|
This is a preprint of an article accepted for
publication by the Journal of Medical Ethics and may not save under the
fair dealing of the provision of the Copyright Designs and Patents Act
(1988) be reproduced without the consent of the BMJ Publishing Group
Embryonic stem cell production through
therapeutic cloning has fewer ethical problems than stem cell harvest
from surplus IVF embryos
John-Erik Stig Hansen, Centre for Rare Diseases and
Disabilities, Copenhagen, Denmark
Abstract
Restrictions on research on therapeutic cloning
are questionable as they inhibit the development of a technique which
holds promise for succesful application of pluripotent stem cells in
clinical treatment of severe diseases. This article argues that the
ethical concerns are less problematic using therapeutic cloning compared
with using fertilized eggs as the source for stem cells. The moral
status of an enucleated egg cell transplanted with a somatic cell
nucleus is found to be more clearly not equivalent to that of a human
being. Based on ethical considerations alone, research into therapeutic
cloning should be encouraged in order to develop therapeutic
applications of stem cells.
Keywords: cloning, stem cells, embryo status,
human emergence
Production of embryonic stem cells from
unfertilized egg cells transplanted with a nucleus from e.g. a patient
cell ('therapeutic cloning') may result in immunologically compatible
replacement tissues in severe degenerative or inherited diseases like
Huntington's chorea, Parkinson's disease, multiple sclerosis or cystic
fibrosis. [1, 2, 3] At present research and development involving human
embryonic stem cells is restricted in many countries, and in some only
the use of embryonic stem cells derived from the blastocyst stage (day
6) of fertilized eggs that are in surplus from fertility treatment is
recommended. [4, 5, 6] Specifically, the Council of Europe has
prohibited the creation of human embryos for research purposes. As stem
cell based treatment may be beneficial to patients suffering from severe
disease and as therapeutic cloning may offer a way to generate
clinically superior stem cells, the present resistance to allow this
technique to be developed through research may seem unethical at first
glance. The resistance, however, is a result of two overriding
concerns.
First, harvest of stem cells include the destruction of the pre-embryo
at the blastocyst stage, and if the pre-embryo at this stage is
recognized as a human being with a inalienable right to life this would
prohibit stem cell harvest whether the blastocyst were a result of
therapeutic cloning or came from a surplus fertilized egg.
Second, the technique of therapeutic cloning is the same technique as
that used in the initial stage of reproductive cloning where an
enucleated egg cell is transplanted with a somatic cell nucleus and
implanted in a susceptible uterus in order to produce an infant.
Development of therapeutic cloning may therefore be feared to pave the
way ('slippery slope') for an otherwise unacceptable use, and this risk
may be considered sufficiently great to prohibit therapeutic cloning
despite the potential benefits to patients.
Would a human being resulting from reproductive
cloning be a regular human with full human rights? Judging from animal
experiments where it has been possible to bring progeny to full term
birth after initial transfer of a somatic cell nucleus to an enucleated
egg cell it is difficult to foresee that such a being would be anything
other than fully human. From experience with reproductive cloning of
animals there is a significant risk that a cloned human being would have
a shortened life span or that it would have various inborn disabilities
or malfunctions. [7, 8] At present, this known risk would make human
reproductive cloning unethical. But like other human beings born with
chromosomal abnormalities or genetic disorders there will probably be no
doubt that a cloned human is a full human being in every important
respect. If that is the case one is naturally confronted with the
question whether an enucleated human egg transplanted with a somatic
cell nucleus - a 'transnuclear egg cell' - is any different from a
fertilized egg which would normally be the initial start of the process
leading to a human being. And if there are no significant differences
then it would follow that an egg cell with a nuclear transplant is a
human being to the same extent that a fertilized egg is - or is not - a
human being. However, I suggest that the biological differences might be
morally significant.
The genetic complement of the fertilized egg is a unique result of a
fusion of a sperm cell and an egg cell, and this may naturally evolve
into an embryo, a fetus and eventually an infant. This is not the case
with an enucleated egg cell that has been transplanted with the nuclear
material from a somatic cell. Neither is the genetic content unique, for
it is identical with the nuclear donor, nor is it occurring naturally
with a natural potential of evolvement into an embryo. It is entirely
artificial and leads its life in the laboratory unless somebody chooses
to implant it into a susceptible female uterus before it can develop to
the blastocyst stage when stem cell harvest is possible.
