University of Alabama

Birmingham, AL

Lori B. Andrews

American Bar Foundation

Chicago, IL

George W. Anstadt

Eastman Kodak Co.

Rochester, NY

Stylianos E. Antonarakis

Johns Hopkins University Hospital

Baltimore, MD

Bonnie Batay

University of Utah Medical Center

Salt Lake City, UT

Edward Bernacki

Tenneco, Inc.

Houston, TX

Paul R. Billings

Pacific Presbyterian Medical Center

San Francisco, CA

Robert H. Blank

Northern Illinois University

DeKalb, IL

Joseph F. Borzelleca

Medical College of Virginia

Richmond, VA

R. Alta Charo

University of Wisconsin

Madison, WI

Carl Cohen

University of Michigan

Ann Arbor, MI

Philip Cohen

Huntington’s Disease Society

of America

New York NY

Robert Cook-Deegan

Derwood, MD

Elaine Alma Draper

University of Southern California

Los Angeles, CA

H. Tristram Engelhardt

Baylor College of Medicine

Houston, TX

John C. Erfurt

University of Michigan

Ann Arbor, MI

John P. Fanning

U.S. Department of Health and

Human Services

Washington, DC

Frederick Hecht

Hecht Associates

Jacksonville, FL

Max A. Heirich

University of Michigan

Ann Arbor, MI

George R. Hoffman

Holy Cross College

Worcester, MA

Barbara S. Hulka

University of North Carolina

Chapel Hill, NC

Eric T. Juengst

Robert I. Field National Center for Human Genome

Dilworth, Paxson, Kalish & Kauffman Research

Philadelphia, PA

Nancy L. Fisher

Swedish Hospital Medical Center

Seattle, WA

Barry Furrow

Widener University School of Law

Wilmington, DE

Glenn C. Graber

University of Tennessee

Knoxville, TN

Ian A. Greaves

University of Minnesota

Minneapolis, MN

Tee L. Guidotti

University of Alberta

Alberta, Canada

Annabelle Harris

International Paper Co.

Purchase, NY

Barbara K. Hecht

Hecht Associates

Jacksonville, FL

Bethesda, MD

Mary Kennard

University of Rhode Island

Kingston, RI

Philip Landrigan

Mt. Sinai Medical Center

New York NY

Timothy D. Leathers

U.S. Department of Agriculture

Peoria, IL

Abby Lippman

McGill University

Montreal, Canada

Karen Messing

University of Quebec-Montreal

Montreal, Canada

Daryl Ann Miller

Howard University

Washington, DC

Aubrey Milunsky

Boston University School of Medicine

Boston, MA

–247 –
248 . Genetic Monitoring and Screening in the Workplace

Joseph Misbrenner

Oil, Chemical & Atomic Workers

Union

Denver, CO

C. Hunter Montgomery

Exxon Co., USA

Houston, TX

John C. Moskop

East Carolina University

Greenville, NC

Arno G. Motulsky

University of Washington

Seattle, WA

Dorothy Nelkin

New York University

New York NY

Nanette Newell

The Synertech Group, Inc.

Research Triangle Park, NC

Gilbert S. Omenn

University of Washington

Seattle, WA

Christopher Pyle

Mount Holyoke College

South Hadley, MA

Kimberly A. Quaid

Johns Hopkins University

Baltimore, MD

Peter T. Rowley

University of Rochester Medical

Center

Rochester, NY

Paul A. Schulte

National Institute for Occupational

Safety and Health

Cincinnati, OH

Paul Seligman

National Institute for Occupational

Safety and Health

Cincinnati, OH

Thomas A. Shannon

Worcester Polytechnic Institute

Worcester, MA

Robyn Shapiro

Medical College of Wisconsin

Milwaukee, WI

Joe Leigh Simpson

University of Tennessee

Memphis, TN

David A. Smith

U.S. Department of Energy

Washington, DC

Frank Rees Smith

Exxon Chemicals

Houston, TX

Marja Sorsa

Institute of Occupational Health

Helsinki, Finland

Lawrence Tancredi

University of Texas Health Science

Center

Houston, TX

Hastings Trigg

E.I. du Pent de Nemours & Co.

Wilmington, DE

Arthur Upton

New York University Medical Center

New York NY

Dorothy Vawter

University of Minnesota Health Center

Minneapolis, MN

Sally Vernon

University of Texas Health Science

Center

Houston, TX

Bruce D. Weinstein

West Virginia University

Morgantown, WV

Alan J. Weisbard

University of Wisconsin

Madison, WI

Dorothy C. Wertz

Boston University

Boston, MA

Gladys B. White

Gaithersburg, MD

Geraldine C. Williamson

American Association of Occupational

Health Nurses

Atlanta, GA

Jan Witkowski

Banbury Center

Cold Spring Harbor, NY
Appendix I

List of Contractor Documents

For this report, OTA commissioned papers on various topics concerning genetic monitoring and

screening in the workplace. The manuscripts are available from the National Technical Information

‘ Service, 5285 Port Royal Road, Springfield, VA 22161, telephone (703) 487-4650.

“Confidentiality of Genetic Information in the Workplace,” Lori B. Andrews, American Bar

Foundation, Chicago, IL.

“The Ethics of Genetic Testing in the Workplace,” Baruch A. Brody, Baylor College of Medicine,

Houston, TX.

