2013Marek Vácha

“Whenever man takes a new step towards subduing nature through the art of organisation and technology, he should previously have taken two steps within himself in order to deepen his ethical thinking”

(Friedrich von Hardenberg, 18th. century)

The doctor diagnoses the 44year patient with Huntington's disease. Female is begging the doctor not to communicate this information at any cost to members of her family. The patient has 3 daughters, ages 16, 21 and 26 years. 26 year-old daughter is shortly before the marriage. Doctor

a. must not succumb to the pressure and tell the information to her husband and two adult children. It is a 50% probability that the children inherited the affected allele. With this information, children have the right to adjust their reproductive choices.

b. The physician has no obligation, however, at his discretion, has the right to to tell the information to the husband and to both adult children. It is a 50% probability that the children inherited the affected allele. With this information, children have the right to adjust their reproductive choices. Doctor may, at its discretion disclose this information also to upcoming husband of the eldest daughter.

c. The patient has a legal duty to disclose information by herself to her husband and to her adult children. Argument is the expected adjustment of reproductive strategies.

d. The physician must respect medical confidentiality and can not disclose anything to adult family members, despite the fact that neither the oldest daughter, who is just about to get married, nor her husband coming will be able to reflect on their reproductive strategy. Nonetheless, the paternalistic approach can be used.

Solution

a. must not succumb to the pressure and tell the information to her husband and two adult children. It is a 50% probability that the children inherited the affected allele. With this information, children have the right to adjust their reproductive choices.

b. The physician has no obligation, however, at his discretion, has the right to to tell the information to the husband and to both adult children. It is a 50% probability that the children inherited the affected allele. With this information, children have the right to adjust their reproductive choices. Doctor may, at its discretion disclose this information also to upcoming husband of the eldest daughter.

c. The patient has a legal duty to disclose information by herself to her husband and to her adult children. Argument is the expected adjustment of reproductive strategies.

d. The physician must respect medical confidentiality and can not disclose anything to adult family members, despite the fact that neither the oldest daughter, who is just about to get married, nor her husband coming will be able to reflect on their reproductive strategy. Nonetheless, the paternalistic approach can be used.

Case 7Fischer, C., (2006) USMLE Medical Ethics: The 100 Cases You Are Most Likely to See on the Exam. Kaplan Publishing, New York.

Your patient has just recently been diagnosed with familial adenomatous polyposis (FAP). This disorder is chronic, progressive, and fatal. There is a genetic test test that can tell whether children of parents with the disease will develop it. The test is very accurate. The patient has become divorced and refuses to give you his consent to inform his ex-wife who now has custody of their three children. He threatens to sue you if you reveal elements of his medical care to his ex-wife.

What should you do?

a. Respect the patient´s right to confidentiality.

b. Transfer tha patient´s care to another physician as long as the patient agrees.

c. Ask the health department to inform the patient´s ex-wife about the disease risk.

d. Seekn a court order to inform the patient´s ex-wife.

e. Inform the patient´s ex-wife of the risk to the children

f. Inform the ex-wife´s doctor

Solution a. Respect the patient´s right to

confidentiality. b. Transfer tha patient´s care to another

physician as long as the patient agrees. c. Ask the health department to inform the

patient´s ex-wife about the disease risk. d. Seekn a court order to inform the patient

´s ex-wife. e. Inform the patient´s ex-wife of the risk to

the children f. Inform the ex-wife´s doctor

Solution The patient´s right to confidentiality ends where it

comes into conflict with the safety of other people. The most important element is that screening for

polyps should begin at the age of 12 with screening sigmoidoscopy every year. Colectomy needs to be done if polyps are found.

The right to ones pesrson´s to privacy is not as important as the right of another porson to safety.

The mother can successfully pursue a legal action stating you, the physician, did not inform her that hed children were at risk of the „injury“ of the gentic disease.

John Sulstone against genetic discrimination

"A hundred years ago, there was no equitable treatment for women; they didn't even have the vote. There was no equitable treatment for people of different races. We've established both of those, and now we need to do it across the board for all genetics.„

http://www.guardian.co.uk/science/2004/may/15/genetics.academicexperts

In 1991 Stephen Mobley shot a Georgia pizza parlor employee in the back of the head and bragged about the shooting to his friends. Later, Mobley appealed his conviction to the state's Supreme Court. His new defense: my genes made me do it.

    Pointing to a long family history of genetic illness and criminal behavior, Mobley's attorneys argue that a range of genetic factors made it almost inevitable that he would eventually come to lead a life of crime. The Mobley case stands at the center of the age-old "nature versus nurture" debate in the development of human behavior.

   

H.G.Brunner

H.G.Brunner

only males 50 % of males X chromosome

Abdelmalek Bayout

Abdelmalek Bayout, an Algerian citizen who has lived in Italy since 1993, admitted in 2007 to stabbing and killing Walter Felipe Novoa Perez on 10 March. Perez, a Colombian living in Italy, had, according to Bayout's testimony, insulted him over the kohl eye make-up the Algerian was wearing. Bayout, a Muslim, claims he wore the make-up for religious reasons.

