Medical Ethics Year 2 1 The Ethics of Genetics Lecture 1 January 20th 2010 Dr. Ruth Pilkington.

Medical Ethics Year 2 1

The Ethics of The Ethics of GeneticsGenetics

Lecture 1Lecture 1January 20th 2010January 20th 2010Dr. Ruth PilkingtonDr. Ruth Pilkington

2Medical Ethics Year 2

Following the announcement of the mapping and sequencing of the first draft of the human

genome in 2000, it was predicted that this would bring about ‘a new understanding of genetic contributions to human disease and the developments of rational strategies for

minimizing or preventing disease phenotypes altogether...’ (Collins 1999)


Other factors come into play Other factors come into play e.g.e.g.PenetrancePenetrance (the % of people with the gene that develop (the % of people with the gene that develop

the corresponding feature), low or no penetrance, the corresponding feature), low or no penetrance, ‘‘forme frusteforme fruste’, may still pass on to next generation ’, may still pass on to next generation and cause a full disease phenotype (and cause a full disease phenotype (i.e.i.e. appears to appears to ‘skip a generation’)‘skip a generation’)

Expressivity Expressivity (the extent to which the gene is expressed (the extent to which the gene is expressed in the person)in the person)

Sex-limited Sex-limited (affected by hormones, (affected by hormones, e.g.e.g. male pattern male pattern baldness)baldness)

Chromosomal inactivationChromosomal inactivation (X chromosome) (X chromosome)Genomic imprinting Genomic imprinting (one parental allele expressed only)(one parental allele expressed only)Codominance Codominance ((e.g.e.g. blood type) blood type)

The belief that there is direct The belief that there is direct causal connection between causal connection between

genotype and disease phenotype genotype and disease phenotype was exaggeratedwas exaggerated


MonogenicMonogenic Only a small number of Only a small number of diseasesdiseases

Polygenic Polygenic Number of gene Number of gene mutations, e.g. mutations, e.g. cancercancer

MultifactorialMultifactorial Most diseasesMost diseases


Monogenic disordersMonogenic disorders Single gene mutation / Rarely complete Single gene mutation / Rarely complete

penetrancepenetrance

Monogenic

Autosomal dominant (e.g. Huntington’s Dx)

Autosomal recessive(e.g Cystic fibrosis)

X-linked(e.g Haemophilia, Duchenne’s Musc. Dystrophy)


Hence, there is ambiguity in the genetic Hence, there is ambiguity in the genetic component in most diseases.component in most diseases.

Having a mutation does not Having a mutation does not necessarily mean that one will necessarily mean that one will develop the disease associated develop the disease associated

with itwith it..


Genetic TestingGenetic Testing& &

Screening Screening


Genetic Testing / ScreeningGenetic Testing / Screening

Genetic testingGenetic testing –for individuals who are –for individuals who are known to be at known to be at increased riskincreased risk of of having a genetic disorder with a having a genetic disorder with a familialfamilial mode of inheritance. mode of inheritance.

Genetic screeningGenetic screening –to test –to test members of a members of a particular particular population for a disorder for population for a disorder for which there may be no family history which there may be no family history or other evidence of its presence.or other evidence of its presence.


Genetic Testing / Screening Genetic Testing / Screening 11

PurposePurpose - - To prevent harmTo prevent harm to people who to people who would develop genetic diseases during their would develop genetic diseases during their lives, lives, e.g.e.g. causing people to exist with these causing people to exist with these diseases can harm them by defeating their diseases can harm them by defeating their interest, once they exist, in living without interest, once they exist, in living without pain, suffering, and limited opportunities, pain, suffering, and limited opportunities, relief of anxiety, etc.relief of anxiety, etc.

DangersDangers – A predisposition to a disease is no – A predisposition to a disease is no guarantee that one will develop that disease guarantee that one will develop that disease (in the case of non-monogenic disease).(in the case of non-monogenic disease).

DangersDangers – Insurers or employers might – Insurers or employers might discriminate against individuals on the basis discriminate against individuals on the basis of the genetic information.of the genetic information.

11Glannon, Biomedical Ethics, OUPGlannon, Biomedical Ethics, OUP


Considerations of HarmConsiderations of Harm

‘‘New knowledge about the risk of New knowledge about the risk of genetic transmission of diseases and genetic transmission of diseases and

other harmful conditions will give other harmful conditions will give individuals both the opportunities individuals both the opportunities and the responsibility to choose and the responsibility to choose

whether to transmit such harms to whether to transmit such harms to their offspring or to risk doing so.’their offspring or to risk doing so.’11

11Buchanan, Brock, Daniels & Wikler, From chance to choice, Cambridge, p.204Buchanan, Brock, Daniels & Wikler, From chance to choice, Cambridge, p.204


Considerations of HarmConsiderations of HarmFor the individual :For the individual :

What actions and interventions What actions and interventions are morally required to prevent are morally required to prevent

harm? harm?

and and

What actions and interventions What actions and interventions are morally permissible to are morally permissible to

prevent harm?prevent harm?


Considerations of HarmConsiderations of Harm

Is there a role for Society?Is there a role for Society?

Education...Education...

Is there a role for the law?Is there a role for the law?

Legal measures...Legal measures...


Huntington’s DiseaseHuntington’s Disease

• Monogenic disease / Autosomal dominantMonogenic disease / Autosomal dominant• 50% of offspring affected 50% of offspring affected • Severe debilitating disease with onset Severe debilitating disease with onset

usu. 30’s – 40’s. Irreversible motor and usu. 30’s – 40’s. Irreversible motor and cognitive degeneration. Ultimately fatal. cognitive degeneration. Ultimately fatal.

• Virtually 100% penetrance hence people Virtually 100% penetrance hence people with the Huntington's mutation are at with the Huntington's mutation are at very high risk of developing the disease very high risk of developing the disease and the consequent physical and and the consequent physical and psychological riskpsychological risk..


Huntington’s DiseaseHuntington’s DiseaseConsiderations of harmConsiderations of harm

• Unfortunately, by the time the symptoms appear, the Unfortunately, by the time the symptoms appear, the affected individual has had children and so the gene affected individual has had children and so the gene and disease may already have passed on into the next and disease may already have passed on into the next generationgeneration

• In spite of there being no treatment for the disease, In spite of there being no treatment for the disease, there would be an there would be an obligationobligation on an individual with a on an individual with a family history and early symptoms to test and so family history and early symptoms to test and so provide the information to children that they might provide the information to children that they might make decisions and life choices based on this make decisions and life choices based on this information while there is time.information while there is time.