“Genetic Predisposition to Occupationally Related Diseases: Current Status and Future Directions,” Edward J. Calabrese, University of Massachusetts, Amherst, MA.

“Genetic Testing in the Workplace: The NLRA, NLRB, and Collective Bargaining,” Hastings S.

Trigg, Jr., E.I. du Pent de Nemours & Co., Wilmington, DE.

“Human Rights and Genetic Testing in the Workplace,” Alan Gewirth, University of Chicago,

Chicago, IL.

“Selected Legal Issues Surrounding Genetic Testing in the Workplace,” Robert I. Field, Dilworth,

Paxson, Kalish & Kauffman, Philadelphia, PA.

–249–
Appendix J

Acronyms and Glossary of Terms

A

ADA

AIDS

ALA

AOMA

APKD

AS

ASO

AT

ATSDR

BC/BS

BLS

c

CA

CAD

CDC

CEHIC

CEO

CHD

CML

COPD

DHHS

DNA

DOD

DOE

DOL

EPA

FA

FPP

G

G-6-PD

GM

GSH

HCS

HDL

HERL

HIV

HLA

HPRT

IDDM

Acronyms

— adenine

— Americans with Disabilities Act

— aryl hydrocarbon hydroxylase

— acquired immunodeficiency syndrome

— aminolevulinic acid

— American Medical Association

— absolute nuclear flourescence intensity

— American Occupational Medical

Association

— adult polycystic kidney disease

— ankylosing spondylitis

— allele-specific oglionucleotide

— ataxia telangiectasia

— Agency for Toxic Substances and Disease

Registry (PHS, DHHS)

— Blue Cross/Blue Shield

— Bureau of Labor Statistics (DOL)

— cytosine

— chromosomal aberration

— coronary artery disease

— Centers for Disease Control (PHS, DHHS)

— Center for Environmental Health and Injury Control (CDC, DHHS)

— Chief Executive Officer

— coronary heart disease

— chronic myelogenous leukemia

— chronic obstructive pulmonary disease

— U.S. Department of Health and Human

Services

— deoxyribonucleic acid

— U.S. Department of Defense

— U.S. Department of Energy

—U.S. Department of Labor

— U.S. Environmental Protection Agency

— Fanconi’s anemia/syndrome

— fetal protection policy

— guanine

— glucose-6-phosphate dehydrogenase

— General Motors

— reduced glutathione

— hereditary cancer syndrome

— Huntington’s disease

— high-density lipoprotein

—Health Effects Research Laboratory (EPA)

— Howard Hughes Medical Institute

— human immunodeficiency virus

— human leukocyte antigen

— hypoxanthine-guanine phosphoribosyltransferase

— insulin-dependent diabetes mellitus

IgA

IOH

LDL

NADH

NAS

NCI

NCTR

NIEHS

NIOSH

NLRA

NLRB

NOES

NRC

NSF

NTP

OCT

OSH Act

OSHA

OSHRC

OTA

PCBs

PCR

PHS

PKU

Px

Rb

RFLP

RNA

SARA

SAT

SCE

SIC

SOD

SRBI

T

TSCA

TSD

VA

XP

— immunoglobulin A

— Institute of Occupational Health (Finland)

— low-density lipoprotein

— medical removal protection

— nicotinamide adenine dinucleotide,

reduced form

— National Academy of Sciences

—National Cancer Institute (NIH, DHHS)

— National Center for Toxicological Research (FDA, DHHS)

— National Institute of Environmental

Health Sciences (NIH, DHHS)

—National Institutes of Health (DHHS)

— National Institute for Occupational Safety

and Health (CDC, DHHS)

— National Labor Relations Act

— National Labor Relations Board

— National Occupational Exposure Survey

(NIOSH)

—National Research Council (NAS)

— National Science Foundation

— National Toxicology Program (PHS,

DHHS)

— ornithine carbamoyl transferase

— Occupational Safety and Health Act

— Occupational Safety and Health Administration (DOL)

— Occupational Safety and Health Review

Commission (DOL)

— Office of Technology Assessment

— polychlorinated biphenyls

— polymerase chain reaction

—U.S. Public Health Service (DHHS)

— phenylketonuria

— phenylthiourea

— peroxidase

— retinoblastoma

— restriction fragment length polymorphism

— ribonucleic acid

— Superfund Amendments and Reauthorization Act of 1986

— serum alpha-l-antitrypsin

— sister chromatid exchange

— standard industrial code

— superoxide dismutase

— Schulman, Ronca, & Bucuvalas, Inc.

— thymine

—Toxic Substances Control Act

— Tay-Sachs disease

— U.S. Department of Veterans Affairs

— xeroderma pigmentosum

–250-
Appendix J--Acronyms and Glossary ● 251

Glossary of Terms

Acetylation: The introduction of one or more acetyl

groups into an organic compound.

Acquired immunodeficiency syndrome (AIDS): The

most severe clinical manifestation of immune dysfunction caused by the human immunodeficiency virus

(HIV).

Allele: Alternative form of a genetic locus (e.g., at a locus

for eye color there might be alleles resulting in blue or

brown eyes); alleles are inherited separately from each

parent.

