Biotech 4BS3 2024 Bioethics pt2 PDF

BIOTECH 4BS3/SEP 6BS3: Biotechnology Regulations BIOETHICS pt2 1 Artificial Reproductive Technologies (ART) 1st test tube baby, Louise Brown, was born in the UK in July 1978 At that time→ IVF was controversial Now → IVF is considered ethical Over five m...

BIOTECH 4BS3/SEP 6BS3: Biotechnology Regulations BIOETHICS pt2 1 Artificial Reproductive Technologies (ART) 1st test tube baby, Louise Brown, was born in the UK in July 1978 At that time→ IVF was controversial Now → IVF is considered ethical Over five million "test tube babies" have now been born around the world (BBC news, 1 July 2012 http://www.bbc.co.uk/news/health-18649582) Autonomy of women and individual rights 2 Artificial Reproductive Medicine Biggest resistance is: By people that follow the “Natural Law” principles ”It’s unnatural” By individuals that consider the embryo with full moral standing By arguing that children from ART have a higher chance of being born with defects Fact: ARTs are big business. 85 % in the US are paid by people and not insurance! Ethical? ARTs raise a justice issue if it was covered by society Why do it when there are many children waiting to be adopted in foster care? Other issues: Right not to procreate Frozen embryos and couples divorce/separate Inheritance 3 Artificial Reproductive Medicine Cytoplasmic Transfer: The girl with three biological parents Alana Saarinen http://www.bbc.com/news/magazine-28986843 4 Embryo Research The genetic identity of a new individual is established at syngamy, about 30 hours after fertilization; followed by cell division By law, experimental procedures on embryos can proceed up until 14 days after the gametes mix, and these are restricted to: -Increasing knowledge about serious diseases or other serious conditions (i.e. congenital issues and miscarriages) -Developing treatments for serious diseases and other conditions -Advancing the treatments for infertility -Developing more effective methods of contraception -Developing methods for detecting genetic, chromosomal or mitochondrial abnormalities in pre‐implantation embryos -Increasing knowledge about the development of embryos. No embryo that research was done on can be implanted 5 When Do Moral Attributes Start? When the sperm and egg make contact? As the sperm penetrates the outer layer of the egg? When the sperm pronucleus is just next to the egg’s? During syngamy? During the first cell division? At the blastocyte stage? At implantation? At the primitive streak stage (nervous system are laid down) When the embryo becomes a fetus? When the mother first feels the fetus move? (Quickening) p. 65 J.A. Bryant 2018 When the fetus reaches viability? After birth? 6 Human Life Begins at Fertilization Pro-lifers No research can be done on the early embryo The creation of spare embryos is wrong Abortion is always wrong Infertile couples can never have a biological child of their own 7 The 14-Day Approach At around the 14th day, the primitive streak appears Between the first day and the 14th day, survival of the embryo is not high: Reach the implantation stage Implantation Staying implanted Prior to 14 days, the nervous system is not evident Thus, it is argued that it is acceptable to use embryos for research prior to the 14 days 8  Biologically, what does it mean to be “human”? If an individual’s genetics were altered to something other than normal – Is he or she still human? What about for medical reasons? Image from: https://genographic.nationalgeographic.com/science-behind/genetics-overview/ 9 Genetic Modifications of Humans Somatic Cell Gene Therapy: This involves the insertion of a gene into a somatic cell But… Corrected gene is not heritable How to incorporate properly functioning gene? Will the gene be expressed? Cystic fibrosis case We would want to target the cells lining the lungs Gene function is only partially restored Cells lining the lungs are constantly being renewed (we must do multiple therapeutic interventions) Severe combined immunodeficiency disease (SCID) case Advantage here is that the target cells are stem cells (self-renewing) Unfortunately, leukemias seem to appear at some point (oncogene activation) Can it be used for enhancing human performance? Not simply inserting a foreign gene, but adding duplicates of an existing, functioning gene 10  Genetic Modifications of Humans Germline Gene Therapy: This involves the insertion of a gene into a germline cells (eggs, sperm, and fertilized eggs) This would allow traits to be inherited from one generation to the next Elimination (from the human gene pool) of some genetic diseases Enhanced human performance Creation of a new “superior species of humans” (the basic concept behind Eugenics) GM humans, is this ok? “Playing God?” IVF success rates are low as it is, this would be even lower (technology will eventually overcome this) This strategy would most likely be used with parents that will have children that are homozygous for debilitating trait Otherwise, why not use IVF and pre-implantation genetic diagnosis (PGD)? ”Three-way” IVF has been approved, why not use this? If we approved this, then it might become more “acceptable for using this technology for enhancing human performance! Can IVF with PGD be used for enhancing human performance? 