prop 71: stem cell hype and hope richard deem, scientists against proposition 71 ()
TRANSCRIPT
Topics What are stem cells
Stem cell types Human cloning
What’s wrong with Proposition 71 Problems Deceptive Claims Cures or hype? ESC/cloning problems Ethical questions
Stem Cell – Definition
A cell that has the ability to continuously divide and differentiate (develop) into various other kind(s) of cells/tissues
Kinds of Stem CellsStem cell
type Description Examples
Totipotent Each cell can develop into a new individual
Cells from early (1-3 days) embryos
Pluripotent Cells can form any (over 200) cell types
Some cells of blastocyst (5 to 14 days)
MultipotentCells differentiated, but can form a number of other tissues
Fetal tissue, cord blood, and adult stem cells
Totipotent
Pluripotent
Multipotent
Sources of Stem Cells
Stem cell type Description
Embryonic Cells from human blastocysts
Fetal stem cells Cells from gonads of aborted fetuses
Umbilical cordstem cells
Cells from the umbilical cord blood of newborns
Placenta derived stem cells
Cells from the placenta of newborns
Adult stem cells Cells from adult tissues
Embryonic
Fetal stem cells
Umbilical cordstem cells
Placenta derivedstem cells
Adult stem cells
Stages of Embryogenesis
Day 1Fertilized egg
Day 1Fertilized egg
Day 22-cell embryo
Day 22-cell embryo Day 3-4
Multi-cell embryoDay 3-4
Multi-cell embryo
Day 5-6BlastocystDay 5-6
BlastocystDay 11-14Tissue Differentiation
Day 11-14Tissue Differentiation
Derivation and Use of Embryonic Stem Cell Lines
Isolate inner cell mass(destroys embryo)
Isolate inner cell mass(destroys embryo)
Heart muscleKidney
Liver
“Special sauce”(largely unknown)
Day 5-6BlastocystDay 5-6
Blastocyst
Inner cells(forms fetus)Inner cells
(forms fetus)
Outer cells(forms placenta)
Outer cells(forms placenta)
Heartrepaired
Culture cellsCulture cells
“CC” Carbon Copy
1996 – Dolly, the sheep cloned
History of Somatic Cell Nuclear Transfer (Cloning)
1998 – Mice cloned 1998 – Cows cloned 2000 – Pigs cloned 2001 – Cat cloned 2002 – Rabbits cloned 2003 – Mule cloned 2004 – Bull serial-cloned
Human Embryo Cloning
2001 – First cloned human embryos (only to six cell stage) created by Advanced Cell Technology (USA)
2004* – First human cloned blastocyst created and a cell line established (Korea)
*Hwang, W.S., et al. 2004. Evidence of a Pluripotent Human Embryonic Stem Cell Line Derived from a Cloned Blastocyst. Science 303: 1669-1674.
Cloned Embryonic Stem Cells – Advantages/Problems
Advantages No rejection, “Perfect match”
Problems Extremely expensive (>$200,000/patient) Only 0.6% (1 out of 176) oocytes
survived to become a cell line (required 16 egg donors to produce one cell line)
“Further improvements in SCNT protocols and in vitro culture systems are needed before contemplating the use of this technique for cell therapy.”
Cloning damages DNA (virtually all cloned mammals suffer genetic damage)
What’s Wrong With Prop 71? Fiscal problems Political appointments Informed consent modifications Provision for backroom meetings Exploitation of women for eggs Limits funding to ESC and cloning Deceptive claims Deceptive list of potentially curable
diseases
Prop 71 Adds $6 Billion to the California Deficit
Research30%
Facilities5%
Interest50%
Indirect12.5%
Administrative3%
Prop 71 $3 Billion Bonds
6% of bond costs will be spent on administration
By comparison, the 2005 NIH budget commits 4% to administration
Research59%
Administrative6%Facilities
10% Indirect25%
Administrative6%
Prop 71 $3 Billion Bonds
25% of bond costs will be spent on indirect costs (goes to institution)
For a $4 million grant, company or institution gets $1 million
Research59%
Administrative6%Facilities
10% Indirect25%
Indirect25%
Prop 71 $3 Billion Bonds
10% of bond costs will be spent on real estate and facilities construction
This is pure pork barrel politics, since investigators already have labs
Research59%
Administrative6%Facilities
10% Indirect25%
Who Supports and Funds Prop 71?Name Interest
Robert Klein Real Estate Development
Joseph Lacob Venture Capital (Biotech)
John Doerr Venture Capital (Biotech)
Brook Byers Venture Capital (Biotech)
William Unger Venture Capital (Biotech)
George Rathmann, William Rutter, James Rooney
Biotech Company executives
Institute Run by Political Appointments
Citizen's Oversight Committee appointed by state politicians: Governor, Lieutenant Governor Treasurer, Controller Speaker of the Assembly President Pro Tem of the Senate.