• Thus testing Thus testing for the prevention of harmfor the prevention of harm, i.e. to allow , i.e. to allow the children make decisions about having children the children make decisions about having children themselves and to allow prudential life choices to be themselves and to allow prudential life choices to be made.made.

• The point is to allow those at risk for the disease to The point is to allow those at risk for the disease to make make informed choices.informed choices.



Familial Breast CancerFamilial Breast Cancer Considerations of harmConsiderations of harm

• BRCA1 and BRCA2 gene mutationsBRCA1 and BRCA2 gene mutations• Significantly high risk of breast (up to 85%) and Significantly high risk of breast (up to 85%) and

ovarian (up to 60%) developing over a lifetime.ovarian (up to 60%) developing over a lifetime.• Female and male offspring - 50% chance of inheritingFemale and male offspring - 50% chance of inheriting• A woman with a suggestive family history but without A woman with a suggestive family history but without

sisters or offspring – has sisters or offspring – has no obligationno obligation to test except to test except for prudential interests, for prudential interests, e.ge.g early mammography early mammography

• A woman with breast cancer and a family or sisters – A woman with breast cancer and a family or sisters – has on the other hand an has on the other hand an obligationobligation –to clarify the risk –to clarify the risk to her familyto her family

• However that obligation not as strong as the one in However that obligation not as strong as the one in the case of Huntington's disease, because the case of Huntington's disease, because 50-85% vs. 50-85% vs. 100%100%



Genetic Genetic Screening Screening


Tay-SachsTay-Sachs

• Recessive disorder, hence parental Recessive disorder, hence parental carriagecarriage

c.f.c.f. Ashkenazi Jewish population Ashkenazi Jewish population• Children born normal but develop Children born normal but develop

degenerative neurological disease degenerative neurological disease culminating in death by age 3 or 4culminating in death by age 3 or 4

• Pre-conceptive genetic screening of an Pre-conceptive genetic screening of an at risk populationat risk population

• Screening couples intending to conceiveScreening couples intending to conceive11Glannon, Biomedical Ethics, OUPGlannon, Biomedical Ethics, OUP


Tay-SachsTay-Sachs

• Decrease in incidence since screening of Decrease in incidence since screening of Orthodox Jewish community since 1970sOrthodox Jewish community since 1970s

• Reduction due to carriers avoiding marriage, Reduction due to carriers avoiding marriage, carrier couples undergoing prenatal testing carrier couples undergoing prenatal testing and terminating affected foetuses or and terminating affected foetuses or embryos, the use of donor gametes, and embryos, the use of donor gametes, and adoptionadoption

• Adolescent screening particularly. Prudential Adolescent screening particularly. Prudential and moral implications – allows ample time to and moral implications – allows ample time to plan future in accord with their values. plan future in accord with their values. Enables them to prevent harm to children Enables them to prevent harm to children who would be born with Tay-Sachs.who would be born with Tay-Sachs.



Phenyketonuria (PKU)Phenyketonuria (PKU)

• The most compelling case for genetic The most compelling case for genetic screening is for disorders that can be treated screening is for disorders that can be treated through non-genetic means, e.g. PKUthrough non-genetic means, e.g. PKU

• PKU recessive disorder, the body fails to PKU recessive disorder, the body fails to metabolise the amino acid phenylalanine. metabolise the amino acid phenylalanine. Can lead to severe mental retardation in Can lead to severe mental retardation in affected children.affected children.

• Special diet limiting the intake of Special diet limiting the intake of phenylalanine avoids the condition hence phenylalanine avoids the condition hence neonatalneonatal screening screening. So prevents harm.. So prevents harm.



Genetic TestingGenetic Testing


Genetic testingGenetic testing

Of NoteOf Note – –

Genetic testing differs from most Genetic testing differs from most other medical testing on a patient in other medical testing on a patient in that results may provide significant that results may provide significant medical information not only for the medical information not only for the patient but also for their genetically patient but also for their genetically

related relatives.related relatives.

Who owns this information?Who owns this information?


Genetic testingGenetic testing

CasesCases


Case 1Case 111

A couple, Anna and Colm attend a genetics clinic. A couple, Anna and Colm attend a genetics clinic. Their newborn baby has been diagnosed with a Their newborn baby has been diagnosed with a

severe & disabling autosomal recessive condition severe & disabling autosomal recessive condition (it is likely that the child will die in the first year). (it is likely that the child will die in the first year).

Prenatal diagnosisPrenatal diagnosis may be possible in a future may be possible in a future pregnancy. pregnancy.

Autosomal Recessive condition, hence there is a Autosomal Recessive condition, hence there is a 25%25% chance that a subsequent child could be chance that a subsequent child could be

affected. The carrier frequency of the recessive affected. The carrier frequency of the recessive gene is gene is 1 in 10001 in 1000. .

11 Adapted from Hope, Savulescu, Hendrik, Medical Ethics and Law (2008) Adapted from Hope, Savulescu, Hendrik, Medical Ethics and Law (2008)


Case 1Case 111

Molecular analysis of blood samples shows that Molecular analysis of blood samples shows that Colm is not the biological father.Colm is not the biological father.

??

Should the geneticist disclose the Should the geneticist disclose the finding of non-paternity to the finding of non-paternity to the

parents?parents? They did not seek information on paternity, They did not seek information on paternity,

however, it is of direct relevance to their however, it is of direct relevance to their understanding of the probability of an affected understanding of the probability of an affected

child in future pregnancies. child in future pregnancies. 1 1 Adapted from Hope, Savulescu, Hendrik, Medical Ethics and Law (2008)Adapted from Hope, Savulescu, Hendrik, Medical Ethics and Law (2008)


Case 1Case 111

‘‘Options’Options’White lie’White lie’ to Colm and to Colm and TruthTruth to Anna to Anna

(anecdotal evidence)(anecdotal evidence)

1 1 Adapted from Hope, Savulescu, Hendrik, Medical Ethics and Law (2008)Adapted from Hope, Savulescu, Hendrik, Medical Ethics and Law (2008)


Case 1Case 111

RespectRespect for Colm’s for Colm’s interestsinterests requires the truth. requires the truth.

