Stem Cells:
Science and Ethics
By Dr. Rizwana Rahim
Chicago, IL
From research labs to the media,
the places of worship, the public squares, the government
corridors to the White House, very few scientific
issues have generated as much interest and controversy
in recent years as have the stem cells. And, if
it weren’t for Dolly, the sheep (first mammal
ever cloned from an adult cell), whose birth was
announced in 1997, most people would have continued
to think of ‘cloning’ as just science
fiction. With all this, also follow public concerns,
confusion and controversies – some of which
even managed to get into last year’s election
debate.
The basic feature of a stem cell is its potential
and ability (i) to become (or differentiate itself
into) any specific type of tissue (liver, nerves,
skin, etc), i.e., it is ‘pluri-potent’
or ‘toti-potent’, and (ii) to divide
and proliferate almost continuously, i.e., its self-renewal
to build a pool of unspecialized and undifferentiated
cells, much like the original stem cell, with the
same ability to grow into any other cell of any
type of tissue (but without actually transforming
themselves into any other specific cell-type, while
kept in culture).
An early embryo is one of the sources of stems cells
of highest quality. In humans, for instance, a 5-7
day old embryo (more than a week before its implantation
in the uterus) is the best source. An egg, when
fertilized (i.e., a zygote), begins to divide and,
in 5-7 days becomes a hollow ball (0.14 mm in diameter)
of about 100 cells (blastocyst) . The inner mass
of the blastocyst contains just a few embryonic
stem cells (ESCs). In a normal, growing embryo,
these ESCs will continue to divide and get programmed
(i.e., committed or destined) to become specialized/differentiated
cells for different organs.
Although the extraction of ESCs kills the embryo,
the ESCs themselves can grow and proliferate in
Petri dish cultures and keep their initial identity
and flexibility. Human embryonic stem cells (HESCs)
in culture can also be induced, when grown in Petri
dishes (in vitro), to differentiate into various
specific tissue-type or organ cells. Most of this
has been done with animal ESCs, and when the induced
ESCs are implanted in animals with injury in that
organ, they migrate to the damage site to regenerate/repair
the damaged tissue. Its therapeutic use in humans
is still years away, but as the animal data are
being confirmed, though on a limited scale, the
prospects of HESC use for therapeutic and regenerative
purposes appear promising and bright. People with
a number of now-incurable tissue injuries or various
diseases (from nervous system-related multiple sclerosis,
Alzheimer's, Parkinson's to Type I diabetes, cancer
and those involving the immune-system) can then
hope to find some cure. Notable in the public pressure
is the advocacy of such celebrity patients as Christpher
Reeves (the ‘Superman’ fought it bravely
till his death) and Michael J. Fox, and the family
of many others (including President Reagan’s).
In addition to early embryos, stem cells can be
extracted from three different places : (i) fetuses
(generally aborted), (ii) umbilical cords, and (iii)
adult tissues. However, stem cells from none of
these sources are in general as flexible as ESCs.
Those from adult tissue, besides being free from
the objections and controversy that others face,
offer occasional hope but these stem cells do not
remain stable in culture (i.e., replicate themselves
indefinitely as the ESCs do), and turn soon into
the specialized cells of that tissue, which limits
their ability to be coaxed into any other tissue
cells. A gene (Oct4) which keeps the ESCs stable
in their original state during their culture has
been isolated; addition of this gene to adult stem
cell cultures could also keep them longer in the
original state and prevent them from becoming a
specialized cell, but it is still in early experimental
stages to materialize as a viable option.
Most of the moral/ethical and religious controversies
surround HESCs, because it involves human experimentation
with, and on, human fetuses, and the embryo is destroyed
when its stem cells are extracted. This also raises
the specter of a possible ‘slippery slope’,
reminders of the ‘Brave New World’ and
‘The Boys from Brazil’ scenarios. That
is, HESCs used in factory-style production of human-organs
and in the universally reprehensible human cloning
and human-engineering for designer genes and traits.
Such fears were triggered in 1997 by the birth-announcement
of cloned Dolly. Since then, a lot has happened.
