The Good The Bad The Bizarre HUMAN CLONING Eliot Grigg Dartmouth College March 25, 2003

Medieval Medicine Experiment without understanding mechanisms Experiment without understanding mechanisms Assumption that all cells in body have same genetic information Assumption that all cells in body have same genetic information Turning back the developmental clock on a cell – reprogramming process not understood Turning back the developmental clock on a cell – reprogramming process not understood

History of Cloning 1960s and 70s: Nuclear transfer in frogs – John Gurdon 1960s and 70s: Nuclear transfer in frogs – John Gurdon 1996: Megan and Morag – lambs created from aborted fetus cells 1996: Megan and Morag – lambs created from aborted fetus cells 1997: Dolly – First mammal cloned from an adult cell – Dr. Ian Wilmut 1997: Dolly – First mammal cloned from an adult cell – Dr. Ian Wilmut

Recent Cloning Events Dolly dies young in February – short telomeres Dolly dies young in February – short telomeres Shorten when cell divides (except cancer cells) Shorten when cell divides (except cancer cells) Italian fertility doctor Severino Antinori Italian fertility doctor Severino Antinori Chinese cloning program Chinese cloning program Clonaid - announced first clone baby born on December 26, 2002 – thought to be a hoax by Raelian movement Clonaid - announced first clone baby born on December 26, 2002 – thought to be a hoax by Raelian movement

How to Clone Nuclear Transfer Nuclear Transfer 1. Extract DNA from oocyte (egg) 2. Extract DNA from donor cell in G0 stage of cycle 3. Inject DNA into empty oocyte and fuse with electricity 4. After a few division in culture, implant in surrogate mother

How to Clone (2)

Technical Hurdles Complications Complications Dolly result of 277 attempts, dies young Dolly result of 277 attempts, dies young 2-3% success rate elsewhere 2-3% success rate elsewhere Developmental problems: lungs, immune system, weight gain Developmental problems: lungs, immune system, weight gain Why? Why? Cell cycle coordination Cell cycle coordination Reprogramming process: time compression Reprogramming process: time compression Methylation: signals to genes disturbed in handling Methylation: signals to genes disturbed in handling Oct4 gene improperly regulating? Oct4 gene improperly regulating?

Animal Cloning Bucardo, Spanish Mountain Goat Bucardo, Spanish Mountain Goat Livestock Livestock Frozen Zoo Frozen Zoo Jurassic Park Jurassic Park

Cloning and Medicine Therapeutic Cloning Therapeutic Cloning Cloning allows for specific genetic engineering because one modified cell grows into an entire organ / organism Cloning allows for specific genetic engineering because one modified cell grows into an entire organ / organism Reproductive Cloning Reproductive Cloning Cloning makes new people from an adult cell Cloning makes new people from an adult cell

Xenotransplantation Transplanting organs from other species Transplanting organs from other species Goldie the pig lacks gene alpha-1- galactosyltransferase: codes for sugar on cell surface that is identified by human antibodies Goldie the pig lacks gene alpha-1- galactosyltransferase: codes for sugar on cell surface that is identified by human antibodies – Randall Prather – Randall Prather Retrovirus in pig DNA transferred to humans? Retrovirus in pig DNA transferred to humans?

Therapeutic Cloning Therapeutic Cloning Therapeutic Cloning 1. Extract DNA from adult cells 2. Create cloned embryos 3. Extract embryonic stem cells 4. Destroy embryo Spare Parts Spare Parts Direct tissue engineering of spare parts on demand – begin with one cell, modify it, and grow into organ Direct tissue engineering of spare parts on demand – begin with one cell, modify it, and grow into organ Genetically identical to recipient – no rejection Genetically identical to recipient – no rejection

Therapeutic Cloning (2) Grow whole organs – alleviate organ shortage Grow whole organs – alleviate organ shortage Grow non-regenerating cells Grow non-regenerating cells Brain cells for Parkinsons Brain cells for Parkinsons Pancreatic islet cells for Diabetes Pancreatic islet cells for Diabetes Note: we do not yet have command of stem cells Note: we do not yet have command of stem cells

Reproductive Cloning Cloning entire people Cloning entire people Infertility Infertility Genetically related offspring for infertile, gay/lesbian couples Genetically related offspring for infertile, gay/lesbian couples Offspring for families with inheritable genetic disorders Offspring for families with inheritable genetic disorders Add genetic engineering for designer babies Add genetic engineering for designer babies Raise the dead [see handout] Raise the dead [see handout]

The Legal Landscape Distinction between Reproductive and Therapeutic Cloning Distinction between Reproductive and Therapeutic Cloning In USA: In USA: Total cloning ban passed the Total cloning ban passed the House but awaits Senate – President Bush support Federally funded institutions Federally funded institutions must only use existing stem cell lines UN: Talks suspended for global cloning ban UN: Talks suspended for global cloning ban Human cloning illegal in South Korea, legal in China Human cloning illegal in South Korea, legal in China If we ban it here, it will happen somewhere else If we ban it here, it will happen somewhere else

Ethics – Patents Patents do not cover things found in nature but do cover things discovered or made by man Patents do not cover things found in nature but do cover things discovered or made by man Patent on a gene Patent on a gene Patent on technique and sometimes its product… Patent on technique and sometimes its product… i.e. drug, novel organism Patent on transgenic organism containing human genes Patent on transgenic organism containing human genes Patent on a human clone? Patent on a human clone?

Ethical Objections Theological Theological Playing God, Taking life Playing God, Taking life Technical Technical Failures and deformities – unsafe (for now) Failures and deformities – unsafe (for now) Creepy Applications Creepy Applications Parent from beyond the grave Parent from beyond the grave Headless organ donors Headless organ donors Identity Identity Is clone a distinct person from DNA donor? Is clone a distinct person from DNA donor?

Clones vs. Twins vs. Carbon Copies Donor DNA Donor DNA Telomere shortening Telomere shortening Epigenetics: turning off one copy of every gene (from mom or dad) Epigenetics: turning off one copy of every gene (from mom or dad) Surrogate mother Surrogate mother Conditions in the uterus Conditions in the uterus Oocyte doing reprogramming Oocyte doing reprogramming Mitochondrial DNA Mitochondrial DNA Nurture – unique upbringing environment Nurture – unique upbringing environment Buttercup Buttercup

Old and New Ethical Dilemmas In Vitro Fertilization (IVF) In Vitro Fertilization (IVF) Accepted by society Accepted by society Abortion Abortion Legal, if contested Legal, if contested Coming soon… Face / Head Transplants Coming soon… Face / Head Transplants Similar identity crisis – dates back to Descartes (at least) Similar identity crisis – dates back to Descartes (at least)

Designer Babies and Genetic Determinism Preventive Genetic Engineering Enhancing Genetic Engineering Preventive Genetic Engineering Enhancing Genetic Engineering In the not-too-distant future, it will In the not-too-distant future, it will be looked at as foolhardy to have a child by normal conception. Dr. Gregory Stock of UCLA Dr. Gregory Stock of UCLA The Genetic Divide The Genetic Divide Eugenics – an advantage for future Eugenics – an advantage for future goals, not a guarantee…

Conclusion Apocalyptic Scenarios Apocalyptic Scenarios Headless organ donors Headless organ donors Genetic Divide Genetic Divide Society without men Society without men Medical tool … Art Form? Medical tool … Art Form? Educate lawmakers / society Educate lawmakers / society If we had cured Beethovens depression, would we still have his music? If we had cured Beethovens depression, would we still have his music? [What is the nature of human nature?]