To What Extent Should Animal
cloning Be Permitted?
Maurizio
Salvi
International
Forum for Biophilosophy, UK Leuven, e-mail: Maurizio.Salvi@cec.eu.int
Introduction
In 1996 the birth of ‘Dolly’, the first mammal cloned, has
opened discussions among biologists and the public about the desirability of
such a technology (Terragni 1999, Dijck 1998). The public has plaid a decisive
role in decisions associated to cloning both in the US and Europe (Simon
1999). This is surprising when we think that cloning (CL) was not a new
technology. The first experiments of nuclear transfer with amphibians (Rana pipiens and Xenoplus
laevis) were performed in the United States and Britain during 1950s
(Gordon & Colman 1999:743-746) to study the irreversibility of the modification of
genetic material of differentiated cells from adult animals. Nuclear transfer
experiments were performed in amphibians in the 1960s, in mice in the 1970s,
in sheep in the 1980s, and in monkeys in the 1990s. They have provided
evidence that fully differentiated somatic cells retain all the genetic
material of the early embryo, and that differentiation is almost entirely
achieved by reversible changes in gene expression.
In
this paper I will deal with implications arising from animal cloning. It is
not my intention to minutely report the history of cloning (see Gordon &
Colman 1999:743-746) or to analyse legal implications that such a technology
may involve. Here I will explore is both the biological and ethical
implications that animal cloning may rise if performed in animal breeding
programmes.
Dolly Superstar.
‘Dolly’
is a well-known name among scientists. She is the first mammal to develop from
a cell derived from adult tissue[1].
Dolly derived from cells that had been taken from the udder of a 6-year old
Finn Dorset ewe and cultured for several weeks in a laboratory. These cells
were then fused with unfertilised eggs from which the genetic material had
been removed. Biologists cultured 276 of these reconstructed eggs' for 6 days
in temporary recipients. Twenty-nine of the eggs that appeared to have
developed normally up until the blastocyst stage were implanted into surrogate
Scottish Blackface ewes. Dolly’s birth
drafted a revolutionary way for producing engineering animals. In fact, the
normal sexual reproduction (the fertilisation of an egg by a sperm and the
inter-parental chromosomes fusion) was substituted with a reproductive system
by which “DNA is removed from an unfertilised egg and the egg fused with a
diploid cell containing a full set of paired chromosomes” (Wilmut, April
1997). Successively, the obtained eggs had been implanted in a surrogate
mother, in whose womb they developed into lambs[2].
The
successful experiment performed by members of the Roslin Institute offered a
new technique for producing genetically modified animals. Instead of
pronuclear injection, which leads to the production of 2-3% of transgenic
animals, the nuclear transfer technique leads to an easier and more successful
production of GM animals[3].
To summarise, Dolly’s birth has achieved the
following scientific goals:
(1) The complete genetic material
from an adult mammalian cell has been used in the development of a new
individual for the first time; and (2) donor cells, induced to exit the growth
phase and become quiescent before being used for nuclear transfer, are more
susceptible to reprogramming by the recipient egg cell and result in the
normal development and birth of cloned offspring (Wilmut et al. 1997).
After
the successful experiment with Dolly, several laboratories have begun to work
on different applications of animal cloning. In 1997, Dr. Pennisi announced
the cloning of a transgenic lamb (Polly)
cloned from cells engineered with a marker gene and an undisclosed human gene.
Dr. Pennisi’s experiment showed that “foreign DNA can be introduced to a
genome without disrupting the genetic interactions that guide a lamb’s
development” (Pennisi 1997). Successively
biologists have also begun to clone goats, cattle[4]
and monkey (see Revel, 2000:43-59). Currently a number of experiments are
taking place to check whether all animal species are clonable (Cohen 2000:4).
Why cloning animals?