11  Germline Genetic Engineering Genetic alteration done in the sperm, egg or early embryo Affects every cell in the body Inheritable alteration Whatever the change made, it is permanent and irreversible Can use the CRISPR/Cas9 system o “Clustered Regularly Interspaced Short Palindromic Repeats” o Naturally found in bacteria, protects against bacteriophage infection o Adapted by scientists as a technique to make precise additions/deletions/substitutions in a target gene → makes germline genetic engineering a REALITY Human CRISPR Experiments in action: https://www.nature.com/news/crispr-fixes-disease-gene-in-viable-human-embryos- 1.22382 12 CRISPR/Cas9 p. 196 J.A. Bryant 2018 13 CRISPR/Cas9 System www.youtube.com/watch?v=2pp17E4E-O8 14 Germline Genetic Engineering In vitro Oocyte Reconstitution October 2016, Japan: successful production of mouse pups derived from lab-made eggs Eggs generated from either induced pluripotent stem cells (iPSCs) or embryonic stem cells (ESCs), cultured in a dish with ovarian cells, fertilized, then transferred into a surrogate mouse O Hikabe et al. Nature 1–5 (2016) doi:10.1038/nature20104 15 Genetic Modifications of Humans Genetic Disease – Like SCID – Such a genetic problem will definitely develop the disease Genetic Attribute – Does NOT mean that the disease exists or that it will develop There could be a chance to get the disease, but it is not a 100% E.g. breast cancer in which genes (BRCA1 and BRCA2 mutations) have been identified that can increase the risk for development of the cancer Does not mean that the disease condition already exists or that it will inevitably develop Genetic engineering in this case goes beyond treatment 16  Case: Prophylactic Mastectomy ANGELINA JOLIE: ‘I MADE A DECISION TO HAVE A PREVENTIVE DOUBLE MASTECTOMY’ “I carry a ‘faulty’ gene, BRCA1, which sharply increases my risk of developing breast cancer and ovarian cancer…. My doctors estimated that I had an 87 percent risk of breast cancer and a 50 percent risk of ovarian cancer…. It is my hope that they, too, (other women) will be able to get gene tested, and that if they have a high risk they, too, will know that they have strong options” The cost of testing for BRCA1 and BRCA2, up to $5,000 in the United States, remains an obstacle for many women http://www.nytimes.com/2013/05/14/opinion/my-medical-choice.html?_r=1& 17 Is it always possible to distinguish between therapy and enhancement? Therapy is returning someone to clinical society's adequate human health Enhancement is beyond what we deem as a normal state of health 18  Therapy or Enhancement? What if the alteration is for non-medical reasons: E.g. Increase muscle mass or oxygen carrying capacity of red blood cells. Could this be prohibited without infringing on the individual rights? 19 Case: Lance Armstrong and Caster Semenya Lance Armstrong Caster Semenya Won the Tour de France 7 Athlete with heightened consecutive times but was found to testosterone levels have used performance enhancing Disorders of sex development (DSD) drugs and stripped of all titles In 2018 she was prevented from Used EPO (erythropoietin) – a competing in some female events protein hormone which stimulates She was ordered to medications to the production of red blood cells, lower testosterone levels increasing oxygen carrying capacity Issues: Sex vs gender Should biological enhancers be Discrimination against some forms allowed in sport as long as they of elevated testosterone (not all) bring concentrations within physiological range? 20 What about cloning? Cloning appears naturally in the form of identical twins What if an ill person required a match - transplant? Is it ok to CLONE to produce the required tissue? Therapeutic Cloning Matched embryonic cells for patients Research models for the study of genetic diseases Strategy is to use embryonic stem (ES) cells for preventing tissue and organ transplant rejection No implantation necessary Can also be used for treating diseases where cells are not functioning properly (i.e. diabetes mellitus type I) In Canada, creating a human clone is illegal irrespective of intentions (reproductive or therapeutic) Could induced pluripotent stem cells (iPS) be the solution? Is therapeutic cloning dead? 21  Cloning Which one is more ethical? Is this human commercialization? 22 Cloning 23 Ethics of Human Cloning From experience with other species, the results are variable at best Questions exist surrounding the health of cloned animals Women taking part in this will be exposed to highly experimental and controversial procedures Risks outweigh the benefits Cloning does not “recreate” a person Potential emotional/psychological problems of cloned children 24 Cloning Non-Human Animals Done for increasing understanding of developmental genetics, epigenetics, and imprinting Done for multiplying useful genotypes (cattle for meat consumption) Done for multiplying endangered species Done for replicating cherished pets Bringing extinct species "back to life" 25 Stem Cells Totipotent: Extra embryonic know the difference between totipotent, multipotent, and pluripotent The zygote (fertilized egg) has