The Cloning Debate: Science, Ethics, and the Law Danielle Haller, Jason Saunders, Lori Short, Jesse Warner Cloning: What is it? The production of multiple, exact copies of a single gene, DNA fragment, cell line, or organism. 3 types of cloning technology today: recombinant DNA technology, reproductive cloning, and therapeutic cloning Cloning: A History 1952: Scientists clone frogs from blastula cells, but fail to produce tadpoles from differentiated cells. 1962: John Gurdon claims to clone frogs using the nucleus of an adult intestinal cell. Others were unable to reproduce his results, his findings were called into question. 1966: Discovery of which codons specify the amino acids. 1973: E. coli turned into first recombinant DNA organism. 1977-1979: Illmensee claims to have cloned mice. Others fail to clone mammals, deem his work “scientifically worthless.” 1983-1986: Various mammals are successfully cloned from embryonic cells. 1990: Human Genome Project begins. 1996: Dolly is born. 2004: Dr. Hwang Woo Suk claims to have cloned human embryos. His work is not able to be replicated. 2006: Dr. Hwang fired from Seoul University as evidence arises he faked some of his work on stem cells. Recombinant DNA Technology aka DNA cloning, gene cloning, or molecular cloning The gene of interest is cut from the genome using restriction enzymes. It is then joined with a similarly cut DNA molecule, a plasmid. The plasmid is known as the cloning vector. Plasmids are circular molecules found in bacteria that are separate from the bacterium’s normal genome. Plasmids are self-replicating, allowing the new recombinant DNA molecule to produce its gene 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_G enome/publicat/primer/fig11a.html Reproductive Cloning The generation of a new animal that has the same nuclear DNA as a previously existing animal. Artificial Embryo Twinning: A blastomere is induced to split, forming identical twins. Nuclear Somatic Transfer: The nucleus of an adult body (somatic) cell is transferred into an egg which has had its nucleus removed. After treatment to make it begin dividing, the embryo is transplanted into a host uterus. Dolly was created using nuclear somatic transfer. Extremely inefficient, most eggs do not develop into an organism. http://upload.wikimedia.org/wikipedia/commons/thumb/6/6b/Cloning_diagram_english.pn g/300px-Cloning_diagram_english.png Therapeutic Cloning Uses the process of nuclear somatic transfer to create an embryo. However, the embryo is destroyed and harvested for stem cells. Stem cells are undifferentiated and retain the ability to develop into many cell types depending on their potency. Totipotent cells can develop into any tissue in the human body, plus tissues needed for development such as placental cells. Pluripotent cells can develop into almost all cells, but cannot produce a new organism. Therapeutic Cloning Also multipotent and unipotent cells that can only develop into a specific tissue or cell type. These are obviously less useful. These cell cultures are maintained in a “lineage.” Dr. Hwang claimed to have several human stem cell lineages. An embryo must be destroyed, whether it be naturally or artificially created. Can possibly use stem cells to treat cancer, regrow damaged nerve or muscle cells, etc. Due to the controversy stirred by recent events, it is unclear how far science has progressed towards creating and maintaing human stem cell lines. But what about behavior? Genetic manipulation can lead to behavioral manipulation as long as there is a genetic component to behavior. The evidence is strong that many behaviors are at least partly affected by genetic components. First, we are infants in this science. Much of what follows is supposition. We estimate there are 30-35,000 genes in the human genome. We do not agree on what constitutes a “gene,” nor do we know what most genes do. Some genes are pleiotropic, meaning they have multiple effects, sometimes at different stages of life. Genetics and Behavior Aggressiveness, altruism, assertiveness, impulsivity, and persistence have an estimated heritability of >40%. Borderline personality trait disorders have an estimated heritability of ~69%. Including all proteins and neurotransmitter systems, behavioral phenotype is around 50% genetically determined give or take a few wild estimates. Possibilities So, cloning could be used to at least influence some aspects of human behavior. Recombinant organisms could produce a specific gene product to be introduced in therapy. The embryo could be manipulated after fertilization. Therapeutic cloning/gene therapy could alter an organism’s genotype. Possible Benefits of Cloning Genetically-Modified Animals The possibility of xenotransplantation (organ transplantation from 1 species to another) Pig hearts, for example Immuno-suppressed animals Disease-resistant Farm Animals Crops that are disease, insect, and drought resistant Transgenic Animals Allows for the creation of a vast amount of new drug development Lower cost Higher efficiency Infertility Patients Will allow infertility patients to have their own biological child (current infertility treatments are only about 10% effective and very costly both monetarily and mentally on the parents) Will allow parents to have offspring that are free of genetic disease (cystic fibrosis, Huntington’s, etc…) Cosmetic Surgery Plastic surgeries, breast augmentations, reconstructive surgeries would be much safer Doctors will be able to manufacture bone, fat, connective tissue, or cartilage that matches the patients tissues exactly This would prevent problems with silicone leaking or immune disease associated with plastic surgery New Possibilities for Organ Transplants Organs, such as livers and kidneys, could be cloned These clones would be more successful than current transplants because they are created from the patient’s body and would be free of immune disease reactions Also, immuno-suppressed animals can harvest organs for more options Rejuvenation A human’s DNA begins to break down when the baby is about 6 months old Some researchers believe that some of the effects of aging could be reversed in the future with the use of cloning Health Improvement Opportunities Heart Disease- New heart cells can be cloned and injected into areas of damaged heart tissue Defective Genes- The average person has 8 defective genes, which could be replaced by cloning Tay-Sach’s Disease- an autosomal recessive genetic disorder that could use cloning to prevent the expression of the gene for the disorder Spinal Cord Injury Victims- New nerves or spinal cord could be re-grown with cloning (this could combat paralysis and allow quadriplegics the opportunity to