During the trial, Bayout's lawyer, Tania Cattarossi, asked the court to take into account that her client may have been mentally ill at the time of the murder. After considering three psychiatric reports, the judge, Paolo Alessio Vernì, partially agreed that Bayout's psychiatric illness was a mitigating factor and sentenced him to 9 years and 2 months in prison — around three years less than Bayout would have received had he been deemed to be of sound mind.

Abdelmalek Bayout

But at an appeal hearing in May this year, Pier Valerio Reinotti, a judge of the Court of Appeal in Trieste, asked forensic scientists for a new independent psychiatric report to decide whether he should commute the sentence further.

For the new report, Pietro Pietrini, a molecular neuroscientist at Italy's University of Pisa, and Giuseppe Sartori, a cognitive neuroscientist at the University of Padova, conducted a series of tests and found abnormalities in brain-imaging scans and in five genes that have been linked to violent behaviour — including the gene encoding the neurotransmitter-metabolizing enzyme monoamine oxidase A (MAOA).

A 2002 study led by Terrie Moffitt, a geneticist at the Institute of Psychiatry, King's College, London, had found low levels of MAOA expression to be associated with aggressiveness and criminal conduct of young boys raised in abusive environments1.

Abdelmalek Bayout

In the report, Pietrini and Sartori concluded that Bayout's genes would make him more prone to behaving violently if provoked. "There's increasing evidence that some genes together with a particular environmental insult may predispose people to certain behaviour," says Pietrini.

On the basis of the genetic tests, Judge Reinotti docked a further year off the defendant's sentence, arguing that the defendant's genes "would make him particularly aggressive in stressful situations". Giving his verdict, Reinotti said he had found the MAOA evidence particularly compelling.

Reinotti made the decision in September 2009

Abdelmalek Bayout

But forensic scientists and geneticists contacted by Nature question whether the scientific evidence supports the conclusions reached in the psychiatric report presented to Judge Reinotti.

"We don't know how the whole genome functions and the [possible] protective effects of other genes," says Giuseppe Novelli, a forensic scientist and geneticist at the University Tor Vergata in Rome. Tests for single genes such as MAOA are "useless and expensive", he adds.

One problem is that the effects of the MAOA gene are known to vary between different ethnic groups, Moffit says. A 2006 study in the United States found that former victims of child abuse with high levels of MAOA were less likely to commit violent crimes — but only if they were white. The effect was not evident in non-white children.

"If the defendant has any African ancestry, this could bring up a question of how well the genotype of that particular gene could relate to his personal behaviour," Moffitt says.

Pietrini and Sartori, however, did not test Bayout for his ethnicity. "The ethnicity of the defendant is irrelevant" in this case, Pietrini told

Nature. He argues that the defendent does not belong to any of the non-white ethnic groups considered in the 2006 study. "Besides, MAOA is just one of the candidate genes we analysed," he added.

Abdelmalek Bayout Cattarossi argues that all evidence that has a bearing on her client's

mental health should be considered by the court. "My client is clearly an ill person and everything that allows the judge to better evaluate the case and to decide the right sentence should be investigated," she says.

Since the 1994 Stephen Mobley case in the United States — the first case in the world in which the defence asked to have their client tested for MAOA deficiency — lawyers have increasingly been trying to bring MAOA deficits and similar genetic evidence into courtrooms worldwide. According to Farahany, who updates a personal database on sentences passed in the United States, in the past five years there have been at least 200 cases where lawyers have attempted to use genetic evidence to support the idea their clients' were predisposed to violent behaviour, depression or drug or alcohol abuse. In Britain, there have been at least 20 such cases in the past five years.

Up to now most such efforts have been unsuccessful in court — although a few have influenced sentencing in the United States. Judges have tended to reject the idea that a person has no control over their choices because of their genes, says Farahany.

Some fear that such cases could lead to the acceptance of genetic determinism — the idea that genes determine the behaviour of an organism — in criminal cases.

Abdelmalek Bayout "90% of all murders are committed by people

with a Y chromosome — males. Should we always give males a shorter sentence?" says Steve Jones, a geneticist at University College London. "I have low MAOA activity but I don't go around attacking people."

Farahany points out that prosecutors could use the same genetic evidence to argue for tougher sentences by suggesting people with such genes are inherently 'bad'.

"The question is where do you stop," Jones adds. 

http://www.nature.com/news/2009/091030/full/news.2009.1050.html

Behavioral Genetics and Moral Responsibility

if some people are identified as violent because of a diagnosable conditions, and receive special allowances because of it, then others who are violent might wonder what really distinguishes them from the „genetically violent“

if some violent behavior can be put down to physical causes, then other violent behavior seems likely to have the same sort of explanation

if all behavior has biochemical and eventually genetic substrata, why should anyone ever be held morally responsible?

(Kaebnick, G.E., (2006) Behavioral Genetics and Moral Responsibility. in Parens, E., Chapman, A.R., Press, N., (eds.) Wrestling with Behavioral Genetics. John Hopkins University Press, Baltimore, p.221)

Genes and Behaviour

60 per cent of murders in America is carried out by African-Americans, though they constitute 12 per cent of the population.

