Transcript Document

GENETIC TESTING IN
THE WORK PLACE AND
FOR PARENTHOOD
BINF705
Takako Takeda
Enrique Herrera
Prof Dr. Jeff Solka
Definition -Genetic testing
"the analysis of human DNA, RNA, chromosomes,
proteins, and certain metabolites in order to detect
heritable disease-related genotypes, mutations,
phenotypes, or karyotypes for clinical purposes."
Holtzman NA, Watson MS, eds. Promoting safe and effective genetic testing in the United
States: final report of the Task Force on Genetic Testing. Baltimore: Johns Hopkins
University Press, 1999.
diagnosis of genetic disease in newborns, children, and adults
identification of future health risks
prediction of drug responses
assessment of risks to future children
QUESTION
Should genetic testing
be required for jobs
or parenthood?
GATTACA
Background
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Early writings occupational disease by Paracelsus,
Agricola, Ramazzini in the 1500’s.
Certain occupations increase the risk for certain diseases.
Ramazzini proposes that certain “morbid constitution”
J.B.S. Haldane in his book Heredity and Politics the
“morbid constitution” could have genetic basis and
suggest genetic testing.
“The majority of potters do not die of bronchitis. It is quite possible that if we
really understood the causation of this disease we should find out that only a
fraction of potters are of a constitution which renders them liable to it. If so,
we could eliminate potters’ bronchitis by regulating entrants into the potters’
industry who are congenitally disposed to it.”
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First genetics screening family history, gender, race and
other phenotypic markers
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Haldene’s times denied employment by tar and creosote
makers, fair-skin as a phenotypic marker, susceptibility to
skin cancer in exposure to coal tar.
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Acute hemolytic anemia among military personnel who
received the antimalarial primaquine and were also
heterozygous for glucose-6-phosphate
dehydrogenase (G6PD) deficiency, in the 1960s
G6PD deficient might also develop anemia under
oxidant stresses from a variety of chemical exposures
suchas aromatic nitro and amino compounds, metal
hydrides, and dyes.
In 1963, Herbert Stokinger and John Mountain were
among the first to propose the use of genetic testing
for G6PD deficiency to eliminate susceptible
individuals from work with such chemicals
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Most important, the determination affords, for the first
time, an opportunity to make a susceptibility evaluation
during the job placement examination, and, thus,
avoids placing a worker in exposures to which he is
inordinatelysusceptible.
Cases
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By 1973 other markers:
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Alpha-1-antitrypsin deficiency,
Sickle cell trait,
Sensitivity to carbon disulfide and organic isocyanates
Applications in the workplace …
In 1978, DuPont testing of African Americans for sickle cell trait
and restricting individuals from work with nitro and amino compounds
Similarly, in the 1970s, the Air Force excluded African Americans with
sickle cell trait from Academy admission and flight training because of
presumed risk in hypoxic atmospheres
At the same time, the Dow Chemical Company engaged in
experimental studies of cytogenetic abnormalities, using them as
genetic markers of acquired susceptibility for presumed future risk of
cancer and reproductive problems among workers exposed to benzene
and epichlorohydrin, although the information was not used
in making employment decisions
• 1,147 Clinics
• 612 Laboratories testing for
• 1,352 Diseases
– 1,063 Clinical
– 289 Research only
http://www.geneclinics.org/
Types of Genetic Testing
classified according to their purpose
– Genetic Screening
– Carrier Testing
– Prenatal Diagnostic Testing
– Newborn Screening
– Pre-symptomatic Testing
– Susceptibility Testing
– Diagnostic Testing
– Forensic/Identity Testing
• Genetic Screening
- to identify individuals who are at risk of developing a
specific disorder. Screening is done so that further testing can
be undertaken.
– Ex. Women may be tested for BRCA1&2 - genes associated with
breast cancer, so that preventative measures and early intervention can
be considered.
• Carrier Testing
- to determine if an individual is a "carrier" of a gene for a
recessive genetic disorder.
Ex. couples undergo carrier testing for disorders such as Tay-Sachs
disease, to assist in their reproductive decisions.
