The Cloning Debate: The Cloning Debate: Science, Ethics, and the Science, Ethics, and the

LawLawDanielle Haller, Jason Saunders, Danielle Haller, Jason Saunders,

Lori Short, Jesse WarnerLori Short, Jesse Warner

Cloning: What is it?Cloning: What is it?

The production of multiple, exact copies of The production of multiple, exact copies of a single gene, DNA fragment, cell line, or a single gene, DNA fragment, cell line, or organism.organism.

3 types of cloning technology today: 3 types of cloning technology today: recombinant DNA technology, recombinant DNA technology, reproductive cloning, and therapeutic reproductive cloning, and therapeutic cloningcloning

Cloning: A HistoryCloning: A History 19521952: Scientists clone frogs from blastula cells, but fail to : Scientists clone frogs from blastula cells, but fail to

produce tadpoles from differentiated cells.produce tadpoles from differentiated cells. 19621962: John Gurdon claims to clone frogs using the nucleus : John Gurdon claims to clone frogs using the nucleus

of an adult intestinal cell. Others were unable to reproduce of an adult intestinal cell. Others were unable to reproduce his results, his findings were called into question.his results, his findings were called into question.

19661966: Discovery of which codons specify the amino acids.: Discovery of which codons specify the amino acids. 19731973: : E. coliE. coli turned into first recombinant DNA organism. turned into first recombinant DNA organism. 1977-19791977-1979: Illmensee claims to have cloned mice. Others : Illmensee claims to have cloned mice. Others

fail to clone mammals, deem his work “scientifically fail to clone mammals, deem his work “scientifically worthless.”worthless.”

1983-19861983-1986: Various mammals are successfully cloned from : Various mammals are successfully cloned from embryonic cells.embryonic cells.

19901990: Human Genome Project begins.: Human Genome Project begins. 19961996: Dolly is born.: Dolly is born. 20042004: Dr. Hwang Woo Suk claims to have cloned human : Dr. Hwang Woo Suk claims to have cloned human

embryos. His work is not able to be replicated.embryos. His work is not able to be replicated. 20062006: Dr. Hwang fired from Seoul University as evidence : Dr. Hwang fired from Seoul University as evidence

arises he faked some of his work on stem cells.arises he faked some of his work on stem cells.

Recombinant DNA TechnologyRecombinant DNA Technology aka DNA cloning, gene cloning, or molecular cloning aka DNA cloning, gene cloning, or molecular cloning

The gene of interest is cut from the genome The gene of interest is cut from the genome using restriction enzymes.using restriction enzymes.

It is then joined with a similarly cut DNA It is then joined with a similarly cut DNA molecule, a plasmid. The plasmid is known as molecule, a plasmid. The plasmid is known as the cloning vector.the cloning vector.

Plasmids are circular molecules found in Plasmids are circular molecules found in bacteria that are separate from the bacterium’s bacteria that are separate from the bacterium’s normal genome.normal genome.

Plasmids are self-replicating, allowing the new Plasmids are self-replicating, allowing the new recombinant DNA molecule to produce its gene recombinant DNA molecule to produce its gene product in its new environment.product in its new environment.

•Plasmids are not the only cloning vectors that can be used, but they are very common.

•Each vector has a limitation to the size (in base pairs) of the DNA fragment that can be cloned.

•This technology has been used since the 1970s; it is fairly common practice in molecular biology labs today.

http://www.ornl.gov/sci/techresources/Human_Genome/publicat/primer/fig11a.html

Reproductive CloningReproductive Cloning

The generation of a new animal that has the same The generation of a new animal that has the same nuclear DNA as a previously existing animal.nuclear DNA as a previously existing animal.

Artificial Embryo TwinningArtificial Embryo Twinning: A blastomere is induced to : A blastomere is induced to split, forming identical twins.split, forming identical twins.

