GENETIC TESTING IN GENETIC TESTING IN THE WORK PLACE AND THE WORK PLACE AND

FOR PARENTHOODFOR PARENTHOODBINF705BINF705

TakakoTakako TakedaTakedaEnrique HerreraEnrique Herrera

Prof Dr. Jeff Prof Dr. Jeff SolkaSolka

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

QUESTIONQUESTION

Should genetic testing Should genetic testing be required for jobs be required for jobs or parenthood?or parenthood?

GATTACAGATTACA

BackgroundBackground

Early writings occupational disease by Paracelsus, Early writings occupational disease by Paracelsus, Agricola, Ramazzini in the 1500’s. Agricola, Ramazzini in the 1500’s. Certain occupations increase the risk for certain diseases.Certain occupations increase the risk for certain diseases.

Ramazzini proposes that certain “morbid constitution” Ramazzini proposes that certain “morbid constitution” J.B.S. Haldane in his book Heredity and Politics the J.B.S. Haldane in his book Heredity and Politics the

“morbid constitution” could have genetic basis and “morbid constitution” could have genetic basis and suggest genetic testing.suggest genetic testing.

““The majority of potters do not die of bronchitis. It is quite possible that if weThe 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 areally 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,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’we could eliminate potters’ bronchitis by regulating entrants into the potters’

industry who are congenitally disposed to it.”industry who are congenitally disposed to it.”

First genetics screening family history, gender, race and First genetics screening family history, gender, race and other phenotypic markersother phenotypic markers

Haldene’s timesHaldene’s times denied employment by tar and creosote denied employment by tar and creosote makers, fair-skin as a phenotypic marker, susceptibility to skin makers, fair-skin as a phenotypic marker, susceptibility to skin cancer in exposure to coal tar.cancer in exposure to coal tar.

Acute hemolytic anemia among military personnel who received Acute hemolytic anemia among military personnel who received the antimalarial primaquine and were also the antimalarial primaquine and were also heterozygousheterozygous for for glucose-6-phosphate dehydrogenase (G6PD) deficiencyglucose-6-phosphate dehydrogenase (G6PD) deficiency, in , in the 1960sthe 1960sG6PD deficient might also develop G6PD deficient might also develop anemia anemia under oxidant under oxidant

stresses from a variety of chemical exposures suchas stresses from a variety of chemical exposures suchas aromatic nitro and amino compounds, metal hydrides, and aromatic nitro and amino compounds, metal hydrides, and dyes. dyes.

In 1963, Herbert Stokinger and John Mountain were among the In 1963, Herbert Stokinger and John Mountain were among the first to propose the use of genetic testing for G6PD deficiency first to propose the use of genetic testing for G6PD deficiency to eliminate susceptible individuals from work with such to eliminate susceptible individuals from work with such chemicalschemicals

Most important, the determination affords, for the first time, an Most important, the determination affords, for the first time, an opportunity to make a susceptibility evaluation during the opportunity to make a susceptibility evaluation during the job job placement examinationplacement examination, and, thus, , and, thus, avoids placing a worker avoids placing a worker in exposuresin exposures to which he is inordinatelysusceptible. to which he is inordinatelysusceptible.

CasesCases By 1973 other markers:By 1973 other markers:

Alpha-1-antitrypsin deficiency,Alpha-1-antitrypsin deficiency, Sickle cell trait,Sickle cell trait, Sensitivity to carbon disulfide and organic isocyanatesSensitivity to carbon disulfide and organic isocyanates

Applications in the workplace …Applications in the workplace …In 1978, DuPont testing of African Americans for sickle cell trait In 1978, DuPont testing of African Americans for sickle cell trait and restricting individuals from work with nitro and amino compoundsand restricting individuals from work with nitro and amino compounds

Similarly, in the 1970s, the Air Force excluded African Americans with Similarly, in the 1970s, the Air Force excluded African Americans with sickle cell trait from Academy admission and flight training because of sickle cell trait from Academy admission and flight training because of

presumed risk in hypoxic atmospherespresumed risk in hypoxic atmospheres

At the same time, the Dow Chemical Company engaged in At the same time, the Dow Chemical Company engaged in experimental studies of cytogenetic abnormalities, using them as experimental studies of cytogenetic abnormalities, using them as genetic markers of acquired susceptibility for presumed future risk of genetic markers of acquired susceptibility for presumed future risk of cancer and reproductive problems among workers exposed to benzene cancer and reproductive problems among workers exposed to benzene and epichlorohydrin, although the information was not used and epichlorohydrin, although the information was not used in making employment decisionsin 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 for a genetic disorder before birth.

