Memorandum 51
Submission from Human Genetics Alert
SUMMARY
Human Genetics Alert is a secular watchdog group
which is not opposed to research on embryos or embryonic stem
cells. We would support a ban on the creation of animal/human
hybrid embryos for the following reasons: (1) the proposed experiments
are of little scientific value; (2) we oppose the creation of
embryos purely for purposes of research and (3) the strong public
concerns about the unnaturalness of creating human/animal hybrids
is valid and must not be ignored. Banning such research would
have a positive effect upon UK stem cell research, since scarce
reserch funding and the time of top scientists would not be diverted
onto research of very little value. In its report, we urge the
committee to present a more balanced and accurate account of the
proposed research than the misleading account its proponents have
put forward, and to move the ethical debate on the status of embryos
on to the ethical middle ground upon which the law is based.
1. INTRODUCTION
Human Genetics Alert (HGA) is an independent
secular watchdog group. We are not opposed to research on embryos
or embryonic stem cells.
The author of this submission, Dr David King,
is the Director of HGA. He is a molecular biologist who has been
working for the past 16 years on ethical and social issues raised
by genetic and reproductive technologies.
2. SCIENTIFIC
ISSUES
2.1 Misleading descriptions
We are very concerned by misleading desciptions
of these experiments which have been made by the scientists themselves
and cannot be blamed upon the media. An egregious example of this
is the suggestion that "these cells are 99.5% human and not
.5% animal", which is no doubt intended to suggest that the
fact that their cells are inter species hybrids is only marginally
relevant, and that biologically they will be practically identical
to human cells. This is based on the grossest form of genetic
reductionism i.e. the assumption that the biological characteristics
of the cells can be read off simply from the respective proportions
of DNA from the different species. In fact, at least up to the
blastocyst stage the vast majority of mass and volume of the embryos
will be of bovine or rabbit origin.
Crucially, the statement ignores the interaction
between cytoplasmic factors in the cow eggs and the human nuclear
DNA, which is essential for the correct reprogramming of the human
nuclei to begin embryonic development. As we will discuss below,
it is very unlikely that correct reprogramming will occur. So,
in reality, the fact that these are inter species hybrids is crucially
relevant to the likely success of the experiments. It is difficult
to avoid the conclusion that scientists who know much better than
this have intentionally misled the public in order to to emphasise
the likely success of their experiments and to suggest that concerns
about the unnaturalness of creating interspecies hybrids are misplaced.
An even worse example of misleading language
occurs in the letter to the Times, which refers to animal eggs
as "the activating casing for cloned human embryos".
Here, the genetic reductionism is so extreme that the egg cytoplasm
is nothing more than "casing", and the emphasis on the
importance of the nuclear DNA is so great that it is seen to actually
make the embryos simply human, rather than interspecies hybrids.
Again, the calculated effect is to dismiss concerns about the
unnaturalness of interspecies hybrids.
The Committee should also noted that the expected
"humanisation" of its mitochondria are a PROBLEM, for
the stem cells, not, as has been suggested, a solution. As the
human nuclear genome becomes active, it will produce many proteins
which will migrate to the animal mitochondria, producing mitochondria
with mixed species proteins. It is very likely that the human
proteins will interact improperly with the animal proteins, thereby
rapidly killing off mitochondria which produce the cell's energy.
It is likely that this is a major source of the poor viability
of such subcellular hybrids.
It is unfortunate that the scientists have not
put any detailed account of the scientific rationale of their
experiments into the public domain, let alone any attempt to deal
with the very serious (and obvious) defects of their plans. Instead,
the the public is presumably supposed to judge whether these experiments
are worthwhile simply on the basis of trust in famous scientists.
We expect that the many senior scientists who signed a letter
to The Times in support of their publicity campaign have not seriously
looked into the details of the planned experiments: instead, as
is sadly too typical of the debate in this country on stem cell
research, they will have signed the letter on the basis of their
general support for scientific research and their disdain for
what they see as woolly-headed and probably religiously-based
ethical concerns. We therefore see the need to enumerate a number
of the serious scientific defects of these experiments, in order
to encourage an informed debate about their merits.