Nuclear Somatic TransferNuclear Somatic Transfer: The nucleus of an adult : The nucleus of an adult body (somatic) cell is transferred into an egg which body (somatic) cell is transferred into an egg which has had its nucleus removed. After treatment to has had its nucleus removed. After treatment to make it begin dividing, the embryo is transplanted make it begin dividing, the embryo is transplanted into a host uterus.into a host uterus.

Dolly was created using nuclear somatic transfer.Dolly was created using nuclear somatic transfer. Extremely inefficient, most eggs do not develop into Extremely inefficient, most eggs do not develop into

an organism.an organism.

http://upload.wikimedia.org/wikipedia/commons/thumb/6/6b/Cloning_diagram_english.png/300px-Cloning_diagram_english.png

Therapeutic CloningTherapeutic Cloning

Uses the process of nuclear somatic transfer to create Uses the process of nuclear somatic transfer to create an embryo. an embryo.

However, the embryo is destroyed and harvested for However, the embryo is destroyed and harvested for stem cells.stem cells.

Stem cells are undifferentiated and retain the ability to Stem cells are undifferentiated and retain the ability to develop into many cell types depending on their develop into many cell types depending on their potencypotency..

TotipotentTotipotent cells can develop into any tissue in the human cells can develop into any tissue in the human body, plus tissues needed for development such as body, plus tissues needed for development such as placental cells.placental cells.

PluripotentPluripotent cells can develop into almost all cells, but cells can develop into almost all cells, but cannot produce a new organism.cannot produce a new organism.

Therapeutic CloningTherapeutic Cloning Also multipotent and unipotent cells that can only Also multipotent and unipotent cells that can only

develop into a specific tissue or cell type. These are develop into a specific tissue or cell type. These are obviously less useful.obviously less useful.

These cell cultures are maintained in a “lineage.” Dr. These cell cultures are maintained in a “lineage.” Dr. Hwang claimed to have several human stem cell Hwang claimed to have several human stem cell lineages.lineages.

An embryo must be destroyed, whether it be naturally or An embryo must be destroyed, whether it be naturally or artificially created. artificially created.

Can possibly use stem cells to treat cancer, regrow Can possibly use stem cells to treat cancer, regrow damaged nerve or muscle cells, etc.damaged nerve or muscle cells, etc.

Due to the controversy stirred by recent events, it is Due to the controversy stirred by recent events, it is unclear how far science has progressed towards unclear how far science has progressed towards creating and maintaing human stem cell lines.creating and maintaing human stem cell lines.

But what about behavior?But what about behavior?

Genetic manipulation can lead to behavioral Genetic manipulation can lead to behavioral manipulation as long as there is a genetic manipulation as long as there is a genetic component to behavior.component to behavior.

The evidence is strong that many behaviors are The evidence is strong that many behaviors are at least partly affected by genetic components. at least partly affected by genetic components.

First, we are infants in this science. Much of First, we are infants in this science. Much of what follows is supposition. We estimate there what follows is supposition. We estimate there are 30-35,000 genes in the human genome. We are 30-35,000 genes in the human genome. We do not agree on what constitutes a “gene,” nor do not agree on what constitutes a “gene,” nor do we know what most genes do. Some genes do we know what most genes do. Some genes are pleiotropic, meaning they have multiple are pleiotropic, meaning they have multiple effects, sometimes at different stages of life.effects, sometimes at different stages of life.

Genetics and BehaviorGenetics and Behavior

Aggressiveness, altruism, assertiveness, Aggressiveness, altruism, assertiveness, impulsivity, and persistence have an estimated impulsivity, and persistence have an estimated heritability of >40%.heritability of >40%.

Borderline personality trait disorders have an Borderline personality trait disorders have an estimated heritability of ~69%.estimated heritability of ~69%.

Including all proteins and neurotransmitter Including all proteins and neurotransmitter systems, behavioral phenotype is around systems, behavioral phenotype is around 50% genetically determined give or take a 50% genetically determined give or take a few wild estimates.few wild estimates.