But before we label blacks particularly murderous, we should note that murder rates in Caribbean countries or African countries are no higher than in other countries. Therefore we must look to environmental factors,

rather some innate genetic characteristic, to explain the extraordinarily high murder rate.

Genes „For“ Criminal Behaviour

Crime = an act or the comission of activity that is forbidden

Criminal behaviour can be a one-time phenomenon can be a profession

shoplifting x pickpocketing leaving lethal nerve gas on a subway station shooting a doctor working in an abortion clinic „white collar crime“

= there is not such thing as „a crime“

Genes and BehaviourThe Question of Responsibility

How much should the fact that one was abused as a child, sexually molested by a religious leader, or were currently attempting to give up a smoking mitigate in a criminal case?

Criminality

in USA there is proportionally 7x more murders than in Great Britain

…is it a proof that Americans have more „genes for aggressive behaviour“?

...almost certainly not, because not long ago it was one single population (of Britons)

Australia was long time a convict colony for prisoners from Great Britain nowadays there is no higher criminality than in the

rest of the world

Criminality

half of our population carries a specific genetic variant that makes them sixteen times more likely to end up in jail than the other half

it is Y chromosome carried by males

XYY males

Are XYY males more likely to be found in prison than are XY males? 1965, Edinburgh: while all of the 197 males in the

account of prison hospital inmates were described as „dangerously violent“, seven had the XYY karyotype

The seven males constituted about 3,5 % of the total.

But since estimates are that only about 1,3 % of all males have the XYY chromosomal makeup, the authors of the study posited that the 3,5 % rate found in the prison population might be 20 times higher than the frequency in the normal population

XYY males

They then generalized from that meager data to claim that men with 47 chromosomes were mentally subnormal and had a tendency to hyperaggressivity and violence

XYY males

Recent evaluation do not find this body of work credible.

XYY males

XYY individuals have been shown to be no more aggressive than average may be taller may be less intelligent hyperactive more impulsive

Nevertheless, the claims made managed to stigmatize a generation of XYY males and apparently led to the abortion of a significant number of fetuses with that karyotype.

(Duster, T., (2006) Behavioral Genetics and Explanations of the Link between Crime, Violence, and Race. in Parens, E., Chapman, A.R., Press, N., Wrestling with Behavioral Genetics. Johns Hopkins University Press, Baltimore. p. 157)

Incarceration of African Americans x European Americans

1933: blacks were incarcerated at a rate approximately twice that of whites

1950: four times 1970: six times mid 1990s: blacks are incarcerated seven times

that of whites there is no genetic explanation these incarceration rates are a function of

social, economic, and political factors (Duster, T., (2006) Behavioral Genetics and Explanations of the Link between Crime,

Violence, and Race. in Parens, E., Chapman, A.R., Press, N., Wrestling with Behavioral Genetics. Johns Hopkins University Press, Baltimore. p. 158)

Artificial selection

Behaviour

terriers are aggressive scrappers spaniels are nonaggressive and people

oriented there are behavioral breed differences in

the development of social relationship, emotionality, trainabiliity, as well as many other behaviors scolding that would be brushed off by a terrier

could traumatize a sheepdog

Mice in an open field

Mice in an open field

Mice in an open field

the difference between the high and low lines steadily increases each generation this outcome is a typical finding from selection

studies of behavioral traits and strongly suggests that many genes contribute to variation in behaivor

Environment

prenatal environmental effects nutritional balance and hormone fluctuation

during pregnancy exposure to drugs, chemicals, toxins etc.

postnatal environmental effects parenting, sibling interactions, peer

relationship, education etc. physical illness, psychological stress, cultural

experiences, birth order etc.

Environment

behaviorism: give me a dozen healthy infants, well-formed,

and my own specified world to bring them up in and I´ll guarantee to take anyone at random and train him to become any type of specialist I might select – doctor, lawyer, artist, merchant-chief and, yes, even beggar-man and thief, regardless of his talents, penchants, tendencies, abilities,vocations, and race of his ancestors.

A man is nothing but a piece of plasticine...

Behaviorism

Animisms

There is no difference between1. person and thing2. living and non-living3. spiritual and material

World of children and world of scienceBeing is being alive

Science Animism

René Descartes

Panmechanismus

from this picture of the world stem the horror of man – after all, this raw and crude material – that´s me!

„in reality, there is nothing but atoms and emptiness“ (Demokritos)

Francis Crick: The Scientific Search for the Soul

Francis Crick : the soul was not discovered...

1470 1994

Replicators and Vehicles

Now (the replicators) they swarm in huge colonies, safe inside gigantic lumbering robots, sealed off from the outside world, communicating with it by tortuous indirect routes, manipulating it by remote control. They are in you and me; they created us, body and mind; and their preservation is the ultimate rational for our existence. They have come a long way, those replicators. Now they go by the name of genes, and we are their survival machines.

(Richard Dawkins: The Selfish Gene)

We are… the computers

Viewed in this light, the question that is sometimes asked — can computers think? — is somewhat ironic. Here of course I mean the computers that we ourselves make out of inorganic materials. What on earth do those who ask such a question think they themselves are? Simply computers, but vastly more complicated ones than anything we have yet learned to make. Remember that our man-made computer industry is a mere two or three decades old, whereas we ourselves are the products of an evolution that has operated over hundreds of millions of years.

