Lecture-8:

Conduct Research
with Stem Cells

Scientific Ethics and

Safety
ENGR / SCI 304
Sherif H. El-Gohary , Phd
Assistant Professor,Biomedical Engineering
shamdy@zewailcity.edu.eg
 A classic bioethical decision
• One heart available  who should get it?
40-year-old school 70-year-old woman
17-year old girl
principal
 A classic bioethical decision
• One heart available  who should get it?
40-year-old school 70-year-old woman
17-year old girl
principal
Introducing….stem cells!
Scientific Ethical

Legal Religious
 Scientific
Ethical
Legal
Religious
 What are stem cells?
• The body is made up of about 200 different
kinds of specialised cells such as muscle cells,
nerve cells, fat cells and skin cells
• All cells in the body come from stem cells
• A stem cell is a cell that is not yet specialised
• The process of specialisation is called
differentiation
• Once the differentiation pathway of a stem cell
has been decided, it can no longer become
another type of cell on its own
What makes stem cells so
valuable?

Pluripotent Tissue stem

stem cells cells
Cell Therapy

Research

New Drugs
Modified from Keller & Snodgrass, Nat Med 1999
No one stem cell type fits all applications.
Research must continue using all types of stem cells.
Why are stem cells special?
Stem cells can:
• Self-renew to make more
stem cells
• Differentiate into a
specialised cell type
Stem cells that can become many Stem cells that can become
types of cells in the body are only a few types of cells are
called pluripotent called multipotent

Embryonic stem cells (pluripotent) Tissue stem cells (multipotent)

 “ADULT” STEM CELLS ARE
OBTAINED IN A VARIETY OF
WAYS

Illustration by Matt Bohan, 2007

 Tissue stem cells
• Often known as adult stem cells
• Also includes stem cells isolated from fetal and cord
blood
• Reside in most tissues of the body where they are
involved in repair and replacement

Bone marrow Kidney Lung

• Generally very difficult to isolate

• Already used to treat patients (haematological
malignancies, diseases of the immune system)
 Where do embryonic stem cells
come from?
• Donated excess IVF embryos Inner cell mass

egg fertilised 2-cell 8-cell blastocyst

egg

Day 0 Day 1 Day 2 Day 3 Day 6

Images from www.advancedfertility.com

Embryonic stem cells
• Derived from donated IVF
embryos
• Can be grown indefinitely in
the laboratory in an
unspecialised state
• Retain ability to specialise
into many different tissue
types – know as pluripotent
human embryonic stem cells
• Can restore function in
animal models following
transplantation

Human embryonic stem cells can become any cell in the body
including these beating heart cells
 Types of cloning
Reproductive cloning uses the cloning procedure to
produce a clonal embryo which is implanted in a
woman's womb with intent to create a fully formed
living child--a clone.

Therapeutic cloning uses the cloning procedure to

produce a clonal embryo, but instead of being
implanted in a womb and brought to term it is used
to generate stem cells.
Therapeutic Cloning: Organogenesis
Not This
What about cloning? Has that got anything to
do with stem cell research?
Somatic Cell Nuclear Transfer – cloning to make Reproductive Cloning
stem cells (therapeutic cloning)

Human cloning is banned in

Dolly the Sheep

Australia and many countries
around the world.

Snuppy the Puppy

Why not just use adult
stem cells?
What embryonic stem cells can do
that adult stem cells cannot do
1. Embryonic stem cells can reproduce almost
limitlessly. Adult stem cells can only reproduce a
limited number of times before they become
“senescent”. Adult stem cell “lines” are not normal
cells and usually have cancerous properties.
2. Embryonic stem cells can make any of the more than
200 different cell types and tissues. Adult stem cells
are only capable of making a limited number of cell
types (e.g. blood cells).
History of Somatic Cell Nuclear
Transfer (Cloning)

• 1952 – Briggs and King cloned tadpoles

• 1996 – The first mammal cloned from
adult cells was Dolly, the sheep.