A number of other cloned animals have been created,
recently a cat. A year ago, a team led by South
Korean scientist, Woo Suk Hwang, created a cloned
human embryo, and about a month ago, they, in collaboration
with US scientists, extracted stem cells from cloned
embryos of a macaque monkey. They also grew 11 batches
of stem cells, derived from the skin cells of patients
of genetic immune disorders, spinal cord injuries,
and diabetes. Since these stem cells came the donors
themselves, they were a genetic match: this important
finding does allay the fears of immunologic rejection
which is likely with established stem cell lines.
The South Korean effort has received a lot of support
($26 million), including another $1 million just
recently; the kind of support that no American researchers
have received from the US Government because of
the restrictions. The UK authorities have just given
permission to Ian Wilmut (Dolly’s ‘creator’)
for research on motor neuron diseases using HESCs.
As if the HESC science itself wasn’t complicated
enough and the public opinion on it weren’t
already too polarized, the government also stepped
in a few years ago. President Bush, in a national
TV address on 9 August 2001, announced that federal
support for research will be restricted ONLY to
the HESC lines established and available up to that
day. No federal support for either the creation
of new HESCs or research on them. These restrictions
do not affect research efforts in the private sector.
He also created “National Bioethics Advisory
Commission” (NBAC) to oversee the implementation
of his decision, and also said that HESC research
raises "fundamental questions about the beginnings
of life and the ends of science." Since the
government funding supports most research conducted
in US academic and research institutions, these
restrictions have had an enormous impact on US research
and scientists. Dozens of congressmen and respected
scientists (many Nobelists, among them) have appealed
Bush’s decision, but without any effect.
Now, access to the approved HESCs itself has become
a major issue. On the day federal restriction went
into effect, there were about 60 such viable HESC
lines. Since then, because of various problems,
only 22 of these lines are now available, which
further strains the scope of federally funded research.
The other major problem is the possible contamination
in the existing HESC lines. Since all available
HESC lines were cultured on a scaffolding of mouse
‘feeder’ cells, it is possible that
human cells may have acquired some features of a
mouse cell, including a mouse cell-surface sugar
which differs from its human counterpart by one
oxygen atom. A lot of basic research done with these
HESCs seems not only compromised, but these HESCs
may also be NOT suitable for clinical studies. If,
for instance, these HESCs (or their derivatives)
are implanted in humans, the mouse cell-surface
sugar may be enough to make them appear as ‘foreign’,
which may provoke a major immunologic response and
eventual rejection of the implanted cells. The private
sector is now busy trying to develop a non-biological
scaffolding for establishing fresh, contaminant-free
HESC lines. It has been reported that Reproductive
Genetics Institute (Chicago) already has 105 HESC
lines from normal embryos, and 20 HESC lines with
mutations.
Since the Presidential restrictions of August, 2001,
one ray of hope is a recent development : just a
few weeks ago, the US House of Representatives passed
the Stem Cell Research Enhancement Act, HR 810 (by
238 votes to 194); its chances in the Senate appear
encouraging. This effort was initiated by Coalition
for the Advancement of Medical Research (CAMR) of
over 90 patient groups, universities and scientific
societies. Though the Presidential threatens to
veto it, a Senate sponsor of the Bill, Republican
Arlen Specter, claims to have enough Senate support
to overrule the Bush veto if it comes to that. The
act would allow federally funded researchers the
use of HESCs derived from spare or rejected IVF
embryos, provided the couples who donate them are
not paid; however, various non-governmental research
groups in the US already have access to hundreds
of cell lines from similar human embryos. NIH Director,
Dr. Elias Zerhouni, and others agree that the current
US Stem cell policy is not sufficient, and have
testified in Congressional committees to that effect
In addition to the scientific and political problems,
HESC research also faces major moral, ethical and
religious questions, arising from concerns over
the protection and destruction of life as an individual.
Some are very basic questions, such as: At what
stage does the life really begin? At fertilization,
or at uterine implantation, or at birth? Is embryo
an individual that needs protection under the law?