Ex. Down's Syndrome

• 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 The rapid advances made in genetic research and technologygenetic research and technology

Mapping of the human genome completed Mapping of the human genome completed on 2003. on 2003. IdentifyIdentify all the approximately 20,000-25,000 all the approximately 20,000-25,000

genes in human DNA, genes in human DNA, DetermineDetermine the sequences of the 3 billion the sequences of the 3 billion

chemical base pairs that make up human DNA, chemical base pairs that make up human DNA, StoreStore this information in databases, this information in databases, ImproveImprove tools for data analysis, tools for data analysis, TransferTransfer related technologies to the private related technologies to the private

sector, and sector, and AddressAddress the ethical, legal, and social issues the ethical, legal, and social issues

(ELSI) that may arise from the project. (ELSI) that may arise from the project.

The rapid advances made in The rapid advances made in genetic research and technology genetic research and technology

Genetic testing comes in two forms: Genetic testing comes in two forms: screeningscreening and and

monitoring.monitoring. Genetic monitoringGenetic monitoring (generally supported by labor (generally supported by labor

advocates) detects genetic abnormalities potentially advocates) detects genetic abnormalities potentially caused by exposure to workplace toxins. It serves as an caused by exposure to workplace toxins. It serves as an alert to hazards in the workplace, similar in principle to alert to hazards in the workplace, similar in principle to radiation detection badges. radiation detection badges.

Genetic screeningGenetic screening , is used to detect either the potential , is used to detect either the potential for hereditary disease or susceptibility to workplace for hereditary disease or susceptibility to workplace toxins. Genetic testing could in principle be used for pre-toxins. Genetic testing could in principle be used for pre-employment testing, employee placement, and risk employment testing, employee placement, and risk avoidance -- all useful tools for employers. avoidance -- all useful tools for employers.

The rapid advances made in The rapid advances made in genetic research and technologygenetic research and technology

METHODS FOR GENE METHODS FOR GENE DISCOVERYDISCOVERY

LINKAGE pedigree basedLINKAGE pedigree based CANDIDATE GENE 1,000 – 2,000CANDIDATE GENE 1,000 – 2,000 GENOME WIDE ASSOCIATIONGENOME WIDE ASSOCIATION

LINKAGE (550 Markers)LINKAGE (550 Markers)

Candidate GeneCandidate Gene

Genome Wide AssociationGenome Wide Association 500,000 Single nucleotide polymorphism 500,000 Single nucleotide polymorphism

(SNP)(SNP)

Extent of Genetic testingExtent of Genetic testing

1982 when the former Congressional Office of Technology 1982 when the former Congressional Office of Technology Assessment (OTA)Assessment (OTA)

N=550 company CEOs (65.2% response)N=550 company CEOs (65.2% response)

19 companies (5%) had or was using genetic testing19 companies (5%) had or was using genetic testing

sickle cell trait, 5 for G6PD deficiency, 5 for alpha-1-sickle cell trait, 5 for G6PD deficiency, 5 for alpha-1-antitrypsin deficiency, 2 for NADH hydrogenase antitrypsin deficiency, 2 for NADH hydrogenase deficiency, 3 for liver enzymes, and 5 for immune deficiency, 3 for liver enzymes, and 5 for immune markers.markers.

