The Good

The Bad

The Bizarre

HUMANCLONING

Eliot GriggDartmouth CollegeMarch 25, 2003

Medieval MedicineMedieval Medicine

Experiment without Experiment without understanding understanding mechanismsmechanisms

Assumption that all Assumption that all cells in body have same cells in body have same genetic informationgenetic information

Turning back the Turning back the developmental clock on developmental clock on a cell – reprogramming a cell – reprogramming process not understoodprocess not understood

History of CloningHistory of Cloning

1960’s and ’70’s: 1960’s and ’70’s: Nuclear transfer in Nuclear transfer in frogs – John frogs – John GurdonGurdon

1996: Megan and 1996: Megan and Morag – lambs Morag – lambs created from created from aborted fetus cellsaborted fetus cells 1997: Dolly – First mammal cloned 1997: Dolly – First mammal cloned from an from an adultadult cell – Dr. Ian Wilmut cell – Dr. Ian Wilmut

Recent Cloning EventsRecent Cloning Events

Dolly dies young in Dolly dies young in February – short February – short telomeres telomeres Shorten when cell Shorten when cell

divides (except cancer divides (except cancer cells)cells) Italian fertility doctor Severino AntinoriItalian fertility doctor Severino Antinori

Chinese cloning programChinese cloning program Clonaid - announced first clone baby Clonaid - announced first clone baby

born on December 26, 2002 – thought born on December 26, 2002 – thought to be a hoax by Raelian movementto be a hoax by Raelian movement

How to CloneHow to Clone

Nuclear TransferNuclear Transfer1. Extract DNA from oocyte (egg)1. Extract DNA from oocyte (egg)

2. Extract DNA from donor cell in G0 2. Extract DNA from donor cell in G0 stage of cyclestage of cycle

3. Inject DNA into empty oocyte and fuse 3. Inject DNA into empty oocyte and fuse with electricitywith electricity

4. After a few division in culture, implant 4. After a few division in culture, implant in surrogate motherin surrogate mother

How to Clone (2)How to Clone (2)

Technical HurdlesTechnical Hurdles

ComplicationsComplications Dolly result of 277 attempts, dies youngDolly result of 277 attempts, dies young 2-3% success rate elsewhere2-3% success rate elsewhere Developmental problems: lungs, immune system, Developmental problems: lungs, immune system,

weight gainweight gain

Why?Why? Cell cycle coordinationCell cycle coordination Reprogramming process: time compressionReprogramming process: time compression Methylation: signals to genes disturbed in handlingMethylation: signals to genes disturbed in handling Oct4 gene improperly regulating? Oct4 gene improperly regulating?

Animal CloningAnimal Cloning Bucardo, Spanish Bucardo, Spanish

Mountain GoatMountain Goat LivestockLivestock Frozen ZooFrozen Zoo Jurassic ParkJurassic Park

Cloning and MedicineCloning and Medicine

Therapeutic CloningTherapeutic Cloning Cloning allows for specific genetic Cloning allows for specific genetic

engineering because one modified cell engineering because one modified cell grows into an entire organ / organismgrows into an entire organ / organism

Reproductive CloningReproductive Cloning Cloning makes new people from an Cloning makes new people from an

adult celladult cell

XenotransplantationXenotransplantation Transplanting organs Transplanting organs

from other speciesfrom other species Goldie the pig lacks Goldie the pig lacks

gene alpha-1-gene alpha-1-galactosyltransferase: galactosyltransferase: codes for sugar on cell codes for sugar on cell surface that is surface that is identified by human identified by human antibodiesantibodies – – Randall PratherRandall Prather

Retrovirus in pig DNA Retrovirus in pig DNA transferred to humans?transferred to humans?

Therapeutic CloningTherapeutic Cloning

Therapeutic CloningTherapeutic Cloning1. Extract DNA from adult cells1. Extract DNA from adult cells

2. Create cloned embryos2. Create cloned embryos

3. Extract embryonic stem cells3. Extract embryonic stem cells

4. Destroy embryo4. Destroy embryo Spare PartsSpare Parts

Direct tissue engineering of spare parts on Direct tissue engineering of spare parts on demand – begin with one cell, modify it, and demand – begin with one cell, modify it, and grow into organgrow into organ

Genetically identical to recipient – no Genetically identical to recipient – no rejectionrejection

Therapeutic Cloning (2)Therapeutic Cloning (2)