Doctors Doctors should not lieshould not lie to their to their patientspatients



Case 2Case 211

A woman whose mother has Huntington’s A woman whose mother has Huntington’s disease tests positive for the gene mutation, disease tests positive for the gene mutation, although she is not, as yet, symptomatic although she is not, as yet, symptomatic herself.herself.

During post test counselling, she reveals During post test counselling, she reveals that she donated eggs to a private fertility that she donated eggs to a private fertility clinic 6 months previously. She refuses clinic 6 months previously. She refuses permission for the counsellor to contact the permission for the counsellor to contact the clinic because she is afraid she will get into clinic because she is afraid she will get into trouble.trouble.



Case 2Case 211

? ?

Should the doctor breach the Should the doctor breach the patient’s confidentiality here.patient’s confidentiality here.



Case 2Case 211

Professional guidelines do not suggest Professional guidelines do not suggest that doctors should break that doctors should break

confidentiality because a patient may confidentiality because a patient may have broken the law; have broken the law;

However here a child may be born with However here a child may be born with a very serious genetic condition.a very serious genetic condition.



Case 3Case 311

Ciara has a child (4 ) just diagnosed with Ciara has a child (4 ) just diagnosed with Duchenne’s Muscular Dystrophy (DMD), a Duchenne’s Muscular Dystrophy (DMD), a severe, progressive muscle-wasting disease severe, progressive muscle-wasting disease assoc. with a life expectancy of 20-30 years. assoc. with a life expectancy of 20-30 years. Ciara is a carrier of this X-linked condition, Ciara is a carrier of this X-linked condition, hence risk of 50% of male children will be hence risk of 50% of male children will be affected.affected.

Niamh, Ciara’s sister is 10 weeks pregnant. She Niamh, Ciara’s sister is 10 weeks pregnant. She doesn’t know of her nephew’s diagnosis or the doesn’t know of her nephew’s diagnosis or the risk to her own child. risk to her own child.

Ciara has told her geneticist that she does not Ciara has told her geneticist that she does not want the information given to her sister, as want the information given to her sister, as she fears she will terminate her pregnancy, she fears she will terminate her pregnancy, which Ciara believes to be wrong.which Ciara believes to be wrong.

1 1 Adapted, Adapted, Parker & Lucassen (1994), as quoted in Hope, Savulescu, Hendrik, Medical Ethics and Law (2008)Parker & Lucassen (1994), as quoted in Hope, Savulescu, Hendrik, Medical Ethics and Law (2008)


Case 3Case 311

Should the geneticist respect Ciara's Should the geneticist respect Ciara's wishes and keep the genetic testing wishes and keep the genetic testing

confidential? confidential?

oror

Should the information from Ciara be used Should the information from Ciara be used to test Niamh and her foetus and provide to test Niamh and her foetus and provide

Niamh with the information she may Niamh with the information she may require to make informed reproductive require to make informed reproductive

choices?choices?

1 1 Adapted,Adapted, Parker & Lucassen (1994), as quoted in Hope, Savulescu, Hendrik, Medical Ethics and Law (2008)Parker & Lucassen (1994), as quoted in Hope, Savulescu, Hendrik, Medical Ethics and Law (2008)


Case 3Case 311

Personal Account ModelPersonal Account ModelConsider if harm to Niamh and her foetus is Consider if harm to Niamh and her foetus is

sufficiently severe to justify a breach of sufficiently severe to justify a breach of confidentiality-confidentiality-

1.1. Would termination of the pregnancy be a Would termination of the pregnancy be a greater harm.greater harm.

2.2. Would the harm of having DMD and not Would the harm of having DMD and not preventing it be worse.preventing it be worse.

3.3. Existing with DMD vs. not existing at allExisting with DMD vs. not existing at all

Adapted, Parker & Lucassen (1994), as quoted in Hope, Savulescu, Hendrik, Medical Adapted, Parker & Lucassen (1994), as quoted in Hope, Savulescu, Hendrik, Medical Ethics and Law (2008)Ethics and Law (2008)


Case 3Case 311

Joint Account / Property ModelJoint Account / Property ModelAnalogous to asking a bank manger not Analogous to asking a bank manger not

to reveal information about a joint to reveal information about a joint account to fellow account holders. account to fellow account holders.

Genetic information belongs not just to Genetic information belongs not just to one person, but to families. The one person, but to families. The presumption then is that genetic presumption then is that genetic

information is to be shared with family information is to be shared with family members, unless there is very good members, unless there is very good

reason to exclude them from knowing. reason to exclude them from knowing.

11Parker & Lucassen (1994), as quoted in Hope, Savulescu, Hendrik, Medical Ethics and Law (2008)Parker & Lucassen (1994), as quoted in Hope, Savulescu, Hendrik, Medical Ethics and Law (2008)


Genetic Testing Genetic Testing of Childrenof Children


Genetic testing and Genetic testing and ChildrenChildren

For For • Beneficial in making lifestyle or career choicesBeneficial in making lifestyle or career choices• Self-knowledge promotes autonomous Self-knowledge promotes autonomous

decision makingdecision making• Testing resolves uncertainty, thus reducing Testing resolves uncertainty, thus reducing

anxietyanxiety• Testing respects parental autonomyTesting respects parental autonomy• Participation of child promotes development Participation of child promotes development

of autonomyof autonomy• Early testing promotes better psychological Early testing promotes better psychological

adjustment than later testing.adjustment than later testing.Adapted from Savulescu (2001), as quoted in Hope, Savulescu, Hendrik, Medical Ethics and Law (2008)Hope, Savulescu, Hendrik, Medical Ethics and Law (2008)



AgainstAgainst• Fails to respect the child’s later autonomy to Fails to respect the child’s later autonomy to

decide whether to have testing or not, and decide whether to have testing or not, and violates the future adult's ‘right not to know.’violates the future adult's ‘right not to know.’

• Breaches child’s confidentialty, as parents Breaches child’s confidentialty, as parents will know the result.will know the result.

• Testing may disturb family dynamics and Testing may disturb family dynamics and thus harm child and involve stigma, thus harm child and involve stigma, discrimination, development of low self discrimination, development of low self esteem, depression and anxiety.esteem, depression and anxiety.