2.2 Scientific defects of the proposed research
2.2.1 Likelihood of obtaining embryonic stem
(ES) cell lines
As far as we are aware there are no authenticated
reports of cloned human ES cell lines, and only one report of
ES cell lines from interspecies hybrids. Various laboratories
around the world have been attempting to create such embryos and
stem cells for at least eight years, and as far as we know this
effort has produced only one, unreplicated published report of
success. Despite considerable effort, it appears very difficult
to obtain ES cell lines from cloned human embryos. It is certainly
to be expected that the efficiency of obtaining stem cell lines
from cloned interspecies hybrid embryos will be even lower. Yet
in order to achieve statistically significant results in their
experiments it will be necessary to obtain at the very least five
experimental and five control cell lines for each condition to
be studied.
The low efficiency of obtaining stem cell lines
from cloned embryos derives, of course, from the unnaturalness
of nuclear transfer which requires the complete reprogramming
of differentiated cell nuclei to an embryonic state. We question
whether a useful strategy for dealing with this problem is to
make the problem even more difficult by making interspecies clones
in which the cytoplasmic factors and their nuclear correlates
will probably be mismatched. This is a strategy of simply applying
brute force (ie creating huge numbers of embryos due to the easy
availability of bovine and rabbit eggs). In our view the lowered
efficiency of interspecies hybrids is likely to mean that that
the scientists will waste a huge amount of time creating thousands
of embryos with very little positive results. If these scientists
must insist on using nuclear transfer, their time would be better
employed in studies of the mechanism of reprogramming, in order
to improve its efficiency.
It is instructive to compare conventional genetic
engineering with the creation of subcellular hybrids. It is now
well known and that genetic engineering of a single gene often
fails because the gene disrupts chromosome stability, or is "silenced"
by the host genome, or the protein disrupts cellular metabolism
or other structures. In the proposed experiments, the scientists
are hoping for hundreds, maybe thousands of cross-species molecular
interactions, between both the mitochondria and cytoplasm of the
egg and nuclear genes and proteins to work perfectly, in order
to produce a normal cell. In our view, it is optimistic in the
extreme to expect this to work.
2.2.2 Embryonic stem cell lines from cloned interspecies
hybrid embryos will be abnormal
Even if ES cell lines can be obtained from hybrid
embryos it is almost certain that they will contain subtle abnormalities
in gene expression which will invalidate any experimental results
obtained with them. It is now well established that cloned animals
are abnormal due to genetic and gene expression defects, and it
is to be expected that these gene expression defects, which result
from incomplete reprogramming of the nuclear DNA will be present
in any stem cell lines derived from cloned embryos. We are aware
that there is some evidence that it is possible to obtain some
cloned stem cell lines which appear normal: however, the burden
of proof must remain upon those who seek to claim that all such
stem cells are normal.
These abnormalities resulting from nuclear transfer
will undoubtedly be compounded by further errors and abnormalities
resulting from the interspecies mismatch, and from the presence
of animal mitochondria. Even worse, it appears that each cloned
stem cell will have a different set of gene expression abnormalities.
Overall, these experiments are likely to be a study primarily
of artefacts. Patient organisations would be wise to treat results
from them with great scepticism.
2.2.3 Necessity of this research
Apart from the methodological problems mentioned
above, the usefulness of these experiments is highly questionable.
The experiments proposed by the Edinburgh and
London groups aim to investigate early molecular events in the
aetiology of late onset conditions which will not manifest symptoms
for several decades. It seems quite unlikely that any relevant
events will be manifested within the time period that it is possible
to culture stem cell lines without accumulating chromosomal and
other abnormalities. Researchers into Motor Neurone Disease already
have at their disposal a mouse model containing SOD1 mutations
which would appear to be perfectly suited to obtaining the kind
of data that these researchers seek.
The experiments proposed by the Newcastle group
appeared to be aimed at developing the methodology for so-called
"therapeutic cloning". It is now accepted by most researchers
(including Professors Wilmut and Austin Smith) that the scenario
of "therapeutic cloning" as a widely used treatment
for disease. is highly unlikely to ever be realised. Biomedical
companies are not pursuing this solution partly because of the
epigenetic defects caused by cloning, and partly because it would
be absurdly expensive, and would only be available to the rich.
It would also be highly impracticable, requiring the acquiring
of expertise in embryo manipulation and tissue culture in each
hospital. There would be further major problems with quality control
for individualised batches of tissue. Instead, biomedical companies
are pursuing alternative approaches to the problem of immune rejection
of tissue.
