Memorandum 21
Submission from Christian Action Research
and Education (CARE)
EXECUTIVE SUMMARY
— There should be prohibition on the
placing of a live human embryo into an animal, on the creation
of an embryo containing cells made up of both human and animal
chromosomes, on the mixing of animal and human gametes for any
purpose and on the placing of a human cell nucleus into a nonhuman
egg stripped of its nucleus because:
— It involves unknown risks (leading
to tumour formation, cancerous cells and disease transmission,
along with the unknown but significant role of maternal mitochondrial
genes on both fertility and health, raising questions about the
purpose of the research).
— It is unnecessary research (the same
objectives for creating hybrid embryos have as much chance of
being realised without involving either cloning or hybrid embryos).
— It is unethical research (The unnatural
entities created will be less human than fully human embryos and
natural boundaries will be violated. In thus crossing the species
barrier, the definition of "being human" would no longer
be clear-cut).
1. INTRODUCTION
1.1 Christian Action Research and Education
(CARE) is a Christian charity, representing around 50,000 supporters,
which seeks to combine practical caring initiatives with public
policy on social and ethical issues.
1.2 The UNESCO Declaration on Bioethics
states that society must "... recognise the importance of
freedom of scientific research and the benefits derived from scientific
and technological developments, while stressing the need that
such research and developments occur within the framework of ethical
principles set out in this declaration and that they respect human
dignity, human rights, and fundamental freedoms."
1.3 The increasingly global character of
science and technology, as well as corporate and scientific interests
that wish to resist and limit regulation, are making it increasingly
challenging—and important—for current regulatory processes
to achieve a balance between democratic freedom and regulation.
However we are encouraged that, despite the vocal demands of some
scientists, the hesitation on the part of the Department of Health
and the HFEA to automatically permit the creation of hybrid embryos
indicates that there is a healthy caution in our regulatory processes.
1.4 Nevertheless, we are concerned that
a small group of scientists, who summarily dismiss the importance
of the 535 public responses that the original Science and Technology
Committee (STC) consultation received, expect their views to automatically
be given over-riding weight. The views of the public are central
to the democratic process because the methods, limits to and outcomes
of, research will impact all of society. The scientific community
cannot expect to regulate itself on matters that involve issues
beyond scientific research, issues touching on the very nature
of humanity by crossing a natural barrier between animals and
humans for the first time. Indeed, preventing the crossing of
this barrier is a principle reason for the enduring existence
of laws forbidding bestiality in this country.
2. UNKNOWN RISKS
2.1 Despite claims in the media and by scientists
that the proposed entities will be 99.5% human and thus will raise
no new safety or ethical issues about mixing animal and human
gametes, it is NOT fully understood what effect maternal mitochondrial
genes do have on an individuals' development and identity. Indeed,
indicators are that maternal mitochondrial genes actually play
a significant role in both fertility and health. The role of the
maternal mitochondrial genes should be neither underplayed nor
ignored by scientists and media. The use of animal eggs should
not be equated to the use of human eggs.
2.2 A research report published in Nature
confirms the significant impact of maternal mitochondrial genes
on development. [7]
2.3 Reprogramming human cells back to an
embryonic state is difficult enough using human eggs; using animal
eggs would introduce more uncertainties. The expression of genes
(through their coding of proteins) can be very different across
species and with the mixing of animal mitochondrial and human
genes current concerns over creating new embryonic abnormalities
will be exacerbated. Even in transgenesis, the interruption of
essential gene functions has severely limited the amount of genes
that can be successfully inserted into animal (or human) genomes.
Indeed, progress with xenotransplantation has stalled as a result
of concerns about inserting a few genes into animals and consequent
unknown development and rejection risks.
2.4 An acknowledged technical difficulty
with using human embryonic stem (hES) cells for both research
and treatment purposes is that the tumorogenic capability of these
cells is difficult, if not impossible, to control. It is quite
possible that the tumor formation in cell lines and gene expression
defects in clones could be a potentially worse development that
the disease itself! And another hindrance to effective or beneficial
research.
