Download Submission - Provisions of the Research Involving Embryos and

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Senate Community Affairs Legislation Committee
Inquiry Into Research Involving Embryos
And Prohibition Of Human Cloning Bill 2002
Submission of Associate Professor Martin F. Pera, BA, PhD
12 September 2002
Monash Institute of Reproduction and Development
Monash University
246 Clayton Road
Clayton 3168 Victoria
Phone 03 9594 7318
Fax 03 9594 7311
Email [email protected]
Statement of professional status and disclosure: I am Associate Professor and CoDirector of the Centre for Early Human Development at the Monash Institute of
Reproduction and Development, Monash University. I have over seventeen years of
research experience in the field of human pluripotent stem cell biology. My laboratory
conducts research on human embryonic stem cells and a closely related cell type derived
from human germ cell tumours of the testis, known as embryonal carcinoma cells. I am a
founding scientist of ES Cell International Pte., an Australian-Singaporean stem cell
research company; I own shares in that company and receive funding from it to support
research in my laboratory. Our research is also supported by the National Health and
Medical Research Council, the Juvenile Diabetes Research Foundation, and the United
States National Institutes of Health. My primary motivation in helping to found ES Cell
International was to obtain financial backing for the research at a time when such support
was not available from governmental or philanthropic bodies.
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1.
Scope of proposed legislation: The proposed legislation will allow
researchers to derive new embryonic stem (ES) cell lines from embryos
surplus to clinical requirement donated with informed consent by couples
having undergone infertility treatment. The legislation will outlaw human
cloning throughout Australia, a ban which will include prohibition of the use
of somatic cell nuclear transfer methodology to create ES cell lines
(therapeutic cloning).
2. No impact of the proposed legislation on the rate of production or
disposal of human embryos: I fully respect the views of those who have
ethical objections to human embryo experimentation, but these views must be
considered in the context of a pluralistic society that has an obligation to use
medical advances to provide optimal care for its sick or injured. Embryo
wastage is an inevitable consequence of both natural conception and assisted
reproduction. The proposed legislation will have no effect whatsoever on the
rate of production and disposal of embryos associated with in vitro
fertilization procedures. Our society and many others, by accepting in vitro
fertilization, therapeutic abortion, and certain forms of contraception, have
already assigned the human embryo and fetus a different ethical and legal
status to that of a child or adult. Blocking ES cell research would not “save”
embryos; it would only ensure that their disposal serves no constructive end.
3. Embryonic stem cells: ES cells are cultured cell lines derived from the early
embryo prior to formation of the tissues of the body. ES cells may be grown
in the laboratory indefinitely in the primitive embryonic state, and they retain
a key property of the embryo cells from they originate: pluripotentiality, or
the ability to give rise to any type of adult body cell. This combination of
properties has not been documented in any type of adult tissue stem cell
isolated to date. These two features mean that ES cells in principle represent
an indefinitely renewable source of human tissue for use in research, or in
transplantation therapy to correct a range of debilitating and currently
intractable medical conditions characterized by cell injury or death. The
potential research applications of human ES cells are equally important to
their applications in transplantation, and they include: the study of early
human development and its disorders, including birth defects and childhood
cancers; the study of how human genes function; the discovery of novel
proteins involved in tissue regeneration and repair; the discovery of new
medicines.
4. Current status of human and mouse embryonic stem cell research:
Human ES cells were first isolated in late 1998. Since that time a number of
groups including our own have confirmed first that pluripotent stem cells can
be isolated from the human blastocyst with relatively high efficiency, and
second that these cells can be propagated indefinitely whilst retaining
pluripotentiality. Published research has documented the production of the
following array of specialised cell types from human ES cells in vitro: heart
muscle, insulin producing cells, nerve cells, endothelial (blood vessel lining)
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cells, blood forming stem cells. Nerve cell precursors derived from human
ES cells have been transplanted into the brains of rodents and shown to
integrate and differentiate normally in the host tissue without tumour
formation (more extensive long-term study is of course required to
demonstrate safety of stem cell grafts). Pre-clinical testing of ES-derived
cells in animal models of disease will be underway shortly in our laboratories
and is probably ongoing in others. In proof of concept experiments, mouse
ES cells, or cells derived from them, have been used successfully to treat
animal models of diabetes, severe immune deficiency, Parkinson’s disease,
myocardial infarction, stroke, and demyelinating disorders. Mouse ES cells
have of course played a revolutionary role in advancing our understanding of
gene function in mammals.