Fred Hoyle, 1964

The genetic engineering is nothing that „revolution of robots“!

Unique characteristics of genetic disorders Genetic disordres strike families, not only

individuals. Knowledge about genetic disease in one family member may have important implications for the health prospects of other family members; the „patient“ may be an entire family rather that just single person

in order to counsel one member of a family it may be necessary to have detailed information about several other family members

Unique characteristics of genetic disorders Inherited disorders may affect more than one

generation. Thus, genetic disease may have serious consequences for people in generations yet unborn

there is a strong need for long term storage (over many generations) of information about genetic disease and for the data protection

genetic diseases also differ from non-genetic diseases in the sense that it is to an increasing degree becoming possible to predict disease risk in people who today are healthy and even people who are not yet born

Unique characteristics of genetic disorders The need for knowledge about disease

risk is to an extent in conflict with the right to privacy of the persons whose disorder is the reason why the risk situation is known. It is necessary to find a suitable balance between one person´s need for knowledge, and the relative´s right to privacy.

Genetic counseling

There are over six thousands genetic conditions, chromosome diorders, and birth abnormalities, that can result in miscarriage, stillbirth, death early in life or problems in childhood or adulthood

Genetic counseling

nondirectiveness; informed consent; confidentiality

Genetic counseling

(1) comprehend the medical facts, including the diagnosis, probable course of the disorder, and the available management

(2) appreciate the way heredity contributes to the disorder, and the risk of recurrence in specified relatives

(3) understand the alternatives for dealing with the risk of recurrence

This process involves an attempt by one or more appropriately trained persons to help the individual or family to

Genetic counseling

(4) choose the course of action which seems to them appropriate in view of their risk, their family goals, and their ethical and religious standards, and to act in accordance with that decision

(5) to make the best possible adjustment to the disorder in an affected family member and/or to the risk of recurrence of that disorder.

Genetic counseling

Test results may be deeply troubling for those who receive a diagnosis of a genetic disorder or carrier status, raising fundamental questions of medical vulnerability, as well as personal and social image and identity.

Individuals may perceive that they are "flawed," "imperfect," "defective," "inadequate," or "abnormal," or may have concerns that others will perceive them or their progeny in these terms

Genetic Counseling- Problems

even the most complete family history in an era of relatively small families may not reveal all of the risk factors

Medical geneticists confront ethical dilemmas:croos-cultural comparisons among 18 nationsby J.Fletcher and D. Wertz Fletcher and Wertz studied responses of

medical geneticists in 18 countries. Of 1053 asked to participate, 677 (64%) responded in 1988 and 1990.

The majority (92-94%) regarded nondirective approaches as appropriate

Medical geneticists confront ethical dilemmas: Greater than 75% consensus disclosure of conflicting diagnostic finding disclosure of ambiguous results disclosure of controversial interpretations protection of mother´s confidentiality in

cases of false paternity

Medical geneticists confront ethical dilemmas: A majority (51-60%) would disclose the diagnosis to relatives at risk

for Huntington disease against the patient´s wishes

disclose which parent carries a translocation causing Down syndrome

disclose XY genotyp in a female

Case Report

Catherine is a 14 year old girl who in the course of her evaluation for primary amenorrhea is found to have complete androgen insensitivity syndrome (CAIS). This syndrome, previously called testicular feminization syndrome, is a genetic disorder in which an XY fetus is insensitive to androgens (male hormones) and is therefore born looking externally like a normal girl. However, internally, there is no uterus, fallopian tubes or ovaries but testes are present either in the abdomen or the inguinal canal. Individuals with the syndrome have no pubic or axillary hair, are sterile and cannot bear children. The syndrome is usually detected at puberty when a girl should but does not begin to menstruate. The testes need to be removed and patients subsequently require estrogen replacement therapy.

Case Report

Should a physician respect the parents’ request not to disclose a diagnosis of “androgen insensitivity syndrome” to their adolescent daughter Catherine is a very good athlete and is very much involved in hockey. Her coach has sponsored her to try out for the Olympics hockey team. The physician talks to the parents regarding the disclosure of the information to Catherine but the parents request that the doctor does not disclose the diagnosis.

DIRECT-TO-CONSUMERDTC

Direct To Consumer

individuals obtain direct analysis of their genome for prediction of future medical risks, without the involvement of a health provider.

Direct To Consumer

it is a natural next step, in the same way that pregnancy tests had left the confines of the physician´s office and found their way onto the pharmacy shelves

(see the lecture Human Genome Project) 23andMe https://www.23andme.com/ Navigenics http://www.navigenics.com/ deCODE http://www.decode.com/

Story of…

Jeffrey Gulcher (48, excellent health) chief scientific officer of deCODE he decided

to undergo the DNA test prediction of a 1,9-fold increased risk of

prostate cancer after biopsy, 3 from the 12 biopsies showed

prostate cancer

Direct marketing of genetic tests to the public (DTC)

A development with important ethical implications is the marketing of genetic tests directly to the public. Such tests are designed to detect differences in DNA, genes or chromosomes that are not provided as part of a medical consultation.

