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07/03/2020
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Ethics of CRISPR and GM Humans
Fr, Joseph Tham, LCSchool of BioethicsRegina Apostolorum
Elements of genetics
• DNA• Transcription• RNA, mRNA• Translation• Protein• https://www.youtube.com
/watch?v=gG7uCskUOrA• Expressions,
differentiation• Epigenetics
By Madprime - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=2068734
Genetic engineering
Selective breeding through the centuries
Viralinfections
Genetic engineering
• GMO by virus vectors– Animals 1972 and plants 1986
Elements of genetics
• Human Genome Project• NIH, Celera, international consortium• Identify and mapping• Human genes and genome• Expecting 100,000, found 21.000 • = 3,2 Gb• Project completed 2006 (2000)
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History of Gene Therapy
• 1970 Homologous recombination
• 1990 Zinc finger nuclease (ZFN) – Jesse Gelsinger, an
American teen died in a recombinant adenovirus gene transfer trial in 1999.
• 2009 Transcriptional activator-like effector nucleases (TALENs)
• 2012 CRISPR-Cas9
Clustered Regularly Interspaced ShortPalindromic Repeats
CRISPR-Cas9• UC Berkeley 2012 / MIT
2014• Genetically remade, 2
components– sgRNA + Cas9– Identifies and cuts any
specific DNA• https://www.youtube.com/
watch?v=2pp17E4E-O8• https://video.wired.com/w
atch/crispr-gene-editing-explained
CRISPR
• Silence, activate or editgenes– Disactivate cancer cells– Produce drugs, factors,
vaccines and hormones– Correct genetic defects of
a base pair– Promote transcription
(DNA expression)– GMO Animals: pigs, dogs,
monkeys, rodents, etc.– Genetic enhancement
Ethics of CRISPR
• Animals and plants
• Human beings
– Somatic cells(Adults)
– Germ cells(Embryos)
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Plants and Animals
• Bacteria• Plants: potatoes,
Spicy tomatoes• Animals: muscular
pigs, pets, immunity, mosquitos
• Ethics (cfr GMO) Neutralize mosquitoes of malaria
Treatments and Diagnosis for Humans
Neutralizeinfections, superbugs, virus, HIV…
Neutralizecancer cellsimmunityGene Markers(defective, imagining)Detectdiseases Ethics of GM Humans
Therapy Nontherapeutic Enhancements
Human Somatic Cells
Human Germ Cells
Ex-vivo vs In-vivo gene
editing
Human Somatic Cells Gene Therapies• Cancer
• Epilepsy
• Prenatal treatment
• Muscular Dystrophy
• Leber’s congenitalamaurosis (LCA10)
• Thalassemia
• Sickle cell disease
• Hemophilia B
• Mucopolysaccharidosis I
• X-linked SCID
• LPLD with Alipogene tiparvovec (Glybera)
• Hunter’s Syndrome
• hypertrophic cardiomyopathy (HCM)• Huntington’s disease• CLL
• Parkinson’s• Epidermolysis bullosa
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Ethics of GM Humans
Therapy Nontherapeutic Enhancements
Human Somatic Cells
Yes
Human Germ Cells
Human Germ cells gene therapy
Human Germcells
• Sperm and Eggs• Embryos
– Creation thru IVF– Freezing– PGD Diagnosis– Screening– Selection and
destruction– Genetic therapies
of sick embryos?
Francis Collins, NIH
A: I’d love to see that pursued by somatic gene editing and I don’t think that presents ethical dilemmas. Let’s talk about the germline approach. You’d have to have a circumstance where you knew you had a family at risk. So you’re worried about having an affected boy. How would you go about doing gene editing? Well, you’d have to do in vitro fertilization [IVF], you’d have to do preimplantation genetic diagnosis [PGD] to identify an embryo that has the mutation. You’ll have at that point multiple embryos and there will be amongst them plenty that are unaffected. Why don’t we just reimplant those and you’re done? You have to do PGD in order to get to the point of being able to do germline gene editing, so it’s PGD alone or it’s PGD plus some highly risky procedure.• https://www.sciencemag.org/news/2018/11/epic-
scientific-misadventure-nih-head-francis-collins-ponders-fallout-crispr-baby-study
Preimplantational Genetic DiagnosisPGD
Edit human embryos to treat geneticdefects?