According
to the Roslin Institute in Edinburgh animal cloning can achieve a number of
scientific goals: 1) Human therapeutic proteins; 2) Organs and tissues for
transplants; 3) Nutriceuticals; 4) 'Humanised' cows milk Animal models of
disease; 5) Cell therapy agents. In April 1997, Dr Wilmut has summarised the
applications of animal cloning as follows:
Applications
in Medicine
Human
Therapeutic proteins |
Transgenic
sheep, goats and cattle can be used as bioreactor to produce human
protein in milk (for example: alpha-1-antitrypsin). Cloning could reduce
the number of animals needed for creating a transgenic line |
Xenotransplantation |
NTT
could lead the production of pigs in which pigs’ proteins inducing
rejection are removed and replaced by their human counterparts. |
Nutriceuticals |
NTT
ought to produce transgenic cows producing human proteins |
Animal
models of disease |
Transgenic
animals can be produced by using different animal species than the used
ones. This extension might allow the creation of better models for
testing treatments for human pathologies |
Cell
therapy |
NTT
could solve immune rejection problems. We could use cells removed from a
patient and successively reintroduce the patient’s cells
(bioengineered) in the organism |
Applications
in Biological Research
Ageing
& Cancer |
NTT
avoids DNA replication’s mistakes –somatic mutations- and subsequent
ageing and cancer processes |
Alternatives
to Embryo Stem Cells |
Embryo
stem cells have only been recovered from two specific strains of mice
(and not from any livestock species). Nuclear transfer would allow gene
targeting in other strains of mice and in other laboratory species such
as rabbits and rats. |
Cloning |
The
ability to produce large numbers of genetically identical animals would
have important benefits in experimental design. The advantages of
genetic uniformity have been amply demonstrated in studies with inbred
lines of mice. Nuclear transfer from cultured cells could provide
alternative approach in species where repeated inbreeding is impractical
or prohibitively expensive. |
Gene
Targeting in Farm Animals
Improving Transgenic Animals
Production |
NTT
can substitute a procedure called 'pronuclear injection'. The limits of
this technique were: 2-3% of GMOs are transgenic, only a portion of
transgenic animals completely express the modified exogenous DNA.
|
Opening new Possibilities |
NTT
opens the possibility of specific genetic manipulations that are
currently impossible, such as the substitution of a single letter in DNA
(typical of many human genetic diseases) |
These
potential applications of the nuclear transfer technique show that both medical research and industrial biotechnology
have an interest in animal cloning. In
this paper, however, I will focus on animal cloning for breeding
program purposes.
The
extremely high similarity between clones’ genotypes, in fact, would allow
manufacturing organisms having improved strains of livestock. One of the major
benefits of cloning, then, is the possibility of creating populations of
genetically determined organisms responding to the needs of both the animal
breeding industry and the research community.
Biological implications of
cloning.
Contrary to the common perception, a clone
is not a carbon copy of its ancestor. Gene plasticity, environmental factors,
and neural topography structures differentiate clones from their parents. Even
if clones have a high genetic similarity compared to their parents, the claim
that a clone is a carbon copy of another individual is biologically false and
it refers to genetic determinism[5].
A number of biological factors deny the claim that clones are carbon copy of
their ancestors (Revel 2000): 1) Dolly’s mitochondrial DNA comes from the
egg donor (usually mitochondrial DNA comes from the mother); 2) Dolly’s
immune system genes are not developed at the embryo stage (Dolly has a
different immune system from her mother).
The
above mentioned differentiation-factors are reinforced by the influence that
environmental factors have towards the phenotypic expression of a genotype.
“Phenotypic identity requires identity between genotypes, which cloning can
ensure, and identity between environmental interactions, which it cannot
ensure.” (Eisemberg, 1999). A cloned DNA, thus, will express differently in
the phenotype of different clones. Nevertheless, the similarity between two
clones is so high as to show two identical individuals. This coincidence is
only apparent, since two clones have a range of constitutive qualitative
dissimilarities (Kolata 1998).