Direct marketing might be seen as a positive step, as individuals take increasing responsibility for their own health and, armed with information about their susceptibility to particular disease conditions, makes lifestyle changes to promote their health

Direct marketing of genetic tests to the public ...but there are at least two potential harms:

the impact on individuals of misinterpreted or erroneous predictive health information that overstates the role of genetics in causing common diseases, and which might result in delays in proper medical advice being sought, or in expensive and unproven dietary or lifestyle changes

the possibility of people performing inappropriate genetic tests on children or other adults without proper consent

Direct marketing of genetic tests to the public for complex disorders such as high blood

pressure, genetic factors may only account for a few percent of the risk, whereas changing habits in relation to diet, exercise, smoking and antihypertensive drug treatment could reduce the risk of a heart attack by up to 80 %.

Questions and problems with DTC

the risk factors detectable by DTC tests are modest in their quantitative contribution to disease for most conditions an individual´s risk will bechanged

only slightly by the result of the test the testing does not incorporate an assessment

of family history DTC tests do not detect the less common but

highly significant genetic mutations that carry a high risk for disease BRCA1/2, Huntington´s disease, fragile X syndrome

Questions and problems with DTC

a substantial fraction of the heritability for most common disease has not been discovered yet.

the possibility of laboratory mistakes the company´s interpretation of the DNA

test results is not entirely trivial most of the current data about risk

prediction from DNA testing are based upon studies done on individuals of northern European background

Questions and problems with DTC

consumers who are provided risk information should be skeptical of claims about interventions is it really necessary to pay hundreds of

dollars for a DNA test to be told that you should eat a balanced diet, engage in regular exercise, and maintain a normal weight?

infomations may cause anxiety, and may require to beconsulted with experts

Huntington´s disease

autosomal dominantinheritance

Huntington´s Disease

= degenerative neuropsychiatric disorder, affecting the basal ganglia but also affecting widespread areas of centra nervous systém

it is inherited as an autosomal dominant: P: Aa x aa F1: Aa aa

1 : 1 = each offspring of an affected parent has

50% risk of inheriting HD gene

Huntington´s Disease

Signs and symptoms usually develop in middle age. Younger people with Huntington's disease often have a more severe case, and their symptoms may progress more quickly. Rarely, children may develop this condition.

Also called Huntington's chorea, Huntington's disease was documented in 1872 by American physician George Huntington. The name "chorea" comes from the Greek word for "dance" and refers to the incessant quick, jerky, involuntary movements that are characteristic of this condition.

Huntington´s Disease

Symptoms personality changes and decreased cognitive

abilities. irritability anger depression difficulty of making decisions learning new information answering questions remembering important information. The family and friends may notice these changes

before the patients become aware of them.

Huntington´s Disease

Symptoms Early physical signs and symptoms of

Huntington's disease may include mild balance problems, clumsiness and involuntary facial movements, such as grimacing. As the disease progresses, you may develop these other Huntington's disease symptoms: Sudden jerky, involuntary movements (chorea)

throughout your body Severe problems with balance and coordination Difficulty shifting your gaze without moving your head Hesitant, halting or slurred speech Swallowing problems Dementia

Huntington´s Disease

Symptoms begin insiduously, between ages 35 and 50

though onset may occur at any time from childhood to old age

death occurs an average of 15 years after symptoms first appear

it is a late-onset disease, the symptoms generally not appearing until after the person has begun to have children

Huntington´s Disease

1983 - gene for HD was localized to the short arm of chromosome four

1993 - gene was isolated the defect is an abnormally long repeated

seqence of three DNA base pairs (CAG)

Huntington´s Disease

The discovery of the HD gene in 1993 resulted in a direct genetic test to make or confirm a diagnosis of HD in an individual who is exhibiting HD-like symptoms. Using a blood sample, the genetic test analyzes DNA for the HD mutation by counting the number of repeats in the HD gene region

therapeutic options are not yet available request to have a DNA test conducted is often

based on a desire to take the test result into consideration in family planning and other planning for life.

Huntington´s Disease

Individuals who do not have HD usually have 28 or fewer CAG repeats.

Individuals with HD usually have 40 or more repeats.

A small percentage of individuals, however, have a number of repeats that fall within a borderline region. (30 - 40)

Huntington´s disease

Note: Dr. Michael McCormack cited a case where a woman had one more repeat than her mother and she was symptomatic at 40, while her mother still showed no signs at 70. Beyond age of onset, we know very little about the variation in the progression of symptoms, for some individuals decline quite rapidly, while others experience a much more gradual deterioration.