all the information to develop an adult mammal (totipotent) The totipotent state remains until the blastocyte stage (5-6 days after fertilization) After this stage, the cells are called embryonic stem (ES) cells (pluripotent) Research on ES is done from unused IVF eggs Against stance for ES research : Each zygote has unique genetic makeup that never existed before and will never exist again (unless the embryo splits into two) Given the right conditions, the embryo will develop into a fetus and then to a child For stance: 70 - 80 % of embryos do not implant At a later stage the embryo can split into two (thus it cannot be regarded as an individual) It is possible for two embryos to join to form one and develop normally (rare, but possible) p. 97 J.A. Bryant 2018 26 Stem Cells and Moral Standings Stem cell research is gaining ground to treat various challenging conditions (Parkinson’s, diabetes, Alzheimer’s..etc) Two moral questions with regards to stem cells 1. Too much changes to the “nature” of our genetic code and cells (embryonic and adult stem cells) 2. The production and growth of stem cells which is of more immediate significance Source of embryonic stem cells requires the destruction of an embryo Those that are against abortion would then be automatically against embryonic stem cell research Growth of these stem cells would result in some ways a new organism (from either adult or embryonic stem cells)! 27  5-day Blastocyst Fetus at 16 weeks gestation www.advancedfertility.com http://www.webmd.com/baby/ss/slideshow-fetal-development Genetic Testing 28 Human Genes and Genomes The Human Genome Project (HGP) opened so many venues for us to explore Genomic Transcriptomics Proteomics Metabolomics In terms of medicine, genetic diagnosis and screening was perhaps the biggest beneficiary of the HGP These can be done at different stages of life: Post-natal After the baby is born Pre-natal Before the baby is born Pre-implantation Before the embryos are implanted Pre-conception Results of these tests can be difficult to ascertain Different people express genes at different extents Gene expression affected by the environment Some genes are multifunctional (difficult to pinpoint effects) 29 Human Genes and Genomes: Discrimination? Known genetic aberrations may lead to life and health insurance discrimination Child born with a genetic defect could be refused health insurance (several examples in the USA; “pre-existing” condition) Underlying assumption by these companies is that a positive genetic test should lead to abortion! Known genetic aberrations may lead to employment discrimination Taking too many days off? Even if the data is protected, data theft occurs frequently Question: Are these types of discriminations new? Prior to genetic testing, would these occur? 30 Cost of Genome Sequencing 31 23andME It is now possible for any individual to undergo genetic testing either for medical purposes or privately E.g. 23andMe - $199 gets you ~80 evaluated traits Provides information about genetic attributes, can confirm undiagnosed genetic diseases (e.g. Cystic fibrosis carrier) Caution: false positives for ovarian or breast cancer may well ‘lead a patient to undergo prophylactic surgery, chemoprevention, intensive screening, or other morbidity‐inducing actions’, while a false negative may ‘result in a failure to recognize an actual risk that may exist’. The burden of knowledge Ignorance is bliss 32  Newborn Genetic Screening Nearly four million newborns undergo genetic screening every year in the United States Most states have mandatory genetic screening programs for newborn babies. Until recently such screening was limited to diseases that were well understood and for which effective treatments were available Now, however, most mandatory screening programs also test for diseases that are not well understood and for which there is no available treatment Some believe this change is ethically justifiable because much knowledge of little understood diseases could be gained and lead eventually to treatment and cure What do you think? The Changing Moral Focus of Newborn Screening, An Ethical Analysis by the President’s Council on Bioethics, Dec 2008 33 Next-Gen Screening: Newborn Genome Sequencing The Hastings Centre, a bioethics research institute recently wrote a report exploring the question: Should all newborn babies have their genomes sequenced? Recommends that genome-wide sequencing of all newborns should NOT be pursued at this time What do YOU think? Summary: https://www.sciencedaily.com/releases/2018/08/180815171100.htm Full Report: https://onlinelibrary.wiley.com/doi/full/10.1002/hast.874 34  What about Prenatal Genetic Testing? Issue with prenatal is that if we get rid of embryos that have a particular condition, are we marginalizing those with the existing condition? Stigma? 