Genetic Choices pp.539-547 pp 539-546 Genetic Choice ● paternalism, autonomy, beneficence, rights, confidentiality, abortion, killing, personhood, reproductive technology, justice in providing health care, research ethics ○ Is it “playing God” to alter someone’s genes to treat diseases or prevent them in future generations? ○ Is it wrong for parents to use preconception genetic testing and embryo selection to avoid having a disabled baby? ○ Do these practices discriminate against disabled people? Genes & Genome ● DNA double helix, AGCT ● Genome -entire complement of DNA ● 23 chromosome (1 pair of sex chromosome) ● many mutations are indeed hereditary and are transmitted through families, triggering the same genetic disease in subsequent generations.The genetic errors are responsible for more than 4,000 hereditary diseases. ○ most cases, genetic diseases arise not from a single gene defect but from many mutations in one or more genes, coupled with a person’s lifestyle habits and environmental influences. Genetic Testing ● check for genetic disorders by looking for changes in a person’s DNA ● Genetic testing--includes over two thousand tests designed to detect disease ○ blood or tissue sample from a patient cna test for lots of genetic mutations and uncover a variety of disorders ■ Newborn Screening ● Uncover genetic diseases for early treatment ● Every state mandates some kind of genetic testing for newborn ○ phenylketonuria-->PKU ■ disorder resulting in profound mental retardation when not treated early with a special diet ■ Carrier testing ● Determine whether someone is a carrier of a type of genetic disease known as an autosomal recessive disorder ○ See if you have two carriers ---> increase chance for disease ○ PKU, CF,Sickle cell anemia , Tay-sachs ■ Predictive Testing ● to find out before any symptoms appear if someone is likely to develop a genetic disease later in life ○ recommended to people who have a family history of a genetic disorder ■ Can predict with high probability that a person will develop a disorder, but usually its implications are much more uncertain. ● Huntingtons → one copy chances higher than rest of pop but not guaranteed to get disease ■ Diagnostic testing ● confirm or rule out a genetic disorder in someone with symptoms ■ Paternal testing ● determine if a fetus has genetic abnormalities likely to cause physical or mental impairments ○ Suspect for genetic risk ■ mother is age 35 or older (Down syndrome babies are more likely in this age group), when inherited disorders are evident in family history, ■ when ancestry or ethnicity suggests a greater chance of particular genetic disorders such as sickle cell and Tay-Sachs ■ Fetuses tested for a long list of genetic disorders ● physical deformities, developmental defects, mental retardation, deafness, blindness, and death ○ news derived from prenatal testing is bad, parents must decide whether to terminate the pregnancy ■ Preimplantation genetic diagnosis (PGD) ● test embryos produced through in vitro fertilization (IVF) for genetic abnormalities ○ those with genetic defects are screened out and only the mutation-free embryos are transferred to the woman’s uterus for implantation ○ remove only one or two cells from a !ve- to eight-cell embryo for testing. ■ $$$$ costly ● usually reserved for cases in which there is a high probability of giving birth to a baby with serious disorders ○ Down syndrome ○ Tay-Sachs disease ● most cases only give probabilities of developing a disease ● convey only in probabilities what ills that mutation might cause ○ BRCA1 or BRCA 2 ■ Greater chance for breast cancer BUT does not guarantee the development of the disorder ● Do not know about all the mutations responsible for a disorder, so available tests may identify only some of them ● environmental influences later in life may cause mutations that earlier tests miss. So a negative test result (no mutation) does not guarantee a disease-free future ● Even when tests correctly predict a genetic disorder, they usually cannot foretell how severe its symptoms will be or when they will appear. ○ 2 people with CF gene differ in severity of respiratory distress ○ Huntington's symptoms in one person a decade before they appear in another person ● power to identify and predict genetic disorders has outpaced our ability to do anything about them ○ Cna test for a lot but only TREAT some ○ Some have no treatment ● Emotional toll ○ Some people find it reassuring/empowering ○ Some get depressed, angry or frightened ○ Survivors guilt for low probability/risk ○ Bad news-->fanatic ○ Good news→ feeling of invulnerability ■ Act recklessly or ignore opportunites to lower risk ○ Positive carriers feel shame/socially stigmatized→ avoid passing on gene ○ Family conflicts ■ can divulge facts not just about the person tested but also about her relatives ■ Ethical issues ● Personal knowledge ○ begin when people suspect they might have a genetic disorder for which testing is available ■ Tested for incurable disease ● Young man tested for huntingtons (no cure not till mid age) ○ understands that testing could confirm or disconfirm his suspicions-> must decide whether to know or not know his status ■ he may choose to know because he wants to confront life’s hazards with his eyes