Huntington´s Diseaseclinical features Emotional, cognitive and motor disturbances the most common disturbances in emotions

are depressive diorders, irritability and apathy, aggressive outbursts, impulsiveness, social withdrawal

disturbances of cognition: loss of cognitive speed and flexibility. In the workplace patient is unable to keep pace with the work

Huntington´s Diseaseclinical features motor disorder: voluntary and involuntary

movements, especially chorea. Patients develop diminished manual dexterity, slurred speech, swallowing difficulties, ultimately become rigid and unable to initiate any movement voluntarily. Patients who survive to the advanced state become confined to bed and area unable to participate in their self-care

Huntington´s Disease

A positive gene test without neurological signs indicates the presence of the HD gene, but not disease onset

Huntington´s Disease

Therapy In 2006, researchers discovered that the protein

expressed by the Huntington's gene interacts with another protein to disturb the way that cholesterol accumulates in the brain.

Cholesterol is essential for healthy brain cells and the network among those brain cells — but the cholesterol needs to be in proper levels and in the proper locations.

When the network of brain cells is disrupted, motor skills, cognitive skills and speech can be affected.

If scientists can figure out a way to disrupt this interaction between the proteins, they may eventually be able to develop a targeted drug therapy.

Huntington´s Disease

Varlam Shalamov(1907 - 1982)

Huntington´s Diseaseethical issues

Nancy Wexler

Huntington´s Diseaseethical issues

Informational self – determination•right to know•right to not know

Case Study

Sue is an 19-year-old college student. Desperate for a little extra spending money, Sue 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, Sue is shocked to learn that she carries the gene for Huntington's Disease. As she researches the disease, she 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. She is baffled however, when she notes that all of her grandparents, both maternal and paternal, have entered their 60s without symptoms. As she begins to research the genetics of the disease, she realizes that one of her grandparents may have had the gene, but never expressed the phenotypic disease. How is that possible?

Huntington´s Disease

Predictive testing Predictive testing should be performed according to the

international guidelines proposed by the World Federation of Neurology (WFN), in which ample pre-test genetic counseling and neuropsychological testing are provided together with posttestb psychotherapeutic support . This is partly intended to reduce the likelihood of serious consequences.

An international collaborative study revealed that out of 4527 participants in predictive testing protocols, 44 (0.97%) had a catastrophic event: five committed suicide, 21 made suicide attempts and 18 had to be hospitalized for psychiatric disturbances.

All of the suicides happened in individuals who had become symptomatic, 11 out of 18 attempted suicides and eight out of 18 hospitalized individuals had also begun to show manifestations of the disease. This means that catastrophic consequences often occur when symptoms begin, which may be a long time after the test result is conferred

Right to not knowHuntington´s disease

Some quotations:„I'm a person who thinks life would be very dull if you had a crystal ball ... that's my way of looking at things ... I'd sooner not know what's going to come up in the future ... I'd sooner live day to daywhy don't you just live everyday as it comes ... live for today and not for tomorrow ... what are you going to achieve by finding out? ... why burden yourself with all that because if you're going to get it [HD] ... you're going to get it ... you could put yourself all through the test and even learn you are gene-positive and you could die with cancer or heart attack long before Huntington's hits you …“

Right to knowHuntington´s disease

Choosing not to know would be ethically questionable if the choice to remain ignorant could have serious consequences for a third party, such as spouse.

A decision to inform one´s spouse (or potential spouse) about a known risk of a serious disorder has to be made by the risk persons themselves

the moral duty to have an open communication with one´s spouse about the risk may not be included in a law

Diskriminacehttp://www.genetichealth.com/ELSI_Genetic_Discrimination_Myth_or_Reality.shtml

A woman with a family history of Huntington's disease tried to apply for health insurance. The company wanted her to prove she didn't have the mutation, but she didn't want to know. She couldn't get coverage without the test.

Another woman's mother had Huntington's. When her employer found out about her plans to get tested, he fired her because of the potential costs of employing someone with the disease.

Discriminationhttp://www.genetichealth.com/ELSI_Genetic_Discrimination_Myth_or_Reality.shtml

Terri Seargent was identified as having Alpha-1, a genetic disorder that can affect the lungs and/or liver. When her employer received a bill for her first preventive treatment, he abruptly fired her, despite having always referred to her job performance as exemplary. Someone with the gene for Alpha -1 will not necessarily become symptomatic. Nevertheless, according to the Alpha-1 Association, at least 30 people have been denied private health or life insurance because of their genetic status.

Familial hypercholesterolemia

Persons with genetic predispositions will not necessarily contract the disease

risk predictions at the practical level will became available wit respect to certain cancers, allergies, psychoses an other common diseases

knowledge of one´s disease risk may be experienced as a challenge and a stimilus to positive action, such as changing life style, diet etc.

Convention on Human Rights and Biomedicine (Oviedo Convention)1997

Article 12 – Predictive genetic tests

Tests which are predictive of genetic diseases or which serve either to identify the subject as a carrier of a gene responsible for a disease or to detect a genetic predisposition or susceptibility to a disease may be performed only for health purposes or for scientific research linked to health purposes, and subject to appropriate genetic counselling.

Sickle cell disease

about one in ten African-American is a carrier

sickle-cell anemia affects about one in 400 African-American babies.