35  Ethics of Prenatal Genetic Tests 3.4 billion base pairs in a haploid human genome Probably 3.4 billion ethical, legal, and social issues along with psychological and economic implications (Dr. Hank Greely, 2011) Prenatal genetic testing: Provides an option of pregnancy termination Limits the proliferation of abnormal genes and chromosomes Limits the psychological and economic implications of caring for children born with genetic and chromosomal disorders Modern Eugenics? https://bioethicsarchive.georgetown.edu/pcsbi/sites/default/files/PrivacyProgress508_1.pdf http://blog.bioethics.gov/2011/02/28/ethics-of-prenatal-genetic-tests/ 36  Preimplantation Genetic Diagnosis (PGD) Genetic screening performed on embryos during IVF One cell is removed and tested. Gives an option for “selection” The earliest way to detect a genetic or chromosomal condition before birth Used for patients with known genetic conditions or with a history of multiple miscarriages Allows parents to “select” the healthy embryos from those with the genetic condition – Is this ethical? Very expensive – up to $6,000 on top of IVF costs 37 Prenatal Genetic Testing Non-Invasive Prenatal Screening Screening tests that estimate risk of a select set of conditions including Down syndrome, Trisomy 18 and 13, and spina bifida Provides a statistical probability that causes many false positives and false negatives Higher risk result may necessitate invasive testing Tests include the integrated prenatal screening (IPS), first trimester screening (FTS), maternal serum screening (MSS-quad), and obstetrical ultrasound 38  Prenatal Genetic Testing Testing fetal cells – Invasive Prenatal Diagnosis Amniocentesis 1st trimester (usually between 9 – 14 weeks of gestation) 2nd trimester (16-18 weeks of gestation)* It has a 0.5-1% risk for complications, including miscarriage. Chorionic villus sampling (CVS) Trans-abdominal or trans-cervical route Performed 11-14 weeks gestation It has a 1-2% risk for complications, including miscarriage. *Best, safest option 39  Prenatal Genetic Testing Non-Invasive Prenatal Genetic Diagnosis (NIPD) Cell-free fetal DNA (cffDNA) in the maternal blood stream ~ 5-10 % of the total free-floating DNA present in maternal blood Easier to isolate and can be used for the same diagnostic purposes as cellular fetal DNA Clears shortly after the end of a pregnancy, direct relevance to the current pregnancy is almost certain Only 10 milliliters of blood from the pregnant mother is required Reliable diagnosis may be performed as early as seven weeks post- conception 40 Prenatal Genetic Testing Non-Invasive Prenatal Genetic Diagnosis (NIPD) No risk of miscarriage Early testing Fast turnaround speed of the results Minimal stress imposed on a pregnant woman Ability to test for multiple diseases and disorders simultaneously Future applications of NIPD are predicted to cover the whole genome and multi-disease detection within the next 10 years 41 NIPD Test Name Company Method Standard Screen Other Diseases (T21, T18, T13, sex aneu., gender) Verifi® and Verifi Illumina Whole genome Yes Verifi Plus: autosomal trisomies, Plus® (Verinata) sequencing 1p36, 4p-, 5p-, Angelman/Prader-Willi DiGeorge Panorama* Natera SNP sequencing Yes Microdeletions: DiGeorge, 1p36, (LifeLabs) Angelman, Cri du Chat, Prader-Willi Harmony * Ariosa Chromosome Yes DiGeorge (22q11.2) selective sequencing InformaSeq Integrated Massive parallel Yes n/a Genetics sequencing (LabCorp) iGene INEX Whole genome Yes T9, T16, T22, Cri du Chat, 1p36, Innovations sequencing DiGeorge, 2q33.1, 1q32.2, 11q23, Willi/Angelman, 16q12.2, 1q32.2 MaterniT21Plus® Sequenom Whole genome Yes Plus: 22q, Cri du Chat, Prader- and sequencing Willi/Angelman, 1p36, 4p, 11q, MaterniTGenome 8q, T16, T22 Genome: Scans ALL chromosomes for deletions 42 Bioethics of NIPD Testing Abortion Some say, NIPD may shift the pro-life focus… from low-income mothers considering adoption choices to high income mothers considering: Not “whether she can raise this child,” but rather if this is “the child she wants to raise” “Every pregnancy becomes a ‘tentative pregnancy’ until the results of NIPD are received NIPD may normalize genetic-based selective abortion 43 Bioethics of NIPD Testing Eugenics Improving the human population by controlled reproduction and decreasing the occurrence of undesirable characteristics and conditions NIPD focuses on earlier and more accurate detection of genetic impairments, not correction → may lead to institutionalized eugenics Crucial difference between “preventing children from being born with Down’s Syndrome,” and “preventing children with Down’s Syndrome from being born” Reduction of Down syndrome population due to pre-natal screening https://www.lozierinstitute.org/new-study-abortion-after-prenatal- diagnosis-of-down-syndrome-reduces-down-syndrome-community-by-thirty- percent/ https://www.cbsnews.com/news/down-syndrome-iceland/ 44 Bioethics of NIPD Testing Disability Rights… Criticism of prenatal testing involves three major contentions: 1) Reinforces the medical model that “disability is a problem to be solved: → overshadows the more important issue of societal discrimination against people with disabilities 2) Supports parental expectations of “perfect children” 3) Selective abortions based on disability is often associated with misinformation about the disability How would you feel about this notion: “someone like you will never be born again” Is “the last child with Down syndrome” more like “the last child with glasses”? Is a disability a mere inconvenience or an identity? 45