|DECLARATION ON THE PRODUCTION AND THE SCIENTIFIC AND THERAPEUTIC USE OF HUMAN EMBRYONIC STEM CELLS|
|Pontifical Academy for Life
first section will very briefly set out the most recent scientific data on
stem cells and the biotechnological data on their production and use.
The second section will draw attention to the more relevant ethical
problems raised by these new discoveries and their applications.
some aspects need to be studied more thoroughly, a commonly accepted definition
of "stem cell"
describes it as a cell with two characteristics: 1) the property of
an unlimited self-maintenance—that is, the ability to reproduce itself
over a long period of time without becoming differentiated; and 2) the capability
to produce non-permanent progenitor cells, with limited capacity for
proliferation, from which derive a variety of lineages of highly
differentiated cells (neural cells, muscle cells, blood cells, etc.).
For about thirty years stem cells have provided a vast field
of research in adult tissue,1
in embryonic tissue and in in vitro cultures of
embryonic stem cells of experimental animals.2
But public attention has recently increased with a new milestone
that has been reached: the production of human embryonic stem cells.
Human embryonic stem cells
the preparation of human embryonic stem cells (human ES cells)
implies the following3:
1) the production of human embryos and/or the use of the
surplus embryos resulting from in vitro fertilization or
of frozen embryos; 2) the development of these embryos to the
stage of initial blastocysts; 3) the isolation of the embryoblast or
inner cell mass (ICM) - which implies the destruction of the
embryo; 4) culturing these cells on a feeder layer of irradiated
mouse embryonic fibroblasts in a suitable medium, where they can multiply
and coalesce to form colonies; 5) repeated subculturing of these
colonies, which lead to the formation of cell lines capable of
multiplying indefinitely while preserving the characteristics of ES cells
for months and years.
ES cells, however, are only the point of departure for the preparation of differentiated
cell lines, that is, of cells with the characteristics proper of the
various tissues (muscle, neural, epithelial, haematic, germinal, etc.).
Methods for obtaining them are still being studied;4
but the injection of human ES cells into experimental animals (mice) or
their culture in vitro in controlled environments to their confluence
have shown that they are able to produce differentiated cells which, in a
normal development, would derive from the three different embryonic tissue
layers: endoderm (intestinal epithelium), mesoderm (cartilage, bone, smooth
and striated muscle) and ectoderm (neural epithelium, squamous epithelium).5
results of these experiments had a great impact on the world of both science
medicine and pharmacology—no less
than the world of business and the mass media. There were high hopes that
the application of this knowledge would lead to new and safer ways of
treating serious diseases, something which had been sought for years.6
But the impact was greatest in the political world.7
In the United States in particular, in response to the long-standing
opposition of Congress to the use of federal funds for research in which
human embryos were destroyed, there came strong pressure from the National
Institutes of Health (NIH), among others, to obtain funds for at least using
stem cells produced by private groups; there came also recommendations from
the National Bioethics Advisory Committee (NBAC), established by the Federal
Government to study the problem, that public money should be given not only
for research on embryonic stem cells but also for producing them.
Indeed, persistent efforts are being made to rescind definitively the
present legal ban on the use of federal funds for research on human embryos.
pressures are being brought to bear also in England, Japan and Australia.
had become clear that the therapeutic use of ES cells, as such, entailed
significant risks, since - as had been observed in experiments on mice—tumours resulted. It would have
been necessary therefore to prepare specialized lines of differentiated
cells as they were needed; and it did not appear that this could be done
in a short period of time. But,
even if successful, it would have been very difficult to be certain that the
inoculation or therapeutic implant was free of stem cells, which would
entail the corresponding risks. Moreover
there would have been a need for further treatment to overcome immunological
incompatibility. For these
reasons, three methods of therapeutic cloning8
were proposed, suitable for preparing pluripotent human embryonic stem cells
with well defined genetic information from which desired differentiation
would then follow.
The replacement of the nucleus of an oocyte with the nucleus of an
adult cell of a given subject, followed by embryonic development to the
stage of blastocyst and the use of the inner cell mass (ICM) in order to
obtain ES cells and, from these, the desired differentiated cells.
The transfer of a nucleus of a cell of a given subject into an
oocite of another animal. An
eventual success in this procedure should lead - it is presumed - to the
development of a human embryo, to be used as in the preceding case.
The reprogramming of the nucleus of a cell of a given subject by
fusing the ES cytoplast with a somatic cell karyoplast, thus obtaining a
is a possibility which is still under study.
In any event, this method too would seem to demand a prior
preparation of ES cells from human embryos.
scientific research is looking to the first of these possibilities as the
preferred method, but it is obvious that—from a moral point of view, as we
shall see—all three proposed solutions are unacceptable.
Adult stem cells
studies on adult stem cells (ASC) in the last thirty years it had been
clearly shown that many adult tissues contain stem cells, but stem cells
capable of producing only cells proper to a given tissue.
That is, it was not thought that these cells could be reprogrammed.
In more recent years,9
however, pluripotent stem cells were also discovered in various human
tissues—in bone marrow (HSCs), in the brain (NSCs), in the mesenchyme
(MSCs) of various organs, and in umbilical cord blood (P/CB, placental/cord
blood); these are cells capable of producing different types of cells,
mostly blood cells, muscle cells and neural cells.
It was learnt how to recognize them, select them, maintain them in
development, and induce them to form different types of mature cells by
means of growth factors and other regulating proteins.