• Parents may develop a sense of guilt.Parents may develop a sense of guilt.Adapted from Savulescu (2001), as quoted in Hope, Savulescu, Hendrik, Medical Ethics and Law (2008)Hope, Savulescu, Hendrik, Medical Ethics and Law (2008)



Most strongly advise against testing Most strongly advise against testing children for a disease in which children for a disease in which surveillance, or pre-emptive or surveillance, or pre-emptive or

definitive medical treatment, is not definitive medical treatment, is not available in childhood.available in childhood.

Inc. UK Clinical Genetics Soc.(1994), Am. Soc. For Human Inc. UK Clinical Genetics Soc.(1994), Am. Soc. For Human Genetics (1995), Human Genetics Soc. Of Australia Genetics (1995), Human Genetics Soc. Of Australia

(2005)(2005)


Incompetent AdultsIncompetent Adults

Testing may amount to Testing may amount to batterybattery in law. in law.


Genetic Genetic CounsellingCounselling


Genetic CounsellingGenetic Counselling

‘‘The process by which patients and The process by which patients and their relatives at risk of a disorder that their relatives at risk of a disorder that may be hereditary are advised of the may be hereditary are advised of the

consequences of the disorder, the consequences of the disorder, the probability of developing and probability of developing and

transmitting it and of the way in which transmitting it and of the way in which this may be prevented or ameliorated.’this may be prevented or ameliorated.’11

11Harper (1988), as quoted in Hope, Savulescu, Hendrik, Medical Ethics and Law (2008)Harper (1988), as quoted in Hope, Savulescu, Hendrik, Medical Ethics and Law (2008)


Non-directive CounsellingNon-directive Counsellingis the idealis the ideal

In response to the coercive practices In response to the coercive practices of eugenics in the early 20of eugenics in the early 20thth century. century.

To distance clinical genetics from To distance clinical genetics from those eugenic practices.those eugenic practices.

Hope, Savulescu, Hendrik, Medical Ethics and Law (2008)Hope, Savulescu, Hendrik, Medical Ethics and Law (2008)


Non-directive CounsellingNon-directive Counselling

Arguments forArguments for• Reduces risk of Reduces risk of coercioncoercion• Patient is Patient is best placedbest placed to make to make

decisions about genetic testingdecisions about genetic testing• Patient’s valuesPatient’s values (not the (not the

counsellor’s) are most importantcounsellor’s) are most important• Promotes Promotes active autonomous active autonomous

decision-makingdecision-making. . • Hope, Savulescu, Hendrik, Medical Ethics and Law (2008)Hope, Savulescu, Hendrik, Medical Ethics and Law (2008)


Non-directive CounsellingNon-directive CounsellingArguments againstArguments against

• Not possible, because there will always be an Not possible, because there will always be an inherent biasinherent bias in presenting the information. in presenting the information.

• Patients may Patients may wantwant and and needneed advice and advice and directiondirection

• Denies patients Denies patients moral dialoguemoral dialogue about their about their choiceschoices

• Allows ‘Allows ‘wrong’wrong’ decision making without decision making without discussiondiscussion

• No place left for No place left for persuasionpersuasion• InconsistentInconsistent with other areas of clinical with other areas of clinical

practice where advice is given.practice where advice is given.



Non-directive CounsellingNon-directive Counselling

However is the non-directive approach However is the non-directive approach

always the correct one? always the correct one?


Non-directive CounsellingNon-directive CounsellingSéan’s CaseSéan’s Case11

Séan’s father died from bowel cancer at a Séan’s father died from bowel cancer at a young age. He had a diagnosis of familial young age. He had a diagnosis of familial adenomatous polyposis coli, a disease adenomatous polyposis coli, a disease which involves the development of which involves the development of multiple bowel polyps. These lesions have multiple bowel polyps. These lesions have a high risk over a lifetime of becoming a high risk over a lifetime of becoming cancerous. Surveillance colonoscopy and cancerous. Surveillance colonoscopy and polyp removal is the treatment of choice. A polyp removal is the treatment of choice. A prophylactic colectomy may be indicated. prophylactic colectomy may be indicated.

11Adapted from Hope, Savulescu, Hendrik, Medical Ethics and Law (2008)Adapted from Hope, Savulescu, Hendrik, Medical Ethics and Law (2008)


Non-directive CounsellingNon-directive CounsellingSéan’s CaseSéan’s Case11

Séan’s genetic counsellor explains these Séan’s genetic counsellor explains these disease facts to him and that there is a disease facts to him and that there is a 50%50% chance of his having inherited the chance of his having inherited the gene for the disease. However Séan gene for the disease. However Séan decides that he will neither have a decides that he will neither have a genetic test nor a colonoscopy. The genetic test nor a colonoscopy. The counsellor finishes by ensuring that counsellor finishes by ensuring that Séan has understood the key facts. Séan has understood the key facts. Two years later Séan develops bowel Two years later Séan develops bowel cancer and dies.cancer and dies.

11Adapted from Hope, Savulescu, Hendrik, Medical Ethics and Law (2008)Adapted from Hope, Savulescu, Hendrik, Medical Ethics and Law (2008)


Genetic Genetic Information Information & The Law& The Law


Clinical PracticeClinical PracticePre-existing common lawPre-existing common law applies, as does applies, as does

legislation regarding legislation regarding consentconsent and and confidentialityconfidentiality regarding the use and disclosure of medical regarding the use and disclosure of medical information, unless specific legislation has been information, unless specific legislation has been put in place.put in place.

International InstrumentsInternational Instruments, e.g. , e.g. Universal Universal Declaration on the Human Genome and Human Declaration on the Human Genome and Human RightsRights (UNESCO, 1997), (UNESCO, 1997), Convention for the Convention for the Protection of human rights and dignity of the Protection of human rights and dignity of the Human Being with regard to the application of Human Being with regard to the application of Biology and Medicine Biology and Medicine (Council of Europe, 1997),(Council of Europe, 1997),

Human Tissue Act, 2004Human Tissue Act, 2004 (UK)– non-consensual (UK)– non-consensual analysis of human DNA is an offence. analysis of human DNA is an offence.


The Law and Genetic The Law and Genetic InformationInformation

• The traditional confidentiality approach – The traditional confidentiality approach – is is medical confidentiality absolute?medical confidentiality absolute?