Treatment
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Ethics of GM Humans
Therapy Nontherapeutic Enhancements
Human Somatic Cells
Yes
Human Germ Cells
IVFRarely necessary
Supermen, Wonderwomen, Perfect babies
Ethics of GM Humans
Therapy Nontherapeutic Enhancements
Human Somatic Cells
Yes
Human Germ Cells
IVFRarely necessary
No
Ethics of CRISPRTherapy vs. enhancement
Ethics of GM Humans
Therapy Nontherapeutic Enhancements
Human Somatic Cells
Yes Why?
Human Germ Cells
IVFRarely necessary
No
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Ethics of GM Humans
• Therapy vs enhancement• Access• Safety• Justice• Dignity• Ethics of technology• Beyond Therapy• Perfection and
Transhumanism• Interreligious perspectives
Access: Easy and cheaphttp://www.the-odin.com/gene-engineering-kits/
AccessEthics of GM Humans
• Safety– Off target
mutations, chimeric tissues
– Errors and horrors– Principle of
precaution– Terrorism– Boys from Brazil
Ethics of GM Humans
Justice Ethics of GM humans
• Live Longer• Healthier• Stronger• Faster• Finer looks• Braver• Sharper minds• Happier souls• Superman or
Supervillian?
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Ethics of technology
• Ambiguity of technology
• Can it save us?
• Can it destroy us?• Technological
Imperative
• Throwaway Culture
Embryos and CRISPRJennifer Doudna
https://www.theguardian.com/science/video/2019/mar/28/the-biggest-revolution-in-gene-editing-crispr-cas9-explained-video
He Jiankui賀建奎
Southern University of Science and Technology, Shenzhen, China
The Story broke
• https://www.youtube.com/watch?time_continue=278&v=th0vnOmFltc
• https://www.wsj.com/articles/gene-edited-babies-experiment-raises-concerns-11544616000?mod=flipboard
• https://www.statnews.com/2018/12/17/crispr-shocker-genome-editing-scientist-he-jiankui/
• 2015 Chinese scientists genetically modify human embryos https://www.nature.com/news/chinese-scientists-genetically-modify-human-embryos-1.17378
• Injected 31 embryos, succeeding with 21. CCR5 mutation uncertain, implanted 11 embryos, 2 born, one more on the way.
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Rogue Scientist–Safety, techniques,
informed consent…
Scape goat–Product of scientific
culture
Germline genome editingNational Academies (USA)
– Caution does not mean prohibition. It recommends that germline editing research trials might be permitted, but only after much more research to meet appropriate risk/benefit standards for authorizing clinical trials.
Nuffield Council (UK)– Germline genome editing morally
permissible only when compatible with the welfare of a future person who may be born as a result. Safety, no alternatives avoidance of heritable genetic disease
Hum
an Genom
e Editing:
Science, E
thics, and G
overnance (2017)
Genom
e editing and human
reproduction: social and ethical issues (2018)
Can the scientificcommunity Self-regulate?
2018 Second International Summit on Human Genome Editing
Time to have a responsible translational pathway to trials of germline editing of human embryo
Ethics of GM Humans
Therapy Nontherapeutic Enhancements
Human Somatic Cells
Yes Caution, what is the goal? What is perfection?
Human Germ Cells
IVFRarely necessary
No
Ethics of GM Humans (future?)
Therapy Nontherapeutic Enhancements
Human Somatic Cells
Yes Yes
Human Germ Cells
Yes Why not?
Broad societal consensus
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Transhuman or Transfiguration Bibliography• Pope Francis, “Encyclical Letter Laudato Si’ (On Care For Our Common
Home).” • Benedict XVI, Spe Salvi Benedict XVI. “Encyclical Letter Spe Salvi,”
November 30, 2007. http://w2.vatican.va/content/benedict-xvi/en/encyclicals/documents/hf_ben-xvi_enc_20071130_spe-salvi.html.
• President’s Council on Bioethics and Leon R. Kass. Beyond Therapy: Biotechnology and the Pursuit of Happiness. October edition. New York: Harper Perennial, 2003.
• MARTIN HEIDEGGER, “The Question Concerning Technology,” in Basic Writings, ed. DAVID KRELL, (New York: HarperCollins, 1993). http://www.psyp.org/question_concerning_technology.pdf
• ROMANO GUARDINI, The End of the Modern World, (London: Sheed & Ward, 1957).