2.5 Several studies have shown that the
longer embryonic stem cells are maintained in the laboratory (or,
presumably, in the tissues of human patients), the more likely
they are to convert to malignant cancer cells. Again, such significant
technical difficulties will severely hamper any usefulness of
the proposed research.
2.6 The many profound genetic and epigenetic
flaws in cloned embryos, in hES cell lines and the risks of mitochondrial
dysfunction are likely to create so many technical obstacles as
to counter any useful scientific benefits. Thus the research could
simply become an opportunity for an academic "study in artefacts"[8]
with no long-term therapeutic benefit to patients. Again, the
public underplaying of the problems associated with the use of
hES cells and the use of animal eggs is disingenuous of scientists.
2.7 There is also a real risk of disease
transmission from viruses crossing the species barrier and developing
in the host. An experiment in which human hematopoietic stem cells
were injected into fetal pigs was reported in Nature Biotechnology
2006. The authors warned that the resulting fused cells were
capable of transmitting a pig virus to uninfected human cells,
jumping the species. [9]
3. UNNECESSARY
RESEARCH
3.1 It is perfectly conceivable that the
same objectives for creating hybrid embryos have as much chance
of being realised without involving either cloning or hybrid embryos.
3.2 Dr William Peacock, Australian Chief
Scientist and acknowledged cloning supporter has stated: "Stem
cell research could proceed without using animal eggs as incubators.
`The use of animal eggs is not necessary.'" Even the Royal
Society states that: "There is at present insufficient scientific
justification for creating human-animal hybrid embryos."
3.3 It is disturbing that, despite promises,
claims and hype, science has so far provided almost no convincing
evidence that embryonic stem cells can be reliably differentiated
into normal adult cell types, to be used in therapies. Before
progressing over this next boundary, it is important to revisit
the promises in light of current research findings. Over the past
five or so years, research has been heavily focused on cloning
as the ideal resolution to the problem of immune rejection and
to provide patient-specific stem cell repair kits. However human
cloning has been far more challenging than anticipated, partly
because human eggs are more fragile than eggs of other mammalian
species and they do not survive the procedures that were successfully
used to clone animals.
3.4 It is extremely difficult to clone any
animal, not just humans. Cloned embryos are generally very abnormal,
with those that are sufficiently normal to survive to live birth
representing between 0.1 and 2%. ".. the claims that `therapeutic
cloning' and embryonic stem cell-based therapies can fix the immune
problem facing humans seems thus far entirely unsupported by the
scientific evidence." [10]Indeed,
when cells derived from embryonic stem cells are transplanted
into adult animals, their most common fate is to die.
3.5 In other words, despite the fact that
researchers have had increased funding to conduct research on
animal embryonic stem cells, the serious scientific problems remain
as problematic as ever. Immune rejection, tumor formation, and
embryonic development have proved to be profoundly serious scientific
challenges, and are likely to remain so for decades into the future.
3.6 Everyone would be delighted to see treatments
developed for debilitating diseases, including ourselves. But
this should be within ethical limits. To this end, we note the
rapid progress in therapeutic research and treatment using alternative
sources of stem cells (such as easily available cord blood, or
amniotic fluid) and recommend that available funding be directed
to this ethical and promising research. A paper published last
week states: "The risk of tumor development from transplanted
embryonic stem cells is an ongoing concern for their use in therapy.
The potential of long-term culture followed by tumor-free cell
transfer thus gives multipotent adult progenitor cells a therapeutic
advantage ..." [11]Many
similar examples can be found at www.cloning.org.uk.
3.7 The promising work being done on "adult"
stem cells not only limits the need for general embryo research;
it makes the need for cloning human hybrid embryos unjustifiable.
And if funding for research is limited it surely makes most sense
to direct it towards research that procures results and cures,
rather than towards unethical, risky research with serious scientific
problems.
3.8 The purpose of UK policy is to support
research that helps identify the most promising avenues for curing
devastating diseases, but within clear boundaries. The goal of
developing new treatments for debilitating diseases is already
being served as we see that non-embryonic cell therapies have,
in the past five years, quickly moved forward to perform many
of the tasks once thought to be possible only with hES cells.
There must be greater openness over the real need or purpose for
creating hybrid embryos for research and whether benefits will
accrue to patients or just to commercial companies and scientists.