In
1997, Prof. Hubbard has explained in an editorial published in The
Nation (1997) the non-coincidence of cloned individuals. He underlined
that “Dolly has the same DNA (or genes) in the nucleus of her genes. But,
although embryologists have a way of forgetting it, an egg is not an empty bag
containing nothing but a nucleus, transplanted or not. Eggs also contain
structural and metabolic equipment, including a complement of extranuclear DNA
specific to that individual. The second ewe did not contribute her nucleus,
but she did contribute the rest of contents of her egg. The reconstituted egg
was than gestation in the uterus of yet another ewe. Dolly is, indeed, a
nuclear DNA clone, but there is more to life than DNA for sheep.”
Biologically speaking, animal cloning involves a number of
implications[6].
We may distinguish two levels of implications: implications for the cloned
organism (individual specific consequences) and implications that such a
technology may cause at a species-specific level. Let us start with the first
kind of implications.
Scientists
observed that the mortality of clones is high. Currently, 50% of clones perish
during pregnancy (perinatal mortality). This abnormal perinatal mortality rate
may suggest that cloned individuals have physiological weakness[7]
(Cohen 1998:4). Another implication of cloning refers to sexual reproduction
mechanisms. A clone develops from a cell derived from an adult tissue. It is
not resulting from a chromosomal fusion (maternal / paternal chromosomes) but
it derives from a cell of only one organism. As such, clones are anomalous
biological individualities since their genotype is a copy of the nucleus of a
donor.
In
parallel, clones do not have a definite age and we cannot say what parental
relation exists with their genitor. As Wilmut noted “One of the more
interesting questions about Dolly concerns her age. As far as her DNA goes, is
she one year old or seven? And will she age prematurely? The premature death
of a number of clones seems to suggest that biologically speaking clones’
biological clock runs faster than other animals (Cohen 1999).
At the species-specific level cloning leads to a number of
biological implications (ecological and evolutionary implications). The first
consequence of cloning would be the impossibility to foresee the long-term
consequences that may arise from the use of such a technology. The affirmation
of bioengineered gene pools, in a repetitive number, could interact with
mechanisms of population genetics by causing the affirmation of specific
allelic frequencies that may lead to epidemics or deleterious outcomes towards
the Natural evolution (adaptation).
We have no ideas about consequences that such a pressure on the Natural
evolution may cause. As Prof. Eisemberg has said, “genetic homogeneity is
compatible with adaptation to a very narrow ecologic niche; when that niche is
perturbed (…) extinction may follow” (Eisemberg 1999:472). Thus, cloning
may cause an increase of pathogenic gene frequencies at a population level or
the loss of adaptive capacities.
In
parallel, a massive use of cloning may seriously damage biodiversity. The
continuous mix of genetic data via sexual reproduction is a basic mechanism of
the Natural evolution. The possibility of continuously recombining genetic
data allows adaptive processes (Gordon 1999). Biologically speaking, the
advantage of biodiversity is without controversy. The primary source of
genetic variations in living beings is genetic mutation ‘and’ cell
division. The first one creates new genetic information that will be naturally
selected over time, the second one reshuffles the random genetic changes
created by mutations. Clearly a large-scale use of cloning may affect
biodiversity and favour the consolidation of specific allelic frequencies at a
population level having a negative impact towards the Natural balances. Seen
in this light, cloning is intrinsically hazardous.
To
summarise, cloning causes a number of biological problems:
1) Clones are not the carbon
copy of their parents, but they have an unnatural similarity rate with them so
high as to distort the population concept.
Members
of a population are reproductively isolated from the others. This clause
refers to species-specific similarities (genetic and phenetic similarities)
making the reproductive apparatus of species-specific individuals compatible.
However, the reproduction-condition among members of a species does not
involve their genetic coincidence. Cloning is biologically problematic since
it may distort the species-concept.
2) Clones can reproduce and
start a cascade of events by which a modified gene lineage could be
artificially consolidated at a population level.
Evolutionary
mechanisms could be completely affected by cloning. Man could cause the
affirmation of gene pools that do not respond to adaptive mechanisms. Clearly,
we have no ideas about the evolutionary response to these pressures.
