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The Science and Ethics of Stem Cell Research

The Life Sciences Revolution in the News. The Human Genome ProjectGenetically Modified CropsBiological Agents in BioterrorismStem Cell TherapyHuman Cloning. Special edition to celebrate the 50th anniversary of the discovery of DNA: February 17, 2003. The Good, the Bad, and the Ugly. Organization of presentation.

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The Science and Ethics of Stem Cell Research

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    1. The Science and Ethics of Stem Cell Research July 12, 2005 VaBIO Board of Trustees Presenter: Thomas F.Huff, Ph.D. Vice Provost for Life Sciences Virginia Commonwealth University

    2. The Life Sciences Revolution in the News The Human Genome Project Genetically Modified Crops Biological Agents in Bioterrorism Stem Cell Therapy Human Cloning

    3. The Good, the Bad, and the Ugly

    4. Organization of presentation A brief tutorial on stem cells, to include a comparison of embryonic and adult stem cells Relationship of embryonic stem cells to cloning VCU Life Sciences survey of American public attitudes, followed by Research ! America survey Stem Cell Commission of the Virginia General Assembly Summary of stem cell legislation in the States and in the Congress Alternative strategies that may avoid some ethical dilemmas

    5. What are stem cells ?

    6. The Cell The basic unit of biological life is the cell. All biological life is cellular. The specialized cells in the body are derived from stem cells.

    7. Stem Cells Stem cells have two defining attributes: The capacity for self-renewal The ability to differentiate into many many different cell types There are about six classes of stem cells. We will discuss the two most important classes of stem cells: Embryonic stem cells Adult stem cells

    9. Embryonic Stem Cells (ESC)

    10. Embryonic Stem (ES) Cells Derived from the inner cell mass of a blastocyst A blastocyst is a hollow ball of cells formed 4-6 days after a human egg is fertilized.

    11. Embryonic Stem Cells and Embryonic Stem Cell Lines Cell lines are from one separated cells and the daughter cells are alike and grow indefinitely.

    12. Adult Stem Cells

    13. Adult Stem Cells Many adult tissues have stem cells. The most well studied are the blood stem cell (hematopoietic stem cell or HSC used in bone marrow transplants) and the neural stem cell Recently, it was discovered that an adult stem cell from one tissue may act as a stem cell for another tissue, i.e. blood to neural

    14. A VCU example: Mast cells from stem cells Cause allergic disease Grown from stem cells in the bone marrow after enormous complexification We have grown mast cells from mouse embryonic stem cells and from adult hematopoietic stem cells

    15. VCU Life Sciences Survey

    16. Multipotential Adult Progenitor Cell (MAPC) Catherine Verfaillie, Director of University Minnesota Stem Cell Institute, has described cells in the adult bone marrow with very similar properties to embryonic stem cells She has dubbed them multipotent adult progenitor cells or MAPCs. These adult stem cells have high telomerase activity.

    17. Multipotential Adult Progenitor Cell (MAPC) “Have we found the ultimate stem cell? One that can deliver all the benefits of embryonic stem cells without having to destroy a potential human life to save an existing one.”

    19. Quotes on ethical issues “The only reason many lawmakers may have felt compelled to “cross the moral line” in backing ESC research is because they believe it’s the only way to get the full benefits” states Richard Doerflinger of the US conference of Catholic Bishops …so MAPCs open up a whole new arena. “We need to keep all options open” states Arthur Caplan,director of the Center for Bioethics at the University of Pennsylvania. “Many scientists are patenting their discoveries which can hinder widespread use …” so ESC research must continue as well.

    20. Current Clinical Uses of Adult Stem Cells Cancers—Lymphomas, multiple myeloma, leukemias, breast cancer, neuroblastoma, renal cell carcinoma, ovarian cancer Autoimmune diseases—multiple sclerosis, systemic lupus, rheumatoid, arthritis, scleroderma, scleromyxedema, Crohn’s disease Anemias (incl. sickle cell anemia) Immunodeficiencies—including human gene therapy Bone/cartilage deformities—children with osteogenesis imperfecta Corneal scarring-generation of new corneas to restore sight Stroke—neural cell implants in clinical trials Repairing cardiac tissue after heart attack—bone marrow or muscle stem cells from patient Parkinson’s—retinal stem cells, patient’s own neural stem cells, injected growth factors Growth of new blood vessels—e.g., preventing gangrene Gastrointestinal epithelia—regenerate damaged ulcerous tissue Skin—grafts grown from hair follicle stem cells, after plucking a few hairs from patient Wound healing—bone marrow stem cells stimulated skin healing Spinal cord injury—clinical trials currently in Portugal, Italy, S. Korea