PossibilitiesPossibilities

So, cloning could be used to at least influence So, cloning could be used to at least influence some aspects of human behavior. some aspects of human behavior.

Recombinant organisms could produce a Recombinant organisms could produce a specific gene product to be introduced in specific gene product to be introduced in therapy.therapy.

The embryo could be manipulated after The embryo could be manipulated after fertilization.fertilization.

Therapeutic cloning/gene therapy could alter an Therapeutic cloning/gene therapy could alter an organism’s genotype.organism’s genotype.

Possible Benefits of CloningPossible Benefits of Cloning

The possibility of xenotransplantation The possibility of xenotransplantation (organ transplantation from 1 species to (organ transplantation from 1 species to another)another) Pig hearts, for example Pig hearts, for example

Immuno-suppressed animalsImmuno-suppressed animals Disease-resistant Farm AnimalsDisease-resistant Farm Animals Crops that are disease, insect, and Crops that are disease, insect, and

drought resistantdrought resistant

Genetically-Modified AnimalsGenetically-Modified Animals

Transgenic AnimalsTransgenic Animals

Allows for the creation of a vast amount of Allows for the creation of a vast amount of new drug developmentnew drug development

Lower costLower costHigher efficiencyHigher efficiency

Infertility PatientsInfertility Patients

Will allow infertility patients to have their Will allow infertility patients to have their own biological child (current infertility own biological child (current infertility treatments are only about 10% effective treatments are only about 10% effective and very costly both monetarily and and very costly both monetarily and mentally on the parents)mentally on the parents)

Will allow parents to have offspring that Will allow parents to have offspring that are free of genetic disease (cystic fibrosis, are free of genetic disease (cystic fibrosis, Huntington’s, etc…) Huntington’s, etc…)

Cosmetic SurgeryCosmetic Surgery

Plastic surgeries, Plastic surgeries, breast breast augmentations, augmentations, reconstructive reconstructive surgeries would be surgeries would be much safer much safer

Doctors will be able to Doctors will be able to manufacture bone, manufacture bone, fat, connective tissue, fat, connective tissue, or cartilage that or cartilage that matches the patients matches the patients tissues exactly tissues exactly

This would prevent This would prevent problems with silicone problems with silicone leaking or immune leaking or immune disease associated disease associated with plastic surgerywith plastic surgery

New Possibilities for Organ New Possibilities for Organ TransplantsTransplants

Organs, such as livers and kidneys, could Organs, such as livers and kidneys, could be clonedbe cloned

These clones would be more successful These clones would be more successful than current transplants because they are than current transplants because they are created from the patient’s body and would created from the patient’s body and would be free of immune disease reactionsbe free of immune disease reactions

Also, immuno-suppressed animals can Also, immuno-suppressed animals can harvest organs for more optionsharvest organs for more options

RejuvenationRejuvenation

A human’s DNA begins to break down A human’s DNA begins to break down when the baby is about 6 months oldwhen the baby is about 6 months old

Some researchers believe that some of Some researchers believe that some of the effects of aging could be reversed in the effects of aging could be reversed in the future with the use of cloningthe future with the use of cloning

Health Improvement OpportunitiesHealth Improvement Opportunities

Heart Disease- New heart cells can be cloned and Heart Disease- New heart cells can be cloned and injected into areas of damaged heart tissueinjected into areas of damaged heart tissue

Defective Genes- The average person has 8 defective Defective Genes- The average person has 8 defective genes, which could be replaced by cloninggenes, which could be replaced by cloning

Tay-Sach’s Disease- an autosomal recessive genetic Tay-Sach’s Disease- an autosomal recessive genetic disorder that could use cloning to prevent the expression disorder that could use cloning to prevent the expression of the gene for the disorderof the gene for the disorder