Consists of UC bureaucrats, members of disease advocacy groups
Prop 71 Will Change Informed Consent Procedures
Studies involving human subjects must inform patients about medical procedures to prevent abuse of patient rights
Proposition 71 initially requires grant recipients to comply with federal regulations
However, the proposition allows for “modifications to adapt to the mission and objectives of the Institute.” (ARTICLE 1. 125281.06 (1))
Prop 71 Exempts Institute From “Open Meeting" Laws
Closed meetings to hand out patents and profits
125281.05 (d) Public Meeting Laws(3) …In addition, the ICOC may conduct closed sessions when it meets to consider or discuss:(B) Matters involving confidential intellectual property or work product, whether patentable or not, including, but not limited to, any formula, plan, pattern, process, tool, mechanism, compound, procedure, production data, or compilation of information…
Prop 71 Will Exploit Poor Women for Their Eggs
Thousands of egg donors will be required to produce the eggs required for human cloning.
Poor women and college students will likely donate eggs to earn quick cash.
However, the procedure to obtain these eggs uses powerful, dangerous drugs that have already resulted in the deaths and hospitalization of hundreds of women.
Prop 71 Research Limited to Human Embryo Cloning and Destruction
According to the legal text:
“In this regard, other research categories funded by the National Institute of Health shall not be funded by the Institute.”
Funding of research that does not destroy human embryos must be approved by a 2/3 vote of the Scientific and Medical Research Funding Working Group
Why Do They Hide the Real Nature of Research Funded?
Words Used Real Meaning
pluripotent stem cells stem cells grown by destroying human embryos
products of in vitro fertilization treatments human embryos
somatic cell nuclear transfer cloning human embryos
Prop 71 Deceptive Claims
Royalties to the state Sales tax will cover bond interest Stem cell research is banned Cures require use of embryonic
cell lines 400,000 embryos will be discarded
anyway Bush policy is based on ideology
and not science
Prop 71 will Provide Patent and Royalty Revenues to the State?
Proposition 71 does not require that one single penny of the patent and royalty revenues that might result from future research be returned to California taxpayers.
The “Institute” established by Proposition 71 may, at its discretion, have taxpayers pay 100% of the costs, and award venture capitalists with 100% of the profits.
Sales Tax Generated by Prop 71 Will to Cover Bond Interest?
“The supporters’ own economic study shows that in the following nine years, when annual debt service on the bonds soars to more than $170 million, the putative tax gains will cover only 11% to 19% of that sum.”
Michael Hiltzik, Los Angeles Times, 8/23/04
Prop 71 Claim: Human ESC Research is Banned
“Some of the most pioneering cures and treatments are right at our fingertips, but because of the stem cell ban, they remain beyond our reach.” John Kerry
False Human embryonic stem cell research for
any purpose is allowed using private funds
Embryonic stem cell research is funded by the NIH for 22 available human lines created before 8/9/01
Prop 71 Claim: Only Embryonic Cells Are Pluripotent
Cells from the umbilical cords of newborns are pluripotent
Researchers have shown the ability of these cells to grow bone, cartilage, hematopoietic (blood), neural (brain, spinal cord, nerves), liver and heart tissue.
Reference:
Kögler, G. et al. 2004. A New Human Somatic Stem Cell from Placental Cord Blood with Intrinsic Pluripotent Differentiation Potential. Journal of Experimental Medicine 200: 123-135.
Reference:
Kögler, G. et al. 2004. A New Human Somatic Stem Cell from Placental Cord Blood with Intrinsic Pluripotent Differentiation Potential. Journal of Experimental Medicine 200: 123-135.
400,000 Embryos are Going to Be Discarded Anyway
88.2% are being held for family building (i.e., babies)
2.2% are slated to be discarded 2.8% are designated for research Of these 11,000 embryos,
optimistically, only 275 cell lines would be expected to established
John Kerry Says George Bush Has “politicized science”
“While the Bush administration has politicized science, Kerry will put America back on the path of scientific excellence with a commitment to scientific research based on fact – not ideology.”
