The Promise of Stem Cell Research Life or Death?:
Session Notes

1. What are stem cells?
   • Not committed to any special function, such as a heart cell
   • Stem cells can divide indefinitely in a culture and can specialize to become any sort of cell.
   • When a sperm fertilizes an egg, the resulting cell is totipotent: Able to form the entire organism
   • In the first few hours, this cell divides into two identical totipotent cells.
   • About 4 days later and after several cycles of cell division, the many totipotent cells start specializing
   • They form a blastocyst: A hollow sphere of cells with an outer layer of cells and inner cell mass.
   • The outer layer forms the placenta and other tissues needed for in utero development
   • The inner mass forms the human.
   • The inner cells are pluripotent: they can form any of 220 cell types of the human, but they cannot form the in utero tissues.
   • These cells eventually specialize further into multipotent cells committed to a certain function
   • For example blood stem cells are multipotent and can specialize into red blood cells, white blood cells, platelets, etc.
   • Multipotent cells are found in adults and children.
   • It is pluripotent stem cells that are used for research
2. What is the promise?
   • Lead to better understanding of cell specialization and cell division
     • abnormal specialization and division: cancer, birth defects
   • allow drug testing of more cell types prior to human testing
   • cell therapies
     1. a renewable source of replacement cells and tissue
     2. Parkinson's, Alzheimer's, spinal cord injury, stroke, burns, heart disease, diabetes, osteoarthritis, rheumatoid arthritis
     3. transplant of healthy heart muscle cells
     4. development of islet cells to produce insulin in Type I diabetes patients
   • therapeutic delivery systems: stem cells as a vehicle to deliver genes to specific tissues
   • technical problems:
     1. still need to understand how it all works!
     2. immune rejection
   • Geron in Menlo Pk, CA is preparing for clinical trials of embryonic stem cell therapies [Weiss]
     1. including nerve cells, heart cells, pancreatic islet cells, liver cells, brain cells
     2. working on spinal cord injuries
3. The controversy
   • Two sources (as of May 2000) of pluripotent stem cells:
     1. Dr. Thomson: pluripotent cells from the inner cell mass of human embryos in the blastocyst stage.
        • embryos from IVF, not for research but for conception
        • informed consent of parents
     2. Dr. Gearhart: pluripotent cells from fetal tissue in region destined for testes or ovaries
        • abortions (fetal tissue)
        • informed consent of woman after decision to terminate pregnancy
   • therapeutic cloning [Weiss]
     1. cloned human embryos are sources of stem cells
     2. not reproductive cloning, which is banned nearly everywhere
     3. In the UK, Dr. Allison Murdoch, U. of Newcastle-on-Tyne
     4. to provide exact genetic fingerprints of a patient
     5. hence no immune rejection
     6. and would allow the study of the progress of patient's disease via excess cloned embryos.
     7. the UK (HFEA, see below) permitted this so long as only rejected eggs are used
     8. so far not successful
     9. However in S. Korea, Woo-Suk Hwang was successful at the Seoul Nat'l U. in Feb 2004 using healthy eggs from volunteer doners.
   • adult stem cells
     1. multipotent cells occur in adult for certain types of cell functions (stem cells have not been found for all cell functions)
     2. In animals, it has been shown that multipotent cells committed to one function can be change to another function (by placing them in an appropriate environment -- putting neural stem cells in bone marrow turns them into blood stem cells)
     3. probably would solve immune rejection problem
     4. would not need embryos or fetal tissue
     5. but ...
        • there may not be adult stem cells for all types of cells and there is no evidence that they are pluripotent
        • only in minute quantities, decreasing with age and difficult to isolate
        • taking cells from a patient requires time to culture them -- for acute disorders, this may be too long
        • and adult stem cells are shorter lived than embryonic stem cells
        • or if the disorder is caused by a genetic disorder, you would not want to use that patient's cells -- the defective gene is used
        • adult cells may contain more DNA abnormalities from exposure to daily living, DNA replication errors, etc.
     6. 2005 update [Carmichael]:
        • Autologous stem cells = adult stem cells from oneself
        • Allogenic stem cells = adult stem cells from a donor (so far doesn't work)
        • Patients' own stem cells have been used to grow bone tissue
        • Genzyme biotech firm
          • makes replacement cartiledge from autologous stem cells
          • experimenting with adult stem cell treatments for maligant lymphomas, mutliple myeoloma, breast, ovarian, testicular tumors, congestive heart failure, myocarditin
          • Future: organ re-generation
        • German doctors have re-generated a lower jaw in a man
        • Japanese doctors have regenerated outer lyers of patients' corneas.
        • umbilical cord blood transplant [Weiss], considered adult stem cells has been used since 1988.
   • Human Dignity [Gilbert]
     1. Human dignity => set apart from the animals: rationality, soul, possibility of redemption
     2. E.g., laws against slavery and cannibalism