Amino acid: Any of a group of 20 molecules that

combine to form proteins in living things. The sequence of amino acids in a protein is determined by the

genetic code.

Autosome: Chromosome not involved in sex determination. In a complete set of human chromosomes, there

are 44 autosomes (22 pairs).

Base pair: Two complementary nucleotides (adenosine

and thymidine or guanosine and cytidine) held together

by weak bonds. Two strands of DNA are held together

in the shape of a double helix by the bonds between

base pairs.

Biochemical genetics: The analysis of mutant genes on

the basis of altered proteins or metabolizes.

Carcinogen/carcinogenesis: A chemical or physical

agent that causes cancer.

Carrier: An individual apparently normal, but possessing

a single copy of a recessive gene obscured by a

dominant allele; a heterozygote.

Cell: The smallest component of life capable of independent reproduction.

Cell culture: Growth in the laboratory of cells isolated

from multicellular organisms. Each culture is usually

of one cell type (e.g., lymphocytes, fibroblasts, etc.).

Chromosomal aberrations: An abnormal chromosomal

complement resulting from the loss, duplication, or

rearrangement of genetic material.

Chromosome: A threadlike structure that carries genetic

information arranged in a linear sequence. In humans,

it consists of a complex of nucleic acids and proteins.

Clastogens: Chromosome-damaging agent.

cloning: The process of asexually producing a group of

cells (clones), all genetically identical to the original

ancestor. In recombinant DNA technology, the process

of using a variety of DNA manipulation procedures to

produce multiple copies of a single gene or segment of

DNA.

Cytogenetics: The study of the relationship of the

microscopic appearance of the chromosomes and their

behavior to the genotype and phenotype of the

individual.

Deoxyribonucleic acid (DNA): The molecule that encodes genetic information. DNA is a double-stranded

helix held together by weak bonds between base pairs

of nucleotides.

DNA: See deoxyribonucleic acid.

DNA adducts: The binding of exogenous and xenobiotic

materials to DNA to form additional products. They

can be viewed as markers of exposure to specific

toxicants.

DNA probes: Segments of single-strand DNA that are

labeled with a radioactive or other chemical marker and

used to identify complementary sequences of DNA by

hybridizing with them.

DNA sequence: Order of nucleotide bases in DNA.

Dominant: An allele that exerts it phenotypic effect when

present either in homozygous or heterozygous form.

Dosimeter: Device or methodology for measuring the

dose of a chemical or ionizing radiation to a biological

system.

Double helix: The shape in which two linear strands of

DNA are bonded together.

Electrophoresis: Technique used to separate molecules

such as DNA fragments or proteins. An electric current

is passed through a medium containing the mixture,

and each kind of molecule travels through the medium

at a different rate, depending on its electrical charge

and size. Separation is based on these differences.

Enzyme: A protein that acts as a catalyst, speeding the

rate at which a biochemical reaction proceeds, without

being permanently altered or consumed by the reaction

so that it can be used repeatedly.

Epidemiologic studies: Studies concerned with the

relationships of various factors determiningg the frequency and distribution of diseases in a human

population.

Gamete: Mature male or female reproductive cell with a

haploid set of chromosomes (23); that is, a sperm or

ovum.

Gel: The semi-solid matrix used in electrophoresis to

separate molecules.

Gene: The fundamental unit of heredity; an ordered

sequence of nucleotide base pairs to which a specific

product or function can be assigned.

Genetic monitoring: Involves periodically examining

employees to evaluate modifications of their genetic

material+. g., chromosomal damage or evidence of

increased occurrence of molecular mutations-that

may have evolved in the course of employment. It

ascertains whether the genetic material of the group of

individuals has altered over time.

Genetic screening: A process to examine the genetic

makeup of individuals for certain inherited characteristics. It can be used to detect occupationally and

nonoccupationally related traits.

Genetic testing: Technologies that determine a person’s

genetic makeup or that identify changes (damage) in

the genetic material of certain cells. As used in the
252 . Genetic Monitoring and Screening in the Workplace

workplace, it encompasses both genetic monitoring

and screening.

Genetics: The study of the patterns of inheritance of

specific traits.

Genome: All the genetic material in the chromosomes of

a particular organism; its size is generally given as its

total number of base pairs.

Genotype: The genetic constitution of an organism, as

distinguished from physical appearance, or phenotype.

Germ cell: The male and female reproductive cells; egg

and sperm.

Hemoglobin: The oxygen-carrying molecule found in red

blood cells.

Hemoglobinopathies: A collection of hereditary disorders of hemoglobin structure and/or function. Examples are sickle cell anemia and thalassemia.

Hemolysis: Condition involving the destruction of red

blood cells.

Heterozygous: Having two different alleles at a particular

locus.

HLA: see human leukocyte antigen.

Homozygous: Having the same allele at a particular

locus.

Human Genome Project: Research and technology

development efforts aimed at mapping and sequencing

some or all of the genome of human beings and other

organisms.

Human immunodeficiency virus (HIV): The retrovirus

that is the etiologic agent of AIDS.

Human leukocyte antigen (HLA): Located on the

surface of most cells, except blood cells, these proteinsugar structures differ among individuals and are

important for acceptance or rejection of tissue or organ

grafts and transplants.

Hybridization: The process of joining two complementary strands of DNA, or of DNA and RNA, together to

form a double-stranded molecule.