wide open and to exert as much control over his fortunes as he can ■ he may forgo the chance to learn his fate, seeking instead to live in hope as long as possible without the weight of a terrible diagnosis pressing down on him ● Many symptomless people at risk of huntington decide no to get tested ● 45 year old women with grown children ○ she has the gene mutation responsible for Huntington’s, then each of her children has a 50 percent chance of inheriting it and thus having the disease ○ average onset of the disorder is 35 to 44 years of age, with death usually occurring 13 to 15 years a%er that (cognitive and motor disability) ■ Duty to be tested? ○ No such obligation because the disease is untreatable ○ Yes, from the principle that we have a duty to prevent harm to others (especially those with whom we have a special relationship) if we are in a position to do so ○ duty to prevent harm to others and the principle of autonomy (typically construed as involving a right to privacy) ■ Maria understands that her siblings could possibly be spared a dreadful disease if they are tested and treated early. But she is ashamed of her condition, especially psychiatric symptoms, and insists that her privacy be respected and that her diagnosis not be disclosed to any of her relatives ● plausible view of the principle of autonomy, Maria should be permitted to make choices affecting her own life, and her privacy should be respected. ● assume that she also has an obligation to prevent harm—speci!cally, a duty to warn her siblings of the danger posed by Wilson’s disease ○ Duty to prevent harm is stronger where as autonomy is NOT absolute ■ violate someone’s autonomy to prevent harm to others. ■ But some would say that autonomy is supreme or that we have no obligation at all to prevent harm, arguing that we do have a duty not to directly harm others but not a duty to save others ● Paternalism,autonomy, and confidentiality ○ Afflict clinics ■ sharply when the duty to maintain patient confidentiality clashes with duty to warn family members of serious genetic peril ● Physician duty bound to respect privacy even if seeing the harm could befall siblings/family members ● equivocal about disclosure of medical information against the patient’s will, ○ some legal cases suggest that physicians may have a duty to warn people who are likely to be seriously harmed ● few physicians have been sued for their failure to inform relatives about genetic risk ● Some physicians argue that breaching confidentiality may be morally permissible if the harm done by keeping silent outweighs harm done by revealing private information about the patient ○ Strict nondisclosure ● likely to try to get around the dilemma by urging patients to warn their own family members ○ beneficence and autonomy collide, and the extent of physician paternalism (best for the patient) is a live issue ■ debated whether they should reveal to a patient the results of a genetic test showing that he or she is at high risk for an unpreventable, untreatable disease ● Doing so in patients best interest? ● Especially when info cant benefit paitent ○ Only cause psych harm ■ many reject this view as strongly paternalistic and argue that the principle of autonomy gives patients the right to know their medical condition, including the results of genetic tests—even if the news is upsetting ○ whether the public availability of genetic tests should be restricted ■ see the wisdom in restricting access to genetic tests that yield misleading, confusing, or otherwise unhelpful information ■ favor restricting access to genetic tests for more paternalistic reasons, arguing that genetic self knowledge causes psychological harms such as depression, anxiety, and panic or that patients cannot understand the complexities and implications of genetic information ■ Disagree-->is no reason to think that most patients will be psychologically wrecked by learning the truth about their genetic risks, that patient autonomy trumps any such concerns, and that the complexity of medical information is usually not considered an adequate justification for overriding patient autonomy ■ wariness is prompted by the possibility of genetic discrimination--> the use of genetic information by employers, insurance companies, and others to discriminate against or stigmatize people ● Fear ways employers weed out people who are healthy now but may get sick later ● cut costs, insurance companies will deny them health coverage or cancel it because genetic tests suggest a likelihood of eventual illness ○ left some people reluctant to undergo genetic testing because the results could be used as evidence against them, and this reluctance has been reinforced by some documented cases of genetic discrimination ■ 2008 Genetic Informatiion Nondiscrimination Act signed ● Prohibiting discrimination by insuarance or employers barring from requesting genetic test ■ main ethical concern here is justice--> whether people are being treated fairly ● Reproductive Decision ○ hope of avoiding birth impairments, the anguish of moral conflict ○ prenatal testing is coupled with the option of abortion and PGD entials embryo selection ■ Nearly all cases -->selective abortion and embryo selection are the only options for avoiding the birth of