Prop 71: Diseases Claimed to be Treatable by ESC
Disease SC Treatable?
Cystic Fibrosis Yes?
Spinal cord injury Yes?
Alzheimer’s disease No
Type I diabetes, type II diabetes Yes?
Multiple sclerosis Yes?
Amyotrophic lateral sclerosis Yes?
Heart disease Yes?
Cancer No
Parkinson’s disease Yes?
Mental health diseases ?
HIV/AIDS No
Prop 71: Adult Stem Cells in Therapy of Cystic Fibrosis
Successes have occurred using adult stem cells (not funded by this proposition) to generate new lung cells
Human cloning would be ineffective for this genetic disease.
Reference:
H. Spencer and A. Jaffe. 2004. The potential for stem cell therapy in cystic fibrosis. J. R. Soc. Med. 97 (Suppl. 44):52–56.
Prop 71: Treatment of Spinal Cord Injuries
Both embryonic and adult stem cells (bone marrow, skin, and umbilical cord derived) have shown promise in treatment of spinal cord injuries.
References:
Oliver Brüstle, et. al. 1999. Embryonic Stem Cell-Derived Glial Precursors: A Source of Myelinating Transplants. Science 285: 754-756.
Ankeny DP, McTigue DM, Jakeman LB. 2004. Bone marrow transplants provide tissue protection and directional guidance for axons after contusive spinal cord injury in rats. Exp. Neurol. 190:17-31.
Li HJ, et. al. 2004. Transplantation of human umbilical cord stem cells improves neurological function recovery after spinal cord injury in rats. Zhongguo Yi Xue Ke Xue Yuan Xue Bao 26:38-42.
References:
Oliver Brüstle, et. al. 1999. Embryonic Stem Cell-Derived Glial Precursors: A Source of Myelinating Transplants. Science 285: 754-756.
Ankeny DP, McTigue DM, Jakeman LB. 2004. Bone marrow transplants provide tissue protection and directional guidance for axons after contusive spinal cord injury in rats. Exp. Neurol. 190:17-31.
Li HJ, et. al. 2004. Transplantation of human umbilical cord stem cells improves neurological function recovery after spinal cord injury in rats. Zhongguo Yi Xue Ke Xue Yuan Xue Bao 26:38-42.
Prop 71: Embryonic Stem Cells as a Cure for Alzheimer’s Disease?
“I think the chance of doing repairs to Alzheimer's brains by putting in stem cells is small.”Michael Shelanski, Taub Institute for Research on Alzheimer's Disease and the Aging Brain (Columbia University Medical Center)
“To start with, people need a fairy tale.” Ronald D.G. McKay, National Institute of Neurological Disorders and Stroke
Reference:
Rick Weiss. Stem Cells An Unlikely Therapy for Alzheimer's. Washington Post Thursday, June 10, 2004; Page A03
Prop 71: Embryonic Stem Cells as Treatment for Diabetes?
Proponents cite studies in which cultured mouse embryonic stem cells produced insulin
However, these cells were not beta cells (of neurological derivation) and insulin secretion was very low and not glucose dependent
Reference:S. Sipione et al. 2004. Insulin expressing cells from differentiated embryonic stem cells are not beta cells. Diabetologia 47: 499-508.
Pancreas
Prop 71: Adult Stem Cells in Treatment of Multiple Sclerosis
Adult stem cells (bone marrow or endogenous neural stem cells), but not embryonic stem cells have been used in numerous studies (including some preliminary clinical trials) to treat multiple sclerosis.
References:Fassas A, Kimiskidis VK. 2004. Autologous hemopoietic stem cell transplantation in the treatment of multiple sclerosis: rationale and clinical experience. J. Neurol. Sci. 15:53-58.Muraro PA, Cassiani Ingoni R, Martin R. 2003. Hematopoietic stem cell transplantation for multiple sclerosis: current status and future challenges. Curr. Opin. Neurol. 16:299-305.
Prop 71: Treatment of Amyotrophic Lateral Sclerosis
Mouse model showed that cord blood stem cells are beneficial in reversing spinal cord injury, even when infused 5 days after injury.