Finally it must be noted that, the target of
the Newcastle experiments, type 1 diabetes, can never be a candidate
for treatment by this method, since it is an autoimmune, not a
degenerative disease. Any transplanted tissue will be destroyed
by the patient's immune system in the same way that he is his/her
own tissue was in the first place.
SUMMARY OF
SCIENTIFIC ISSUES
Reporting and public debate on these issues
has been based upon an assumption that the proposed research is
of high quality and likely to produce important data which could
contribute to cures for serious diseases. In our view, because
of the the methodological problems inherent in creating cloned
interspecies hybrids and other problems with the experimental
designs, this is very far from true. Whilst there are always uncertainties
in medical research, these experiments must be viewed as extremely
long shots. The responsibility for such misrepresentation must
rest squarely with the scientists and their publicists, who, as
we have shown above seem to have no scruples about using language
which obfuscates the nature of the embryos being created and to
minimise the methodological problems. This is disappointing but
not shocking: experience with the stem cell debate for the last
eight years has shown such linguistic manipulations and misrepresentations
of science to be the norm rather than the exception. However,
it is the role of the Science and Technology Committee not to
be taken in by such misrepresentation and to present a more balanced
account of the science as a basis for ethical discussions.
3. ETHICS
A crucial question in deciding whether the proposed
research should go ahead is the ethical status of the embryos
created. It is a completely unsatifactory situation that the debate
in Britain has become polarised between scientists, who view the
embryos as having no moral status and pro-lifers who view the
embryo as a person, whereas the law is based on a compromise position,
which views the embryo as a morally significant entity, which
must be treated with respect. As a result there is very little
debate on the ethical middle ground, which HGA supports and which
is supported by the majority of the UK population. It is the duty
of the Science and Technology Committee to restore the debate
to this middle ground. Those who are not pro-lifers are not absolved
of the duty of thinking about the ethics of maniplulating embryos.
The question of the moral status of embryos
created by these experiments is complicated by their inter-species
nature. It is certainly questionable whether scientists should
be permitted to create entities whose ethical status is uncertain.
However, in our view, they must be treated as human embryos for
the purposes of ethical discussion, for the following reasons.
Firstly, as the scientists argue that they are sufficiently biologically
equivalent to human embryos for valid medical research to be conducted
on them. Secondly, the HFEA has concluded that they fall under
the HFE Act. Thirdly, although it would be completely unethical
to do this, if such embryos were implanted and brought to term,
it seems probable that the resulting creature would be enough
like a human being to claim legal personhood. If that is so, it
follows that we should treat the embryos as a human embryo, from
an ethical point of view.
If that is the case, then these experiments
raise important ethical issues, since they would create an embryo
purely for the purposes of research. We do not believe that embryos
are persons with a right to life. However, UK law is based on
the concept that embryos are morally significant entities and
must be treated with respect. We believe that the creation of
embryos purely as a source of biological raw material and as a
means to an end (as a tool for research), and not for the purpose
of reproduction, fails to respect their moral status. It is this
view of the embryo as a mere thing which underlies efforts by
companies to obtain patents on embryos as, in patent parlance,
"compositions of matter".
This distinction between the use of surplus
embryos and the creation of embryos purely for research is widely
recognised around the world. Although there are many countries
which allow embryo research, the UK is one of only five countries
worldwide which permits the creation of embryos purely for research,
and we understand that even here, it is done very rarely.
We recognise that there may be different opinions
on this issue, which has barely been discussed in the UK. We urge
the Science and Technology Committee to discuss this issue and
not to fall into the usual polarised stalemate.
4. "UNNATURALNESS"
A dominant theme in the public reaction to proposals
to create interspecies hybrids has been revulsion, which has been
expressed in the argument that such hybrids are unnatural. The
Committee should not be misled by efforts to suggest that this
is a minority reaction based on religious or pro-life views. It
is undoubtedly the feeling of the vast majority of the population,
even when the same individuals also argue strongly in favour of
medical research. After 20 years of experience with GM food and
other issues, policymakers should know better than to dismiss
such views as "irrational". The point is that, in an
inarticulate form, they express extremely valid concerns about
science and the manipulation of nature. We should also bear in
mind the important distinction between facilitating a natural
process (as in IVF) and forcing nature to do something which it
would never do naturally (as in cloning and creation of interspecies
hybrids). Although it can be argued that all of modern medicine
is unnatural, some things are more unnatural than others.