Subsequent mutational factors could consolidate gene frequencies (at a
population level) that are different from the desired ones.
The
above mentioned factors show that cloning is biologically problematic.
Nevertheless, we should be aware that these implications concern also other
applications of animal genetics (for example, transgenic animals or chimeras).
Consequently, I claim that cloning does not posit different ethical implications
than the ones of transgenic animals and chimeras. To what extent are we allowed
to interact with the Natural evolution to create new-organisms responding to
human needs? Are we under the obligation to consider unforeseeable long-term
consequences of bioengineering Life as a ‘reasonable risk to pay’ in the
name of the human progress (or economic benefits)?
Animal Cloning.
To
date, a number of research institutes perform animal cloning experiments every
day all across the globe. This means that this application of animal
biotechnology has been considered morally legitimate. This is because, as I have
already said, one of the main benefits of animal cloning is the more rapid
dissemination of genetic progress from elite herds to the commercial farmer.
Thus, animal cloning constitutes an ideal tool to optimise both the cost/benefit
model and the effectiveness of animal breeding programmes. Let us start to
analyse the ethical legitimacy animal cloning by considering the benefits that
such a technology may bring forward.
According
to Dr Wooliams “The basic benefit for the biotechnology industry of cloning
will (be) … that it will lead to a high optimisation of engineering
organisms’ production. (…) Cloning could substitute artificial insemination
and embryo transfer in breeding programmes.
Farmers could receive cloned embryos of the most productive cows of elite
herds. Biotechnology industries could create catalogues that describe the
genetic merit of cloned organisms, their fertility, health and longevity[8]
(Woolliams 1997)”.
The
first objection to the ethical legitimacy of Woolliams’ hypothesis refers to
the effectiveness of cloning. The mortality rate of cloning is high. (1 out 277
tries to clone Dolly.) At the present, both the percentage of implanted embryos
that had a full-term development (2.5%, due to failure of genomic reprogramming
or imprinting –Revel, 2000:45) and the incidence of perinatal mortality, make
this technology really inefficient. However, although this ineffectiveness seems
to impede the use such a technology in human genetics (human reproductive
cloning), it does not represent a significant obstacle to obstruct animal
cloning. We can assume that, in a future, animal cloning will be more efficient
(Gordon & Colman 2000:743-746). Or we can argument that other techniques
used in animal biotechnology (pronuclear injection, for example) do involve a
high mortality rate as well (in transgenic animals production 95-98% of
genetically modified embryos are usually damaged and only 2-3% of the animals
born are transgenic). According to this, as we accept the high mortality rate of
producing transgenic animals, we should not think of this side effect of cloning
as a relevant problem. Otherwise we should be in opposition to both animal
cloning and transgenic animals production for safety reasons.
From
a philosophical point of view, the capacity to better derive live animals from
cultured cells may be considered as a pro cloning argument. In fact, as we think
ethically legitimate the production of transgenic animals in both animal
industry and research, we should claim the usability of animals in the fields of
animal cloning as well. We have seen that animal cloning can increase the
effectiveness of transgenic animals production[9].
As such it might be accepted by animal rights advocates as a way to decrease
both the mortality rate of animals used in research and animal suffering
(clearly in the respect of the animal welfare clause). Ontological approaches to
the animal rights issues (Regan’s theory, for example), should lead to similar
conclusions as well. If animals have an intrinsic value (or a moral status as subjects-of-a-life)
the production of newborn organisms (clones) should be considered legitimate in
itself. Particularly in those cases where clones inherit a healthy genotype that
has not been
modified to cause animal suffering (phenotypic expression of the cloned
genotype). What arguments can we provide to discuss animal cloning, which differ
from the ones posited to discuss the ethical implications of producing
transgenic animals?
Can
we say that two transgenes have a different moral status than two clones? Why?
What difference would diversify the moral implications arising from the
production of a transgene via pronuclear injection compared to the ones arising
from animal cloning?