Indeed noteworthy progress has already been made in the experimental
field, applying the most advanced methods of genetic engineering and
molecular biology in analyzing the genetic programme at work in stem cells,10 and in importing the desired genes into
stem cells or progenitor cells which, when implanted, are able to restore
specific functions to damaged tissue.11
It is sufficient to mention, on the basis of the reported references,
that in human beings the stem cells of bone marrow, from which the different
lines of blood cells are formed, have as their marker the molecule CD34; and
that, when purified, these cells are able to restore entirely the normal
blood count in patients who receive ablative doses of radiation and
chemotherapy, and this with a speed which is in proportion to the quantity
of cells used. Furthermore,
there are already indications on how to guide the development of neural stem
cells (NSCs) through the use of various proteins—among them neuroregulin
and bone morphogenetic protein 2 (BMP2)—which can direct NSCs to become
neurons or glia (myelin-producing neural support cells) or even smooth
note of satisfaction, albeit cautious, with which many of the cited works
conclude is an indication of the great promise that "adult
stem cells" offer for effective treatment of many pathologies. Thus the affirmation made by D. J. Watt and G. E. Jones: A
The muscle stem cell, whether it be of the embryonic myoblast lineage, or of
the adult satellite status, may well turn out to be a cell with far greater
importance to tissues other than its tissue of origin and may well hold the
key to future therapies for diseases other than those of a myogenic nature"
(p. 93). As J. A. Nolta and D.
B. Kohn emphasize: "Progress
in the use of gene transfer into haemotopoietic cells has led to initial
clinical trials. Information
developed by these early efforts will be used to guide future developments.
Ultimately, gene therapy may allow a number of genetic and acquired
diseases to be treated, without the current complications from bone marrow
transplantation with allogeneic cells." (p. 460); and the confirmation
offered by D. L. Clarke and J. Frisén: "These studies suggest that
stem cells in different adult tissues may be more similar than previously
thought and perhaps in some cases have a developmental repertoire close to
that of ES cells" (p. 1663) and "demonstrates
that an adult neural stem cell has a very broad developmental capacity and
may potentially be used to generate a variety of cell types for
transplantation in different diseases" (p. 1660).
progress and results obtained in the field of adult stem cells (ASC) show
not only their great plasticity but also their many possible uses, in all
likelihood no different from those of embryonic stem cells, since plasticity
depends in large part upon genetic information, which can be reprogrammed.
it is not yet possible to compare the therapeutic results obtained and
obtainable using embryonic stem cells and adult stem cells.
For the latter, various pharmaceutical firms are already conducting
which are showing success and raising genuine hopes for the not too distant
future. With embryonic stem
cells, even if various experimental approaches prove positive,13
their application in the clinical field—owing precisely to the serious
ethical and legal problems which arise—needs to be seriously reconsidered
and requires a great sense of responsibility before the dignity of every
the nature of this article, the key ethical problems implied by these new
technologies are presented briefly, with an indication of the responses
which emerge from a careful consideration of the human subject from the
moment of conception. It is
this consideration which underlies the position affirmed and put forth by
the Magisterium of the Church.
first ethical problem, which is fundamental, can be formulated
thus: Is it morally licit to produce and/or use living human embryos for
the preparation of ES cells?
answer is negative, for the following reasons:
1. On the basis of a complete biological analysis, the living human embryo is—from the moment of the union of the gametes—a human subject with a well defined identity, which from that point begins its own coordinated, continuous and gradual development, such that at no later stage can it be considered as a simple mass of cells.14
2. From this it follows that as a "human individual" it has the right to its own life; and therefore every intervention which is not in favour of the embryo is an act which violates that right. Moral theology has always taught that in the case of "jus certum tertii" the system of probabilism does not apply.15
Therefore, the ablation of the inner cell mass (ICM) of the
blastocyst, which critically and irremediably damages the human embryo,
curtailing its development, is a gravely immoral act and consequently
is gravely illicit.
No end believed to be good, such as the use of stem cells for
the preparation of other differentiated cells to be used in what look to be
promising therapeutic procedures, can justify an intervention of this
kind. A good end does not
make right an action which in itself is wrong.
For Catholics, this position is explicitly confirmed by the
Magisterium of the Church which, in the Encyclical Evangelium Vitae,
with reference to the Instruction Donum Vitae of the Congregation for
the Doctrine of the Faith, affirms: "The
Church has always taught and continues to teach that the result of human
procreation, from the first moment of its existence, must be guaranteed that
unconditional respect which is morally due to the human being in his or her
totality and unity in body and spirit: 'The
human being is to be respected and treated as a person from the moment of
conception; and therefore from that same moment his rights as a person must
be recognized, among which in the first place is the inviolable right of
every innocent human being to life'"(No. 60).16
The second ethical problem can be formulated thus: Is it morally licit to engage in so-called "therapeutic cloning" by producing cloned human embryos and then destroying them in order to produce ES cells?
answer is negative, for the following reason:
The third ethical problem can be formulated thus: Is it morally
licit to use ES cells, and the differentiated cells obtained from them, which
are supplied by other researchers or are commercially obtainable?
answer is negative, since: prescinding
from the participation—formal or otherwise—in the morally illicit intention of the principal agent, the case in question
entails a proximate material cooperation in the production and manipulation of
human embryos on the part of those producing or supplying them.
Vatican City, August 25, 2000.
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Congregation for the Doctrine of the Faith, Instruction on Respect for
Human Life in Its Origins and on the Dignity of Procreation "Donum
(22 February 1987), Acta Apostolicae Sedis 1988, 80, 70-102.
Congregation for the
Doctrine of the Faith, op. cit., I, no. 6;
C.B.Cohen (ed.), "Special Issue:
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T. Shapiro, "Ethical and Policy Issues of Human Cloning", Science
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A. Serra, "Verso la Clonazione dell'Uomo? Una
Nuova Frontiera della Scienza",
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ibid., "La Clonazione Umana in Prospettiva 'Sapienziale'",
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