    21. Evidence of Plasticity among Adult Stem Cells

    22. Pros and cons of stem cell sources

    23. Conclusions of the NIH Study on Stem Cells “During the next several years, it will be important to compare embryonic stem cells and adult stem cells in terms of their ability to proliferate, differentiate, survive and function after transplant and avoid immune rejection”

    25. Stem Cells and Regenerative Medicine With stem cell therapy (embryonic or adult), there is enormous promise of treating diseases previously thought to be unmanageable

    26. Ethical overlap: Human cloning and stem cells Mike West, chief executive of Advanced Cell Technology of Worcester, Mass says they are trying to use cloning technology to create human embryos for deriving stem cells that would be a perfect match for patients. He describes his work as “the dream of transplant medicine”

    28. Human Cloning Therapeutic versus reproductive cloning

    29. How are embryonic stem cells technically related to cloning ? The two issues are related or not related based on the answer to the following question: “Where did the nucleus come from in the fertilized egg used to make the embryonic stem cell.”

    30. Fertilization versus cloning Fertilization of the egg by the sperm brings together two different sets of DNA to encode for a unique individual. Somatic cell nuclear transfer does not.

    32. Cloning of human embryos: South Korea 2004

    33. VCU Life Sciences Survey Method http://www.vcu.edu/lifesci/centers/cen_lse_surveys.html Fifth Annual VCU Life Sciences Survey Conducted by VCU Center for Public Policy National Telephone Survey of 1002 Randomly-Selected U. S. Adults Data Collected September 14 through 29, 2005 Margin of Error ± 3% at 95% Confidence Level This is the fourth annual VCU Life Sciences Survey. It was sponsored by VCU Life Sciences, Virginia Commonwealth University’s matrix academic organization that integrates the campuses around the life sciences. The survey was conducted by the VCU Center for Public Policy. The sample is a randomly-selected sample of 1004 adults living in the continental U.S. Data collection took place from September 7 through September 17, 2004. Questions answered by the full sample of adults are subject to a sampling error of plus or minus approximately 3 percentage points at the 95 percent level of confidence. This is the fourth annual VCU Life Sciences Survey. It was sponsored by VCU Life Sciences, Virginia Commonwealth University’s matrix academic organization that integrates the campuses around the life sciences. The survey was conducted by the VCU Center for Public Policy. The sample is a randomly-selected sample of 1004 adults living in the continental U.S. Data collection took place from September 7 through September 17, 2004. Questions answered by the full sample of adults are subject to a sampling error of plus or minus approximately 3 percentage points at the 95 percent level of confidence.

    34. VCU Life Sciences Survey 2005 Fifth Annual VCU Life Sciences Survey Overall, a majority of Americans—58 percent—now strongly or somewhat favor embryonic stem cell research, up from 53 percent in the 2004 survey and 47 percent in the 2003 survey. Greatest promise: Embryonic stem cells – 14% Adult stem cells – 7% Other sources (umbilical cord blood) – 37% Continued strong resistance to human coning This is the fourth annual VCU Life Sciences Survey. It was sponsored by VCU Life Sciences, Virginia Commonwealth University’s matrix academic organization that integrates the campuses around the life sciences. The survey was conducted by the VCU Center for Public Policy. The sample is a randomly-selected sample of 1004 adults living in the continental U.S. Data collection took place from September 7 through September 17, 2004. Questions answered by the full sample of adults are subject to a sampling error of plus or minus approximately 3 percentage points at the 95 percent level of confidence. This is the fourth annual VCU Life Sciences Survey. It was sponsored by VCU Life Sciences, Virginia Commonwealth University’s matrix academic organization that integrates the campuses around the life sciences. The survey was conducted by the VCU Center for Public Policy. The sample is a randomly-selected sample of 1004 adults living in the continental U.S. Data collection took place from September 7 through September 17, 2004. Questions answered by the full sample of adults are subject to a sampling error of plus or minus approximately 3 percentage points at the 95 percent level of confidence.