•
Prenatal Diagnostic Testing
- to determine whether a fetus is affected by, or at risk
genetic disorder before birth.
Ex. Down's Syndrome
for a
• Newborn Screening
- focus on the identification of metabolic disorders in
newborns. Early detection and treatment may be crucial to
reduce the progression of such diseases.
Ex. phenylketonuria (PKU). --Dietary intervention allows individuals with
this condition to lead healthy and productive lives.
– The most widely performed type in the United States today.
– exist in all fifty states,
– Most states mandate newborn screening and do not require parental
consent.
•
Pre-symptomatic Testing
- conducted on healthy individuals to determine whether or not
they carry a genetic mutation that increases their likelihood of
developing late-onset diseases and disorders.
Ex. Huntington's disease and Alzheimer's disease.
• Susceptibility Testing
- to identify individuals with genetic mutations that make them
more susceptible to developing a disease when exposed to
certain environmental elements.
- often used to identify workers who may be susceptible to
toxic substances that are found in their workplace which may
cause disabilities.
• Diagnostic Testing
- to confirm a diagnosis already made by other methods.
Ex. to confirm the diagnosis of certain forms of cystic
fibrosis (CF).
• Forensic/Identity Testing
- to discover genetic linkages in criminal investigations
between suspects and evidence or between children and their
biological parents.
http://www.biobasics.gc.ca/english/View.asp?x=780
Reproductive genetic testing
• Carrier testing
• Preimplantation diagnosis is used following in vitro
fertilization to diagnose a genetic disease or condition in a
preimplantation embryo.
• Prenatal diagnosis is used to diagnose a genetic disease or
condition in a developing fetus. If the fetus is found to be
affected with a disorder, the couple can plan for the birth of
an affected child or opt for elective abortion.
• Newborn screening
The rapid advances made in
genetic research and technology
Mapping of the human genome completed
on 2003.
Identify all the approximately 20,000-25,000
genes in human DNA,
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Determine the sequences of the 3 billion
chemical base pairs that make up human DNA,
Store this information in databases,
Improve tools for data analysis,
Transfer related technologies to the private
sector, and
Address the ethical, legal, and social issues
(ELSI) that may arise from the project.
The rapid advances made in
genetic research and technology
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Genetic testing comes in two forms: screening and
monitoring.
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Genetic monitoring (generally supported by labor
advocates) detects genetic abnormalities potentially
caused by exposure to workplace toxins. It serves as an
alert to hazards in the workplace, similar in principle to
radiation detection badges.
Genetic screening , is used to detect either the potential
for hereditary disease or susceptibility to workplace
toxins. Genetic testing could in principle be used for preemployment testing, employee placement, and risk
avoidance -- all useful tools for employers.
The rapid advances made in
genetic research and technology
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METHODS FOR GENE
DISCOVERY
LINKAGE pedigree based
 CANDIDATE GENE 1,000 – 2,000
 GENOME WIDE ASSOCIATION
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LINKAGE (550 Markers)
Candidate Gene
Genome Wide Association
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500,000 Single nucleotide polymorphism
(SNP)
Extent of Genetic testing
1982 when the former Congressional Office of Technology
Assessment (OTA)
N=550 company CEOs (65.2% response)
19 companies (5%) had or was using genetic testing
sickle cell trait, 5 for G6PD deficiency, 5 for alpha-1antitrypsin deficiency, 2 for NADH hydrogenase
deficiency, 3 for liver enzymes, and 5 for immune
markers.
Reason “Avoid lawsuits”
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Al Gore (then chair of house subcommittee):
“potential to serve as a marvelous tool to protect the
health of workers or a terrible vehicle for invidious
discrimination”
Extent of Genetic testing
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The U.S. Congress' Office of Technology Assessment
(OTA) reported that instances of screening jumped from
9,310 tests in 1991 to 63,000 tests in 1992
Around 1994 a study by Northwestern National Life
Insurance Corporation of 400 firms found that “15% of the
companies reported that by the year 2000 they planned to
check the genetic status of prospective workers and their
dependents before making employment offers”
By 1996, based on survey data from Geller et al. ,the
Council for Responsible Genetics had identified over 200
cases of genetic discrimination
1999 American Management Association 1054
companies (16.7% reported using genetic testing)
General guidelines for genetic testing were issued by the
NIH Task Force on Genetic Testing in 1997
PROs
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Reduction in costs for employers, costs associated with
occupational disease, loss of productivity, excess
absenteeism, worker compensation premiums and legal
liability.