Cloning
is only a technique! The ethical legitimacy of such a technology refers to the
conceptual reasons by which biologists and regulatory bodies have justified the
moral legitimacy of producing transgenic animals. This does not mean that animal
cloning is ethically unproblematic. It simply means that the moral implications
of animal cloning can be equated with the ones of manufacturing transgenic
animals. Those philosophical theories that do not accept the instrumental use of
animals for human purposes will automatically oppose animal cloning. On the
contrary, those views that admitted such a use of animals will consider animal
cloning as ethically legitimate.
In
my opinion, the main problem of animal cloning refers to the ethical legitimacy
of using animals for human purposes. And also in this case, my response to this
puzzle does not differ from the one I have claimed elsewhere (Salvi 2001):
animals are moral entities, but we can instrumentally use them in a restrictive
way (in those cases in which the expected goals are so good to justify the use
of animals, no alternatives are available and both the number and the suffering
of animals is minimised). Then I do not oppose animal cloning, but I wonder
whether we really need to clone animals. Industrial applications of cloning do
not justify animal cloning, since already existing technique used in animal
breeding programmes could be used to have improved strains of livestock. On the
contrary, research applications of animal cloning having a clear and
well-documented scientific goal (for example to explore the chemical process
inducing specific cell differentiation of ES cells), should be allowed when no
alternatives are available. This is not because animal cloning is ethically
legitimate from a moral point of view, but simply because the value of the
expected scientific goal is higher than the one of other industrial applications
of animal breeding. Therefore it is the relevance of expected goal that reflects
on the ethical implication of animal cloning and not the value attributed a
priori to such a demonised technology (a value that does not exist to me).
I
do know that some people will stress the relativity of the weighting system used
to define the goodness of the chosen scientific goal. But I do think that people
would accept that a clinical (or research) trial regulated by good clinical (or
research) practice protocols and scientifically justified as the only tool to
explore a scientific avenue which otherwise could not be followed, is not
equivalent than an application of animal cloning performed to have a easier
production of, say, goats with liver dysfunctions to produce higher quantity of 'pâté de fois gras'.
As
I have said, we do know that cloning is a technique
of molecular biology performed from long time. And we do also admit the
possibility of animal experimentation for research purposes (regulated by 3Rs
and animal welfare). Then, I do not see arguments to allow animal applications
of other routine techniques of Natural sciences (such as the production of
transgenic animals for research purposes) and reject cloning. If we follow the
anthropocentric view that legitimates the first conclusion, we then should
extend this claim to animal cloning as well. This means that I do disagree with
the claim that both animals and human beings occupy the same position into a
moral taxonomy. To me both the biological (linguistic and cognitive capacities)
and the socio-cultural (human beings as moral-community makers) features of
human beings justify the prevalence of human beings in a moral taxonomy and deny
biocentric ethics. But this does not imply that I deny the moral status of
non-human beings. It simply means that since human beings define the moral
relevance of the actions they do animal cloning needs to be absolutely
unavoidable and strictly regulated. And, following this line of reasoning, I do
not see moral arguments to oppose to animal cloning for research purposes but I
also do not see any reason to accept cloning as a technique to use in animal
breeding programmes when the expected goals are oriented only to maximise and
accelerate the animal breeding industry- oriented process.