• A human rights approach A human rights approach c.f. Article 8(2) of c.f. Article 8(2) of Human Rights Act would justify breaching Human Rights Act would justify breaching confidentialty???confidentialty???

• A property approach A property approach e.g.e.g. Data Protection Act, FOIData Protection Act, FOI• GMC standard GMC standard -- a breach of confidentiality is a breach of confidentiality is

justified onlyjustified only ‘ where failure to do so may expose ‘ where failure to do so may expose the patient or others to risk of death or serious the patient or others to risk of death or serious harm’harm’

• Where possible gain the patient’s consent to Where possible gain the patient’s consent to inform relatives. inform relatives.



Clinical PracticeClinical Practice

1.1. ConsentConsent

2.2. ConfidentialityConfidentiality

3.3. CommunicationCommunicationUncertainty of much of information / Realistic Uncertainty of much of information / Realistic expectations / Avoidance of exaggeration of expectations / Avoidance of exaggeration of genetic riskgenetic risk


Genetic Information Non Genetic Information Non Discrimination Act (GINA) Discrimination Act (GINA)

20082008The Genetic Information Non-discrimination Act The Genetic Information Non-discrimination Act

of 2008 of 2008 (GINA)(GINA)• A law in the US designed to prohibit the improper A law in the US designed to prohibit the improper

use of genetic information in health insurance and use of genetic information in health insurance and employment. It prohibits group health plans and employment. It prohibits group health plans and

health insurers from denying coverage to a healthy health insurers from denying coverage to a healthy individual or charging that person higher premiums individual or charging that person higher premiums

based solely on a genetic predisposition to based solely on a genetic predisposition to developing a disease in the future. The legislation developing a disease in the future. The legislation

also bars employers from using individuals’ genetic also bars employers from using individuals’ genetic information when making hiring, firing, job information when making hiring, firing, job

placement, or promotion decisions. placement, or promotion decisions. • ? The "first major new civil rights bill of the new ? The "first major new civil rights bill of the new

century" century" (Senator Ted Kennedy)(Senator Ted Kennedy)


EugenicsEugenics


‘‘Eugenics casts a long shadow Eugenics casts a long shadow over contemporary genetics.’over contemporary genetics.’11

11 Wikler (1999)Wikler (1999)


EugenicsEugenics

• Francis GaltonFrancis Galton, cousin of Darwin coined , cousin of Darwin coined the term and launched the movement, the term and launched the movement, based on selective breeding and applying based on selective breeding and applying the theories of natural selection to the the theories of natural selection to the human population.human population.

• Eugenics [Greek] ‘Eugenics [Greek] ‘Good Creation’ Good Creation’ • ‘‘The use of science to improve the human The use of science to improve the human

genome’ genome’ • Extremely popular among scientists, Extremely popular among scientists,

doctors, leaders of society (1880s – doctors, leaders of society (1880s – 1945).1945).


EugenicsEugenics

• GaltonGalton believed that the talented and believed that the talented and favoured of society should be encouraged to favoured of society should be encouraged to have many children (have many children (positive eugenicspositive eugenics) and ) and those with ‘less to offer’ should be those with ‘less to offer’ should be discouraged from reproducing (discouraged from reproducing (negative negative eugenicseugenics). Strong eugenics movements in ). Strong eugenics movements in many countries, inc. US, Canada, UK, many countries, inc. US, Canada, UK, Germany.Germany.

• Adopted by the Nazis, imposed sterilisation Adopted by the Nazis, imposed sterilisation and mass murder; fell into disrepute from and mass murder; fell into disrepute from 1945.1945.


EugenicsEugenics

Now an offensive concept, but ‘is Now an offensive concept, but ‘is clinical genetics simply eugenics clinical genetics simply eugenics

under a different name?’under a different name?’11

PositivePositive and and NegativeNegative eugenics are eugenics are distinct practices motivated by distinct practices motivated by

distinct aims.distinct aims.

1Wikler, JME 1999


Negative Negative EugenicsEugenics11

? Forms of negative eugenics - genetic ? Forms of negative eugenics - genetic testing and screening, PIGD, gene testing and screening, PIGD, gene

therapy therapy

Thus the aim ofThus the aim of negative negative eugenics is eugenics is to prevent or limit / control diseaseto prevent or limit / control disease



PositivePositive Eugenics Eugenics11

An example of An example of positivepositive eugenics might eugenics might be genetic enhancement i.e. be genetic enhancement i.e. improving normal traits and improving normal traits and

capacitiescapacities



EugenicsEugenics11

‘‘If there is a decisive reason and thus an If there is a decisive reason and thus an obligation to prevent or control diseases, then obligation to prevent or control diseases, then

we are we are obligatedobligated to practice to practice negative negative eugenicseugenics.’.’

‘‘If there is no decisive reason and thus no If there is no decisive reason and thus no obligation to improve normal capacities, then obligation to improve normal capacities, then

there is no obligation to practice there is no obligation to practice positive positive eugenics.’eugenics.’

Indeed should positive eugenicsIndeed should positive eugenicsbe prohibited?be prohibited?



Gene TherapyGene Therapy



Gene therapy is in its infancy. Gene therapy is in its infancy.

Options – germline and somatic.Options – germline and somatic.



SomaticSomatic• Uses genetic methods to treat disease Uses genetic methods to treat disease

in an individual. Thus the treatment in an individual. Thus the treatment only affects the targeted individual. only affects the targeted individual.

• Aims to cure disease in the same way Aims to cure disease in the same way as other disease treatment. as other disease treatment.

• Risks as with all new therapies. Risks as with all new therapies. • However ?future potential of However ?future potential of

enhancement of human enhancement of human characteristics.characteristics.



GermlineGermline

The therapeutic intervention affects The therapeutic intervention affects the targeted individual, but also the targeted individual, but also future generations by genetic future generations by genetic

changes to the germline cells. Thus changes to the germline cells. Thus risks such as cancer inducing genes, risks such as cancer inducing genes, etc.etc. may affect future generations,... may affect future generations,...


CloningCloning


Cloning

TherapeuticTo harvest ES cells for therapy

ReproductiveTo produce a new human being

Controversy as to whether therapeutic cloning should be allowed /

However most agree reproductive cloning should be prohibited


CloningCloning

• A cloned cell has a genome that is a near-A cloned cell has a genome that is a near-identical copy of the genome of its parent or identical copy of the genome of its parent or ‘progenitor’ cell.‘progenitor’ cell.