It may not be economically feasible to ask the company to
eliminate all the substances that put some individuals at
risk.
Discriminatory? Employee selection is a screening, a
individual does not have the right to work at a specific
company or to hold a specific position (requirements of
the job)
Helps both employees and employers by maintaining a
healthy work place
Employers have a general ethical obligation of minimize
the likelihood of illness or injury in the workplace.
Testing will provide workers with information at to what
work environments to avoid
PROs
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Drastically reduce the allele frequency of
carriers for a deleterious trait.
Reduce health insurance and society
burdens.
Increase the unexpected portion positive
variation.
Reduce absorptive mating
Identify potentially conflict personality traits
in the parents
Regulations
• The Health Insurance Portability and Accountability
Act of 1996 (HIPPA) prohibits
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denial of coverage or assignment of higher premiums based
on genetic information
– the use of genetic test results on defining preexisting
conditions in the absence of a corroborating medical
diagnosis.
There is no valid justification for employers to perform mandatory
DNA testing on their employees.
• The Americans with Disabilities Act (ADA) forbids
using DNA testing information in employee evaluations.
Regulations
• Currently in the United States, no regulations are in place
for evaluating the accuracy and reliability of genetic
testing.
• Most genetic tests developed by laboratories are
categorized as services, which the Food and Drug
Administration (FDA) does not regulate. Only a few states
have established some regulatory guidelines.
• The National Human Genome Research Institute (NHGRI)
has a program, ethical, social, and legal implications (ELSI)
research program
Cons
Limited regulations
-Although legal protections for health and genetic
information confidentiality exist on both the federal and
state levels, they are often limited in scope and do not
provide adequate safeguards.
www.health.state.ny.us/nysdoh/taskfce/screening.htm
Accuracy, reliability of the test
possibility for laboratory errors
-sample misidentification, contamination of the
chemicals used for testing, or other factors
Cons
Difficulties in interpreting a positive result
• “The ability to identify particular genes precedes a thorough
understanding of the implications of the presence of a defective gene
and effective treatment. “(textbook by Maicna )
– some people who carry a disease-associated mutation never
develop the disease
– How a test may guide clinical decisions? In some circumstances,
predictive genetic testing may not provide medical preventive or
treatment options.
– The link between certain genetic traits, exposure to certain
environments, and the likelihood of developing disease many
years into the future is not well understood.
http://www.health.state.ny.us/nysdoh/taskfce/screening.htm
Cons
Psychological burden
The psychological burden of being informed that one will develop a debilitating,
fatal disease, such as Huntington's Disease, for which there is no cure, could be
devastating.
Anxiety about false positive results =>Created fear and anxiety could affect a
person’s performance
Parent-child relationship
harm that can be caused to the parent-child relationship by parental
misperceptions about the meaning of a child's carrier status and the possibility that
children will be subjected to needless, and potentially risky, medical interventions
or monitoring.
http://www.health.state.ny.us/nysdoh/taskfce/screening.htm
Unjust
Cons
• While a person's skills, knowledge, or experience may be relevant in
deciding whether a person is currently capable of performing a job, a
person's genetic traits are not.
http://www.health.state.ny.us/nysdoh/taskfce/screening.htm
Health Care
• “faced with the specter of an ever expanding pool of genetically defective
"unemployables," dependent on the government for income and lacking
access to health care” - “uninsurables”.
– Persons who qualify for genetic testing may believe it is more
difficult to obtain insurance because of the testing or are afraid to
change jobs because of fear of losing health insurance. Allowing
insurers' access to genetic information prevents patients from getting
needed help
Cons
Employers have an obligation to provide a safe workplace,
which should translate to removing the causes of
occupational illness, rather than the victims.
