Download Submission - Provisions of the Research Involving Embryos and

Monday 23rd September 2002Elton Humpreys
Senate Community Affairs Legislation Committee
Parliament House
Canberra, 2600
Dear Senators,
Re: Research Involving Embryos Bill 2002
On behalf of the Coalition for the Advancement of Medical Research Australia (CAMRA) and the
Juvenile Diabetes Research Foundation I would like to thank the Senate Community Affairs
Legislation Committee for inviting us to present our case on the Embryonic Research Bill.
We appreciate this is a challenging issue, which is complex from both a scientific and a moral
perspective. As representatives of those who live with debilitating diseases every day of their lives,
we do believe this research offers a realistic hope of improving the quality of life for many
Australians.
I have been encouraged by the healthy debate this bill has seen in Parliament, and we would also
like to reiterate that Australian parliamentarians are not alone in making a decision on this subject.
Following the most rigorous and comprehensive research, debate and consultation, legislators in the
UK and Sweden have given embryonic stem cell research the go-ahead.
We enclose a complete copy of our submission, as you did not receive the whole copy for our
hearing, along with a document showing JDRF’s research funding in Australia.
I would be happy to answer any specific questions you or your committee may have. Please call me
on 02 996 0404.
Regards
Sheila Royles
Spokesperson for CAMRA and CEO of the Juvenile Diabetes Research Foundation.
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Restoration of Normal Blood Glucose Levels
Restoring normal blood glucose levels by successfully transplanting the pancreas or insulin
producing cells would end insulin injections and blood testing.
A marker to monitor the viability of transplanted porcine pancreatic tissue
Bernard Tuch, MD PhD, Prince of Wales Hospital, Randwick, NSW
Innovative Grant - $55,000
Transplantation of insulin-producing pig cells into diabetic recipients offers hope as a therapy for
type 1 diabetes. The cells for such transplants are usually obtained from fetal or neonatal pigs
because their isolation is technically simpler than isolating cells from adult pigs. The drawback
from using these immature pig cells is that they do not begin to produce insulin until several
weeks after they are transplanted. To be able to monitor the viability of the cells in the first weeks
after they are grafted has been a problem until now. Dr Anil Amaratunga, Professor Bernie Tuch
and colleagues at the Prince of Wales Hospital in Sydney have developed an assay to measure
the production of another hormone from the graft, called porcine icosapeptide, during this time. It
is hoped that measurement of this hormone will be useful in monitoring the viability of pig cells in
the early stages after they are transplanted into people with diabetes.
Creating Beta Cells from Precursor Cells
Andrew G. Elefanty, MD, Ph.D.
Senior Research Fellow
The Walter and Eliza Hall Institute of Medical Research, Melbourne
JDRF/NHMRC Special Program Grant
Recent advances in islet transplantation suggest that the right protocol could free patients from
the need to take insulin indefinitely. However, this procedure is hampered by a severe shortage of
available islets and beta cells. The problem of supply could potentially be solved through the
creation of insulin-secreting beta cells. Embryonic stem (ES) cells, which have not yet
differentiated and have the capacity to develop into any cell type, could be a source for beta cells,
as could certain cells in the pancreas.
Dr. Elefanty’s team will try to create insulin-producing beta cells by identifying the molecules that
are normally required to transform them from undifferentiated cells into beta cells (the cells that
produce insulin). They will use embryonic stem (ES) cells and fetal mouse pancreas and adult
pancreas duct cells as sources for the precursor cells. The researchers will develop culture
systems for the various cell types to learn which growth factors coax them to reproduce and
develop into insulin-producing beta cells.
The overall program is divided into three projects. Project 1 will study mouse ES cells; Project 2
will investigate human ES cells; and Project 3 will focus on mouse fetal pancreas cells and mouse
and human adult pancreas duct cells.
If functional beta cells could be derived from human ES cells or pancreas duct cells, it should be
possible to restore beta cell function in people. This also might occur if the researchers are able to
identify the growth factors that regenerate the beta cells. In both cases, implantation or injection
with the right immunotherapy could restore beta cell function in people with type 1 diabetes.
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Transplanting Pig Islets to Restore Glucose Control
Professor Len Harrison, Walter & Eliza Hall Institute of Medical Research (VIC)
Special Grant, 2000-05, $5 million
Professor Len Harrison is investigating the immune mechanisms of beta cell life and death with
his team of researchers at the Walter & Eliza Hall Institute of Medical Research and University of
Melbourne.