    35. Top 5 Reasons Why People Favor Embryonic Stem Cell Research To prevent and cure disease (25%) To help people with disease (13%) It saves/prolongs life (9%) The potential/benefits (9%) Research/benefits to science (6%) We asked people to tell us why they favored or opposed embryonic stem cell research. Among people who favored embryonic stem cell research, the most frequently mentioned reasons were: To prevent and cure disease, mentioned by 25 percent of those in favor. To help people with disease, mentioned by 13 percent. Because it saves or prolongs life, mentioned by 9 percent. Because of the potential or benefits the research can provide, mentioned by 9 percent. Or because of the research or benefits to science, mentioned by 6 percent. We asked people to tell us why they favored or opposed embryonic stem cell research. Among people who favored embryonic stem cell research, the most frequently mentioned reasons were: To prevent and cure disease, mentioned by 25 percent of those in favor. To help people with disease, mentioned by 13 percent. Because it saves or prolongs life, mentioned by 9 percent. Because of the potential or benefits the research can provide, mentioned by 9 percent. Or because of the research or benefits to science, mentioned by 6 percent.

    36. Top 5 Reasons Why People Oppose Embryonic Stem Cell Research It’s part of a living person (19%) Just think it’s wrong/immoral/pro-life (16%) Against God/religion (11%) It’s from an embryo (10%) We have no business going to that extent (4%) Among people who opposed embryonic stem cell research, the most frequently mentioned reasons were: Because it’s part of a living person, mentioned by 19 percent of those opposed. Because it’s wrong, immoral, or in opposition to a pro-life viewpoint, mentioned by 16 percent. Because it’s against God or religious beliefs, mentioned by 11 percent. Because it’s from an embryo, mentioned by 10 percent. Or simply that we have no business going to that extent, mentioned by 4 percent. Among people who opposed embryonic stem cell research, the most frequently mentioned reasons were: Because it’s part of a living person, mentioned by 19 percent of those opposed. Because it’s wrong, immoral, or in opposition to a pro-life viewpoint, mentioned by 16 percent. Because it’s against God or religious beliefs, mentioned by 11 percent. Because it’s from an embryo, mentioned by 10 percent. Or simply that we have no business going to that extent, mentioned by 4 percent.

    38. Survey Highlights (2004) Objections to Human Cloning Remain Strong Even Under Limited Conditions By a slight majority, more Americans Now Favor Embryonic Stem Cell Research Limited Knowledge of Human Genome Project, but Faith in the Future of Genetic Research An overwhelming majority of Americans (85 percent) believe that science and technology have made society better, but at the same time a majority (72 percent) also believe that science doesn’t pay enough attention to moral values. Among the highlights of the survey are the following: Objections to human cloning remain strong even under limited conditions. More Americans now favor embryonic stem cell research than in the previous years of the survey. Americans continue to see clear benefits of science to society, but they are ambivalent about the role of science in society. There is limited knowledge of the Human Genome Project, but nevertheless, people have faith in the future of genetic research. Americans express concerns about keeping their health information and the results of their genetic testing private. There continues to be a high degree of interest in scientific and medical discoveries. I will now provide some details about each of these highlights.Among the highlights of the survey are the following: Objections to human cloning remain strong even under limited conditions. More Americans now favor embryonic stem cell research than in the previous years of the survey. Americans continue to see clear benefits of science to society, but they are ambivalent about the role of science in society. There is limited knowledge of the Human Genome Project, but nevertheless, people have faith in the future of genetic research. Americans express concerns about keeping their health information and the results of their genetic testing private. There continues to be a high degree of interest in scientific and medical discoveries. I will now provide some details about each of these highlights.

    39. Research! America survey (released July 2005) Six in 10 Americans (58%) say they support using embryonic stem cells in medical research, according to a new national poll by Research!America and PARADE magazine. Three in 10 (29%) are opposed. The poll asked 1,000 adults their views on embryonic stem cell research and the importance of maintaining U.S. leadership in research.