Collins, F., (2010) The Language of Life. Profile Books LTD. London, GB. p. 97

in 1933, Diggs and collegues estimated that about 7,5 % of the African population had at least one copy of the HbS allele

it was found that P. falciparum infection increased the rate of sickling and dehydration of blood cells containing a mixture of HbS and HbA proteins. This led to destruction of the blood cells – and the parasite within it.

thus it seems that the red blood cells of heterozygotes are not as good incubators for Plasmodium larvae as are normal erythrocytes.

(Gilbert, S.F., Epel, D., (2009) Ecological Developmental Biology. Sinauer Associates, Inc. Sunderland, MA. p. 314-315)

Allison found that different African tribes had very different frequencies of the HbS allele.

In some tribes, as many as 40 % of the population was heterozygous faor the HbA allele, while in others almost no one carried HbS

It was found, that the HbS allele has evolved at least five separate times!

(Gilbert, S.F., Epel, D., (2009) Ecological Developmental Biology. Sinauer Associates, Inc. Sunderland, MA. p. 314-315)

we still have no genetic therapy for sickle cell anemia one of the reasons is that sickle cell anemia is a gain-of-

function mutation „sticky“ proteins form cables that give the mutant blood cell

its sickled shape and limit its flexibility, eventually resulting in clogged blood vessels and early death.

It is easier to cure a loss-of-function mutation, in which the functioning gene is simply missing. in loss-of-function, one can add a functioning gene where

there was no functioning gene; in treating gain-of-function, you have to get rid of the mutant gene and then substitute the wild-type, functioning gene

(Gilbert, S.C., Tyler, A.L., Zackin, E.J., (2005) Bioethics and the New Embryology. Sinauer Associates, Inc. W.H. Freeman & comp. Sunderland, MA U.S.A. p. 193)

Sickle cell disease

The disease results from an altered hemoglobin, in which the aminoacid valin substitutes for glutamic acid at position 6 in the β-globin chain.

Sickle cell disease

The early 1970s saw the establishment of a sickle cell anemia screening program in the US, which probably provides an example of all the mistakes that need to be avoided in such a program.

It focused on African Americans, referring to the disorder as a communicable disease. The State laws were scientifically inaccurate because they did not reflect a clear understanding of human genetics and the screening tool they were using, with the results that carriers of the sickle cell treat were stigmatized.

This included not only attempts to prevent marriage, they were also denied health and life insurance. Employment opportunities were denied, including acceptance into the US Airforce Academy

X-linked Diseases

Jewish Perspective: genetic testing the Talmud advises a man not to marry into a

family where leprosy or epilepsy has appeared in at least three people.

it is generally not permissible to screen specifically for gender just because one wants a boy or girl or to screen for any characteristic other than disease (e.g., height or intelligence)

screening for gender is thus only acceptable when there is a family history of gender-related diseases linked to the chromosome for the child´s gender

Tay-Sachs Disease: Jewish Perspective there is an effort to have couples undergo

genetic testing before marriage or shortly thereafter so that they know whether they need to have any future fetus of theirs tested for the disease

an abortion of a fetus afflicted with Tay-Sachs would be warranted

if parents allow the fetus to be born, no active measures may then be taken to hasten its death, and both the child and the parents must just wait out the ravage of the disease

Tay-Sachs Disease: Jewish Perspective palliative care must be administred to

make the child as comfortable as possible, but aggresively treating the child with medications, machines, or surgery to prolong life is neither necessary nor wise.

by analyzing the expressions of many genes in breast cancer patients, researchers carrying out one genome-wide association study were able to identify 70 genes whose expression pattern could be correlated with the likelihood that the cancer would recur.

Given that low-risk patients have a 96% survival rate over a ten-year period with no treatment, gene expression analysis allows doctors and patients access to valuable information when they are considereing treatment options

(Reece, J.B., Urry, L.A., (2011) Campbell Biology. 9th. ed. Pearson Publication, Inc. , New York. p. 464)

TESTING RECEIVING INFORMATIONS

preimplantation genetic diagnosis

prenatal diagnosis predictive genetic

testing

before pregnancy during pregnancy after birth

Genetic Screening = programs designed to identify persons in a subpopulation whose genotypes suggest that they or their offspring are at higher risk for a genetic disease or condition

Genetic testing = medical procedures tat determine the presence or absence of a disease, condition, or marker in individual patients.

Innocence Project

STRs

short tandem repeats = tandemly repeated units of 2 - 5 base

sequences in specific regions of tahe genome.

The number of repeats present in these regions is highly variable from person to person (polymorphic) and for one individual, the two alleles of an STR may even differ from each other

STRs

f.e. one individual may have the sequence ACAT repeated 30 times at one genome locus and 15 times at the same locus on the other homolog,

whereas another individual may have 18 repeats at his locus on each homolog.

DNA Database

1. The use of DNA in postconviction cases to determine whether or not there was a wrongful conviction, the kind of situation that would help to free the innocent

2. The collection of DNA of „suspects“ or arrestees in pretrial circumstances to increase the DNA database, which in turn is designed to help law enforcement to determine if there is „match“ with tissue sample left at some unsolved crime – the net to catch the guilty

3. The advocacy of increasing the collection of DNA from a wider and wider band of felons in the postconviction period, so that there is a record on file in the event of recidivism

(Duster, T., (2006) Behavioral Genetics and Explanations of the Link between Crime, Violence, and Race. in Parens, E., Chapman, A.R., Press, N., Wrestling with Behavioral Genetics. Johns Hopkins University Press, Baltimore. p. 162)

Innocence Project

nonprofit organization dedicataed ato overaturning wrongful convications, uses STR analysis of archived samples from crime scenes ato revisit old cases.