5. Significance of the legislation to the future of human embryonic stem cell
research: The key impact of the new legislation will be to allow the
derivation of new stem cell lines from spare IVF embryos. New cell lines are
essential for four reasons. First, the existing cell lines have almost all been
derived using mouse helper cells or feeder cells which produce as yet
unidentified substances necessary for stem cell growth. Regulatory agencies
including the United States Food and Drug Administration have expressed
concern over the possible transmission of pathogens, in particular viruses,
from these mouse cells to human stem cells. New techniques will allow the
production of safer stem cell lines without the use of animal cells. Second,
clinical therapy with ES cells will have to address the possible rejection of
stem cell derived grafts by the recipient’s immune system. We need the
flexibility to allow us to develop larger panels of cell lines which may well
required to achieve adequate tissue matching to avoid immune rejection.
Third, since our understanding of human ES cells is still at an early stage, it is
likely the future improvements to the methodology for initiating and growing
these cell lines will enable us to produce second generation ES cells with
desirable improved properties. Finally, most existing cell lines have been
derived with commercial funding and have some restrictions on their use.
Many investigators feel that ES cell lines should be available in the public
domain to researchers without such restrictions.
6. Adult and embryonic stem cell research: During the course of this debate,
some have argued that research on adult stem cells, in particular results from
recent studies which demonstrate that adult stem cells are more versatile than
previously expected, has already demonstrated that adult stem cells will fulfill
all the potential roles in research and therapy envisioned for ES cells. Such
claims are premature. While there is little scientific argument regarding the
potential for ES cells to give rise to all tissues of the body, claims for
pluripotentiality of adult stem cells (stem cell plasticity) remain controversial
or preliminary. In some cases, the initial exciting reports have proven
difficult to repeat, or alternative explanations have emerged to account for the
results. In many instances where the bona fide conversion of adult stem cells
to different cell types is proven, the events only occur at very low frequency
in the context of severe tissue damage. Adult stem cells often represent
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minority populations within a tissue, and unlike ES cells they may be difficult
to isolate and impossible to expand in numbers outside the body. While
research on adult stem cells and their plasticity is very important, it is
premature to assert that adult stem cells with properties equivalent to ES cells
have been identified, or to make definitive claims for the future roles of either
cell type in therapy.
7. Therapeutic cloning: Therapeutic cloning combines cloning techniques with
stem cell technology to produce ES cell lines which are custom made for
individual patients. Grafts derived from such cell lines would in principle
avoid the problem of immune rejection. Practical problems with this
approach, including the requirement for large numbers of human eggs, the
time delay in delivering the therapy to individual patients, and the need to
evaluate the safety of the custom made cells, may severely limit its
application in the clinic. However, therapeutic cloning and related techniques
provide a very promising experimental approach to the study of adult cell
plasticity, since the procedure effectively reprograms an adult cell back to a
pluripotent state. Thus although the scientific case for the clinical application
of therapeutic cloning in man is not compelling at present, basic research on
reprogramming in humans may eventually be very important to successful
development of adult stem cell based therapies. I therefore endorse in
principle the original recommendation of the report of Mr. Kevin Andrews’
committee of inquiry for a moratorium, rather than a ban, on this area of
research.
8. Importance of the legislation for Australian science: Australia is fortunate
to have an outstanding group of researchers in the fields of embryonic and
adult stem cell research. These research areas are complementary and
synergistic; the review panel that awarded the Biotechnology Centre of
Excellence grant to the National Stem Cell Centre clearly recognized the
unique potential of a consortium of these workers and its high
competitiveness internationally. Defeat of this legislation will severely
restrict the ability of Australian scientists to remain at the forefront of
embryonic stem cell research. Defeat of the legislation will return us to an
unsatisfactory position in which contradictory piecemeal regulations govern
embryo research in the various States and Territories. Most importantly,
although some stem cell research could continue, defeat of the legislation
would send a strong negative message about Australian scientific policy to
the research community locally and internationally. The proposed legislation
is an effective compromise between the more liberal approach taken in the
United Kingdom and the more restrictive policy governing federally funded
research in the United States. It is a compromise that will enable Australian
embryonic stem cell research to proceed on an ethical basis. It is a
compromise that will enable us to maintain our international standing in
exciting new area, the potential significance of which has been repeatedly
endorsed in extensive reviews conducted by scientific academies and
governmental agencies throughout the world. It is a compromise that the
Parliament should support.