Among the arguments put forward to consider a fertilized egg a human
being one key argument is that the genome is unique from fertilization
onwards and that the development of a unique individual is a consequence
of the workings of this unique genome. It is argued (e.g. in Donum
Vitae) that the individual person is determined by the unique genome,
and from the time this genome arises, one should consider the person to
be present. [9]
The genome in question is the nuclear genome, for the mitochondrial DNA
of the egg cell cytoplasm is not unique to a particular fertilized egg
since it is inherited without the recombination at fertilization between
the maternal and paternal nuclear DNA. Indeed, apart from random
mutations occuring rather infrequently, the mitochondrial DNA is
identical through the maternal blood-line over generations. Therefore,
the uniqueness of every human person cannot in any case be based on
mitochondrial DNA, and the fact that in a transnuclear egg cell the
nuclear genome is combined with a non-natural mitochondrial genome has
no bearing on the genetic uniqueness that is suggested to be the basis
for human uniqueness. To use an analogy one might say that the heart (=
mitochondrial DNA) in a heart transplanted patient has no relevance for
the identity of the patient even though the combination is 'unique' in
this particular patient.
Apart from the reductionism implied, in my opinion the entire argument
of deriving human uniqueness from genetic uniqueness is flawed since
identical twins have identical genomes but are evidently separate
individuals. However if emphasis is none the less placed on the
uniqueness of the new genetic complement (the nuclear genome) of a
fertilized egg the differences between a fertilized egg and a
transnuclear egg cell would be significant and the transnuclear egg cell
could not be considered a human being even if a naturally fertilized egg
cell were to be so considered. The genome of the transnuclear egg cell
already exists in the cells of the donor of the nucleus. So either one
must give up the notion that human individuality is related to genetic
uniqueness or accept that a transnuclear egg cell is not a human
individual.
It has been argued that all existing humans have started as a fertilized
egg and as this is perceived to be the common root of all human beings a
special moral significance must be warranted. [6] The fertilized egg has
been the natural beginning of every human being regardless of whether
this has come about through sexual intercourse, artificial insemination
or in vitro fertilisation. It is therefore argued that the purpose
embedded in nature itself of a fertilized human egg is to develop into a
human being.
While the concept of natural purpose may be dubious - consider for
instance that the far majority of naturally fertilized eggs perish
before term - the purpose of a transnuclear egg cell is clearly not
defined by nature. [10] Therefore, if emphasis is placed on the natural
purpose of a fertilized egg to evolve into an embryo and eventually a
human being, the transnuclear egg cell would fall outside the category
of human beings as there are no natural occurences where a transnuclear
egg cell develops into a fetus. As all other artifacts it's purpose is
properly defined through human design.
It may therefore be questionable whether the biological in vitro entity
resulting from therapeutic cloning should be considered a human embryo
or pre-embryo at all. Rather it seems to be a modified egg cell that
might be turned into an embryo through further artificial procedures.
It could be argued that the potential of an in
vitro blastocyst to develop into a fetus after a series of contingent
procedures including succesful implantation confers a special moral
status whether the blastocyst is a result of in vitro fertilization or a
result of nuclear transfer from a somatic cell to an unfertilized,
enucleated egg cell. The 'potentiality' argument has been used to argue
in favour of full human moral status of the fertilized egg from
fertilization onwards: what might naturally (i.e. without further
external intervention) become a human being should be considered a human
being already.
In the strict sense potential means that an entity can perform or be
something that it at present doesn't or isn't. This requires first
identity (i.e. that it remains what it is in some key aspect) and second
that the potential is inherent (i.e. that it doesn't require something
essential from outside). In the case of the in vitro blastocyst having
potential for personhood neither of these two conditions are met.
Evidently the blastocyst cannot be a newborn child, it may become one,
and while this process could happen 'in the ordinary course of events'
it might also result in two or more children (twinning) or it might not
happen at all, whether through natural malfunction or through a decision
not to implant the fertilized or transnuclear egg. From this it may be
seen that neither is identity necessarily preserved nor is the process
independent of external conditions and contingent decisions by other
actors. Although the in vitro blastocyst may form an essential basis for
the subsequent emergence of a person it isn't one in itself, and human
moral status cannot be inferred from a potential which it doesn't
inherently have in the first place.