Since extraction of HESCs leads to the destruction
of embryo, is it considered tantamount to deliberate
killing or murder of an individual? For in vitro
fertilization (IVF), embryos are created and frozen
for later use, and extra ones are sometimes discarded:
Is using extra, to-be-discarded embryos for HESC
extraction also equivalent to killing individual
life? Is work with embryos a form of human experimentation?
What guarantees are there that HESC research would
not go down the ‘slippery slope’ to
human organ factories and human (or reproductive)
cloning?
Scientific interpretations of when the individual
life actually begins may not offer much help to
theologians and ethicists. For instance, biologically
and genetically, one could say the life starts when
the egg is fertilized. Embryologically, it is more
complicated: Since twins can be formed as late as
12 days after conception, one could say that the
individual life starts after this period, which
ensures that an embryo produces one individual,
not two. Physiologically, one can view individual
life starting when the fetus is able to survive
on its own, separately and independently (that is,
at birth after cutting the umbilical cord) .
The NBAC sought and included Judeo-Christian and
Islamic perspectives in its report (but unfortunately
none from Hindu, Sikh and Buddhist religious scholars
and groups). Jewish and Islamic (Sharia) perspectives
seem, by and large, clearer than those of Christianity.
The report notes many qualms over HESC research
and the views on when the individual life really
begins vary a lot, but no clear consensus even within
one faith group. These opinions are summarized as
follows:
Jewish : Abortion to save a mother’s life
is allowed; opinions on using such fetuses for research
“morally neutral.” A fetus is considered
part of woman’s body (not a separate individual
life) up to 40 days after fertilization. HESCs in
culture are not considered human because they do
not exist in the womb.
Christian: Considerable variation exists. The Catholics
think life begins at fertilization and deliberate
destruction of an embryo (for research or any other
purpose) immoral, and abortion is tantamount to
taking life. The Protestant view seems a little
flexible. According to an ABC News poll (2000),
among evangelical white Protestants, 50% supported
stem cell research, with 40% opposing. The same
poll showed 54% of Catholics favoring this research,
but in a church poll in which embryo destruction
was mentioned in the question a great majority of
Catholics (70%) opposed the research. A research
poll which mentioned possible cure of ‘deadly
diseases’ but didn’t mention embryo
destruction received 77% support.
Islamic (Sharia): Minor differences exist between
Sunni and Shia views. Abortion for health reasons
is allowed, and since ‘ensoulment’ is
believed to occur 4 months after fertilization,
only after this is the fetus considered sacred life.
It is neutral on HESCs and research on them.
If you wondered why so much fuss about human embryonic
stem cells, this account would give you just a glimpse
of the bioethics and bio-politics involved.
Selected References:
1. http://stemcells.nih.gov/index.asp
[NIH Stem cell Info page]
2. National Academy of Sciences Committee on the
Biological and Biomedical Applications of Stem Cell
Research, Board on Life Sciences National Research
Council, and Board on Neuroscience and Behavioral
Health Institute of Medicine. "Stem Cells and
the Future of Regenerative Medicine." Washington,
D.C.: National Academy Press, 2001. http://www.nap.edu/books/0309076307/html/
3. Bush, President George W. "Remarks by the
President on Stem Cell Research" made on August
9, 2001. http://www.whitehouse.gov/news/releases/2001/08/20010809-2.html
4. National Bioethics
Advisory Commission. "Ethical Issues in Human
Stem Cell Research, Volume III: Religious Perspectives."
Rockville, Maryland: NBAC, 2000. http://bioethics.gov/pubs.html
(Dr Rizwana Rahim
holds a PhD in Biological Sciences. She has been
a senior researcher with Toxicology-Cancer, Chicago,
and has taught courses in various biology areas
from general, cell and molecular biology to human
physiology & anatomy and ecology in different
Chicago-area universities and colleges. Her articles
in science, politics and other areas have been published
in various English and Urdu newspapers of the Indo-Pak
subcontinent, including Dawn, Nation, Pakistan Journal,
Pakistan Link, India Worldwide, Deccan Chronicle,
Siasat, Rahnuma-e-Deccan)
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