• The 5 day old embryo is called a The 5 day old embryo is called a blastocystblastocyst and and embryonic stem (ES)embryonic stem (ES) cells can be derived from cells can be derived from this and grown on in culture to produce ES cell this and grown on in culture to produce ES cell lines. These cells are lines. These cells are totipotenttotipotent and have the and have the ability to regenerate tissue. Hence the potential ability to regenerate tissue. Hence the potential to cure or alleviate diseases such as Parkinson’s, to cure or alleviate diseases such as Parkinson’s, diabetes, heart disease, etc.diabetes, heart disease, etc.

• 2 methods of genome cloning – Fission vs. Fusion2 methods of genome cloning – Fission vs. Fusion


Therapeutic CloningTherapeutic Cloning

Research in this area remains one of the Research in this area remains one of the most dynamic in genetics with massive most dynamic in genetics with massive

potential both scientific and commercial.potential both scientific and commercial.

20042004 fraudulent claim by Korean scientist, fraudulent claim by Korean scientist, Woo Suk HwangWoo Suk Hwang that his team had that his team had

successfully cloned a human embryo and successfully cloned a human embryo and derived a ES cell line from it.derived a ES cell line from it.


Cloning Cloning Cloning by fissionCloning by fission

Blastocyst divisionBlastocyst division

Twinning is induced in the blastocyst Twinning is induced in the blastocyst

by the application of heat or by the application of heat or mechanical mechanical

stress. Splits in two, and the two stress. Splits in two, and the two halves halves

continue to grow into complete continue to grow into complete embryos. embryos.

Max. two identical embryos.Max. two identical embryos.


CloningCloning Cloning by fissionCloning by fission

Blastomere separationBlastomere separation

The coating of an early The coating of an early embryo (blastocyst) is embryo (blastocyst) is removed and the cells removed and the cells (blastomeres) are placed in a (blastomeres) are placed in a solution that separates solution that separates them. Each of these them. Each of these blastomeres is blastomeres is undifferentiated and can undifferentiated and can grow into an embryo. This grow into an embryo. This technique can produce eight technique can produce eight embryos at most, but can be embryos at most, but can be repeated on each new repeated on each new embryo to produce a larger embryo to produce a larger number.number.


CloningCloningCloning by fusion (SCNT)Cloning by fusion (SCNT)

Fusion is achieved through the Fusion is achieved through the process of process of somatic cell nuclear somatic cell nuclear transfer (transfer (SCNTSCNT).). The nucleus is The nucleus is removed from a somatic cell and removed from a somatic cell and implanted into the cytoplasm of a implanted into the cytoplasm of a denucleated egg. denucleated egg.

The egg reprograms the somatic The egg reprograms the somatic cell’s DNA to a totipotent state, so cell’s DNA to a totipotent state, so that a complete embryo can be that a complete embryo can be grown out of this cell. A grown out of this cell. A theoretically endless number of theoretically endless number of clones can be created from the clones can be created from the same individual in this way. same individual in this way.

SCNT is the only method currently SCNT is the only method currently available that might be used to available that might be used to clone existing or pre-existing clone existing or pre-existing people.people.

Enucleated Egg

Somatic cell


Therapeutic CloningTherapeutic Cloning

Centres on the concept of stem cells. Stem cells Centres on the concept of stem cells. Stem cells have the ability to develop into different mature have the ability to develop into different mature cell types.cell types.

TotipotentTotipotent stem cells have the potential to form a stem cells have the potential to form a complete animal if placed in a uterus. They are complete animal if placed in a uterus. They are early embryos.early embryos.

Pluripotent Pluripotent stem cells are immature with the stem cells are immature with the potential to develop into any of the mature cell potential to develop into any of the mature cell types in the adult but cannot form a complete types in the adult but cannot form a complete animal if placed in a uterus.animal if placed in a uterus.

This is regenerative medicine – ‘The holy grail’ of This is regenerative medicine – ‘The holy grail’ of medicine.medicine.


Therapeutic CloningTherapeutic CloningHopes forHopes for

1.1. There is a shortage of tissue for transplantationThere is a shortage of tissue for transplantation2.2. There are problems with the compatibility of tissue There are problems with the compatibility of tissue

transplanted from one individual to another, transplanted from one individual to another, requiring immunosuppressive drugs with severe requiring immunosuppressive drugs with severe side-effects. Whereas cloned tissue from an side-effects. Whereas cloned tissue from an individual would be compatible.individual would be compatible.

3.3. The role of transplantation might be expanded to The role of transplantation might be expanded to include heart attack and CVAinclude heart attack and CVA

4.4. Cloning may prove cost-effective means of Cloning may prove cost-effective means of preventing disability and morbidity, and of preventing disability and morbidity, and of promoting distributive justice.promoting distributive justice.

5.5. Research into disease and drug testing using ESC Research into disease and drug testing using ESC lines in the lab.lines in the lab.

6.6. Reduced need for animal experimentation.Reduced need for animal experimentation.


Cloning by Cloning by (SCNT) (SCNT) Possible futurePossible future therapeutic therapeutic applicationapplication

Enucleated Human or Animal Egg

Skin cell from leukemic patient

e.g.e.g. LeukaemiaLeukaemia

Derive ESC line

Blood stem cells transferred post chemotx


Objections toObjections to Therapeutic Therapeutic CloningCloning11

Objections to therapeutic cloning concern the Objections to therapeutic cloning concern the morality of creating a human embryo with the morality of creating a human embryo with the intention of destroying it to harvest ES cells for intention of destroying it to harvest ES cells for research into future therapies. This it is argued research into future therapies. This it is argued that it amounts to destroying potential human that it amounts to destroying potential human life. In so far as the potential of an embryo to life. In so far as the potential of an embryo to become a human being gives it the become a human being gives it the right to liferight to life, , therapeutic cloning violates this life and thus therapeutic cloning violates this life and thus should be prohibited. should be prohibited. Does the embryo have Does the embryo have the same moral status as a human being?the same moral status as a human being?

1Glannon, Biomedical Ethics, OUP



If an embryo has the same moral status as a If an embryo has the same moral status as a person, then embryo research, in vitro person, then embryo research, in vitro fertilisation (IVF) and any termination of fertilisation (IVF) and any termination of pregnancy is wrong.pregnancy is wrong.

