Unit 7: the human practice of science: cloning

Types of cloning: Gene cloning (the same technology as gene therapy) Therapeutic cloning (to make embryonic stem cells) Reproductive cloning (to make identical organisms)

Gene cloning (the same technology as gene therapy) Researchers routinely use cloning techniques to make copies of genes that they wish to study. The procedure consists of inserting a gene from one organism, often referred to as "foreign DNA," into the genetic material of a carrier called a vector. Examples of vectors include bacteria, yeast cells, viruses or plasmids, which are small DNA circles carried by bacteria. After the gene is inserted, the vector is placed in laboratory conditions that prompt it to multiply, resulting in the gene being copied many times over.

Gene cloning (the same technology as gene therapy) What factors have kept gene therapy from becoming an effective treatment for genetic disease? Short-lived nature of gene therapy - Before gene therapy can become a permanent cure for any condition, the therapeutic DNA introduced into target cells must remain functional and the cells containing the therapeutic DNA must be long-lived and stable. Problems with integrating therapeutic DNA into the genome and the rapidly dividing nature of many cells prevent gene therapy from achieving any long-term benefits. Patients will have to undergo multiple rounds of gene therapy. Immune response - Anytime a foreign object is introduced into human tissues, the immune system is designed to attack the invader. Furthermore, the immune system's enhanced response to invaders it has seen before makes it difficult for gene therapy to be repeated in patients. Problems with viral vectors - Viruses, while the carrier of choice in most gene therapy studies, present a variety of potential problems to the patient --toxicity, immune and inflammatory responses, and gene control and targeting issues. In addition, there is always the fear that the viral vector, once inside the patient, may recover its ability to cause disease. Multigene disorders - Conditions or disorders that arise from mutations in a single gene are the best candidates for gene therapy. Unfortunately, some the most commonly occurring disorders, such as heart disease, high blood pressure, Alzheimer's disease, arthritis, and diabetes, are caused by the combined effects of variations in many genes. http://www.ornl.gov/sci/techresources/Human_Genome/medicine/genetherapy.shtml#factors

Therapeutic cloning (to make embryonic stem cells) From individual whose cells are being cloned Contains DNA Pluripotent stem cells: may theoretically become any cell type (pancreas, liver, lung, heart, neuron, etc.) E http://commons.wikimedia.org/wiki/File:Cloning_diagram_english.svg

Reproductive cloning (to make identical organisms) From individual whose cells are being cloned Contains DNA E http://commons.wikimedia.org/wiki/File:Cloning_diagram_english.svg

Reproductive/therapeutic cloning (to make identical organisms/stem cells) 1. What are some of the great benefits to being able to create genetic clones? http://science-education.nih.gov/home2.nsf/Educational+ResourcesTopicsGenetics/BC5086E34E4DBA0085256CCD006F01CB

Reproductive/therapeutic cloning (to make identical organisms/stem cells) 1. What are some of the great benefits to being able to create genetic clones? Applications in regenerative medicine: recent breakthroughs for diabetes, neurodegenerative diseases (Parkinsons), skin replacement (burn patients), cardiomyocytes (heart attacks). Therapeutic cloning constitutes a promising tool in tissue engineering and might offer the possibility of synthesizing organs de novo, which would solve the problems of immune rejection and organ shortage for transplantation. Generating animal models of human diseases. Patient-specific treatment regimens could be developed in animals containing the patient’s own cells (cancer cells, etc.) Cancer diagnosis. A patient’s cancer cells could be cloned and studied to determine how the cells became cancerous (the molecular mechanism). Therapeutic cloning in the the context of gene therapy. Cloned cells could be injected back into patient to address genetic diseases. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2323472/ http://www.cloningresources.com/Archives/September_2010.asp

Reproductive/therapeutic cloning (to make identical organisms/stem cells) 2. What are some of the great dangers?