Spinal Cord Injury Victims- New nerves or spinal cord Spinal Cord Injury Victims- New nerves or spinal cord could be re-grown with cloning (this could combat could be re-grown with cloning (this could combat paralysis and allow quadriplegics the opportunity to walk paralysis and allow quadriplegics the opportunity to walk again)again)

Genetic Testing- Cloning could make it easier to test for Genetic Testing- Cloning could make it easier to test for as well as to cure genetic diseasesas well as to cure genetic diseases

Scientific Concerns/Risks Scientific Concerns/Risks Involved in CloningInvolved in Cloning

Extremely High Failure RateExtremely High Failure Rate

Animal cloning has proven highly unsuccessfulAnimal cloning has proven highly unsuccessful Dolly (sheep)- only 20 embryos grew out of over Dolly (sheep)- only 20 embryos grew out of over

400 attempts400 attempts Snuppy- due to the highly complicated Snuppy- due to the highly complicated

reproductive system of dogs, the South Korean reproductive system of dogs, the South Korean team only obtained three pregnancies from more team only obtained three pregnancies from more than 1,000 embryo transfers into 123 recipients than 1,000 embryo transfers into 123 recipients

Kittens have very little success as wellKittens have very little success as well

Problems During Later Problems During Later DevelopmentDevelopment

Out of the 20 sheep embryos that grew, 19 were Out of the 20 sheep embryos that grew, 19 were either stillborn or stopped developing due to either stillborn or stopped developing due to birth defects (Dolly was the only survivor out of birth defects (Dolly was the only survivor out of over 400 attempts)over 400 attempts)

1 of the 3 puppy embryos that was growing 1 of the 3 puppy embryos that was growing miscarried and 1 died shortly after birth (Snuppy miscarried and 1 died shortly after birth (Snuppy was the only survivor out of over 1,000 attempts) was the only survivor out of over 1,000 attempts)

Most clones are born with Large Offspring Most clones are born with Large Offspring Syndrome (they are abnormally large) Syndrome (they are abnormally large) This This means they have larger organs, which leads to means they have larger organs, which leads to breathing, blood flow, and other problems breathing, blood flow, and other problems

Abnormal Gene ExpressionAbnormal Gene Expression

Direct comparison of gene expression profiles of more Direct comparison of gene expression profiles of more than 10,000 genes showed that for both donor cell types than 10,000 genes showed that for both donor cell types approximately 4% of the expressed genes in the NT approximately 4% of the expressed genes in the NT placentas differed dramatically in expression levels from placentas differed dramatically in expression levels from those in controls and that the majority of abnormally those in controls and that the majority of abnormally expressed genes were common to both types of clones expressed genes were common to both types of clones

This study done by MIT on mice also showed an This study done by MIT on mice also showed an abnormal gene expression in the livers of cloned miceabnormal gene expression in the livers of cloned mice

The clones may express different amounts of different The clones may express different amounts of different genes than normal humans or animals at different timesgenes than normal humans or animals at different times

Telomeric DifferencesTelomeric Differences

As cells divide, their chromosomes get As cells divide, their chromosomes get shorter because their telomeres shrink shorter because their telomeres shrink each timeeach time

If the transferred nucleus is older, If the transferred nucleus is older, telomeres could be shorter than normal in telomeres could be shorter than normal in the clones producedthe clones produced

Dolly had shorter than normal telomeresDolly had shorter than normal telomeres Scientists do not know the ramifications of Scientists do not know the ramifications of

differences in telomeric lengthdifferences in telomeric length

Is Cloning Ethical?Is Cloning Ethical?

Yes or No?Yes or No?

What do you think?What do you think?

Aspects of EthicsAspects of Ethics

Nonmaleficence (Doing No Harm)Nonmaleficence (Doing No Harm) Beneficence (Doing Good)Beneficence (Doing Good) AutonomyAutonomy JusticeJustice

FormalFormal MaterialMaterial

Does Cloning Maintain Non-Does Cloning Maintain Non-Maleficence?Maleficence?

