The Science and Ethics of Stem Cell Research

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 VCU Life Sciences James Madison University lecture: November 18, 2005 1 The Life Sciences Revolution in the News • The Human Genome Project • Genetically Modified Crops • Biological Agents in Bioterrorism • Stem Cell Therapy • Human Cloning Special edition to celebrate the anniversary of the discovery of DNA: February 17, 2003 2 50th VCU Life Sciences James Madison University lecture: November 18, 2005 The Good, the Bad, and the Ugly VCU Life Sciences James Madison University lecture: November 18, 2005 3 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 VCU Life Sciences James Madison University lecture: November 18, 2005 4 What are stem cells ? VCU Life Sciences James Madison University lecture: November 18, 2005 5 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. VCU Life Sciences James Madison University lecture: November 18, 2005 6 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 VCU Life Sciences James Madison University lecture: November 18, 2005 7 VCU Life Sciences James Madison University lecture: November 18, 2005 8 Embryonic Stem Cells (ESC) VCU Life Sciences James Madison University lecture: November 18, 2005 9 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. VCU Life Sciences James Madison University lecture: November 18, 2005 10 Embryonic Stem Cells and Embryonic Stem Cell Lines • Cell lines are from one separated cells and the daughter cells are alike and grow indefinitely. VCU Life Sciences James Madison University lecture: November 18, 2005 11 Adult Stem Cells VCU Life Sciences James Madison University lecture: November 18, 2005 12 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 VCU Life Sciences James Madison University lecture: November 18, 2005 13 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 VCU Life Sciences James Madison University lecture: November 18, 2005 14 VCU Life Sciences Survey • VCU Life Sciences James Madison University lecture: November 18, 2005 15 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. VCU Life Sciences James Madison University lecture: November 18, 2005 16 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.” VCU Life Sciences James Madison University lecture: November 18, 2005 17 ESCs versus MAPCs VCU Life Sciences James Madison University lecture: November 18, 2005 18 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. VCU Life Sciences James Madison University lecture: November 18, 2005 19 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 VCU Life Sciences James Madison University lecture: November 18, 2005 20 Evidence of Plasticity among Adult Stem Cells VCU Life Sciences James Madison University lecture: November 18, 2005 21 Pros and cons of stem cell sources Type ES Advantage grow well pluripotent Problem non-self directed differentiation ES contamination in product directed differentiation labor intensive, inefficient, oocyte supply ES contamination in product growth, numbers, cell types ES-self (therapeutic cloning) grow well pluripotent self Neonatal (eg cord blood) availability, could be self unexpected plasticity could be self Adult stem cells grow poorly, accessibility numbers, interconversions may be very rare VCU Life Sciences James Madison University lecture: November 18, 2005 22 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‖ VCU Life Sciences James Madison University lecture: November 18, 2005 23 VCU Life Sciences James Madison University lecture: November 18, 2005 24 Stem Cells and Regenerative Medicine With stem cell therapy (embryonic or adult), there is enormous promise of treating diseases previously thought to be unmanageable Valid and Invalid Controversy The question is not whether or not to use stem cells. The question is whether to use adult or embryonic stem cells. VCU Life Sciences James Madison University lecture: November 18, 2005 25 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” VCU Life Sciences James Madison University lecture: November 18, 2005 26 VCU Life Sciences James Madison University lecture: November 18, 2005 27 Human Cloning Therapeutic versus reproductive cloning VCU Life Sciences James Madison University lecture: November 18, 2005 28 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.‖ VCU Life Sciences James Madison University lecture: November 18, 2005 29 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. VCU Life Sciences James Madison University lecture: November 18, 2005 30 VCU Life Sciences James Madison University lecture: November 18, 2005 31 Cloning of human embryos: South Korea 2004 VCU Life Sciences James Madison University lecture: November 18, 2005 32 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 VCU Life Sciences James Madison University lecture: November 18, 2005 33 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 VCU Life Sciences James Madison University lecture: November 18, 2005 34 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%) VCU Life Sciences James Madison University lecture: November 18, 2005 35 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%) VCU Life Sciences James Madison University lecture: November 18, 2005 36 VCU Life Sciences Survey “All in all, how serious do you think the ethical concerns are over embryonic stem cell research.” Very Serious 43% Somewhat Serious 36% Not Too Serious 12% Not at All Serious VCU Life