In vitro: Literally, “in glass,” pertaining to a biological

process or reaction taking place in an artificial environment, usually a laboratory.

In vivo: Literally, “in the living,” pertaining to a

biological process or reaction taking place in a living

cell or organism.

Linkage: The proximity of two or more markers (e.g.,

genes, RFLP markers) on a chromosome; the closer

together the markers are, the lower the probability that

they will be separated during meiosis and hence the

greater the probability that they will be inherited

together.

Locus: A specific, physical position on a chromosome.

Lymphocyte: One of the major groups of white blood

cells.

Marker: An identifiable physical location on a chromosome (e.g., restriction enzyme cutting site, gene, RFLP

marker) whose inheritance can be monitored. Markers

can be expressed regions of DNA (genes) or some

segment of DNA with no coding function but whose

pattern of inheritance can be determined.

Metaphase: see mitosis.

Micronuclei: Result from the exclusion of fragments or

whole chromosomes from nuclei formed at mitosis.

Their presence can be taken as an indication of the

previous existence of chromosomal aberrations.

Mitosis: The process of division involving DNA replication that results in two daughter cells with the same

number of chromosomes and cytoplasmic material as

the parent cell.

Mutagen/mutagenicity: A substance capable of inducing a heritable change in the genetic material of cells.

Mutation: Changes in the composition of DNA.

Neoplasm: A localized population of proliferating cells in

an animal which are not governed by the usual

limitations of normal growth. The neoplasm is said to

be benign if it does not undergo metastasis and

malignant if it undergoes metastasis.

Nucleotide: The unit of DNA consisting of one of four

bases—adenine, guanine, cytosine, or thymine—

attached to a phosphate-sugar group. The sugar group

is deoxyribose in DNA. (In RNA, the sugar group is

ribose and the base uracil substitutes for thymine.)

Oncogene: A gene, one or more forms of which is

associated with cancer. Many oncogenes are involved,

directly or indirectly, in controlling the rate of cell

growth.

Phenotype: The appearance of an individual or the

observable properties of an organism that result from

the interaction of genes and the environment.

Polymerase chain reaction (PCR): An in vitro process,

through which repeated cycling of the reaction reproduces a specific region of DNA, yielding millions of

copies from the original.

Polymorphism: The existence of more than one form of

a genetic trait.

Protein: A biological molecule whose structure is determined by the sequence of nucleotides in DNA. Proteins

are required for the structure, function, and regulation

of cells, tissues, and organs in the body.

Recessive: An allele that exerts its phenotype effect only

when present in homozygous form, otherwise being

masked by the dominant allele.

Recombinant DNA technology: Processes used to form

a DNA molecule through the union of different DNA

molecules, but now commonly used to refer to any

techniques that directly examine DNA.

Reliability: The ability of a test to accurately detect that

which it was designed to detect and to do so in a

consistent fashion.

Replication: The synthesis of new DNA from existing

DNA. PCR is an in vitro technology based on the

principles of replication.

Restriction endonuclease: An enzyme that has the

ability to recognize a specific DNA sequence and cut
Appendix J--Acronyms and Glossary ● 253

it at that sequence.

Restriction enzyme: See restriction endonuclease.

Restriction fragment length polymorphism (RFLP):

Variations in the size of DNA fragments produced by

a restriction endonuclease at a polymorphic locus.

RFLP analysis: DNA techniques using single-locus or

multilocus probes to detect variation in the DNA

sequence by revealing size differences in DNA fragments produced by the action of a restriction enzyme.

See restriction fragment length polymorphism.

Sensitivity: The ability of a test to identify correctly those

who have a disease.

Single gene disorders: Hereditary disorders caused by a

single gene (e.g., Duchenne muscular dystrophy,

retinoblastoma, sickle cell disease).

Sister chromatid exchange: Crossing over between the

sister chromatics (two daughter strands of a duplicated

chromosome) during cell division (mitosis).

Somatic cells: Any cells in the body except reproductive

cells and their precursors.

Southern blot: The nylon membrane to which DNA has

adhered after the process of Southern blotting.

Specificity: The ability of a test to identify correctly those

who do not have the trait or disease which is being

tested.

Teratogen/teratogenesis: A physical or chemical agent

(e.g., radiation, alcohol) that can cause congenital

abnormalities as a result of exposure in utero.

Trait: A distinguishing feature; a characteristic or property of an individual.

Validity: The extent to which a test will correctly classify

true susceptible and true nonsusceptible individuals;

sensitivity and specificity are components of validity.
Index
Index

Acetylation phenotype, role in occupational health, 85

Acquired immunodeficiency syndrome (AIDS)

interest in testing workers for, 32, 151-152

testing for, 8, 31, 161

Addictive disorders, predisposition to, 92

Adult polycystic kidney disease, 80

Agency for Toxic Substances and Disease Registry

(ATSDR), 109,110,209-210

Air Force Academy (U.S.), sickle cell and pilot training

policy of, 42-43

Alcoholism, predisposition to, 92

Allele-specific oligonucleotide (ASO) probes, 78,81

Allied Chemical & Alkali Workers of American Local No.