The goal of his research program is to prevent and cure type 1 diabetes in people through
strategies designed to regulate immune response and genetically modify islet tissue to prevent its
immune rejection.
The strength of this program is in the interdisciplinary, collaborating group of basic and clinical
scientists, backed by a major research institute, who have demonstrably translated basic research
knowledge into tools for the prevention and cure of type 1 diabetes. The group possesses unique
research animal models and oversees at-risk human populations already participating in
prevention trials. The group’s shared goal is a future without type 1 diabetes.
Professor Kevin Lafferty and co-investigators
John Curtin School of Medical Research (ACT)
JDF/NHMRC Program Grant, 1998-2002, $2.6 million
Transplantation of islet cells is the key focus of this research.
One project in this collaborative grant is researching the role of “NK” T cells in regulating diabetes
in specially bred mice. NK T cells seem to prevent the development of the automatic immune
system response that causes islet cell destruction and development of Type 1 diabetes.
Other research includes the role of antigens in the prevention of diabetes in specially bred mice
and as a potential treatment for transplantation rejection. Antigens stimulate the production of
antibodies and these antibodies fight off foreign substances in the body.
Genetically Modified Hepatocytes that Secrete Insulin: Susceptibility to Autoimmune
Destruction
Professor Bernard Tuch, Prince of Wales Hospital NSW
Research Grant
Type 1 diabetes is a disorder which results from destruction of insulin-producing cells in the
pancreas by a self destruct mechanism. Because this process involves cells of the immune system of
the person with diabetes, the mechanism of destruction is called autoimmune. Currently treatment
of this type of diabetes is by the daily injections of insulin, but this will not necessarily achieve
perfect control of the glucose levels in the blood. This imperfection may lead to the development of
diabetic complications, such as loss of vision and kidney failure. Perfect control of glucose levels
can be achieved by transplantation of a pancreas or insulin-producing cells from another person or
animal, but rejection of this tissue by the immune system of the person is a major problem yet to be
satisfactorily overcome. An alternative strategy worthy of examination is the use of non-pancreatic
cells taken from the person with diabetes and genetically altered to produce insulin. The advantage
of this technique is that rejection of the cells cannot occur because they are part of the body of the
person with diabetes.
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Using this strategy Professor Tuch and his Unit have been successful in showing that liver cells are
a suitable target cell for such gene manipulation. Cells from 2 human liver cell lines were
genetically altered by the insertion of a number of genes including that for human insulin. The cells
created are capable of producing insulin in a manner similar to that of a normal pancreatic insulinproducing cell. A number of other research groups have genetically altered liver cells from animals
so as to produce insulin. These cells are not quite as mature as normal pancreatic insulin-producing
cells or the cell created from the human liver cell lines, and attempts are being made to perfect this.
One of the questions raised by the modification of liver cells to produce insulin is whether such
cells will be sensitive to autoimmune attack as are insulin-producing pancreatic cells. More
particularly, if such an autoimmune response was provoked, it is possible that it may occur by a
process known as "epitope spreading" and cause chronic inflammation of the liver cells. If so,
enthusiasm for the use of these cells to reverse diabetes may be dampened. The Principal
Investigator and his group have shown that in the laboratory such cells are resistant to toxins and
chemicals produced by the immune system of the body that normally destroy pancreatic insulin
producing cells. Others have shown that these toxins also do not adversely affect genetically altered
liver cells that produce insulin in rodents. Whether cells of the immune system which destroy
pancreatic insulin producing cells in Type 1 diabetes have an adverse effect is not known.
It will be the aim of this project to ascertain whether such toxic effects occur. For this purpose two
sets of experiments will be conducted. Firstly, the effects of the various mechanisms involved in the
autoimmune process which kill pancreatic b cells will be examined in insulin-producing liver cells
in the laboratory. In addition, possible protective mechanisms which may be involved in the
observed resistance of the insulin-producing cells will also be investigated. Secondly, special strains
of mice will be created which not only develop Type 1 diabetes but also produce insulin from many
of their liver cells. Once such animals have been created the sensitivity of their insulin-producing
liver cells to autoimmune destruction will be examined. As well, the ability of such cellular
destruction to cause inflammation of the liver cells not producing insulin will be determined.
Information gained from these studies will allow a greater understanding of the potential benefit of
genetically engineered liver cells that produce insulin for the treatment of Type 1 diabetes.
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