Sciences 4% 0 20 40 60 80 37 James Madison University lecture: November 18, 2005 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. VCU Life Sciences James Madison University lecture: November 18, 2005 38 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. VCU Life Sciences James Madison University lecture: November 18, 2005 39 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. VCU Life Sciences James Madison University lecture: November 18, 2005 40 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 ? VCU Life Sciences James Madison University lecture: November 18, 2005 41 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. VCU Life Sciences James Madison University lecture: November 18, 2005 42 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 VCU Life Sciences James Madison University lecture: November 18, 2005 43 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 VCU Life Sciences James Madison University lecture: November 18, 2005 44 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 VCU Life Sciences James Madison University lecture: November 18, 2005 45 State Landscape to Date Reproductive Cloning Ban California Missouri Virginia Rhode Island New Jersey Reproductive & Pro Stem Cell Therapeutic Ban Research Michigan California ($3b) Iowa New Jersey ($380m) Arkansas North Dakota South Dakota * A Louisiana law prohibiting reproductive cloning expired in 2003. VCU Life Sciences James Madison University lecture: November 18, 2005 46 2005 State Legislation Wisconsin: $375m Illinois: $1b New York: $300 m Connecticut: $100m PASSED New Jersey: $380m Maryland: $25m - DEAD Virginia: $1m - DEAD North Carolina $10m Florida $10m Texas:$900m DEAD? Pro-stem cell legislation Anti-cloning legislation Both forms of legislation State $ Pledged for Stem Cell Research VCU Life Sciences James Madison University lecture: November 18, 2005 47 State Laws Regarding Stem Cell Research and/or Human Cloning ND SD CA MI IA RI NJ MO VA AR Safe Harbor for SCR Ban on All Cloning Ban on Reproductive Cloning VCU Life Sciences James Madison University lecture: November 18, 2005 48 NAS Support for Stem Cell Research National Academy of Sciences: ―The scientific and medical considerations that justify a ban on human reproductive cloning at this time are not applicable to nuclear transplantation to produce stem cells. Because of the considerable potential for developing new medical therapies to treat life-threatening diseases and advancing biomedical knowledge, the panel supported the conclusion of a previous National Academies’ report—Stem Cells and the Future of Regenerative Medicine—that recommends that biomedical research using nuclear transplantation to produce stem cells be permitted.‖ VCU Life Sciences James Madison University lecture: November 18, 2005 49 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. VCU Life Sciences James Madison University lecture: November 18, 2005 50 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 VCU Life Sciences James Madison University lecture: November 18, 2005 51 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." VCU Life Sciences James Madison University lecture: November 18, 2005 52 A Blueprint For Research at VCU ENABLING RESEARCH Genetics/Omics Cardiopulmonary Disease Maternal & Child Health Regenerative Medicine Aging and Metabolism Behavioral Medicine Pathogens & the Environment Bioinformatics/ Computational Biology Neurosciences Microbiology & Immunology Cellular & Molecular Biology Structural Biology MISSION-BASED RESEARCH VCU Life Sciences James Madison University lecture: November 18, 2005 53 Cancer Regenerative Medicine at VCU Rationale Unmet Needs Accessibility Reduced Cost • • • • Demographics and the increasing burden of chronic disease Expense of current therapies Trauma, war, natural disasters, bioterrorism Training of health care professionals in new technologies VCU Life Sciences James Madison University lecture: November 18, 2005 54 The appeal of embryonic stem cells Pluripotency: From one cell type, many Criteria: Immortality Clonality Undifferentiated Wide developmental potential VCU Life Sciences James Madison University lecture: November 18, 2005 55 The challenge of embryonic stem cells Definitive proof of principle lacking The purity problem The immunology problem The cancer problem The production problem The ethics problem VCU Life Sciences James Madison University lecture: November 18, 2005 56 Stem cell biology research questions Embryonic vs. adult stem cells more effective? Alternative means of generating pluripotent cells ? Developing appropriate preclinical models ? I.P. in the public or private domain ? VCU Life Sciences James Madison University lecture: November 18, 2005 57 Alternatives to stem cell therapeutics Human SCNT into animal oocytes Activation of endogenous stem cells Chemical or genetic initiation of nuclear reprogramming of adult cells Dedifferentiation Transdifferentiation VCU Life Sciences James Madison University lecture: November 18, 2005 58 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 VCU Life Sciences James Madison University lecture: November 18, 2005 59 Secrets of the Sequence www.vcu.edu/lifesci/sosq 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 VCU Life Sciences James Madison University lecture: November 18, 2005 60 Thank you for your attention VCU Life Sciences James Madison University lecture: November 18, 2005 61