1 v. Pittsburgh Plate Glass Co., 123

Alpha-l-antitrypsin

hypersusceptibility due to deficiency in, 41,80

role in occupational health, 86

American Board of Medical Genetics, 166

American College of Occupational Medicine, 120, 122,

147

American Conference of Governmental Industrial Hygienists, 56

American Hospital Association, 146

American Medical Association (AMA), Hippocratic oath

and, 116, 117, 120, 146

Americans with Disabilities Act of 1990 (ADA), 16,

114-116, 130, 139, 147, 151

Ames test, 10,60-61

Aryl hydrocarbon hydroxylase, cytochrome P-450 and

role in occupational health, 86

Ataxia telangiectasia (AT), role in occupational health,

86-87

Atherosclerosis, predisposition to, 93-94

Benzene, elevated CAs in workers exposed to, 65

Biochemical genetic tests

diagnosis with, 10,77

see also Genetic screening

Biological monitoring, 5,57,60-61

Blue Cross/Blue Shield, reimbursement for genetic services, 166

Bureau of Labor Statistics (BLS), 45

Cancer

bladder, 91-92

chronic myelogenous leukemia (CML), 90

colon, 90-91

detection programs in the workplace, 7,34

DNA adducts and, 67

low-level radiation and, 57-58

lung, 92

oncogenes and, 88, 90-92

retinoblastoma, 90

role of genetics in, 11, 14, 55, 59, 92

tumor suppressor genes and, 90

see also Mutagenicity; Mutation; Oncogenes

Center for Environmental Health & Injury Control—

CDC, 209-210

Centers for Disease Control (CDC), 47,210

Cetus Corp. (California), 81

Chemicals

chromosomal abnormalities and, 9,63

cytogenetic surveillance to detect damage by, 9,56

effects on sperm of, 62

health effects compared to radiation, 9,56-57

sister chromatid exchange analysis to detect damage

by, 63

types of DNA lesions produced by, 58

Chernobyl (U.S.S.R), 57,209

Cholesterol. See atherosclerosis

Chromosomal aberrations (CAs)

as a cause of genetic disease, 195-196

chemically induced, 56

elevation in certain worker populations, 65

genetic monitoring to detect, 58,63

radiation induced, 56, 195-196

tests on sperm, 62

use by regulatory agencies to set exposure standards, 66

Coke oven workers, increase SCE and elevated CAs in, 65

Collective bargaining

arbitral review, 126

duty to bargain over genetic monitoring and screening,

16, 123-125

NRLA preemption of common law torts, 126

refusals, 125-126

see also National Labor Relations Act; National Labor

Relations Board

Company-sponsored health promotion programs. See

“Wellness” programs

Comprehensive Environmental Response, Compensation, and Liability Act, 109

Confidentiality

American College of Occupational Medicine role in,

120, 122

occupational health physicians role in, 120, 122

of OTA survey, 198

right to, 116-120

State provisions for genetic health care information,

119

Congress, U.S.

historical interest in genetic monitoring and screening

of, 6, 8, 36-37,45

policy issues and options for, 24-29

see also House Committee on Energy and Commerce;

House Committee on Science and Technology;

House Committee on Science, Space, and Technology; Office of Technology Assessment; Senate

Committee on Commerce, Science, and Transpor-

–257–
258 ● Genetic Monitoring and Screening in the Workplace

tation

Constitution (U.S.). See Confidentiality; Legal considerations; Privacy

Coronary artery disease (CAD), screening for, 162

Costs. See Economics

Crick, Francis H. C., 6,41

Cytochrome P-450, aryl hydrocarbon hydroxylase and

role in occupational health, 86

Cytogenetic tests

application of, to occupational exposures, 9,65-66

appropriateness for use in occupational testing of, 9,

65-66

confounders and limitations on analysis using, 9,64

industry involvement in, 6, 44-45

Department of Energy (U.S.), 36,209

Department of Health and Human Services (U.S.),

209-211

Department of Health, Education, and Welfare (U.S.), 43

Department of Labor (U.S.), 45, 197

Department of Veterans Affairs (U.S.), 211

Diabetes, predisposition to, 94

Directory of National Unions and Employees Association, 197

Discrimination

American With Disabilities Act of 1990, 16, 114-116

associated with sickle cell screening programs, 6, 42

Rehabilitation Act of 1973, 15, 113-114

Title VII of the Civil Rights Act of 1964, 15-16, 103,

110-111, 126-128, 147

DNA

composition and structure of, 3, 191

probes, 81

variation in sequence of, 78

see also DNA tests; Genetic tests

DNA adducts

genetic monitoring to detect, 58,67-68

relationship with cancer, 67

DNA quantification, carcinogen exposure and, 68

DNA repair, determination of, and genetic damage, 68

DNA tests

automation of, 11, 82-83

companies offering diagnostic, 94

diagnosis with, 10,80

limits of, 83

mutation analysis with, 81

polymerase chain reaction and, 81-82

Dow Chemical, 44,45

Drug testing, interest in use in workplace, 32

Dun & Bradstreet, 197

DuPont Corp., 44,45

Ecogenetics, 83

Economics

as justification for genetic monitoring and screening, 6,

46

of genetic services, 166

of health care costs to business, 5-6, 33

of occupational illness, 6,45-46

Education, employee health risk, 7,34

Employment-at-will, doctrine of, 14, 126, 127

Environmental agents, genetic factors affecting susceptibility to, 10-12,83-87

Environmental Protection Agency (EPA), 46, 50, 65,

109-110,211

Ethical considerations

criteria for workplace genetic monitoring and screening

programs, 19, 147

difference between monitoring and screening, 17,

140-141

fair treatment, 17, 147

fetal protection policies, 148

moral considerations for workers and employers,

141-145

privacy, 16-17, 146-147

protection of worker health, 151-153

social value of work, 142

using workplace screening as power, 149

Ethylene oxide

monitoring for effects on chromosomes of, 44, 66

Expenses. See Economics

Exxon Chemical Americas, 7,34

Federal Employees Compensation Act, 111

Federal Government (U. S.)