     3. In the past, this led to objection to "vaccinations", since the antiserum came from animals and it was an affront to human dignity to have animal tissue injected in a human.
     4. Another idea of human dignity is that disease often robs people of their dignity
     5. Medical research, such as stem cell research, can restore human dignity (e.g., Alzheimer's)
     6. Included is this that part of human dignity is using our talent to relief suffering.
     7. It is more important to restore the dignity of an adult, than preserve an abstract notion for an undeveloped cell mass.
     8. Problem with this: slippery slope of if can be done, then do it.
     9. Which is it? Our apartness at conception or the concrete, visible adult?
   • Scientific positions of when life begins [Gilbert]:
     1. "genetic view": at conception, when the egg and sperm nuclei fuse at fertilization
     2. "embryologic view": when embryo becomes an individual, 14 days after fertilization when each embryo can produce only a single human. This is the UK position
     3. "EEG view": when human-specific electroencephalogram is acquired around 25 weeks (society has defined death when the EEG pattern is lost)
     4. "birthday view": when fetus can be independent of mom
   • Bush's policy [Gilbert]
     1. USA scientists receiving federal funding can only use current stem cell lines; no new lines
     2. Will Bush's policy stop stem cell research in the USA?
     3. Other countries are proceeding with stem cell research
     4. Not clear how many cell lines are available and what their condition is
     5. Many may be at their limits of totipotency
     6. Given this "ban", only corporations and foreign nations will be able to afford to pursue stem cell research in USA
   • Corporate control [Gilbert]
     1. responsibility, motivation, accountability
     2. market the only regulator
     3. cure or eugenics?
     4. (the genes in stem cells can be manipulated)
     5. rich vs poor
     6. In UK, Human Fertilisation and Embryology Authority licenses and regulates [UK report]
        • Research licences are issued if the HFEA is satisfied research is necessary or desirable for [Box 14]:
          1. promoting advances in infertility treatment;
          2. increasing knowledge about the causes of congenital disease;
          3. increasing knowledge about the causes of miscarriages;
          4. developing more effective techniques of contraception;
          5. developing methods for detecting the presence of gene or chromosome abnormalities in embryos before implantation
        • controls on embryo research [Box 15]:
          1. requires a licence
          2. only for the purposes above
          3. embryos for research kept no more than 14 days (excluding storage)
          4. only used if consent give by donors
        • Principles governing the use of fetal tissue (Polkinghorne guidelines) [Box 16]
          1. clear separation between decisions/actions re. terminating pregnancey and decisions/actions re. using fetal tissue for research
          2. decision to terminate pregnancy must not be influence by research potential
          3. management of the pregnancy must not be influence by research potential of fetus
          4. no inducements, financial or otherwise
          5. mother not informed of the specific use of the fetal tissue
          6. written consent of mother required
          7. consent of mother to terminate pregnancy must be before consent is sought for research
     7. In the USA the NIH would perform the function of HFEA [Weiss]
        • The Clinton administration devised ethics guidelines much like the UK.
          1. See clinton administration nih guidelines for embryonic stem cell funding; Monitoring Stem Cell Research; The President's Council on Bioethics
          2. Pres. Bush did NOT implement
4. Religious concerns
   • Are the Polkinghorne guidelines satisfactory for the use fetal tissue?
   • When is the image of God instill in a person?
     1. When does a embryo or fetus become a person?
     2. At conception? At birth? At awareness?
     3. Or somewhere in the middle [UK Report, Box 17]:
        • The embryo of human species has a special status but not the same status as a living child or adult
        • The human embryo is entitle to a measure of respect beyond that accorded to an embryo of other species
        • Such respect is not absolute and may be weighed against the benefits arising from proposed research
        • The embryo of the human species should be afforded some protection in law
   • When is it moral to sacrifice embryonic life?
     • Using spare embryos for research.
     • Specifically creating or cloning embryos for research
     • When clear rules and procedures are followed for beneficial research?
     • For the greater good?
   • Is it ethical to clone an embryo for research, but not for development?
   • Is in vitro a moral method of conception, given that surplus fetus' are not used (destined for disposal)?
   • Does God intend all fetal life to develop? Or are some "called out" for the sake of others' lives?
   • Is it wrong to adjust the genome of the embryo (oocyte nucleus transfer)?

References

1. Stem Cells: A Primer; National Institutes of Health; May 2000.
2. Carmichael, Mary; Organ Under Construction; Newsweek, summer 2005, p46ff.
3. Gilbert, Scott; A Primer on Human Embryonic Stem Cells; Metanexus.
4. Stem Cells: Scientific Progress and Future Research Directions; National Institutes of Health; June 2001
5. Stem Cell Research: Medical Progress with Responsibility; Department of Health (UK); June 2000.
6. Weiss, Richard; The Power to Divide; National Geographic, July 2005.