Grow whole organs – alleviate Grow whole organs – alleviate organ shortageorgan shortage

Grow non-regenerating cellsGrow non-regenerating cells Brain cells for Parkinson’sBrain cells for Parkinson’s Pancreatic islet cells for DiabetesPancreatic islet cells for Diabetes

Note: we do not yet have Note: we do not yet have command of stem cellscommand of stem cells

Reproductive CloningReproductive Cloning

Cloning entire peopleCloning entire people InfertilityInfertility

Genetically related offspring for infertile, Genetically related offspring for infertile, gay/lesbian couplesgay/lesbian couples

Offspring for families with inheritable genetic Offspring for families with inheritable genetic disordersdisorders

Add genetic engineering for designer Add genetic engineering for designer babiesbabies

Raise the dead [see handout] Raise the dead [see handout]

The Legal LandscapeThe Legal Landscape

Distinction between Distinction between ReproductiveReproductive and and TherapeuticTherapeutic Cloning Cloning

In USA: In USA: Total cloning ban passed the Total cloning ban passed the

House but awaits Senate – House but awaits Senate – President Bush supportPresident Bush support

Federally funded institutions Federally funded institutions must only use existing stem cell linesmust only use existing stem cell lines

UN: Talks suspended for global cloning banUN: Talks suspended for global cloning ban Human cloning Human cloning illegalillegal in South Korea, in South Korea, legallegal in in

ChinaChina

If we ban it here, it will happen somewhere elseIf we ban it here, it will happen somewhere else

Ethics – PatentsEthics – Patents

Patents do not cover “things Patents do not cover “things found in nature” but do found in nature” but do cover “things discovered or cover “things discovered or made by man”made by man” Patent on a genePatent on a gene Patent on technique and Patent on technique and

sometimes its product…sometimes its product…i.e. drug, novel organismi.e. drug, novel organism

Patent on transgenic organism Patent on transgenic organism containing human genescontaining human genes

Patent on a human clone? Patent on a human clone?

Ethical ObjectionsEthical Objections

TheologicalTheological Playing God, Taking lifePlaying God, Taking life

TechnicalTechnical Failures and deformities – unsafe (for now)Failures and deformities – unsafe (for now)

Creepy ApplicationsCreepy Applications Parent from beyond the graveParent from beyond the grave Headless organ donorsHeadless organ donors

IdentityIdentity Is clone a distinct person from DNA donor? Is clone a distinct person from DNA donor?

Clones vs. Twins vs. Carbon Clones vs. Twins vs. Carbon CopiesCopies

Donor DNADonor DNA Telomere shorteningTelomere shortening Epigenetics: turning off one Epigenetics: turning off one

copy of every gene (from mom copy of every gene (from mom or dad)or dad)

Surrogate motherSurrogate mother Conditions in the uterusConditions in the uterus Oocyte doing reprogrammingOocyte doing reprogramming Mitochondrial DNAMitochondrial DNA

Nurture – unique upbringing Nurture – unique upbringing environmentenvironment ButtercupButtercup

Old and New Ethical Old and New Ethical DilemmasDilemmas

In Vitro Fertilization (IVF)In Vitro Fertilization (IVF) Accepted by societyAccepted by society

AbortionAbortion Legal, if contestedLegal, if contested

Coming soon… Face / Head Coming soon… Face / Head TransplantsTransplants Similar identity crisis – dates back to Similar identity crisis – dates back to

Descartes (at least)Descartes (at least)

Designer Babies and Designer Babies and Genetic DeterminismGenetic Determinism

Preventive Genetic Engineering Preventive Genetic Engineering Enhancing Enhancing Genetic EngineeringGenetic 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 be looked at as foolhardy to have a

child by normal conception.” child by normal conception.”

Dr. Gregory Stock of UCLADr. Gregory Stock of UCLA The Genetic DivideThe Genetic Divide Eugenics – an advantage for future Eugenics – an advantage for future

goals, not a guarantee…goals, not a guarantee…

ConclusionConclusion Apocalyptic ScenariosApocalyptic Scenarios

Headless organ donorsHeadless organ donors Genetic DivideGenetic Divide Society without menSociety without men

Medical tool … Art Form?Medical tool … Art Form? Educate lawmakers / societyEducate lawmakers / society

If we had cured Beethoven’s depression, If we had cured Beethoven’s depression, would we still have his music? would we still have his music? [What is the nature of human nature?] [What is the nature of human nature?]