The hard cell

Advocates and opponents of stem cell research across Australia are gearing up for the reignition of the debate that polarised Australia's state and federal governments in 2002.

The Research Involving Human Embryos Act 2002 and the Prohibition of Human Cloning Act 2002 were passed in December 2002, after more than six months of fiery political and public debate. By law, they were scheduled for review two years after they received royal assent. But that anniversary has come and gone, and scientists and other interested parties are waiting with bated breath for the terms of reference of the review, as well as the composition of the panel that will be responsible for the review.

A spokesperson for Julie Bishop, the federal minister for ageing under health minister Tony Abbott, said the federal government was in discussion with the states to decide these very issues. At the time of writing, no timeline had been set for an announcement of either the terms of reference or the review panel.

The delay is of concern to many with an interest in the outcome of the debate. Australian Democrats senator Natasha Stott Despoja, an ardent support of stem cell research, says she is worried that with the review now at least three months behind schedule, it won't be tabled in Parliament by December 19 this year, as required by the legislation.

But also worrying supporters of embryonic stem cell (ES cell) research is the evidence that there is a core group within the government whose opposition to the research is influencing government decisions.

Late last year, Australia's support for a Belgium-led proposal to the UN to ban reproductive cloning while allowing therapeutic cloning, better known as nuclear transfer, was quietly reversed, with support instead going to the Costa Rica-US proposal to ban all forms of cloning.

And late last month it was revealed that prime minister John Howard had written to state governments suggesting that enactment of a sunset clause in the Research Involving Human Embryos Act 2002, which will allow researchers to access embryos created after April 5, 2002, be delayed for a year. The state governments refused to consider the PM's suggestion, and he has since backed down on his request.

Stott Despoja believes there is a behind-the-scenes campaign building up against ES cell research by various conservative members of the Coalition -- a view shared by others too. Realistically, however, the debate is unlikely to really fire up until the legislative review is tabled in Parliament at the end of the year.

"It would be unwise to pre-empt the inquiry," Stott Despoja says. "The debate is likely to happen after the review... early in 2006."

Is the law working?

When the review panel is formed, it will firstly need to consider whether the legislation is working -- are scientists being unduly restricted by the laws, or are they too lax? Most scientists are cautiously optimistic about the legislation as it stands right now, although there are some changes they'd like to see.

One of the major problems to date has been a delay in giving researchers access to embryos for research use. The NHMRC's embryo research licensing committee was formed in June 2003 to consider each application for research involving embryos -- but it took until April 2004 for the first licence to be granted and very few of them have been issued to date.

"The NHMRC licensing process has been satisfactory but it's taken an enormous amount of time -- over a year -- putting us in the position that we had to delay starting our work," says Monash University researcher Prof Alan Trounson, who recently received a licence to create new ES cell lines. "But I don't think that will be repeated."

With the sunset clause issue of using embryos created since April 5, 2002, resolved satisfactorily -- at least to the proponents of the research -- the other main focus is the more controversial area of therapeutic cloning, better described as nuclear transfer, which was the subject of a three-year moratorium legislated in the Prohibition of Human Cloning Act 2002.

This is a technique that involves the transfer of the nucleus from an adult cell into an enucleated egg cell, with the aim of reprogramming the adult nucleus back to its pluripotent state, similar to the method that was used to clone Dolly the sheep. It's a technology that offers much promise in the creation of patient specific cell lines for treatment of disease, as well as the development of cell lines as disease models. But opponents of the technology fear that the reprogrammed cells represent new lives, despite limited evidence that the cells could go on to become viable embryos.

"Let's be realistic about what we are trying to achieve," says Prof Bernie Tuch, whose Diabetes Transplant Unit at the Prince of Wales Hospital and the University of NSW is interested in using these techniques to develop new cell lines for the study and treatment of diabetes. "We're not trying to clone humans. Nuclear transfer should be allowed in this country -- we're not necessarily ready for it but we shouldn't restrict progress either."

Compelling reasons

Other researchers are also cautious about moving forward with the technology, but agree it should be available. "There are compelling reasons for pursuing limited research in this area," says the Australian Stem Cell Centre's Assoc Prof Martin Pera. "I'm not sure how useful the technology will be -- safety is still a question -- but the technology is still important for making banks of cell lines. And it's also important from a basic research point of view -- genetic reprogramming could provide breakthroughs that allow us to reprogram cells without using any ES cells."