In natural conception, for every new life, 5 In natural conception, for every new life, 5 embryos die (embryos die (HarrisHarris, 2000). We implicitly , 2000). We implicitly accept this is a price worth paying in accept this is a price worth paying in naturally conceiving a child, then is it not a naturally conceiving a child, then is it not a price worth paying to save an existing life.price worth paying to save an existing life.

11Hope, Savulescu, Hendrik, Medical Ethics and Law (2008)Hope, Savulescu, Hendrik, Medical Ethics and Law (2008)



A further objection to therapeutic cloning is the A further objection to therapeutic cloning is the concern that in creating human embryos to concern that in creating human embryos to destroy them represents destroy them represents a violation of the a violation of the sanctity of lifesanctity of life from conception and thus should from conception and thus should be prohibited.be prohibited.

The fact that therapeutic cloning blocks the The fact that therapeutic cloning blocks the embryo’s potential to become an actual person, embryo’s potential to become an actual person, thus their right to life is removed and so should thus their right to life is removed and so should be prohibited, even if therapeutic cloning would be prohibited, even if therapeutic cloning would benefit those benefit those existing peopleexisting people, already alive, , already alive, suffering from degenerative diseases, who suffering from degenerative diseases, who would benefit from future ESC therapies. would benefit from future ESC therapies. 1Glannon, Biomedical Ethics, OUP


Objections toObjections to Therapeutic Therapeutic CloningCloning

SCNT requires a supply of fresh human eggs SCNT requires a supply of fresh human eggs (unless animal human hybrid research, using (unless animal human hybrid research, using e.g.e.g. rabbit eggs, becomes acceptable). These rabbit eggs, becomes acceptable). These must be provided by donation from women, must be provided by donation from women, who need to undergo arduous and sometimes who need to undergo arduous and sometimes painful ovarian stimulation and egg retrieval. painful ovarian stimulation and egg retrieval. Risk of OHSS. Egg donors may have restricted Risk of OHSS. Egg donors may have restricted autonomy, perhaps due to poor economic autonomy, perhaps due to poor economic circumstances, circumstances, etcetc..

As a new technology, will this be available only As a new technology, will this be available only for the rich, while the egg supply may be for the rich, while the egg supply may be provided by those less well off, perhaps in provided by those less well off, perhaps in developing countries.developing countries.


Support forSupport for Therapeutic Therapeutic CloningCloning11

Others argue that an embryo is merely a clump of not Others argue that an embryo is merely a clump of not integrated cells and cannot have interests and rights. integrated cells and cannot have interests and rights. Thus if an embryo cannot have interests or rights, it Thus if an embryo cannot have interests or rights, it cannot be harmed or wronged by not becoming a cannot be harmed or wronged by not becoming a person.person.

Thus objections to therapeutic cloning rest on the Thus objections to therapeutic cloning rest on the absolute claim that embryos have a right to life which absolute claim that embryos have a right to life which outweighs any potential benefit to existing people. But outweighs any potential benefit to existing people. But while embryos cannot suffer from or be harmed by not while embryos cannot suffer from or be harmed by not realizing their potential, existing people can suffer realizing their potential, existing people can suffer from and be harmed by disease. These existing people from and be harmed by disease. These existing people could benefit from treatments resulting from could benefit from treatments resulting from therapeutic cloning research. Embryos cannot be therapeutic cloning research. Embryos cannot be harmed or wronged by being created for this harmed or wronged by being created for this research.research.1Glannon, Biomedical Ethics, OUP


Support forSupport for Therapeutic Therapeutic CloningCloning11

Sanctity of lifeSanctity of life If it is argued that embryos embody sanctity of life, If it is argued that embryos embody sanctity of life, then existing people also do. So it may be agreed then existing people also do. So it may be agreed that embryos and people have equal moral status. that embryos and people have equal moral status. Yet in terms of suffering, embryos cannot suffer Yet in terms of suffering, embryos cannot suffer whereas existing people can suffer. The combination whereas existing people can suffer. The combination of of sanctity and sufferingsanctity and suffering vs. vs. sanctitysanctity seems to carry seems to carry more moral weight. If the suffering of existing more moral weight. If the suffering of existing people is morally worse than the creation and people is morally worse than the creation and destruction of embryos then it follows, we should be destruction of embryos then it follows, we should be more concerned about this. If embryos cannot be more concerned about this. If embryos cannot be harmed, then therapeutic cloning should be harmed, then therapeutic cloning should be permitted, permitted, i.e.i.e. we should do more for the needs of we should do more for the needs of existing people than for the putative needs of existing people than for the putative needs of merely potential people (embryos).merely potential people (embryos).



Other options?Other options?

Adult stem cells avoid this issue, but Adult stem cells avoid this issue, but research has shown them not be ‘as research has shown them not be ‘as plastic’ as ES cells, in terms of plastic’ as ES cells, in terms of potential to generate as many cells potential to generate as many cells types. In addition they are likely to types. In addition they are likely to be more immunogenic than ESC.be more immunogenic than ESC.


Other options?Other options?

Human-animal Human-animal hybrids hybrids Cloning by Cloning by SCNT SCNT An enucleated An enucleated animal rather than animal rather than human egg is used human egg is used and the human and the human somatic cell nuclear somatic cell nuclear material is inserted material is inserted into it, thus into it, thus creating a creating a hybridhybrid..

Animal (e.g. Rabbit)Enucleated Egg

HumanSomatic cell


Other Options?Other Options? Human-Animal Hybrid / Chimera Human-Animal Hybrid / Chimera

TechnologyTechnology Ethically these may be seen as unnatural Ethically these may be seen as unnatural

and crossing a moral line, but with close and crossing a moral line, but with close regulation and destruction of the regulation and destruction of the embryos following use, and an embryos following use, and an understanding that this is the creation of understanding that this is the creation of new biological tissue rather than new new biological tissue rather than new species would this be morally more species would this be morally more acceptable? acceptable?

Risk of harm in future – Possibility of Risk of harm in future – Possibility of introducing new infections (introducing new infections (zoonoseszoonoses) ) into the human population.into the human population.