a severely impaired baby ● genetic mutation is discovered, there is little or nothing that can be done to correct the mutation or the disorder ○ opposed to all abortions and the screening or destruction of embryos will judge these procedures morally impermissible, and they may see no wrong in permitting the birth of children with serious abnormalities ○ many think that abortion and embryo selection may be justi!ed when used to avoid having babies with such terrible defects. ● wrong not to prevent devastating diseases or disabilities in a child ● failure to prevent defects would be wrong, however, is not as easy as it might seem. We could say that failing to prevent an impairment is wrong because the child would be better o$ if the impairment were prevented ○ Disagree *Brock*-->failing to prevent the handicap has not made her child worse of, then failing to prevent the handicap does not harm her child ● failing to prevent a serious disability does not wrong the child, the failure is still morally wrong for other reason ○ contributes to overall suffering in the world/it treats children unfairly by disregarding their legitimate interests in having a decent chance at a good life ○ amounts to disrespect or discrimination against people with disabilities ■ opposed to testing, claiming that its purpose is to eliminate an entire class of people (the disabled), which puts genetic testing in the same moral category as heinous attempts to eradicate whole races of people ■ Not discriminatory, others say, genetic testing is meant to prevent the existence of the disabled and make possible the existence of the normal, and that fact sends a message of disrespect to people now living with disability ● Better if diabled didn’t exist ■ Genetic testing is discriminatory if it involves violating people’s rights, and it is disrespectful if it entails an attitude of contempt or condescension. ■ discrimination or disrespect for persons is not entailed by genetic testing ● what is involved in equality of respect is compatible with screening ● Aiming for normal people at conception is not discrimination against disabled (still seen as equals) ○ Medical treatment presupposes that health is better than sickness, but those who believe in it treat sick people as their equals. ■ anti-testing attitudes themselves have unsavory moral implications ● Wrong to avoid disabled child for having non disabled child ○ Mandatory to allow one to have disabled child rather than screen to have a nondisabled child→ MUST to allowed to cause one to have a disabled child rather than non disabled ○ wrong deliberately to cause a disabled child to exist instead of a healthy child pp.547-557 Gene Therapy (GT) ● AKA Genetic Engineering: the manipulation of someone’s genetic material to prevent or treat disease; an attempt to alter the working of cells by: ○ Replacing a missing or defective gene within a normal one. ○ Repairing a faulty gene so it will function properly. ○ Activating or deactivating a gene. ● Most uses of gene therapy have been to insert a normal copy of a gene into cells to do the job that defective or absent genes should be doing. ○ Can be tricky because it must be done with a carrier (typically a virus) ○ Ex. To treat Hemophilia A or B, scientists used viruses to transfer normal copies of blood clotting genes. ● Two types of GT: Somatic Cell and Germ-Line Cell ○ Somatic: altering genes in a person’s body cells to treat a disorder (e.g. liver or muscle cells) ■ Can help the person suffering from the disease but are not inheritable for offspring ■ Affects the genome of person but not the genome of subsequent generations. ■ Regulatory agencies and review boards oversee clinical trials and to ensure an acceptable balance of risk and benefit. ○ Germ-Line: not yet feasible, but the notion evokes the dream of eradicating mutations for future generations. ■ These are inheritable. ■ It can also introduce nightmare of fabricating designer babies. ■ Safety concerns are so worrisome that it is generally thought to be normally unacceptable. ■ Scientists do not fully understand the likely ramifications of refashioning the genetic machinery of germ-line cells. ■ The addition or modification of cells might make a condition worse or prevent one disease but cause others. ■ The child can be born with a fatal result born to a child of engineering; worse is that the resulting disorder can be inheritable to future generations. ● In order to create any kind of gene therapy, scientists have to solve several technical problems. ○ Risk of viruses causing disease or provoking harmful immune system response, accurately deliver a virus to genes. ○ Ex. 4 y/o with Adenosine Deaminase Deficiency (ADA), which weakens immunity severely, had no system of defense against life-threatening infections. With a virus carrier, the girl’s immune system soon began to function normally for years. ○ Ex. 18 y/o Jesse Gelsinger experienced multiple organ failures and died during GT to treat ornithine transcarboxylase deficiency (OTCD), with the cause of death traced back to the immune system’s reaction to a virus carrier. ● Arguments that favor GT mirror those made for RT and GT: if it is within our power to correct genetic flaws and prevent/cure diseases, aren’t we obligated to do