Bibliography
·
Dijck
J. (1998) Imagenation of Genetics,
Huondsmills London, Macmillan Press
·
Eisemberg
L. (1999) ‘Would cloned humans really be like sheep?’ New England Journal of Medicine (340) 6:471-474
·
Gordon
J. & Colman A. (2000) ‘The
future of cloning’ Nature
(402):743-743
·
Gordon
J. (1999) ‘Genetic enhancement in humans’ Science
(283):2023-2024
· Kolata G. (1998) Clone: The Road to Dolly & the Path Ahead Morrow/Avon ISBN 0-68815-6924
·
Revel M. (2000)
'State-of-the-art on Research on Cloning of Whole Organisms', UNESCO IBC
Proceedings of the Sixth Session, pp. 57- 58
·
Salvi
M, (2001) ‘Transforming Animal Species: the Case of ‘Oncomouse’, Ethics
and Engineering Life (7), Boston-London: MIT, pp. 15-28
·
Terragni
F. (1999) Il Clone e il suo doppio, Milano, Mondadori
·
Wachbroit
R.,(1997) Genetic Encores: The Ethics of
Human Cloning, Report for the Institute of Philosophy and Public Policy
·
Cohen P. (1999) ‘Dolly’s
mixture’ New Scientist 1999, 4
September, p.5
·
Cohen P. ‘Dolly’s mixture’ New
Scientist 1999, 4 September, p.5
·
Cohen P. (1998) ‘Cloning by
numbers’ New Scientist
19/26 December 1998:28-29
[1]
The invention is covered by two patent applications filed by Roslin
Institute (Edinburgh) with a priority date of 31st August 1995:
PCT/GB96/02099, entitled Quiescent
cell populations for nuclear transfer and PCT/GB96/02098 entitled Inactivated
oocytes as cytoplast recipients for nuclear transfer. Roslin Institute
(Edinburgh) does not expect any granted patents to issue for at least
another 2-3 years.
[2]
The innovation of the nuclear transfer technique (NTT) was the use of
unfertilised eggs and their fusion with a cell that contained the genetic
endowment of only one organism.
[3]
“In cloning procedures generally, nuclei are extracted from cultured cells
that might have come originally from an embryo, a fetus or an adult
organism. The nuclei are inserted into egg cells which have had their
original nucleus removed, a process called nuclear transfer. In the initial
work at the Roslin Institute, the egg cells along with their transplanted
nuclei were then implanted directly into a foster mother, where they
developed and, in the case of Dolly, resulted in a viable offspring.” (http://www.sciam.com/explorations/090297clone/beardsley.html).
[4]
The NTT technique is actually used in Denmark and Australia to clone cattle
(Viborg Laboratories of Denmark’s National Institute of Animal Science,
and Monash University). The Danish team is using genetic material from dead
cows. They emptied oocytes of their DNA, take adult cells from cows’
ovaries, they fuse the empty oocyte with the empty cells and finally implant
the obtained blastocyst in a surrogate cow. On this topic see Coghlan A., New
Scientist 17, January 1998
[5]
“Yet it seems clear that some of these concerns, at least, are based on
false beliefs about genetic influence and the nature of the individuals that
would be produced through cloning. Consider, for instance, the fear that a
clone would not be an "individual" but merely a "carbon
copy" of someone else -- an automaton of the sort familiar from science
fiction. As many scientists have pointed out, a clone would not in fact be
an identical copy, but more like a delayed identical twin. And just as
identical twins are two separate people -- biologically, psychologically,
morally and legally, though not genetically -- so, too, a clone would be a
separate person from her non-contemporaneous twin. To think otherwise is to
embrace a belief in genetic determinism -- the view that genes determine
everything about us, and that environmental factors or the random events in
human development are insignificant.” (Wachbroit 1997)
[6] A biological implication of CL is that it has
revolutionised the concept of totipotency. At present, we cannot think of
germ cells as the ‘only’ totipotent cells anymore because NTT allows
somatic cells to originate a new organism. (ES cells have this capacity as
well.) In the light of this, we can think of totipotency as a capacity to
differentiate into nearly any cell type.
[7]
This mortality rate may decrease in a future when biologists will get a
better understanding of what determinants cause the death of clones during
pregnancy.
[8]
They could choose the sex of the embryo (male for beef and female for milk)
and would be guaranteed a genotype of proven performance in either low or
high input systems. The cloned embryo would be delivered to the farm in much
the same way as semen straws are today, perhaps from breeding companies
based overseas. (John Woolliams, Cloning
in farm animal production, 1997, RIO)
[9]
The claim the cloning does involve a high mortality rate would offer a
strong argument against cloning. However, new discoveries of biological
sciences (the possibility to use embryonic stem cells rather than eggs –New Scientist, 29 January 2000) can offer technical solutions for
this problem.
.