agencies involved in occupational safety and health,

46-50

workplace safety oversight by, 103-116

see also, individual agencies and departments

Fetal protection policies, 128, 148

Finland, occupational safety and health in, 48

Florida, law prohibiting genetic discrimination, 17, 42,

130

Food and Drug Administration (U.S.), 95,210

Fortune Magazine, OTA survey population drawn from,

197

Fourth Amendment rights, 130

Funding, human genome project research, 8,36-37

General Motors, 148

Genetic counseling

availability and access to services, 20, 165-166

conveying genetic risk, 19, 159

conveying uncertainty in prognosis through, 19-20,

161-162

ethical issues, 18, 140

for families, 19, 160-164

individual uses of genetic information from 19-20,

157-168

informed consent in, 150-160

intervention, 19, 161

need for sufficient and appropriate, 158-160
Index ● 259

OTA survey of companies using, 166-167

survey of attitudes toward workplace screening, 18,

144

Genetic disease

incidence, 55

role of environmental agents in, 11, 84

Genetic monitoring

battery approach, 70-71

congressional interest, 6, 36

considerations for use in workplace, 4, 32-33, 36

criticisms of, 5-6, 33, 36

definition and use in OTA report, 3,4,31,55

detecting mutations with, 9-10,55-56

distinction from genetic screening, 5-6,32

ethical considerations of, 17-19, 139-153

genetic counseling issues of, 19-20, 157-167

historical perspective, 6,41-45

in Finland, 48

legal considerations of, 12-17, 103-134

methodologic considerations, 10,69-70

occupational disease and, 3-4,65

procedural safeguards for and difficulties with, 10,70

state-of-the-art, 8-10, 55-71

Genetic screening

congressional interest, 6, 36

considerations for use in workplace, 5, 32-33, 36

criticisms of, 5-6, 33, 36

definition and use in OTA report, 3,5,31-32,55

detecting nonoccupationally related disease by, 5,

31-32,87-88,90-94

detecting occupationally related disease by, 3, 31-32,

83-87

distinction from genetic monitoring, 5-6,32

ethical considerations of, 17-19, 139-153

genetic counseling issues of, 19-20, 157-167

historical perspective, 6,41-45

in Finland, 48

legal considerations of, 12-17, 103-134

methodologic considerations, 10,69-70

procedural safeguards for and difficulties with, 10,70

state-of-the-art, 10-12,77-95

Genetic services

availability of and access to, 20, 165-167

barriers to provision of, 20, 165

costs of, 166

see also Genetic counseling

Genetic testing

definition and use in OTA report, 3,31-32

methodologic considerations, 10,69-70

procedural safeguards for and difficulties with, 10,70

see also Genetic monitoring; Genetic screening

Genetic tests

availability for certain disorder, 15, 95

commercial development of, 12, 15,94-95

Genome. See Human genome project

Genotoxicity. See Chemicals; Ecogenetics; Mutation;

Mutagenicity; Radiation

Glucose-6-phosphate dehydrogenase (G-6-PD)

deficiency and role in occupational health of, 11,85

historical perspective and hypersusceptibility of carriers for, 6, 41

Griggs v. Duke Power Co., 110

Haldane, J.B.S., 6,41

Hazard Communication Standard, 15, 16, 108

Health Effects Research Lab-EPA, 211

Health insurance, costs as justification for genetic monitoring and screening, 5-6,33,46

Hemoglobinopathies, 192

High Risk Occupational Disease Notification and Prevention Act, 108-109

Hippocratic oath, 116, 117, 120

Hiroshima, Japan, 58,209

History, genetic monitoring and screening, 6,41-45

of congressional interest concerning genetics in the

workplace, 6, 8, 36-37

House Committee on Energy and Commerce (U.S.), 3

House Committee on Science and Technology (U.S.), 3,

6,36

House Committee on Science, Space, and Technology

(U.S.), 3

Howard Hughes Medical Institute (HHMI), 209

HPRT Mutational Spectra Repository, 66

Human genetics. See DNA; Genetic disease; Genetic

monitoring; Genetic screening; Genetic testing;

Genetic tests

Human genome project

impact on screening and monitoring technologies of, 8,

36

Program Advisory Committee on the Human Genome

and ethical issues, 8, 36-37

Human leukocyte antigen (HLA)

association with genetic disease, 80-81

role in occupational health, 87

Huntington’s disease

psychological considerations and genetic testing for,

20, 163

survey of attitudes of population at risk for, 20, 163

test for, 20,92-93

Hypersusceptibility

genetic factors and, 84

historical concept of, 41,50

Hypoxanthine-guanine phosphorbosyltransferase (HPRT)

measuring mutation frequencies with gene for, 66

relationship between mutations, exposures, and cancer,

66

Industry

DNA-based diagnostic tests offered by, 94-95

genetic screening and monitoring involvement by, 6,

44-45

occupational illness’ costs to health insurance, 5, 6,
260 . Genetic Monitoring and Screening in the Workplace