Reason “Avoid lawsuits”Reason “Avoid lawsuits”

Al Gore (then chair of house subcommittee):Al Gore (then chair of house subcommittee):

“ “potential to serve as a marvelous tool to protect the potential to serve as a marvelous tool to protect the health of workers or a terrible vehicle for invidious health of workers or a terrible vehicle for invidious discrimination”discrimination”

Extent of Genetic testingExtent of Genetic testing

The U.S. Congress' Office of Technology Assessment The U.S. Congress' Office of Technology Assessment (OTA) reported that instances of screening jumped from (OTA) reported that instances of screening jumped from 9,310 tests in 1991 to 63,000 tests in 19929,310 tests in 1991 to 63,000 tests in 1992

Around 1994 a study by Northwestern National Life Around 1994 a study by Northwestern National Life Insurance Corporation of 400 firms found that “15% of the Insurance Corporation of 400 firms found that “15% of the companies reported that by the year 2000 they planned to companies reported that by the year 2000 they planned to check the genetic status of prospective workers and their check the genetic status of prospective workers and their dependents before making employment offers”dependents before making employment offers”

By 1996, based on survey data from Geller et al. ,the By 1996, based on survey data from Geller et al. ,the Council for Responsible Genetics had identified over 200 Council for Responsible Genetics had identified over 200 cases of genetic discriminationcases of genetic discrimination

1999 American Management Association 1054 companies 1999 American Management Association 1054 companies (16.7% reported using genetic testing)(16.7% reported using genetic testing)

General General guidelinesguidelines for genetic testing were issued by the for genetic testing were issued by the NIH Task Force on Genetic Testing in 1997 NIH Task Force on Genetic Testing in 1997

PROsPROs

Reduction in costs for employers, costs associated with Reduction in costs for employers, costs associated with occupational disease, loss of productivity, excess occupational disease, loss of productivity, excess absenteeism, worker compensation premiums and legal absenteeism, worker compensation premiums and legal liability.liability.

It may not be economically feasible to ask the company to It may not be economically feasible to ask the company to eliminate all the substances that put some individuals at eliminate all the substances that put some individuals at risk. risk.

Discriminatory? Employee selection is a screening, a Discriminatory? Employee selection is a screening, a individual does not have the right to work at a specific individual does not have the right to work at a specific company or to hold a specific position (requirements of company or to hold a specific position (requirements of the job)the job)

Helps both employees and employers by maintaining a Helps both employees and employers by maintaining a healthy work placehealthy work place

Employers have a general ethical obligation of minimize Employers have a general ethical obligation of minimize the likelihood of illness or injury in the workplace.the likelihood of illness or injury in the workplace.

Testing will provide workers with information at to what Testing will provide workers with information at to what work environments to avoidwork environments to avoid

PROsPROs

Drastically reduce the allele frequency of Drastically reduce the allele frequency of carriers for a deleterious trait.carriers for a deleterious trait.

Reduce health insurance and society Reduce health insurance and society burdens.burdens.

Increase the unexpected portion positive Increase the unexpected portion positive variation.variation.

Reduce absorptive matingReduce absorptive mating Identify potentially conflict personality traits Identify potentially conflict personality traits

in the parentsin the parents

Regulations

• The Health Insurance Portability and Accountability Act of 1996 (HIPPA) prohibits

– 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 relationshipharm 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• 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

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

• 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

Cons

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 study2http://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)CASE: (Opinion)

Lawsuit :Lawsuit :This is not genetic testing exactly, but illustrative This is not genetic testing exactly, but illustrative Hepatitis C infected individual sued Chevron Oil Hepatitis C infected individual sued Chevron Oil

Company for denial of employmentCompany for denial of employmentCompany argued hepatotoxic chemical exposure in the Company argued hepatotoxic chemical exposure in the

coke oven job exposed threat to his own heath.coke oven job exposed threat to his own heath.

The Supreme Court, in interpreting the ADA job The Supreme Court, in interpreting the ADA job qualification standard that “an individual shall not qualification standard that “an individual shall not pose a direct threat to the health and safety of other pose a direct threat to the health and safety of other individuals in the workplace,” allowed Chevron’s individuals in the workplace,” allowed Chevron’s proposed extension of this to include the worker proposed extension of this to include the worker himself.himself.

GENETIC TESTING IN THEWORKPLACE: Ethical,GENETIC TESTING IN THEWORKPLACE: Ethical,Legal, and Social Implications Annu. Rev. Public Health 2004. 25:139–53Legal, and Social Implications Annu. Rev. Public Health 2004. 25:139–53

GATTACA the job interviewGATTACA the job interview