The Slippery SlopeThe Slippery Slope

Some would argue that while therapeutic Some would argue that while therapeutic cloning might be morally permissible, it cloning might be morally permissible, it

should be prohibited as it could lead should be prohibited as it could lead down the down the slippery slopeslippery slope to reproductive to reproductive

cloning, which would not be morally cloning, which would not be morally permissible.permissible.

‘‘? Throwing the baby out with the bath ? Throwing the baby out with the bath water’water’


Reproductive CloningReproductive CloningThe production, by cloning, of an identical or The production, by cloning, of an identical or

near identical genetic copy of an existing near identical genetic copy of an existing person or a person who previously existed. person or a person who previously existed.

[Agricultural industry - [Agricultural industry - e.g.e.g. cattle have been cloned in cattle have been cloned in this way using both fission and fusion.]this way using both fission and fusion.]

The Human Reproductive Cloning Act (2001)The Human Reproductive Cloning Act (2001) UKUK- states that, states that, ‘‘A person who places in a woman a A person who places in a woman a

human embryo which has been created human embryo which has been created otherwise than by fertilisation is guilty of an otherwise than by fertilisation is guilty of an offence.’offence.’

Also an offence in many other countries and a Also an offence in many other countries and a number of international declarations forbid it.number of international declarations forbid it.


Cloning Cloning Cloning by fissionCloning by fission

Blastocyst divisionBlastocyst division

Twinning is induced in the blastocyst Twinning is induced in the blastocyst

by the application of heat or by the application of heat or mechanical mechanical

stress. Splits in two, and the two stress. Splits in two, and the two halves halves

continue to grow into complete continue to grow into complete embryos. embryos.

Max. 2 identical embryos.Max. 2 identical embryos.


CloningCloning Cloning by fissionCloning by fission

Blastomere separationBlastomere separation

The coating of an early The coating of an early embryo (blastocyst) is embryo (blastocyst) is removed and the cells removed and the cells (blastomeres) are placed in a (blastomeres) are placed in a solution that separates solution that separates them. Each of these them. Each of these blastomeres is blastomeres is undifferentiated and can undifferentiated and can grow into an embryo. This grow into an embryo. This technique can produce 8 technique can produce 8 embryos at most, but can be embryos at most, but can be repeated on each new repeated on each new embryo to produce a larger embryo to produce a larger number.number.


CloningCloningCloning by fusion (SCNT)Cloning by fusion (SCNT)

Fusion is achieved through the Fusion is achieved through the process of process of somatic cell nuclear somatic cell nuclear transfer (transfer (SCNTSCNT).). The nucleus is The nucleus is removed from a somatic cell and removed from a somatic cell and implanted into the cytoplasm of a implanted into the cytoplasm of a denucleated egg. denucleated egg.

The egg reprograms the somatic The egg reprograms the somatic cell’s DNA to a totipotent state, so cell’s DNA to a totipotent state, so that a complete embryo can be that a complete embryo can be grown out of this cell. A grown out of this cell. A theoretically endless number of theoretically endless number of clones can be created from the clones can be created from the same individual in this way. same individual in this way.

SCNT is the only method currently SCNT is the only method currently available that might be used to available that might be used to clone existing or pre-existing clone existing or pre-existing people.people.

Enucleated Egg

Somatic cell


Arguments made in favour of reproductive Arguments made in favour of reproductive cloningcloning11

Reproductive cloningReproductive cloning

Liberty Medical reasons

Freedom of scientific inquiry To achieve a sense of immortality

Eugenic selection Treatment of infertility

Replacement of a dead relative ‘Clonism’ – a new form of discrimination

Clones are not the same person 1Hope, Savulescu, Hendrik, Medical Ethics and Law (2008)


Arguments made against reproductive Arguments made against reproductive cloningcloning11

Reproductive cloningReproductive cloning

An affront to Human Dignity(But are twins an affront to human dignity?)

Liable to abuse, e.g. evil dictator cloning armies or copies of self

Instrumentalisation of human beings

Clones will live in the shadow of the original person

Allows eugenic selectionBut many current technologies

could also be used for eugenics, e.g. PIGD

Cloning would reduce genetic variation

Right to genetic individuality Safety

1Hope, Savulescu, Hendrik, Medical Ethics and Law (2008)


Reproductive CloningReproductive Cloning

Concerns about cloning violating human Concerns about cloning violating human dignity are misguided because they dignity are misguided because they

concentrate too much on the biology of concentrate too much on the biology of our entry into the world. We have our entry into the world. We have

human dignity because we are persons human dignity because we are persons with autonomous desires, beliefs, and with autonomous desires, beliefs, and

intentions that are not entirely intentions that are not entirely functions of our biology.functions of our biology.



Reproductive CloningReproductive Cloning11

SafetySafety

Probably the strongest reason for banning it is Probably the strongest reason for banning it is that it would result in harm to the cloned that it would result in harm to the cloned

child. child. c.f.c.f. ‘Dolly’ the sheep (b. 1996) aged at a ‘Dolly’ the sheep (b. 1996) aged at a faster rate than normal and needed to be faster rate than normal and needed to be

euthanized. Thus risk of premature aging and euthanized. Thus risk of premature aging and disease (through mutations?).disease (through mutations?).

So perhaps the only valid reason to ban So perhaps the only valid reason to ban reproductive cloning is that it could result in reproductive cloning is that it could result in physical harm to individuals who might be physical harm to individuals who might be

cloned. cloned. 1Glannon, Biomedical Ethics, OUP, Hope, Savulescu, Hope, Savulescu, Hendrik, Medical Ethics and Hendrik, Medical Ethics and Law (2008)Law (2008)


Reproductive CloningReproductive Cloning11

Cloning is in its infancy. Cloning is in its infancy. If however, reproductive cloning and If however, reproductive cloning and other forms of artificial reproduction other forms of artificial reproduction were to become, in time, were to become, in time, safer and safer and

more efficientmore efficient than natural than natural reproduction, would we have a reproduction, would we have a

moral duty to promote these over moral duty to promote these over natural methods of reproduction?natural methods of reproduction?

1Hope, Savulescu, Hendrik, Hope, Savulescu, Hendrik, Medical Ethics and Law Medical Ethics and Law (2008)(2008)

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Medical Ethics Year 2 1 The Ethics of Genetics Lecture 1 January 20th 2010 Dr. Ruth Pilkington.

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