4. UNETHICAL
RESEARCH
4.1 There is an apparent fear by scientists
that some current chimeric and transgenic research might also
be outlawed in the process of limiting human/animal hybrid research.
Clearly there needs to be differentiation between the different
types and purposes of research and the STC must distinguish between
that which is ethical and necessary and that which is unethical
and unnecessary.
4.2 The insertion of a single human gene
into another species appears not to cause observable changes in
the resulting transgenic animal and does not change the animal's
phenotype, nor does it produce observable human characteristics.
Thus we have fewer ethical concerns with the insertion of single
human gene or cells into a animal to address a serious disease.
4.3 However the more we cross the species
barrier, the less clear cut will become the definition of being
human. When more human DNA is mixed with animal DNA we need to
ask what percentage of human genes make an animal more than just
animal and what percentage of animal genes make a human less than
human?
4.4 Even transgenics harbours significant,
albeit potential, problems in the future. Weissman has already
proposed experiments with human neural stem cell transplants,
to make mice with brains that are partly or wholly human. Thus
begging the ethical question: could mice with human brain cells
have human consciousness?
4.5 The proposed research to create hybrid
embryos would take us well beyond current practices. To many people,
mixing human and animal reproductive cells to create new animal-human
entities will give rise to real concerns. The mixing of human
and animal would challenge the very concept of being entirely
human. The unnatural entities created will be less human than
fully human embryos and natural boundaries will be violated. In
crossing the species barrier, the definition of "being human"
would no longer be clear-cut.
4.6 What weight or significance should we
give intuitive public revulsion (the "yuk" factor) to
crossing species boundaries? How can we judge the humanity or
moral worth of ambiguous hybrids? Some researchers claim that
these hybrids would simply be cells in a dish, with no moral status,
to which we may therefore do what we like. Yet this is out of
step with UK law, which takes the view that human embryos, whilst
not having the status of people, should be accorded moral status
above that of other cells. If that is so, would hybrid embryos
derived from human nuclear DNA and animal cytoplasm also have
moral status, depending how "human" they are? Scientists
currently claim they are "human", thus presumably they
will be offered some protection and limits to research?
4.7 It is wrong to summarily dismiss those
who feel, or sense, that this is a threshold that should not be
crossed, or ignore those who hold a natural revulsion to the introduction
of animal reproductive cells into homo sapiens, whatever stage
of life "it" is at. Humans are unique and distinct from
animals, with a higher moral status, yet this proposed research
will blur the boundaries between the two and demean what is fully
human by degrading the life in question with animal content.
4.8 Once a line is crossed, it will become
harder to say "no" to further research and more mixing.
4.9 In fact, to permit this research will
only lead to even further difficult questions, that need to be
considered now:
How much further mixing between humans and animals
should be permitted?
On what basis will limits be set?
Will human embryos be regarded as having little
more value than animal embryos?
What should our moral obligations be to transgenic
or hybrid animals?
Which parts of the body are more "functional",
and which are more linked to the "identity" of a person?
What should we think of combining human embryonic
stem cells with animal embryos, or blending animal genes with
human embryos?
Will this lead to germline engineering?
What about using mammalian eggs, such as from
closely related primates, to create hybrids?
Will human embryos become ever more dispensable?
What are the implications for animal welfare?
4.10 The question as to whether an embryo
formed from an animal egg with human DNA is a human or animal
embryo is not just a theoretical question because in most other
European countries human embryos are offered far greater protection
than the UK. The UK stands out on a limb in not signing the Council
of Europe Convention on Human Rights and Biomedicine[12]
which states in Article 18(2) (Research on embryos in vitro) that:
"The creation of human embryos for research purposes is prohibited."
4.11 This question is of central importance
to the HFEA also. Whether or not research comes under current
UK legislation mainly depends on whether or not the entities created
can be properly described as "human". The HFE Act does
not currently provide adequate clarification on the specific nature
and status of human-animal entities. If they are defined as "human"
embryos, then their creation for research purposes needs a license
from the HFEA. Our concern is that the HFEA has no power to regulate
many experiments fusing human and animal material because loopholes
and a lack of legal clarity allows scientists to create hybrid
cells without need for a licence.