45-46

1989 OTA survey of, 173-184

Informed consent

role of genetic counseling in, 159-160

State statutes relating to, 160

see also Confidentiality; Privacy

Institute of Occupational Health, Finland, 48

Integrated Genetics (Massachusetts), 95

International Commission for Protection Against Environmental Mutagens and Carcinogens, 65

International Commission on Radiological Protection, 56

International United Rubber, Cork, Linoleum, and Plastic

Workers of America, 7,34

Intervention, for genetic disorders

when it is available, 161

when it is unavailable, 19-20, 161

Johnson & Johnson, 44

Johnson Controls, Inc., 148

Jones Act, 111

Kelsey-Seybold Foundation, 7,34

Korean conflict, military use of antimalarial drug and

hypersusceptibility in, 6,41

Lead standard, 106

Legal considerations

collective bargaining, 16, 122-126

common law right to a safe workplace, 128-129

confidentiality and privacy, 12, 14, 116-122

employee rights to know results, 129

employee rights to refuse monitoring and screening,

129-131

employment-at-will, 14, 126-127

Federal responsibility, 15-16, 103-116

fetal protection policy, 128

judicial uses of genetic data, 131-133

liability, 131, 132

limiting employer testing rights, Fourth Amendment

considerations, 130

State responsibility, 16-17, 111-113, 130

States explicitly prohibiting genetic discrimination, 17,

130

use of test results in employment decisions, 12,

126-131

see also Collective bargaining; Confidentiality; Discrimination; Privacy; Workers’ compensation

Legislation

occupational heath and safety oriented, Federal, 15-17,

46-50, 110-111, 113-116, 122-130

State anti-discrimination, 17,42, 127, 130

see also, individual statutes

Liability

of employer for inaccurate results, 131

other issues, 132

Linkage analysis, 78,79, 83

,

see also Restriction fragment length polymorphism

Longshore and Harbor Workers’ Compensation Act, 111

Louisiana, law prohibiting genetic discrimination, 17,42,

130

Medical records, access to under OSH Act, 15, 106-107

Mental disorders, predisposition to, 11,92-93

Micronuclei assay

increase in certain worker populations, 54

limitations using, 65

relationship to chromosomal aberrations, 64

Mutagenicity

analysis at molecular level of, 9-10,66-69

tests of, 9-10,60-62

see also Chemicals; Mutation; Radiation

Mutation

chemical induced, 9,56-57

DNA adducts and, 10,67-68

health effects of, 8-10,55-56

inheritance of, 192-194

role in cancer, 55,

see also Chemicals; Mutagenicity; Radiation

Nagasaki, Japan, 58,209

National Academy of Sciences (NAS)

report on genetic screening programs, 42

report on inborn errors of metabolism, 164

report on sickle cell screening and the armed forces, 42

see also National Research Council

National Cancer Institute (NCI)

cancer prevention training and education of workers, 7,

34

estimate of bladder cancer by, 92

National Center for Toxicological Research-FDA, 210

National Institute for Occupational Safety and Health

(NIOSH)

coordination with OSHA, 16,47

role in genetic monitoring and screening, 47-48, 109,

210

surveys of workplace safety and health, 49

National Institute of Environmental Health Sciences, 210,

211

National Institutes of Health (NIH)

report on newborn screening for sickle cell, 43

role in research in genetic monitoring and screening,

210-211

National Labor Relations Act (NLRA), 16,48-49, 103

National Labor Relations Board (NLRB), 48-50,122-126

National Occupational Exposure Survey--(NIOSH), 49

National Occupational Hazard Survey--(NIOSH), 49

National Priorities List, 110

National Radiological Protection Board, United Kingdom, 63

National Research Council (NRC)

report on health effects of low levels of radiation, 58
Index ● 261

see also National Academy of Sciences

National Science Foundation, 211-212

National Sickle Cell Anemia Control Act, 6,36,43

National Sickle Cell Anemia, Cooley’s Anemia, TaySachs, and Genetic Diseases Act, 6,36,43

National Toxicology Program-DHHS, 209,210,211

New Jersey, law prohibiting genetic discrimination, 17,

42, 127, 130

Nixon, President Richard M., 41

North Carolina, law prohibiting genetic discrimination,

17,42, 130

Nuclear fuels production

genetic monitoring of workers at, 57-58

see also Radiation

Occupational health physicians, legal duties, 14,120,122

Occupational illness

as defined by the Department of Labor, 45

costs, 6,45-46

ethical considerations of reducing incidence of, 145

historically, 104

prevalence, 45

Occupational and Safety Health Act (OSH Act)

coverage and duties, 15, 16, 46-47

general duty clause of, 105

genetic monitoring and screening under, 15,103, 104,

105-106

medical and exposure records access, 15-16, 106-107

medical testing under, 105

Occupational Safety and Health Administration (OSHA)