 1998 – Mice cloned

 1998 – Cows cloned
 2000 – Pigs cloned
 “CC” Carbon Copy

History of Cloning
• 2001 – Cat cloned
 2002 – Rabbits cloned
 2003 – Mule cloned
 2004 – Bull serial-cloned
 2005 – Dog cloned
Using stem cells to conduct medical
research and treat disease is
acceptable?
• Don’t know 3% Biotechnology
Australia –
• No 5% Community
Attitudes to
Biotechnology
• Yes 92*% (2007)

* Compares to 80% in 2005 survey

But which type of stem cells?
- pluripotent stem cells (embryonic, stem cells)
- tissue stem cells (foetal, cord, adult)
Do you approve of the extraction
of stem cells from human embryos
for medical research?
• Don’t know 5%

• No 13% Roy Morgan

Poll (2006)

• Yes 82%
Legal Considerations:
Embryonic Stem Cell Research

1973 – moratorium on government



financing for human embryo research

1988 – NIH Panel voted 19-2 in


favor of government funding

Legal 1989 – DHHS Secretary Sullivan


extended the moratorium

Legal Issues:
Embryonic Stem Cell Research
1990 – Congress voted to override the


moratorium, vetoed by President

George H.W. Bush
1993 – President Clinton lifted the ban


1994 – the Human Embryo Research



Panel favored research, but Clinton

overrode the panel
1995 – Congress banned federal funding

Legal Consideration:
Embryonic Stem Cell Research
 August 25, 2000, President Clinton
allowed funding of research based
on cells from (aborted) human
fetal lines, but not embryonic cells
 On August 9, 2001, President Bush
announced his decision to allow
Federal funds to be used only for
research on existing human
embryonic stem cell lines
created prior to his announcement
Embryonic Research
Cloning Laws Worldwide
Legislation on Reproductive/Therapeutic Cloning,
Embryo Research,
and Stem Cell Research 2003
Reproductive Cloning allowed None
Therapeutic Cloning (SCNT) allowed 5
(US, UK, Netherlands, Japan, Israel)
(General) Research on Embryos allowed 13
+Australia, Brazil, Canada, Finland,
France, Iceland, Spain, Sweden
Stem Cell Research on Spare Embryos 12
allowed
Source: Encyclopedia of Bioethics
Allow for the procurement of
human embryonic cells from
supernumerary embryos by law
• Finland
• Greece
• The Netherlands
• Sweden
• United Kingdom

Prohibit procurement but allow by law the import

and use of human embryonic stem cell lines
Germany
 Special Respect

Category Questions
Replacement Can the research goals be met without destroying a human
embryo and with an alternative approach that raises less
severe ethical challenges?
Refinement If the research goals are best met by using human embryos,
is it possible to do so without destroying the embryo or it is
possible to do so by means that will not impair possible
future development of the embryo?
Reduction Can the research goals be met with the use of fewer human
embryos?

Russell and Burch, 1959

 Why Cloning Humans is
Ethically Unacceptable

• Controlling Someone Else's Genetic Makeup

• Child can reject any aspect of its upbringing, but it could

never reject the genes that were chosen for it
• Such control by one human over another is incompatible
with the ethical notion of human freedom, in the sense of
that each individual's genetic identity should be inherently
unpredictable and unplanned.
Hwang Woo Suk
• Veterinary Researcher,
Seoul National University,
South Korea
• Stem cell research funded extensively by Korean
government and international community
• Collaboration with U.S. scientist:
Gerald Schatten
• June 2005, Science: Nuclear transfer into 11 human eggs
Hwang Woo Suk
What went wrong?
• Standards of research
• Falsification of data
• Fabrication of data

• And it was stem cell research…

Professional Ethics
Case Study Example
• Stem Cell Case (2005-2006)
• Dr. Hwang Woo-Suk, a researcher
and professor at Seoul National
University, published two papers
in the journal Science that
claiming his team had succeeded
in creating human embryonic
stem cells through cloning.
• Allegations followed from a co-
worker that these paper was
based on fabricated data.
• As a result:
• the papers were editorially
retracted.
• Dr. Hwang lost his position at Seoul
National University.
• The South Korean government
ended its financial and legal
support of his research.
November 24, 2005

“Being too focused on scientific development, I may

not have seen all the ethical issues related to my
research.”