Risk factors involved Risk factors involved Mother/Surrogate, even CloneMother/Surrogate, even Clone High percentage of animal clones have not High percentage of animal clones have not

implanted or gestated due to genetic implanted or gestated due to genetic abnormalitiesabnormalities

Reports of congenital malformationReports of congenital malformation To date 5% of cloned animals live birthsTo date 5% of cloned animals live births

Paul Billings, co-founder of GeneSage, Paul Billings, co-founder of GeneSage, says that Cloning is not safe , Cloning is says that Cloning is not safe , Cloning is not medically necessary, Cloning could not medically necessary, Cloning could not be delivered in an equitable mannernot be delivered in an equitable manner

Billings has also said that stem cell Billings has also said that stem cell therapies have been “wildly oversold”therapies have been “wildly oversold”

http://http://www.genesage.com/index.htmlwww.genesage.com/index.html

Oldest clone to date lived for 5 years Oldest clone to date lived for 5 years Premature agingPremature aging Immuno-failuresImmuno-failures Copying an aged cell (Dolly)Copying an aged cell (Dolly) Dolly developed arthritis very early onDolly developed arthritis very early on Cells being cloned may develop genetic Cells being cloned may develop genetic

mutations very early onmutations very early on

Recessive traits could be phased outRecessive traits could be phased out Recessive traits critical to evolutionRecessive traits critical to evolution Allele extinction can occurAllele extinction can occur Lack of alleles mean less diversityLack of alleles mean less diversity

Does cloning maintain Does cloning maintain BeneficenceBeneficence

Improve the quality of life Improve the quality of life Can avoid defects that occur naturallyCan avoid defects that occur naturally Preserve and perpetuate good genes like Preserve and perpetuate good genes like

intelligence, physical attributes, and intelligence, physical attributes, and physical skillsphysical skills

Allows infertile couples to have childrenAllows infertile couples to have children Also gives same sex couples ability to Also gives same sex couples ability to

have children have children In both cases the offspring can have traits In both cases the offspring can have traits

from each parentfrom each parent

Ideal transplant donors for terminally illIdeal transplant donors for terminally ill Guaranteed match for specific blood type Guaranteed match for specific blood type

and DNA matchand DNA match Would ensure organs won’t be rejectedWould ensure organs won’t be rejected Could replace a loved one who died Could replace a loved one who died

prematurely prematurely You are clonesYou are clones

Autonomy of CloningAutonomy of Cloning

Does the clone consent to existDoes the clone consent to exist They could be used and abusedThey could be used and abused DNA could be used without consent, living DNA could be used without consent, living

or dead to make a cloneor dead to make a clone They would be property in most casesThey would be property in most cases Expectations to live up toExpectations to live up to

JusticeJustice

FormalFormal Cloning is very expensiveCloning is very expensive Rich would benefit, cloning would only be available to Rich would benefit, cloning would only be available to

themthem Superior, genetically altered race vs. normal, natural Superior, genetically altered race vs. normal, natural

racerace Clone won’t stand next to humans as equal, they’re Clone won’t stand next to humans as equal, they’re

created, propertycreated, property Billings says we need to work to better the situation of Billings says we need to work to better the situation of

the poor so that access to therapies is improvedthe poor so that access to therapies is improved

MaterialMaterial Should the government fund researchShould the government fund research Currently USA is not funding any new researchCurrently USA is not funding any new research Future of cloning is internationalFuture of cloning is international Dolly was cloned in ScotlandDolly was cloned in Scotland Should healthcare help lower the cost for people with Should healthcare help lower the cost for people with

terminal illnessesterminal illnesses Billings favors the “go slow approach”, until the Billings favors the “go slow approach”, until the

therapies are proven affectivetherapies are proven affective

Legal Aspects & IssuesLegal Aspects & Issues

Past Legal StandardsPast Legal Standards

Abortion is legal… why wouldn’t cloning be the same?Abortion is legal… why wouldn’t cloning be the same? Diamond v. ChakrabartyDiamond v. Chakrabarty

Question: Is the man-made creation of a live organism Question: Is the man-made creation of a live organism patentable?patentable?