Nevertheless, on the basis of the essential role the fertilized egg or
blastocyst has in the formation of the biological matrix from which a
person could emerge one might decide to confer some special respect or
moral status to it or even respect it as if it were a human person.
Whether such a social construct is well-founded or not falls outside the
scope of this paper, but has been discussed elsewhere. [11]
As any other cell of the human body, the
unfertilized egg cell is a physical component of a human being. Isolated
in the laboratory as human cells in culture are in thousands of
laboratories, such cells are biological matter without any reasonable
claim on special rights or status by themselves even though they are
indeed human and alive, as are blood cells donated for transfusion or
organs donated for transplantation. If experiments are made with such
cell cultures this does not change the moral status of the cells.
Chemical components may be injected, DNA transferred and life
extinguished without such cells changing moral status. If the nucleus is
removed and another put in, and the transnuclear cell grown for a few
days while dividing and forming a culture as all cells will do in the
proper artificial circumstances, would this make a human being appear
when the cell in question was an egg cell rather than, say, a muscle
cell? Clearly not. The knowledge that if further potential procedures
were in fact undertaken, namely transfer into a prepared female uterus
at a specific time, this might subsequently result in a pregnancy and
eventually the birth of a 'cloned' human being cannot change the status
of the transnuclear egg cell from a cell in culture to a human being in
unusual circumstances. This would run contrary to all cause-effect
relations both temporally and logically.
So, it would seem that an egg cell in moral
respects is just like any other cell, and that it doesn't change moral
status after it's being enucleated and subsequently transplanted with a
nucleus from a somatic cell. However, after implantation in a uterus and
at least after nine months of cell divisions and further development an
unquestionably human being may evolve. If one considers personhood to be
something inherent rather than a social construct, then there must
necessarily be a time when the human personhood appears. For the
transnuclear egg cell the earliest time could possibly though not
necessarily begin after the last contingent, artificial intervention
would have been necessary, i.e. when the transnuclear egg cell was
implanted in a susceptible female uterus.
Implantation is, at the present technological stage, an absolute
requirement, and it must take place in a very brief window of time (in
the first 2-4 days of development). If it is not implanted, further
development in vitro allows formation of the blastocyst, from which stem
cells may be harvested, but embryonic and fetal development does not
take place. So, in the series of decisions and manipulations in vitro
which a transnuclear egg used to establish a pregnancy would have been
the object of before it passes beyond the direct voluntary control of
the technician (and others), implantation is the last, contingent
artificial intervention. If it is decided to implant the transnuclear
egg at the right time, it will begin embryonic development; if it is
decided not to implant, the transnuclear egg will form an in vitro
culture from which stem cells can be harvested, and these stem cells may
possibly be kept alive for many years in embryonic stem cell banks
without reason to suggest that cells or tissues derived therefrom should
begin to develop personhood and human moral status.
Recognizing that an implanted transnuclear egg changes status and
develops human personhood at some time within the nine months of
pregnancy, implantation represents the earliest possible timepoint when
this may begin to happen. One might also say the same for an IVF
fertilized egg, but as the previous sections have shown, the case for
the transnuclear egg cell not being endowed with personhood or human
moral status is even stronger than for the fertilized egg, and
consequently the necessity of a change in status is that much
clearer.
If blastocysts by some future technical development could be maintained
in culture and fetal development sustained, a human being would
eventually emerge. The time at which this emergence might be possible
depends on the criteria used for personhood. Twinning may occur
spontaneously until formation of the primitive streak after 14 days of
pre-embryonic development and until that time individuality is not a
property of the pre-embryo. As individuality is a sine qua non for
personhood it seems safe to consider 14 days of normal embryonic
development to be the minimum requirement before a human being can
emerge. Other criteria might place the earliest time-point at a later
stage, e.g. 28 days when the neural tube closes and the development of a
central nervous system necessary for rationality begins. Or with
Aristotle and St. Thomas Aquinas one might consider 40-90 days of
development to be necessary to allow a human soul to be present, or as
the Roman Catholic church taught for centuries one might require body
form and movement to be present before full human status was recognized.
[12] In the context of stem cell harvest from the inner cell mass of the
blastocyst at day 6, which is about the time when an IUD ('coil') blocks
implantation in women using this device to avoid pregnancy, none of
these considerations of the earliest possible time for emergence of a
human being support the blastocyst as a person.