    40. The Other Stem Cell Debate While the objections to stem-cell research have largely revolved around the ethics of using human embryos, there is another debate bubbling to the surface: how ''human'' are chimeric creatures made from human stem cells? Fueling the anxiety has been the lack of coherent regulations in the United States governing the creation of chimeras. The President's Council on Bioethics has twice taken up the issue in recent weeks, and Senator Sam Brownback, the Kansas Republican and outspoken social conservative, has introduced legislation to restrict chimeric experiments. Meanwhile, the National Academy of Sciences is expected to issue guidelines later as part of a widely anticipated report on the proper use of human stem cells.

    41. Important Questions: What features does (a) human life have to have in order to have moral standing, and a right to life in particular ? How much potential efficacy do human embryonic stem cells in regenerative medicine really have ? Is it even possible to stop the inexorable march of knowledge and its technological usage ? How much should we engineer the human germline genome ? Is it eugenics ? Who decides ?

    42. The Law As of August 2002, human cloning is legally permitted in the U.S.. In 2001 the House of Representatives passed the Human Cloning Prohibition Act of 2001, which bans cloning for any purpose (reproductive or research/therapeutic). The Senate has not passed a comparable bill In July 2002, the President’s Council on Bioethics recommended unanimously (17/17) a ban on reproductive cloning. Since 1995, it has been illegal for the federal government to fund any research in which human embryos are created or destroyed. So, human cloning cannot be done with federal funds.

    43. What about Virginia ? House Joint Resolution 588 (2005) Establishing a joint committee to study medical, legal, ethical, and scientific issues related to stem cell research conducted in the Commonwealth. Study. 15 members; 8 legislative, 7 non-legislative Meetings completed by November 30, 2005

    44. Roster of Members The Honorable Robert G. Marshall (Chair) The Honorable Kenneth C. Alexander The Honorable Kathy J. Byron The Honorable David A. Nutter The Honorable John M. O'Bannon, III The Honorable Richard L. Saslaw (Vice-Chair) The Honorable Janet D. Howell The Honorable Harry B. Blevins Dr. Paul J. Hoehner (UVa) Jacob F. Mayer, Jr. Ph.D (EVMS) Kelly Hollowell, JD, Ph.D. Eileen M. Hall, RN Thomas F. Huff, Ph.D. (VCU) Kris Gulden Dr. Dennis Fisher

    45. Schedule of Meetings Tuesday, June 21, 2005 - 2:00 p.m. Wednesday, August 17, 2005 - 10:00 a.m. Wednesday, September 21, 2005 - 10:00 a.m Tuesday, November 15, 2005 - 2:00 p.m. Comments about final meeting last week

    46. State Landscape to Date

    49. NAS Support for Stem Cell Research

    50. Late Breaking news in the Congress Arlen Specter, chairman of the Health and Human Services Appropriations Subcommittee, has invited Dr. Robert Lanza, of the Worcester, Mass.-based Advanced Cell Technology Inc., to testify next week about work his company has been conducting that removes cells from mouse embryos without harming them -- cells that could potentially be cultivated as embryonic stems cells useful for research.

    51. Some Web Sites National Bioethics Advisory Commission Reports: http://bioethics.georgetown.edu/nbac/pubs.html Research Involving Human Biological Materials: Ethical Issues and Policy Guidance (1999): Ethical Issues in Human Stem Cell Research (1999): Two volumes. President’s Council on Bioethics Report on Cloning (July 2002): www.bioethics.gov “Stem Cells: A Primer” from National Institutes of Health: http://www.nih.gov/news/stemcell/primer.htm

    52. VCU’s official position "There are no federal or Virginia legal prohibitions with respect to the conduct of stem cell research. Our investigators continue to consider research opportunities using stem cells from a variety of sources in order to develop the promising field of regenerative medicine."

    53. A Blueprint For Research at VCU

    54. Regenerative Medicine at VCU

    56. The challenge of embryonic stem cells

    57. Stem cell biology research questions

    58. Alternatives to stem cell therapeutics

    59. Bioinformatics and Bioengineering Summer Institute Activity of CSBC Jointly funded by NIH/NSF Only 9 funded in US June 1- August 9 2 summers and intervening academic year 12 students; >80% not VCU Mostly college sophomores apply; minorities sought http://www.vcu.edu/csbc/bbsi

    60. 50 free 8 minute videos with accompanying lesson plan VCU/Cambridge/Harvard/Michigan/Wisconsin/UCSF Funded by the National Academies of Science and the Pfizer Foundation

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