Download Stem Cell Research: Status and Ethics

Prop 71: Stem Cell
Hype and Hope
Richard Deem,
Scientists Against Proposition 71
(www.NoOn71.us)
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 Cells
Stem cell
type
Description
Examples
Totipotent
Cells from early
Each cell can develop
(1-3 days)
into a new individual
embryos
Pluripotent
Cells can form any
(over 200) cell types
Multipotent
Cells differentiated,
Fetal tissue, cord
but can form a number blood, and adult
of other tissues
stem cells
Some cells of
blastocyst (5 to
14 days)
Sources of Stem Cells
Stem cell type
Description
Embryonic
Cells from human blastocysts
Fetal stem cells
Cells from gonads of aborted
fetuses
Umbilical cord
stem 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
Stages of Embryogenesis
Day 1
Fertilized egg
Day 2
2-cell embryo
Day 11-14
Tissue Differentiation
Day 3-4
Multi-cell embryo
Day 5-6
Blastocyst
Derivation and Use of
Embryonic Stem Cell Lines
Isolate inner cell mass
(destroys embryo)
Outer cells
(forms placenta)
Inner cells
(forms fetus)
Day 5-6
Blastocyst
Culture cells
“Special sauce”
(largely unknown)
Liver
Kidney
Heart muscle
Heart
repaired
History of Somatic Cell
Nuclear Transfer (Cloning)
“CC” Carbon Copy



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


1996 – Dolly, the sheep cloned
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 ESC Differentiate
Into Different Tissue Types
Neural
Bone
Retinal
Cartilage
Epithelial
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
Research
30%
Indirect
12.5%
Facilities
5%
Interest
50%
Administrative
3%
Prop 71 $3 Billion Bonds
Facilities
10%


Research
59%
Administrative
6%
Indirect
25%
6% of bond costs will be spent on
administration
By comparison, the 2005 NIH
budget commits 4% to
administration
Prop 71 $3 Billion Bonds
Facilities
10%
Research
59%
Administrative
6%
Indirect
25%

25% of bond costs will be spent on
indirect costs (goes to institution)

For a $4 million grant, company or
institution gets $1 million
Prop 71 $3 Billion Bonds
Facilities
10%
Research
59%
Administrative
6%
Indirect
25%

10% of bond costs will be spent on
real estate and facilities construction

This is pure pork barrel politics,
since investigators already have labs
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
human embryos
fertilization treatments
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.
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
Cystic Fibrosis
Spinal cord injury
Alzheimer’s disease
Type I diabetes, type II diabetes
Multiple sclerosis
Amyotrophic lateral sclerosis
Heart disease
Cancer
Parkinson’s disease
Mental health diseases
HIV/AIDS
SC Treatable?
Yes?
Yes?
No
Yes?
Yes?
Yes?
Yes?
No
Yes?
?
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

References:
Both embryonic and adult stem
cells (bone marrow, skin, and
umbilical cord derived) have shown
promise in treatment of spinal cord
injuries.
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.
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
References:

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 recovery
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
Human
Embryos
Human
Clones
Cost
Low(?)
(IVF
leftovers)
High
Works for
Tissue
Ethical
genetic
rejection Problems diseases
Unique
Yes
human
Yes
embryos
Cloned
None
human
No
embryos
Adult
Low
Autologous
None
None
No
Adult
Donated
Yes
None
Yes
Low
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
Reference:

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.
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 populationdoubling 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?
Laurie Zoloth, Northwestern University:
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."
Testimony before the US Senate 9/29/2004