One of the advantages of the technology is that it could potentially be harnessed to study serious multigenic diseases such as heart disease that rely on the subtle effects of many genetic variations rather than one mutation, allowing researchers to specifically target genetic loci to understand the roles played by each gene. Pera says the technique could result in information on these diseases that would be difficult to acquire in other ways. Overseas, cell lines are already being created from non-obese diabetic mice precisely for this purpose.

Premature

At the heart of the matter is the fear that, by shutting off ES cell research including nuclear transfer, whole avenues of research leading to cures and therapies might be closed off.

"From a therapeutic point of view, the whole area of nuclear reprogramming is most important," says Prof Paul Simmons, an adult stem cell researcher who heads the stem cell laboratory at the Peter MacCallum Cancer Centre. "If you look at the panoply of different diseases, we don't yet know which are more suited to an adult stem cell approach or an embryonic stem cell approach. We don't know very much at all about the resident stem cells in large organ systems -- it may be easier to generate them from embryonic stem cell-based sources. It's really premature to be trying to make decisions on whether or not to have both forms."

But not all researchers agree with the need to change the legislation. Prof Peter Rathjen, an ES cell researcher at the University of Adelaide, says he's happy with how it stands at the moment. "I think we have enough room under the existing legislation to do the research," he says. "People think that nuclear transfer will get them to the clinic faster, but that's not necessarily the case."

Opponents of ES cell research point out that it has not yet yielded any evidence of clinical benefit -- a specious argument, considering that the field of research has only been around since the mid-1990s. Meanwhile, adult stem cell research, with its 30-year history, has yielded major advances in haematopoietic stem cell therapies such as blood and bone marrow transplants.

Simmons says there is a big difference now in how the research is done. The original adult stem cell research that yielded bone marrow transplants and related therapies used an empirical approach, but these days there is a tendency for scientists to want to know everything before attempting clinical applications -- an approach he believes can inhibit progress.

"We should go into the clinic with embryonic stem cells to learn what does and does not work," he says. "We need a balance between participating in clinical research in a rational manner with the fundamental research that underpins that. But it's a difficult ethical area. And there's a difference between being able to grow stem cells and being able to apply them in the clinical environment."

Flexible approach

Ultimately, the debate is going to come down to whether the scientists can communicate to the political decision-makers the need for a flexible approach. No one is advocating a free-for-all environment, but researchers want to be able to use the best tools for the job.

"The important thing is to allow the research to be carried out without major hindrances and with the appropriate checks and balances, to see what pans out," says Tuch.

It's an approach that meets the approval of patient advocacy group CAMRA (the Coalition for the Advancement of Medical Research Australia), set up in 2002 by a number of groups including SpinalCure Australia, the Australian & NZ Society for Cell and Developmental Biology, the Australian Society for Medical Research, the Diabetes Transplant Unit of the Prince of Wales Hospital and University of NSW, and the Juvenile Diabetes Research Foundation.

"Our aim with the original review was to ensure at that stage that embryonic stem cell research be allowed to continue. But now we see it as too restrictive as researchers are not able to do nuclear transfer experiments," says spokeswoman Joanna Knott. "We're going to fall behind other first world countries -- Australian patients will suffer if we are not at the leading edge of research. We should be looking at every avenue." CAMRA plans to continue its lobbying role as it did in 2002, presenting a unified and powerful voice on behalf of its members, Knott says.

"Our moral view is that many hundreds of thousands of Australians are suffering from serious incurable diseases and conditions... we believe our government has the responsibility to help. Time is crucial -- people with motor neuron disease don't have the time to wait," she says. "We can't let politics get in the way."

So how do the researchers at the front line believe the debate will go? Pera says he's hoping to at least preserve the status quo.

"I'd like to hope for an open and rational discussion of the technology and its benefits," he says. "We need to look at the facts afresh, look at the science and look at the ethics and make a decision on whether the legislation is still appropriate. It's a rapidly evolving area of science -- we need regulation, but not too rigid as the science moves so fast."