Violation of an individual's right to privacy.
– Employers have no right to require that an individual
submit to genetic testing when that person shows no
signs of a disease
– Misuse of the information
– The use of stored genetic information as an individual
identifier.
Cons
Quality of life
“Our culture does not reflect the ways in which people with
disabilities experience and value our bodies and our lives,…
I understand that it may be difficult for able-bodied
people— particularly those in the health professions— to
believe that disability may be experienced as different, not
less.”
by DeRogatis, a nurse who speaks her own disability.
from textbook by Maicna p.251
Cons
• Society
– the ability to eliminate potential offspring with genetic defects
contributes to making society overall less tolerant of disability.
– a decision to terminate a pregnancy is controversial.
– a way of creating social categories.
People with positive test results would be treated differently because
of real or perceived genetic difference.
Employee with genetic defects would be treated as “risk” groups
– Since some genetic disease are associated with specific ethnic
backgrounds (ex. Sickle cell anaemia in people of African decent),
screening negatively impact on historically disadvantaged groups.
Mcdonald & Williams-Jones, Journal of business ethics35: 235-241 2002
What is Huntington's Disease (HD)?
• causes uncontrolled movements, loss of intellectual faculties, and
emotional disturbance.
• a familial disease, passed from parent to child
• each child of an HD parent has a 50-50 chance of inheriting the HD
gene.
• If a child does not inherit the HD gene, he or she will not develop the
disease and cannot pass it to subsequent generations.
• A person who inherits the HD gene will sooner or later develop the
disease.
• Whether one child inherits the gene has no bearing on whether others
will or will not inherit the gene.
(http://www.ninds.nih.gov/disorders/huntington/huntington.htm)
Case study 1 (Textbook p.263 10.4 )
• 39 years old man comes for presymptomatic DNA testing
– asymptomatic
– His father died with Huntington disease at age 50.
– paying out-of-pocket to avoid his health insurance carrier
– insists absolute confidentiality of test results
– intends to tell no one, regardless of the outcome
– His test is positive.
– You happen to notice
his occupation: pilot
his employer :TransCoastal Airlines.
• What do you intend to do under these circumstances?
• Should he tell his employer?
Case study2
http://www.woodrow.org/teachers/esi/2002/Biology/Projects/p8/ethics.htm
Sue : an 19-year-old college student.
-responds to an ad in the local paper and volunteers to donate a
blood sample to a company setting up a
genetic database.
-on her follow-up visit, learns that she carries the gene for
Huntington's Disease.
-realizes that one of her parents must also express the Huntington's
gene and that they will most likely become
symptomatic in the next
ten years.
-notes that all of her grandparents, both maternal and paternal, have
entered their 60s without symptoms.
-realizes that one of her grandparents may have had the gene, but
never expressed the phenotypic disease.
1. Should she tell her parents? Knowing that they
are unable to have more children.
2. Assuming that she is relatively close to her
parents, is there really any way she could (or
would) keep this information from them? But do
her parents have a right "not to know"?
3. Recently Sue and her boyfriend, Steve, have
discussed marriage. Does her boyfriend have a
right to know of her status before he makes plans
to marry and have children? She knows that if she
chooses to have children, there is a 50% chance
that her child will inherit the disease.
5. When Sue begins applying for jobs, does
she have to enter this information into her
medical history? What are potential
repercussions if she does/does not offer
this information?
CASE: (Opinion)
Lawsuit :
This is not genetic testing exactly, but illustrative
Hepatitis C infected individual sued Chevron Oil
Company for denial of employment
Company argued hepatotoxic chemical exposure in the
coke oven job exposed threat to his own heath.
The Supreme Court, in interpreting the ADA job
qualification standard that “an individual shall not
pose a direct threat to the health and safety of other
individuals in the workplace,” allowed Chevron’s
proposed extension of this to include the worker
himself.
GENETIC TESTING IN THEWORKPLACE: Ethical,
Legal, and Social Implications Annu. Rev. Public Health 2004. 25:139–53
GATTACA the job interview