In view, public reactions about the unnaturalness
of creating hybrid embryos is about two main concerns: (i) the
lack of any respect for natural limits in the ideology of science,
and (ii) the importance and meaning of species barriers.
4.1 Science and natural barriers
It is beyond the scope of this response to make
general statements about science and the manipulation of nature,
other than to emphasise that the current environmental crisis,
and earlier events of the 20th century have surely demonstrated
adequately that such concerns are very real. A naive equation
of science and technology with progress will simply no longer
do. In the present context, it is important to realise that the
public's concerns about the unnaturalness of cloned interspecies
hybrids is less about the question raised by conventional and
academic ethics—"is this right or wrong?"—as
about the question, "is this wise?". The question about
scientists' wisdom refers to science's inherent unwillingness
to respect any natural limits or barriers and its determination
to overcome them "by any means necessary". This can
be seen at work in the present context: when scientists find that
an unnatural technique (cloning) works very poorly, precisely
because of its unnaturalness (cell differentiation in development
normally works in one direction only because this is needed to
create a predictable body plan for the organism), they seek to
overcome this by brute force of numbers, by using animal eggs;
but in doing so they add a further level of unnaturalness to the
process (the species barrier), thereby increasing the odds against
success. Is this intelligent or wise? We are not surprised that
the public views this as a prime example of scientific lack of
wisdom. Although philosophers like to dismiss the naturalistic
fallacy in ethics, it would appear that the question of naturalness
is, after all, relevant, at least to the question of whether particular
scientific interventions are wise.
Concerning the existence of limits to scientific
manipulations of nature, there is an important distinction between
different types of interspecies hybrid. Scientists have assumed
that it is enough to reassure the public that no monster will
be born and that all they are doing is manipulating a few cells.
But paradoxically, public concern about the proposed experiments
is, in all probability, to some extent heightened rather than
diminished by the fact that we are talking about the manipulation
of embryos rather than animals or human beings. If we transplant
animal tissue into a human being, the result will unquestionably
be a human being. Manipulations at the level of organs or fully
developed organisms (other than brain or reproductive organs)
do not raise questions about the identity or species status of
the resulting entity. However, manipulations at the subcellular
level (as here), which can only be accomplished by intervening
at the earliest stage of organismal development, can potentially
result in much more profound changes in the resultant physiology
and behaviour of the fully developed organisms, which do raise
questions about the species status of the resulting entity. It
is the vulnerability of the embryo to such profound manipulation
which excites concern, and raises valid questions about whether
there should be a limit to scientists' manipulation of nature.
4.2 Species barriers and their meaning
Before discussing the reason for public revulsion
at interspecies hybrids it is first necessary to clear away one
piece of dead wood. It is true that interspecies hybridisation
does occur in nature. However, it only happens between closely
related species and the offspring are generally infertile. These
are merely exceptions which proves the general rule that the biological
utility of speciation is the creation of separate gene pools.
Hybridisation across orders and at the subcellular level is completely
unnatural.
In order to understand public revulsion, it
is necessary to explore a fundamental difference in philosophical
worldview between scientists and ordinary people. According to
the materialist and molecular reductionist worldview of scientists,
biological nature is composed of several types of complex macro
molecules, which are composed of strings of small molecules common
to all species. The only difference between species derives from
minor differences in the ordering of small molecules within the
long chains. In principle, for example, the difference between
mitochondria from cattle and humans could be completely described
by compiling a catalogue of the sequence differences in the genes
that code for mitochondrial proteins etc.
This worldview does not admit of the idea of
qualitative breaks in nature: nature looks rather like a well-blended
soup. Within this paradigm, species differences are a matter of
drawing an arbitrary line, and are to some degree illusory and
unreal, a matter of quantitative not qualitative differences.
This worldview is clearly apparent in the statements that stem
cells derived from hybrid embryos are '99% human, 0.5% animal,
or even that, rounding up, they are simply "human".
Like genetic engineering, the mixing of human DNA and animal eggs
is unproblematic in this view, because the two are not 'really'
different in kind.