A 2004 review of scientific literature indicated that adult stem cell treatments showed promise for treatment of ALS.References:
Garbuzova-Davis, Svitlana, et al. 2003. Intravenous Administration of Human Umbilical Cord Blood Cells in a Mouse Model of Amyotrophic Lateral Sclerosis: Distribution, Migration, and Differentiation. Journal of Hematotherapy and Stem Cell Research 12: 255–270.Silani V, Cova L, Corbo M, Ciammola A, Polli E. 2004. Stem-cell therapy for amyotrophic lateral sclerosis. Lancet 364:200-2.
Both Adult and Embryonic Stem Cells Treat Myocardial Infarction
Rat embryonic stem cells were used in rat model of myocardial infarction to improve ventricular function and repair damaged heart tissue
Mesenchymal stem cells (MSCs) when introduced into the infarcted heart, prevented deleterious remodeling and improved recoveryReferences:
Hodgson DM, et. al. 2004. Stable benefit of embryonic stem cell therapy in myocardial infarction. Am. J. Physiol. Heart Circ. Physiol. 287:H471-H479.Pittenger MF, Martin BJ. 2004. Mesenchymal stem cells and their potential as cardiac therapeutics. Circ. Res. 95:9-20.
Prop 71: Treatment of Cancer?
Cancer is caused by cells of the body multiplying uncontrollably due to genetic mutation or viral infection, in some cases.
Stem cells would not be useful in therapy. This wide spectrum of diseases was added simply because there are a lot of people who have been affected who might vote for the initiative.
Prop 71: Embryonic Stem Cells as Treatment for Parkinson’s?
Only 50% of rats experienced improvement of symptoms
25% of rats developed brain tumors and died
Who wants to signup for the first clinical trial?
Reference:Bjorklund, L. M., R. Sanchez-Pernaute, et al. 2002. Embryonic stem cells develop into functional dopaminergic neurons after transplantation in a Parkinson rat model. Proceedings of the National Academy of Sciences 99: 2344-2349.
Prop 71: Treatment of Mental Health Diseases?
Since the cause of most mental health diseases is unknown, it is not known whether stem cells could be useful in therapy.
However, since many people suffer from these diseases, it was added to garner additional support for the proposition.
Prop 71: Embryonic Stem Cells as a Cure for HIV/AIDS?
AIDS is caused by an infectious virus (HIV) that attacks the immune system
Stem cell treatments could improve the function of the immune system, but the effect would be temporary until the new stem cells became infected themselves
Adult (not embryonic) stem cells would be the preferred treatment
Adult Stem Cell Success:Liver Cells from Bone Marrow
Multipotent adult progenitor cells have been shown to differentiate into functional, hepatocyte-like (liver) cells.
Reference:
Schwartz, R. E., et al. 2002. Multipotent adult progenitor cells from bone marrow differentiate into functional hepatocyte-like cells. Journal of Clinical Investigation 109: 1291-1302.
Adult Stem Cell Success: Cord Blood Stem Cells and Stroke
When umbilical cord-derived stem cells were given intravenously along with the drug mannitol, which can penetrate the brain's protective blood-brain barrier, stroke size was reduced by 40 percent.
Reference:Cesar V. Borlongan, et al. 2004. Central Nervous System Entry of Peripherally Injected Umbilical Cord Blood Cells Is Not Required for Neuroprotection in Stroke. Stroke 35:2385.
Adult Stem Cell Success:New Jaw Bone
Man’s jaw bone was removed due to cancer
Replacement jaw bone was grown for 7 weeks in his back muscles using his own adult stem cells enclosed in a titanium frame with cow-derived bone mineral blocks and human bone growth factor
Reference:
Rookmaaker MB, Verhaar MC, Van Zonneveld AJ, Rabelink TJ. 2004. Progenitor cells in the kidney: Biology and therapeutic perspectives. Kidney Int. 66:518-22.
Adult Stem Cell Success: Kidney Stem Cells
Stem cells have been demonstrated in the kidneys
Adult stem cells can dedifferentiate into progenitors
Stem cells from alternate sources can be differentiated into kidney cells
Reference:
Rookmaaker MB, Verhaar MC, Van Zonneveld AJ, Rabelink TJ. 2004. Progenitor cells in the kidney: Biology and therapeutic perspectives. Kidney Int. 66:518-22.
Adult Stem Cell Success: Stem Cells for Hearing Loss
Stem cells in the adult inner ear are capable of differentiating into hair cells
Reference:
Li H, Corrales CE, Edge A, Heller S. 2004. Stem cells as therapy for hearing loss. Trends Mol Med. 10:309-15.
