Declaration on the Production and the Scientific and Therapeutic Use of Human Embryonic Stem Cells, Vatican City, August 25, 2000.
document seeks to contribute to the debate on the production and use
of embryonic stem cells which is now taking place in scientific
and ethical literature and in public opinion. Given the growing relevance
of the debate on the limits and liceity of the production and use of
such cells, there is a pressing need to reflect on the ethical implications
which are present.
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 Astem
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,[i]
in embryonic tissue and in in vitro cultures
of embryonic stem cells of experimental animals.[ii]
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 following[iii]:
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;[iv]
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,
results of these experiments had a great impact on the world of both
science and biotechnology -
especially 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.[vi]
But the impact was greatest in the political world.[vii]
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 cloning[viii]
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
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
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 "cybrid". This
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,[ix]
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,[x] and in importing the desired genes into
stem cells or progenitor cells which, when implanted, are able to restore
specific functions to damaged tissue.[xi]
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 Aadult
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: AProgress
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 Ademonstrates
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@
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
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,[xiii]
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
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.[xiv]
From this it follows that as a Ahuman
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 Ajus
certum tertii" the system of probabilism does not apply.[xv]
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
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:
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).[xvi]
The second ethical problem can be formulated thus: Is it morally licit to engage in so-called Atherapeutic cloning" by producing cloned human embryos and then destroying them in order to produce ES cells?
The answer is negative, for the following
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
The 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.
In conclusion, it is not hard to see the seriousness
and gravity of the ethical problem posed by the desire to extend to the
field of human research the production and/or use of human embryos, even
from an humanitarian perspective.
The possibility, now confirmed, of using adult
stem cells to attain the same goals as would be sought with embryonic
stem cells - even if many further steps in both areas are necessary before
clear and conclusive results
are obtained - indicates that adult stem cells represent a more reasonable
and human method for making correct and sound progress in this new field
of research and in the therapeutic applications which it promises.
These applications are undoubtedly a source of great hope for a
significant number of suffering people.
The Vice President
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