administration of OSH Act by, 47

cancer prevention and training of workers, 7, 34

coordination with NIOSH, 16,47

exposure standards set by, 47

hazard communication standard of, 15, 108

policy on genetic monitoring and screening, 16,47

recordkeeping requirements of, 107-108

role in genetic monitoring and screening, 16, 103, 104

see also Occupational and Safety Health Act

Office of Health and Environmental Research-DOE,

209

Office of Technology Assessment (OTA)

congressional issues and options identified by, 24-28

1983 report, 6,8,36,65-66,77,78,83, 85-86,139,171

report on U.S. investment in biotechnology by, 209

results of 1986 survey of human genetics by, 171-172

results of 1988 survey of commercial development of

DNA tests by, 165

scope of 1990 report, 3, 37

survey of genetic monitoring and screening in the

workplace by, 3,20-24,166-167,171-188, 197-200

Oncogenes

genetic monitoring and activation of, 58,68-69

role in cancer of, 88, 90-92

suppressor genes, 90

workers exposed to PCBs and activation of, 69

see also Cancer

Paraoxonase variants, role in occupational health, 87

Pennzoil Company, cancer detection program used by, 7,

34

Phenylketonuria, 10,77

Philadelphia chromosome, 90

Policy, issues and options for Congress, 24-29

Polychlorinated biphenyls (PCBs), oncogene activation

in workers exposed to, 69

Polymerase chain reaction (PCR)

amplification of DNA using, 10-11, 81-82

genetic screening using, 10-11,91

Predictive value

concepts of in genetic testing, 10, 69-70

of molecularly based tests, 83

President’s Commission for the Study of Ethical Problems in Medicine, Biomedical and Behavioral

Research, 164

Privacy

ethical considerations of, 17-18, 146-147

legal considerations of, 14,119-120

see also Privacy

Protein adducts, 68

Public Health Service (U. S.) 47

Radiation

health effects compared to chemicals, 9,56-57

low-level, 56-58

mutagenic effects, 9-10, 56-58

Ramazzini, Bernardino, 103

Recordkeeping, OSHA, 107-108

Rehabilitation Act of 1973, 15, 103, 113-114, 130

Relative risk, 69

Reliability

concepts of in genetic testing, 10, 69-70

of molecularly based tests, 83

Research

role of Federal agencies, 209-212

role of NIOSH in, 16, 47, 109

see also NIOSH

Restriction fragment length polymorphisms

analysis using, 10-11,78-80

population studies with, 80

Retinoblastoma, 90

Schulman, Ronca, & Bucuvalas, Inc., 20, 171, 197, 198

Senate Committee on Commerce, Science, and Transportation (U.S.), 3

Serum oncogene proteins, cancer diagnosis and detection

of, 68-69

Sickle cell anemia and trait

description of, 77, 85

detection using RFLP analysis of, 81

frequency of, 77

hypersusceptibility and, 41
262 . Genetic Monitoring and Screening in the Workplace

role in occupational health, 85

screening programs in the United States for, 6, 41-44

State laws requiring screening for, 41

U.S. Air Force Academy pilot training policy, 42-43

Sister chromatid exchange

elevation in certain worker populations, 65

genetic monitoring to detect, 58,63-64

increase in as a result of chemical exposure, 63

use as predictor of health risk, 64

Southern blotting, 78

Southern, E.M., 78

Superfund Amendments and Reauthorization Act (SARA),

109, 110

Survey

attitudes of medical geneticists toward workplace

genetic screening, 18, 144

attitudes of toward testing of those at risk for Huntington’s disease, 20, 163

attitudes towards employer use of genetic tests (Lou

Harris-Business Week), 171-172

instruments for OTA, 1982 and 1989, 213-246

of companies developing DNA tests, 165

of genetic counselors on genetic risk, 160

of human genetics offered in U.S. medical schools, 165

of public perceptions of human gene manipulation,

162, 171-172

methodology, 197-200

results of 1982 OTA, 22, 23,201-208

results of 1989 OTA, 20-24, 166-167, 171-188

Tay-Sachs disease

screening programs in the United States for, 42, 43

use in prenatal diagnosis, 163

Texas, cancer screening program at Pennzoil facility in, 7,

34

Thalassemia, role in occupational health, 85

Three Mile Island (Pennsylvania), 57

Title VII of the Civil Rights Act, 15, 103, 110-111,

126-128, 130, 147

Toxic Substances Control Act (TSCA), 61, 109

United Rubber, Cork, Linoleum, and Plastic Workers

America, 7,34

validity

concepts of in genetic testing, 10-11,69-70

of molecularly based tests, 83

of

Vinyl chloride, increased CAs in workers exposed to, 65,

66

Wards Cove Packing v. Atonio, 15, 110, 111

Watson, James D., 6,41

“Wellness” programs

genetic screening for nonoccupational disease through,

87-94

operation and example of corporate-sponsored, 6-7,

33-35

Whalen v. Roe, 119

Wilson’s disease, 79

Work, social value of, 142

Workers’ compensation

admissibility of genetic monitoring and screening data

in cases of, 16-17, 113

coverage of susceptible employees, 112-113

potential for lower costs as justification for genetic

monitoring and screening, 6, 32-33,46, 111

State role in, 16-17, 111-113

test results as evidence in claims for, 17, 113

World Medical Association, 146