Adult Stem Cell Success: Corneas From Adult MSC
Adult stem cells taken from patients were grown in culture before transplantation onto the damaged eyes. Sixteen of the 20 patients had improved vision.
Reference:
Schwab, IR et al. 2000. Successful transplantation of bioengineered tissue replacements in patients with ocular surface disease. Cornea 19: 421-426.
Adult Stem Cell Success: Treatment of Retinitis Pigmentosa
An injection of adult stem cells saved the sight of mice who would otherwise have gone blind.
Such treatment could be used for a group of eye diseases called retinitis pigmentosa, in which cells in the retina break down over time, causing gradual loss of vision and sometimes blindness.
Reference:
Otani A., et al. 2004. Rescue of retinal degeneration by intravitreally injected adult bone marrow–derived lineage-negative hematopoietic stem cells. J. Clin. Invest., 114. 765 - 774.
Adult Stem Cells Work as Well as Embryonic Stem Cells
Both adult mesenchymal stem cells and embryonic stem cells produced teeth in mice
Reference:
Ohazama A, Modino SA, Miletich I, Sharpe PT. 2004. Stem-cell-based tissue engineering of murine teeth. J. Dent. Res. 83:518-522.
Summary of Advantages/Disadvantages
Stem Cell CostTissue rejection
Ethical Problems
Works for genetic diseases
Human Embryos
Low(?)(IVF leftovers)
YesUnique human embryos
Yes
Human Clones High None
Cloned human embryos
No
AdultAutologous Low None None No
AdultDonated Low Yes None Yes
Embryonic Stem Cell Problems: Chromosomal Abnormalities
Recently, abnormalities in chromosome number and structure were found in three human ESC lines.
References
1. Draper, J.S., et al., "Recurrent gain of chromosomes 17q and 12 in cultured human embryonic stem cells," Nature Biotechnology December 7, 2003, advance online publication.
2. C. Cowan et al. 2004. Derivation of Embryonic Stem-Cell Lines from Human Blastocysts. New England Journal of Medicine 350: 1353-1356.
Embryonic Stem Cell Problems: Epigenetic Defects
“…increasing evidence from a range of mammals shows a propensity for epigenetic errors with embryo technologies. If paralleled in human embryos, the effect on tumorigenic and differentiation properties of embryonic stem cells needs to be established.”
Reference
1. Allegrucci C, Denning C, Priddle H, Young L. 2004. Stem-cell consequences of embryo epigenetic defects. Lancet 10;364(9429):206-8.
Embryonic Stem Cell Problems: Cancer and Tumors
Rapid growth of embryonic stem cells brings the potential of introducing cancer into patients.
An embryonic stem cell therapy stroke model in mice found that treated mice developed highly malignant teratocarcinomas at the site of implantation, even when pre-differentiated into neural cells.Reference:
Erdo F, Trapp T, Buhrle C, Fleischmann B, Hossmann KA. 2004. Embryonic stem cell therapy in experimental stroke: host-dependent malignant transformation. Orv. Hetil. 145:1307-1313.
Embryonic Cloning Problems: Not Enough Human Eggs
“The poor availability of human oocytes (eggs), the low efficiency of the nuclear cell procedure, and the long population-doubling time of human ES cells make it difficult to envision this [therapeutic cloning to obtain stem cells] becoming a routine clinical procedure even if ethical considerations were not a significant point of contention”
Reference:
Odorico JS, Kaufman DS, Thomson JA. 2001. Multilineage differentiation from human embryonic stem cell lines. Stem Cells 19:193-204.
Embryonic Stem Cell Problems: Tissue Rejection
Possibility of rejection of stem cell transplants as foreign tissues is very high.
Hundreds of thousands of stem cell lines would be required to serve the majority of patients
What’s Wrong With Adult Stem Cells?
Can’t be patented, since they are derived from the patient
Can’t be marketed and sold at inflated prices due to inability to patent
Is the Embryo Human Life?
Brownback: "What would have happened had we experimented on you at the blastocyst stage?"
Zoloth: "Well, that's an obvious question, If I was... It's an odd theoretical one. If I could somehow be . . ."
Brownback: "It's not a theoretical, I'm just asking biologically."
Zoloth: "If I could have been taken out of my mother's womb, which is different from our situation..."
Brownback: "What if it happened to you?"
Zoloth: "Then I wouldn't . . . I wouldn't have existed."
Laurie Zoloth, Northwestern University:
Testimony before the US Senate 9/29/2004