4.12 One of the chief ethical concerns raised
by the creation hybrid embryos is that it would necessitate the
use and destruction of human embryos. Even among many who do not
assign fully human embryos the moral standing of "full persons",
intentional destruction of developing human life is a cause for
ethical disquiet. To regard developing human life as a mere means—even
a means to a good end, such as the alleviation of suffering—presents
a moral problem. Embryos produced solely for research purposes
are treated purely instrumentally. They simply become a "resource"
or tool for gaining scientific and medical knowledge. It is even
harder to see what respect is being shown in creating an embryo,
solely to extract cells from it, which is a hybrid of human and
animal, and thereby so disrupted that it could never be viable.
4.13 As research in this area progresses
and draws more funding, it is important that limits are set to
prevent the fusion of animal and human genomes and, more specifically,
the placing of human cell nucleus into an animal egg. The danger
is that by trying to solve one ethical dilemma (that of using
ova from women) another ethical dilemma is created instead.
5. CONCLUSION
AND RECOMMENDATIONS
5.1 All too often it seems that economics,
practicalities and safety considerations have become society's
determining values or "ethics". As a result, in the
absence of a clear ethical or moral foundation for humanness,
"ethical" decision-making is increasingly being driven
by the combined interests of private entities—biotechnology
firms, scientists, lawyers and sometimes physicians. These are
entities over which the public has very little control because
they are private or non-democratic. We sincerely hope that the
STC committee, and Parliament, will follow the lead of the many
countries that have already banned this research, such as France,
Germany, Italy, Netherlands, Belgium, Canada and most recently
Australia. And that close note will be taken of public views in
the UK on this issue, because science and Parliament must be fully
accountable to the public for whose benefit this research is proposed.
5.2 There should be prohibition on the placing
of a live human embryo into an animal (or vice versa),
on the creation of an embryo containing cells made up of both
human and animal chromosomes, on the mixing of animal and human
gametes for any purpose and on the placing of a human cell nucleus
into a nonhuman egg.
5.3 The UK should sign and ratify the Council
of Europe Convention on Human Rights and Biomedicine, to stay
in line with the majority of European countries on embryo research
and other bioethical issues.
5.4 Clarity is recommended for the definition
and nature of the proposed human/animal entities and their legal
status, because the HFEA does not necessarily have responsibility
to license their creation.
5.5 There should be a fuller, longer and
more open public debate on such a significant issue as this. Providing
less than two weeks to respond excludes many members of the public
who do not have time to grasp the issues and respond in such a
short length of time.
January 2007
7 "... Mitochondria carry genes that are passed
unchanged from mother to child. But when Wallace's group created
mice with mitochondria from two mothers, the mitochondria swapped
genetic material in the offspring. Wallace says these mice had
fewer pups, implying an effect on fertility and possibly on health.
Wallace is worried that assisted reproduction may subvert a natural
system that protects mitochondria from changes that could perturb
their function. "Mitochondrial DNA programs are highly adapted
and integrated. It's extremely bad planning to put those different
programs in the same cell ... " Gene study raises fears
for three-parent babies, Nature 438, 12 (3/11/05). Back
8
SCHB report on Embryonic, Fetal and Post-Natal Animal-Human
mixtures. Back
9
"Platt also found that whereas porcine endogenous retrovirus
isn't normally infectious to people, the fused cells were capable
of transmitting the virus to uninfected human cells. `We think
viral and host cell fusion and genetic recombination turns on
the virus,' Platt says. `We noticed it only during one passage
of cells-it didn't persist beyond that.' This phenomenon may help
explain how a retrovirus can jump from one species to another
and shed light on the origin of diseases, such as AIDS and severe
acute respiratory syndrome." Chimeras in the crosshairs,
Nature Biotechnology, Vol 24 No. 5 May 2006. Back
10
Condic, M. Back
11
Cell replacement therapy-are MAPCs the answer? Published
online 16 Jan 2007, doi:10.1084/jem.2041iti1, The Journal of
Experimental Medicine. Back
12
Signed by 31 of the 45 Council of Europe Members States, http://conventions.coe.int/Treaty/en/Treaties/Word/164.doc Back
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