As of 2010, more than 250 innocent people had been released from prison as a result of forensic and legal work by this group

Innocence Project

In 1984, Earl Washington was convicted and sentenced to death for the 1982 rape and murder of Rebecca Williams.

His sentence was commuted to life in prison in 1993 due to new doubts about he evidence.

In 2000, STR analysis by forensic scientists associated with The Innocence Project showed conclusively that he was innocent

in forensic cases using STR analysis with 13 markers, the probability of two people having identical DNA profiles is somewhere between one chance in 10 billion and one in several trillion

THE TUSKEGEE SYPHILIS STUDY

For forty years, from 1932 to 1972, 399 Afroamerican males were denied treatment for syphilis and deceived by officials of the United States Public Health Service

as a part of a study, sharecroppers were told that they were being treated for „bad blood“.

THE TUSKEGEE SYPHILIS STUDY

At the start of the study, there was no proven treatment for syphilis. But even after penicillin became a standard cure for the disease in 1947, the medicine was withheld from the men. The Tuskegee scientists wanted to continue to study how the disease spreads and kills. The experiment lasted four decades, until public health workers leaked the story to the media.

THE TUSKEGEE SYPHILIS STUDY Researches used various offers to

stimulate and sustain the subjects´interest in continued participation. these offers included free burial assistance

and insurance, free transportation to and from the examinations, and a free stop in town on the return trip

subjects received free medicines and free hot meals on the days of examination

THE TUSKEGEE

In fact, the physicians in charge of the study ensured that these men went untreated

By then, dozens of the men had died, and many wives and children had been infected.

The Presidential Apology

" No power on Earth can give you back the lives lost, the pain suffered, the years of internal torment and anguish. "What was done cannot be undone. But we can end the silence. We can stop turning our heads away. We can look at you in the eye and finally say, on behalf of the American people: what the United States government did was shameful. "And I am sorry."

Herman Shaw, Tuskegee Study participant, after the White House ceremony.

"We were treated unfairly, to some extent like guinea pigs,"

THE TUSKEGEE

16 May, 1997 president Clinton apologized on behalf of the United States government to the surviving participants of the study. These men were invited to the White House to witness the apology

The study has become a powerful symbol of racism in medicine, ethical misconduct in human research and government abuse of the vulnerable

Discrimination

We are not responsible for the genes we are equipped with

it cannot be accepted that society adds stigmatisation to at risk persons´ burden

a persons´genes shoul be considered as the individual´s own property

Discrimination

Kare Berg: I would like to see a system where it is

explicitly forbidden for third parties to request genetic tests to ask if genetic tests have been conducted or if there is a genetic disease in the family

The „third parties“: the employment or insurance market

Convention on Human Rights and Biomedicine (Oviedo Convention)1997

Article 11 – Non-discrimination

Any form of discrimination against a person on grounds of his or her genetic heritage is prohibited.

Nancy Wexler (president of Hereditary Disease Foundation):I´ve heard people say – including people in the Congress and even some scientists – that the public can be hurt by genetic information. It´s true that in the past that information has been used against people. But genetic information itself is not going to hurt the public; what could hurt the public is existing social structures, policies and prejudices against which information can ricochet. We need genetic information right now in order to make better choices so we can live better lives. We need the improved treatments that will eventually be developed using genetic information. So I think the answer is certainly not to slow down the advancing science, but to try, somehow, to make the social system more accomodating to the new knowledge.

Reproductive decision-making

potential parents who know they have, or might be carriers of, genetic disorders are faced with difficult decisions about whether to have children of their own, The options are: to proceed with a planned pregnancy not to have children to adopt children to use donor eggs, sperm or embryos to avoid the

risk of the child being born with the genetic disorder

Some comments...

"I find it interesting how some people so quickly reduce a disabled or ill person's life to a 'life of misery', and therefore a life that shouldn't be if at all possible. I would want to know how many disabled people those who hold such opinions actually know. It is possible to live a full life with disabilities - just more challenging."

"I am 32 and still suffering from my father's hereditary disability and I can tell you that I hate him for that. He knew he will pass it on to any child of his and yet that wasn't bad enough. I regret his selfish attitude and I haven't spoken to or seen him in many years because of this. You are right to ask you some questions: make sure you find the right answers not just the ones that suits you."

"The assumption that the less-abled live exclusively painful, distressing lives is troubling. Yes, it is hard and difficult. Are many of you really suggesting they are better of dead, or not existing at all? Perhaps you should ask a few disabled people. Yes, they suffer but few want to die, and those that do, require more care and love, not to hear that science should eradicate their very existence"

http://www.nytimes.com/1999/04/25/nyregion/disabled-married-their-own-mount-kisco-couple-are-among-those-with-handicaps.html