CRISPR 2020 - Catholic Information CenterCRISPR • Silence, activate or edit genes – Disactivate cancer cells – Produce drugs, factors, vaccines and hormones – Correct genetic

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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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