so? ○ RT has limits and Germ-Line therapy crosses the line; manipulating or destroying embryos may occur expressing disrespect for human life or discriminate against those with disabilities. ○ Some argue that GT should not be allowed due to eugenics (deliberate attempt of improving the genetic makeup of humans by manipulating reproduction). ■ Negative Eugenics: involve the prevention or treatment of diseases, typically through GT, embryo selection, selective abortion, or germ-line therapy. ● Prenatal screening is a type of negative eugenics. ■ Positive Eugenics: is said to include attempts to improve on normal functioning. Stem Cells ● Early cells are undifferentiated, but they are pluripotent (able to become differentiated). Under normal circumstances, they quickly differentiate into different cells; however, when extracted from the blastocyst, they can remain undifferentiated and retain their power. ○ This is the hallmark of embryonic stem cells because they are regenerative at large supplies. ● Adult stem cells stand ever ready to differentiate themselves to replace worn out or damaged cells. ○ Generate new bones, cartilage, skin, muscle, blood, etc. ○ Potential to produce diverse kinds of cells are constrained. ● Getting stem cells to differentiate into particular kinds of cells, new cells and tissues can be generated to treat diseases and injuries characterized by a lack of functioning cell types. ○ Therapeutic possibilities for Alzheimers, strokes, spinal cord injuries, burns, and arthritis. ● Most moral controversy over embryonic stem cells focused on the source: the blastocysts that are inevitable destroyed when retrieving cells. ○ The majority of embryos are produced through IVF. Leftover blastocysts are frozen and can neither be implanted nor discarded but can be used to extract stem cells. ● Research (Therapeutic) Cloning vs. Reproductive Cloning. ○ Research Cloning: stem cells are derived from the blastocyst. An advantage is that body tissues derived from the stem cells would be genetically matched to the nucleus donor, so new tissues could be used to treat donor with less risk of rejection. ○ Reproductive Cloning: blastocyst would be implanted in the uterus to continue the reproductive process to birth. ● Research is heavily influenced by existing laws and policies. ○ 2001: Bush declared no federal funding may support research that obtains stem cells by destroying embryos. ○ 2009: Obama issued an executive order that revoked Bush’s restriction to support and conduct responsible, scientifically worthy stem cell research. ○ The core question still remains: Is it morally permissible to destroy human embryos in a search for cures? ● A utilitarian perspective likely favors genetic testing and GT if they promote the general welfare, providing useful information about people’s genetic risk. ○ Benefits must be weighed against misleading test results, genetic discrimination, and breaching confidentiality. ○ Morally acceptable because they can prevent devastating diseases and disabilities in children as well as emotional or economic suffering in families. ○ Would not hesitate to employ positive eugenics if altering the human genome would increase happiness and ease suffering. In Class Notes: Genetics ● Routine in IVF: screening for known genetic diseases. ● Screening techniques: A person may harvest 15-20 embryos. Of those embryos, some percentage will have those traits. You choose the ones that already naturally have those traits. ● What rules or principles should be in place and how would they apply if: ○ A deaf couple wanted to keep their child deaf? ■ Autonomy of the parents. ■ Conflicts with Paternalism. ■ IE crossing Substantial Harm ○ A couple wants to have a particular eye/hair color. ■ Positive eugenics: enhancement. ■ How do we find seeking a certain color superficial or an enhancement? ■ How likely does it have to be to be considered a detriment? ○ Sex selection - (China?) ■ Wrong bcs it’s not “natural” ● Group 1: Extreme, life threatening life conditions to screen is ok; not for superficial ● ● ● ● ● ● ● ● ● traits; normal functioning → expand to include deafness? Group 2: No enhancement, cosmetic vs. necessary, egalitarian wants to make sure that the extreme things are okay. Group 3: Psychological screening of parents: embryo for good parents but not for bad parents. Group 4: Screen parents + waiting period; allow disability if both parents have it. Group 5: Look at family makeup to screening. Parents going through IVF go through more hoops than most parents do; is it morally correct? Nothing can be 100% guaranteed, but the percent of risk can compound based on family history, potential spontaneity of acquiring an illness, etc. Huntingtons has late onset; BRCA can live 70 years still fine. ○ Most at risk for Huntington's (+family history) does not get tested. Ancestry is run through Mormons; but 23andMe is chill. When we think about making judgments on what makes a normal risk profile, we have to have someone in mind. Sickle cell anemia (Black)? TSACS(Jewish)? Cystic Fibrosis? ○ White risk profile being the normal risk profile; does judging others by that risk profile work? ○ We don’t treat it everything as a baseline, sometimes we treat as if it were an exception in a specific group.