The ordinary person's worldview, which focuses
on organisms rather than molecules is quite different. In this
view, species are very definitely distinct, integrated wholes,
different "kinds". Their characteristics are quite different
and are what define the species: leopards have spots, zebras have
stripes. Children's stories and folktales are preoccupied with
these differences and their origin. We are not experts in anthropology,
and we recommend that the Committee call anthropologists as witnesses;
however we would conjecture that species differences are crucial
in constructing a view of nature and of the world as composed
of qualitatively different entities. Although apples and pears
are closely related species, it is proverbially impossible to
substitute one for the other, because they are qualitatively different.
It may be further conjectured that the human psyche has a need
for clear categories and for putting different items into separate
pigeon holes.
The basis of revulsion, and of taboos is the
inadmissible mixing of things that are different and should be
kept apart, and the creation of entities that do not fit neatly
into existing categories. In this view, hybrid animals, such as
a pig with a head of a chicken, which cannot be clearly put in
one box or the other are monsters, not merely because of their
hideousness (which is merely an aesthetic expression of a lack
of wholeness), but because they are not integrated wholes. A something-in-between
has no place in the world. Such feelings are obviously heightened
when one of the hybrid species is human, since additional issues
of identity, legal rights and psychological issues come into play.
There is no doubt that the scientific materialist
worldview is correct, at one level. However, where it fails is
in providing any satisfactory account of how assemblages of very
similar molecules come to produce species as obviously different
as rabbits, cows and humans. There is as yet no good theory of
the generation of "emergent properties" in complex biological
systems.
An emergent property of very complex systems
that emerge through long processes of evolution is an integrity
and internal harmony and a rigidity to manipulation that we might
call wholeness. Even natural selection cannot produce arbitrary
concatenations of physiological characteristics that we see in
fanciful or mythical hybrids: there is more than one physiological
reason why pigs do not fly. In the same way, as we noted in section
1, it is asking a very great deal for subcellular interspecies
hybrids to work. It is not necessary to invoke mystical or Aristotelian
concepts of "telos" to recognise that the wholeness
and qualitative difference in embodied in different species is
real and cannot be wisely or profitably tampered with, willy-nilly.
Yet in contrast to evolution's slow process of elimination of
that which does not work well together, scientists persist with
trying to use the crude tools at their disposal to bodge something
together in a hurry. They should not be surprised that these efforts
are regarded with derision and revulsion by the public.
The wholes (species) that evolution produces
do have to be regarded as qualitatively distinct, and the barriers
between them need to be respected. It seems that the commonsense
view of nature is, at the organism and species level, not only
a better description than the molecular reductionist view, but
is based on necessities of physiology and ecology that we might
call, "the wisdom of nature".
SUMMARY OF
SECTION 4
Expressions of revulsion, and unnaturalness,
are based on legitimate concerns about science and its unwillingness
to set limits on manipulations of nature. Such views are not dependent
upon particular religious convictions and have no lobby groups
to represent them, as do scientists and patients, which is partly
why we have been at such pains to explain them. The problem is
not so much public misunderstanding as scientists' misunderstanding
of the public. Scientists' inability to understand revulsion at
breaching species barriers is based on a difference of fundamental
worldview. Both worldviews have their merits: what is needed is
mutual understanding, not dismissals of the public as irrational.
5. CONCLUSION
Human Genetics Alert supports the Government's
decision to ban such research. In our view, it is unethical and
of extremely little scientific value. The strong public opposition
to such research cannot be dismissed as due to misunderstanding
or "irrationality", as if scientists had some monopoly
on rationality. It is based on serious concerns, about science
and its lack of respect for natural limits. Instead of lecturing
the public on its irrationality, scientsts would do better to
critically rexamine their own worldview, and their often emotional
and knee-jerk reactions to the idea of curbs on research.
In our view the Government should not insert
the power to make regulations to overturn the ban into the Act.
As with the genetic engineering of human embryos, it is important
that any decision to reverse the ban should receive full parliamentary
scrutiny, and the possibility to amend the text, which is afforded
by debate on primary legislation, but not when changing regulations.
We believe that the decision to ban such research
would have a positive effect on UK stem cell research, by not
diverting research funding and the effort of top scientists into
research will have little value.
January 2007
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