Answer:Answer:– Yes. “In a 5-to-4 decision, the Court explained that a live artificially-Yes. “In a 5-to-4 decision, the Court explained that a live artificially-

engineered microorganism is patentable. The creation of a engineered microorganism is patentable. The creation of a bacterium that is not found anywhere in nature, constitutes a bacterium that is not found anywhere in nature, constitutes a patentable "manufacture" or "composition of matter.” Moreover, the patentable "manufacture" or "composition of matter.” Moreover, the bacterium's man-made ability to break down crude oil makes it very bacterium's man-made ability to break down crude oil makes it very useful. ” *useful. ” *

– What does this mean for future precedence?What does this mean for future precedence?

*source was http://www.oyez.org/oyez/resource/case/1125

Weldon AmendmentWeldon Amendment

Proposed by Representative Dave WeldonProposed by Representative Dave Weldon Passed in the House and moved to the Passed in the House and moved to the

Senate in 2003, making it illegal to patent a Senate in 2003, making it illegal to patent a human organism, including a cloned one.human organism, including a cloned one. Big step for Pro-Life supportersBig step for Pro-Life supporters

•Wording is vague for “human organism”… what could this mean?

California Proposition 71California Proposition 71

2004- Regulations allowing $300 million 2004- Regulations allowing $300 million per year for 10 years on embryonic and per year for 10 years on embryonic and adult stem cell research was “approved” adult stem cell research was “approved” by the votersby the voters

Created the California Institute for Created the California Institute for Regenerative MedicineRegenerative Medicine Independent facility that is awarded state Independent facility that is awarded state

grant moneygrant money

Proposition 71Proposition 71

This could be seen as a means to go This could be seen as a means to go around a federal funding ban on new around a federal funding ban on new embryonic stem cell research.embryonic stem cell research. Is this ok?Is this ok?

•Could be a means to cure Alzheimer’s disease or even diabetes… is it worth the legal risks and ethical compromises?

Human Cloning Prohibition ActsHuman Cloning Prohibition Acts

2001- Initial attempt2001- Initial attempt 2003- Passed in the House and placed on the 2003- Passed in the House and placed on the

Senate CalendarSenate Calendar Amendment to Title 18 to the United States Code, Amendment to Title 18 to the United States Code,

which defines terms and calls for financial reviewwhich defines terms and calls for financial review

2005- Senate Proposed2005- Senate Proposed Amendment to the Public Health Services Act, which Amendment to the Public Health Services Act, which

makes definitions more clearmakes definitions more clear Also calls for a determination if new medical Also calls for a determination if new medical

technologies are acceptable.technologies are acceptable.

Current Legal StandardsCurrent Legal Standards

State Human Cloning LawsState Human Cloning Laws The Human Cloning Prohibition Acts of The Human Cloning Prohibition Acts of

2001, 2003 & 2005 are currently being 2001, 2003 & 2005 are currently being heavily debated in Congress– no doubt heavily debated in Congress– no doubt there will be many more… will government there will be many more… will government give in?give in?

Arguments on each sideArguments on each side Supporters of Pro-LifeSupporters of Pro-Life Supporters of medical researchSupporters of medical research

Future Legal ConsiderationsFuture Legal Considerations

The fight to defend and protect the cloning The fight to defend and protect the cloning process is a two sided battleprocess is a two sided battle Who is really fighting for the overall legal Who is really fighting for the overall legal

rights of people?rights of people? Pro-life for the legal rights of cloned embryos?Pro-life for the legal rights of cloned embryos? Pro-research for the legal rights of ill people that Pro-research for the legal rights of ill people that

are currently dieing?are currently dieing?

• Needs to be a compelling state interest in order to ban cloning. Will this ever be realistic?

Thank you!Thank you!