walk again) Genetic Testing- Cloning could make it easier to test for as well as to cure genetic diseases Scientific Concerns/Risks Involved in Cloning Extremely High Failure Rate Animal cloning has proven highly unsuccessful Dolly (sheep)- only 20 embryos grew out of over 400 attempts Snuppy- due to the highly complicated reproductive system of dogs, the South Korean team only obtained three pregnancies from more than 1,000 embryo transfers into 123 recipients Kittens have very little success as well Problems During Later Development Out of the 20 sheep embryos that grew, 19 were either stillborn or stopped developing due to birth defects (Dolly was the only survivor out of over 400 attempts) 1 of the 3 puppy embryos that was growing miscarried and 1 died shortly after birth (Snuppy was the only survivor out of over 1,000 attempts) Most clones are born with Large Offspring Syndrome (they are abnormally large) This means they have larger organs, which leads to breathing, blood flow, and other problems Abnormal Gene Expression Direct comparison of gene expression profiles of more than 10,000 genes showed that for both donor cell types approximately 4% of the expressed genes in the NT placentas differed dramatically in expression levels from those in controls and that the majority of abnormally expressed genes were common to both types of clones This study done by MIT on mice also showed an abnormal gene expression in the livers of cloned mice The clones may express different amounts of different genes than normal humans or animals at different times Telomeric Differences As cells divide, their chromosomes get shorter because their telomeres shrink each time If the transferred nucleus is older, telomeres could be shorter than normal in the clones produced Dolly had shorter than normal telomeres Scientists do not know the ramifications of differences in telomeric length Is Cloning Ethical? Yes or No? What do you think? Aspects of Ethics Nonmaleficence (Doing No Harm) Beneficence (Doing Good) Autonomy Justice Formal Material Does Cloning Maintain NonMaleficence? Risk factors involved Mother/Surrogate, even Clone High percentage of animal clones have not implanted or gestated due to genetic abnormalities Reports of congenital malformation To date 5% of cloned animals live births Paul Billings, co-founder of GeneSage, says that Cloning is not safe , Cloning is not medically necessary, Cloning could not be delivered in an equitable manner Billings has also said that stem cell therapies have been “wildly oversold” http://www.genesage.com/index.html Oldest clone to date lived for 5 years Premature aging Immuno-failures Copying an aged cell (Dolly) Dolly developed arthritis very early on Cells being cloned may develop genetic mutations very early on Recessive traits could be phased out Recessive traits critical to evolution Allele extinction can occur Lack of alleles mean less diversity Does cloning maintain Beneficence Improve the quality of life Can avoid defects that occur naturally Preserve and perpetuate good genes like intelligence, physical attributes, and physical skills Allows infertile couples to have children Also gives same sex couples ability to have children In both cases the offspring can have traits from each parent Ideal transplant donors for terminally ill Guaranteed match for specific blood type and DNA match Would ensure organs won’t be rejected Could replace a loved one who died prematurely You are clones Autonomy of Cloning Does the clone consent to exist They could be used and abused DNA could be used without consent, living or dead to make a clone They would be property in most cases Expectations to live up to Justice Formal Cloning is very expensive Rich would benefit, cloning would only be available to them Superior, genetically altered race vs. normal, natural race Clone won’t stand next to humans as equal, they’re created, property Billings says we need to work to better the situation of the poor so that access to therapies is improved Material Should the government fund research Currently USA is not funding any new research Future of cloning is international Dolly was cloned in Scotland Should healthcare help lower the cost for people with terminal illnesses Billings favors the “go slow approach”, until the therapies are proven affective Legal Aspects & Issues Past Legal Standards Abortion is legal… why wouldn’t cloning be the same? Diamond v. Chakrabarty Question: Is the man-made creation of a live organism patentable? Answer: – Yes. “In a 5-to-4 decision, the Court explained that a live artificially- engineered microorganism is patentable. The creation of a bacterium that is not found anywhere in nature, constitutes a patentable "manufacture" or "composition of matter.” Moreover, the bacterium's man-made ability to break down crude oil makes it very useful. ” * – What does this mean for future precedence? *source was http://www.oyez.org/oyez/resource/case/1125 Weldon Amendment Proposed by Representative Dave Weldon Passed in the House and moved to the Senate in 2003, making it illegal to patent a human organism, including a cloned one. Big step for Pro-Life supporters •Wording is vague for “human organism”… what could this mean? California Proposition 71 2004- Regulations allowing $300 million per year for 10 years on embryonic and adult stem cell research was “approved” by the voters Created the California Institute for Regenerative Medicine Independent facility that is awarded state grant money Proposition 71 This could be seen as a means to go around a federal funding ban on new embryonic stem cell research. 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 Acts 2001- Initial attempt 2003- Passed in the House and placed on the Senate Calendar Amendment to Title 18 to the United States Code, which defines terms and calls for financial review 2005- Senate Proposed Amendment to the Public Health Services Act, which makes definitions more clear Also calls for a determination if new medical technologies are acceptable. Current Legal Standards State Human Cloning Laws The Human Cloning Prohibition Acts of 2001, 2003 & 2005 are currently being heavily debated in Congress– no doubt there will be many more… will government give in? Arguments on each side Supporters of Pro-Life Supporters of medical research Future Legal Considerations The fight to defend and protect the cloning process is a two sided battle Who is really fighting for the overall legal rights of people? Pro-life for the legal rights of cloned embryos? Pro-research for the legal rights of ill people that are currently dieing? • Needs to be a compelling state interest in order to ban cloning. Will this ever be realistic? Thank you!