• LEON R. KASS, “L’Chaim and Its Limits: Why Not Immortality?” in First Things (New York, N.Y.), no. 113 (May 2001): 17–24. https://www.firstthings.com/article/2001/05/lchaim-and-its-limits-why-not-immortality
• MacIntyre, Alasdair. “Seven Traits for the Future.” The Hastings Center Report 9, no. 1 (1979): 5–7. https://doi.org/10.2307/3561692.
• Jonas, Hans. “The Burden and Blessing of Mortality.” The Hastings Center Report 22, no. 1 (1992): 34–40. https://doi.org/10.2307/3562722.
• Bioethics, President’s Council on. Being Human, Readings from the President’s Council on Bioethics. President’s Council on Bioethics, 2003.
• WHO, Advisory Committee on Developing Global Standards for Governance and Oversight of Human Genome Editing, Report of the First meeting (18-19, March 2019), https://www.who.int/ethics/topics/human-genome-editing/GenomeEditing-FirstMeetingReport-FINAL.pdf?ua=1
• Committee on Human Gene Editing: Scientific, Medical, and Ethical Considerations, National Academy of Sciences, National Academy of Medicine, and National Academies of Sciences, Engineering, and Medicine. Human Genome Editing: Science, Ethics, and Governance. Washington, D.C.: National Academies Press, 2017. https://doi.org/10.17226/24623.
• MacIntyre, Alasdair. “Seven Traits for the Future.” The Hastings Center Report 9, no. 1 (1979): 5–7. https://doi.org/10.2307/3561692.
• Jonas, Hans. “The Burden and Blessing of Mortality.” The Hastings Center Report 22, no. 1 (1992): 34–40. https://doi.org/10.2307/3562722.
• Bioethics, President’s Council on. Being Human, Readings from the President’s Council on Bioethics. President’s Council on Bioethics, 2003.
• WHO, Advisory Committee on Developing Global Standards for Governance and Oversight of Human Genome Editing, Report of the First meeting (18-19, March 2019), https://www.who.int/ethics/topics/human-genome-editing/GenomeEditing-FirstMeetingReport-FINAL.pdf?ua=1
• Committee on Human Gene Editing: Scientific, Medical, and Ethical Considerations, National Academy of Sciences, National Academy of Medicine, and National Academies of Sciences, Engineering, and Medicine. Human Genome Editing: Science, Ethics, and Governance. Washington, D.C.: National Academies Press, 2017. https://doi.org/10.17226/24623.
• Nuffield Council on Bioethics, Genome Editing: An Ethical Review. 2016 http://nuffieldbioethics.org/project/genome-editing/ethical-review-published-september-2016.
• Nuffield Council on Bioethics, Genome editing and human reproduction, 2018 http://nuffieldbioethics.org/wp-content/uploads/Genome-editing-and-human-reproduction-FINAL-website.pdf
• National Academies of Sciences, “Statement by the Organizing Committee of the Second International Summit on Human Genome Editing.” Dec. 3, 2015 http://www8.nationalacademies.org/onpinews/newsitem.aspx?RecordID=11282018b.
• National Academies of Sciences, “On Human Gene Editing: International Summit Statement.” November 29, 2018. http://www8.nationalacademies.org/onpinews/newsitem.aspx?RecordID=12032015a
• Tham, Joseph, Chris Durante, and Alberto García Gómez. Interreligious Perspectives on Mind, Genes and the Self: Emerging Technologies and Human Identity. Routledge, 2018.
• JOSEPH THAM, “Resisting the Temptation of Perfection”, in National Catholic Bioethics Quarterly, 17.1, (2017), 51-64.
• JOSEPH THAM “Gilbert Meilaender, Should We Live Forever? The Ethical Ambiguities of Aging, Eerdmans, 2013 [Book Review]” StudiaBioethica. 6.1 (2013), 77-78.
• JOSEPH THAM “Suffering Technology: Philosophical overview and a theological Response of Spe Salvi (Part 2),” Studia Bioethica 7.2(2014), 50-56.
• JOSEPH THAM “Suffering Technology Part 1,” Studia Bioethica 7.1(2014), 55-61.
• J. THAM – M. LOSITO (eds.), Bioetica al Futuro: Tecnolocizzare l’uomo o Umanizzare la tecnica, Libreria Editrice Vaticana, Vatican City, 2010.
• JOSEPH THAM “Dal Tecnopotere alla Conversione Ecologica,” in A. GARCÍA GÓMEZ, M. LOSITO, J. THAM (eds.), Bioetica questione ambientale ed ecologia umana, Amazon 2017, 97-110.
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