Reproductive/therapeutic cloning (to make identical organisms/stem cells) 2. What are some of the great dangers? Oocyte (egg cells) availability: regulations and ethical concerns. A major roadblock in the feasibility of human therapeutic cloning is the low availability of oocytes for research purposes. Currently, due to low SCNT efficiency, it is estimated that 280 human oocytes would be needed in order to derive one observe patient-specific ntESC line. Mitochondrial heteroplasmy. Mitochondrial DNA in the oocyte can cause immune rejection of the cells. Mitochondrial DNA is DNA in the mitochondria, not in the nucleus. Transfer of animal contaminants. This could occur if non-human oocytes are used. Tumorgenesis and spontaneous differentiation. NtESC are subjected to the same tumorigenicity potential as wild-type stem cells. The formation of teratomas after transplantation is due to co-purification of pluripotent stem cells along with the wanted differentiated cells. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2323472/

Reproductive/therapeutic cloning (to make identical organisms/stem cells) 2. What are some of the great dangers? Ethical Considerations Destruction of IVF. Therapeutic cloning and stem cell research stir an ethical controversy due to the source of embryonic stem cells, taken from aborted fetuses, unutilized zygotes (49) and embryos morphologically incapable of in utero implantation, the latter representing 60% of all embryos (50) created through IVF. Moral status of the IVF embryo and the argument of potential. The main ethical roadblock against therapeutic cloning is the destruction of the generated embryos in order to collect cells that would further be differentiated in vitro. Embryo destruction is viewed as morally objectionable by the Pro-life partisans because they grant the early embryo potential for personhood following development to term. Knowing that only 1 to 2 % of cloned mice produce viable organisms, the probability of producing a viable cloned human embryo is even slimmer. However, the detractors of research using embryos would argue that the potential for personhood ought not to be granted on the basis of probability because a minority - one out of three -of zygotes conceived by natural means might implant in utero and be carried to term. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2323472/

Reproductive/therapeutic cloning (to make identical organisms/stem cells) 3. If you were in charge of the nation’s cloning policy, what rules would you establish and why? The FDA has regulatory jurisdiction over clinical research using cloning technology in humans, and the National Institutes of Health Human Embryo Research Panel has developed a science policy report. A policy brief on human cloning with a summary of both sides of the legislative debate is provided by the American Association for the Advancement of Science The Dickey-Wicker Act of 1996 prohibited use of taxpayer dollars in any research that destroys a human embryo. The Human Cloning Prohibition Act of 2007 (H.R. 2560) was introduced on June 5, 2007 and defeated in the House. Republicans called it a "phony ban" that does not prohibit cloning but only the implanation of a clone into a woman. The Human Cloning Prohibition Act of 2003 (H.R.234) passed the House of Representatives on 27 Feb, 2003 but was not acted upon by the Senate. This bill is almost identical to the Human Cloning Prohibition Act of 2001 (H.R. 2505) which was passed in the House on 31 July, 2001 but which also was not acted upon by the Senate. The National Bioethics Advisory Committee on June 9, 1997 submitted a full report on cloning human beings including several commissioned papers by various experts and addressing scientific, religious, legal, and ethical considerations. This committee was dissolved in October, 2000, and President George W. Bush replaced it by The President's Council on Bioethics. At this point, no new stem cell lines (other than the 21 already available) could be created by cloning. In 2009, President Obama gave an Executive Order expanding stem cell research (to 75 cell lines) and allowing the use of federal funding to support it. In June 2010, US District Judge Royce Lamberth blocked federal funding of stem cell research (which he ruled violoated the Dickey-Wicker act), including projects that were already receiving such funding. Within days, the Justice Department asked a federal judge to lift Lamberth’s restraining order. http://www.aaas.org/spp/cstc/briefs/cloning/index.shtml http://staff.lib.msu.edu/skendall/cloning/laws.htm

Reproductive/therapeutic cloning (to make identical organisms/stem cells) 4. What creature is the most complex creature that should be allowed to be cloned, and why? 5. Should humans be cloned? Why or why not? http://news.bbc.co.uk/2/hi/asia-pacific/4554704.stm