Hwang Woo Suk

Morality of Human
Reproductive Cloning

• “Be fruitful and multiply” – assumed to be

natural, but IVF and cloning not mentioned in the
Bible
• Problems with cloned animals – most suffer
premature aging and other genetic problems.
Might be avoidable with better techniques?
• Biblical basis to condemn human reproductive
cloning?
Is adult human DNA cloning
moral?
• Some talents seem to be genetically influenced.
Musical ability seems to run in families. Cloning
using the DNA from the cell of an adult with the
desired traits or talents might produce an infant
with similar potential.

Yes
?
• A heterosexual couple in which the husband was
completely sterile could use adult DNA cloning to
produce a child. An ovum from the woman would
be coupled with a cell from the man's body. Both
would contribute to the child: the woman would
provide the "factory" for creating cells; the man
would provide the "genetic information." They
might find this more satisfactory than using the
sperm of another man.
Yes
?
 • Two lesbians could elect to have a
child by adult DNA cloning rather
than by artificial insemination by a
man's sperm. Each would then
contribute part of her body to the
fertilized ovum: one woman would
donate the ovum, which contains
some genetic material in its
mitochondria; the other woman the
Yes nuclear genetic material. Both would
have parts of their bodies involved in
? the conception. They might find this
more satisfactory than in-vitro
fertilization using a man's sperm
 • There is no guarantee that the first
cloned humans will be normal. The
No fetus might suffer from some disorder
that is not detectable by ultrasound.
They may be born disabled. Disorders
? may materialize later in life. Such
problems have been seen in other
cloned mammals. There is no reason
to assume that they will not happen
in humans.
 • Cells seem to have a defined life span built into
them. "Dolly" was created from a cell that was
about six years old; this is middle age for a ewe.
There were some indications that Dolly's cells

No were also middle-aged. She was believed to be, in

essence, about six years old when she was born.
She was expected to live only for five years, which
? is shorter than the normal life span of 11 years. If
this is also true of humans, then cloned people
would have a reduced life expectancy. The cloning
technique could take many years off their life.
[These fears proved to be unfounded. "Dolly" has
grown into a comfortable middle age with signs of
normal aging for her age.]
• Dolly was conceived using a ewe's egg and a cell from
another ewe's body. It is noteworthy that no semen from a
ram was involved. If the technique were perfected in
humans, and came into general usage, then there would be
no genetic need for men. All of the human males could be
allowed to die off. [The author of this essay is a male and
does not think kindly of such a future. However, some
readers might not object to this eventuality.]

No
?
• Large scale cloning could deplete genetic
diversity. It is diversity that drives evolution and
adaptation. It prevents an entire species from
disappearing because of susceptibility to a disease.
[It is doubtful that cloning would ever be used at
a level to make this a significant threat.]

No
?
• Some people have expressed concern about the
effects that cloning would have on relationships.
For example, a child born from an adult DNA
cloning from his father would be, in effect, a
delayed twin of one of his parents. That has never
happened before and may lead to emotional
difficulties.

No
?
There are religious objections to
cloning.
• Most pro-life supporters believe that a fertilized
ovum is a full human person. When its nucleus is
removed during cloning, that person is, in effect,
murdered.
• A secondary concern is the whole business of
collecting surplus embryos and simply storing
them in a deep-freeze as a commodity.

No
?
• Some claim that cloned humans may be born without souls.
They speculate that the soul enters the body when a sperm
fertilizes an ovum. Since there is no sperm involved in
cloning, perhaps the fetus would develop without a soul.
There is no way to know whether a soul is present; it has no
weight, it cannot be seen, touched, smelled, heard, or
detected in any other way. In fact, many people believe that
souls do not exist. Speculation on this topic can never be
resolved.

No
?
Fun of Human Cloning