Having considered the possible moral status of the
transnuclear egg cell resulting from therapeutic cloning and having
found that stem cell production including destruction of the blastocyst
does not violate the fundamental human right to life it may still be
warranted to prohibit this technique as it may be percieved to pave the
way for reproductive cloning. However, there is no inherent necessity
why this should be so. Refinement of the technique of therapeutic
cloning to produce stem cells does not automatically result in
reproductive cloning. It requires a separate decision to implant the
transnuclear egg cell before it reaches the blastocyst stage where stem
cell harvest is possible. Indirectly, the technical expertise learned
from therapeutic cloning could be seen as instrumental in reproductive
cloning, as would other kinds of technical expertise involving e.g. cell
culture or hormonal regulation.
If therapeutic cloning is recognized as of potential benefit to
patients, where no other curative remedies exist, it seems ethically
questionable to block development of this technology based on a
hypothetical misuse of that technology. Generalising such a position to
other areas of medicine one would quickly end in absurdity. It would
clearly be unethical to abstain from treating a heart patient with
digitalis based on the fear that somebody else might use digitalis as a
deadly poison. If reproductive cloning should not be allowed to happen,
then that is what should be prohibited. Specifically this would require
prohibition of implantation in a female uterus of a transnuclear egg
cell.
Six days after in vitro fertilization or nuclear
transplantation the blastocyst forms a ball of cells. From this
biological matter in vitro, pluripotent stem cells or other biological
products of value for the treatment of medical illnesses may be derived
without compromising the fundamental human right to life even though
such a procedure entails the destruction of the blastocyst and thus the
irreversible elimination of the possibility for fetal development after
implantation into a uterus. Production of embryonic stem cells from
transnuclear unfertilized egg cells seems to entail even fewer ethical
problems than harvest of stem cells from fertilized eggs in surplus from
fertility treatment. Combined with the considerable therapeutic
potential in production of immunologically compatible - and perhaps even
genetically modified - tissue from such transnuclear stem cells, this
should make somatic nuclear transfer into unfertilized egg cells a
preferred technique that warrants encouraging incentives and focused
research effort rather than legal restrictions.
References
1 Liu S, Qu Y, Stewart TJ, Howard MJ, Chakrabortty
S, Holekamp TF, McDonald JW. Embryonic stem cells differentiate into
oligodendrocytes and myelinate in culture and after spinal cord
transplantation. Proceedings of the National Academy of Science USA
2000;97:6126-31.
2 Schuldiner M, Yanuka O, Itskovitz-Eldor J,
Melton DA, Benvenisty N. Effects of eight growth factors on the
differentiation of cells derived from human embryonic stem cells.
Proceedings of the National Academy of Science USA 2000;97:11307-12.
3 Munsie MJ, Michalska AE, O'Brien CM, Trounson
AO, Pera MF, Mountford PS. Isolation of pluripotent embryonic stem cells
from reprogrammed adult mouse somatic cell nuclei. Current Biology
2000;10:989-92.
4 Lenoir N. Europe confronts the embryonic stem
cell research challenge. Science 2000;287:1425-7.
5 Nuffield Council on Bioethics. Stem cell
therapy: the ethical issues. London: Nuffield Council on Bioethics,
2000.
6 Det Etiske Råd. Kloning. Copenhagen: The Danish
Council of Ethics, 2001.
7 Hill JR, Roussel AJ, Cibelli JB, Edwards JF,
Hooper NL, Miller MW, et al. Clinical and pathologic features of cloned
transgenic calves and fetuses (13 case studies). Theriogenology
1999;51:1451-65.
8 Smith LC, Bordignon V, Babkine M, Fecteau G,
Keefer C. Benefits and problems with cloning animals. Canadian
Veterinary Journal 2000;41:919-24.
9 Congregation for the doctine of the faith.
Instruction on respect for human life in its origin and on the dignity
of procreation (Donum vitae). Acta Apostolica Sedis 1988;80:65-105.
10 Hertig AT. The overall problem in man. In:
Benirschke K, ed. Comparative aspects of reproductive failure. New York:
Springer Verlag, 1967; p. 11-41.
11 Watt H. Potential and the early human. Journal
of Medical Ethics 1996;22:222-6.
12 Donceel JF. Immediate animation and delayed
hominization. Theological Studies
1970;31:76-105.
|
