Monday, May 3, 2010

The great divide: therapeutic cloning

Should Australia lift its ban on therapeutic cloning? Few topics in Australian science have generated such strong opinions. Ruth Beran reports.

The independent committee appointed to review Australia's federal stem cell legislation has a busy few weeks ahead. Chaired by retired Federal Court judge John Lockhart, the committee has until December 19 to report back to the parliament on whether changes should be made to the Research Involving Human Embryos Act 2002 and the Prohibition of Human Cloning Act 2002.

It received more than 800 submissions from researchers, the public and special interest groups -- and most of them concern whether Australia should lift its ban on so-called 'therapeutic cloning', otherwise known as 'somatic cell nuclear transfer' (SCNT), a technique whereby an embryo is created by removing the nucleus of an egg and replacing it with the nucleus of a donor somatic cell.


"Therapeutic cloning is a bit of a presumption," says Kathleen Woolf. "Scientifically it doesn't exist. Either you're cloning to make an embryo or you're not. The purpose of it is in the mind of the scientist doing the cloning." Woolf, the spokesperson for the Australian Federation of Right to Life Associations, is, not surprisingly, strongly opposed to therapeutic cloning. "I just can't see that you could ever say one human being -- no matter what the stage of development -- is fodder for experimentation," she says.

Dr Bridget Vout, executive officer for the Life Office of the Catholic Archdiocese of Sydney, holds a similar view. "We're against all forms of human cloning," she says, "whether it be therapeutic or reproductive cloning."

Reproductive cloning differs from therapeutic cloning in that it is intended to create another human by placing the cloned embryo into a uterus, in the same way Dolly the sheep was created. Vout views the term therapeutic cloning as "a misnomer".

"Therapeutic cloning certainly isn't therapeutic for the embryo that is produced, commodified and then destroyed for its stem cells," she says. She would prefer to use the terms 'cloning for biomedical research' or 'cloning to produce children' because "all human cloning gives rise to a living human embryo".

Allaying fears

Many scientists prefer not to use the term 'cloning' at all and instead follow the International Society of Stem Cell Research's recommendation to replace the term therapeutic cloning with 'somatic cell nuclear transfer' (SCNT).

"We're not cloning in the sense that people understand we're cloning," says Monash Immunology and Stem Cell Laboratories head Prof Alan Trounson. "Nor, necessarily, are we focused on a therapeutic. So somatic cell nuclear transfer is more descriptive of what we're trying to do."

Prof Bernie Tuch, head of the Diabetes Transplant Unit at the Prince of Wales Hospital, agrees. "If you mention the word 'cloning', the public thinks that you're trying to produce another person. Therapeutic cloning has got nothing to do with that," he says.

Another reason for changing the terminology according to Paul Bello, program manager for biotech company Stem Cell Sciences, is that embryos produced from SCNT will not only be used for therapeutics. "There's also cell-based assays," he says.

As well, embryos created from SCNT are "never intended to ever give rise to a human," he says, "and I think that's the public's greatest fear".

However, Dr Gregory Pike, director of the Southern Cross Bioethics Institute, calls the name change "semantic gymnastics".

"What is in fact cloning is now masked behind a cloudy vagueness," he says. "It has made it difficult for the public to know what actually is being talked about."

The promise

So why do some sections of the community, including researchers and patient advocacy groups, want the ban on SCNT in Australia lifted?

Joanna Knott, spokesperson for the Coalition for the Advancement of Medical Research Australia and a director of the SpinalCure, an organisation set up to raise funds for spinal cord research, represents hundreds of thousands of Australians living with conditions such as motor neuron disease, diabetes, and Alzheimer's disease. "They want to hear about hope," she says. "This is potentially hope."

The hope that Knott is talking about lies in the potential benefits of creating stem cell lines from SCNT embryos. Although Knott freely admits that she is not a scientist, she is well versed on SCNT. She also has a spinal injury and is wheelchair bound.

"This is something that society as a whole we have to embrace," Knott says. "Just because someone's lucky enough not to have any of these things right now, the potential of it happening to them or someone they know is really quite high."

According to Dr Andrew Elefanty, director of the Australian Stem Cell Centre's blood program and head of Monash University's Immunology and Stem Cell Laboratories, the main promises of SCNT are twofold. "One is as a research tool, to study and learn about diseases," he says. "The other is a practical way of helping minimise transplant incompatibility when we get to the stage of having cells that we would be able to transplant into patients."

The first of these potential benefits of SCNT relies on the creation of a stem cell line from an embryo using the somatic cell nucleus of a person who has a genetic defect or complex disease such as cancer, Alzheimer's or Huntington's disease.

"I think it's terribly important to make disease-specific stem cells," says Trounson. "A lot of people think that we will see things happening to those cells that we wouldn't be able to predict if we're looking at patients with the full expression of the disease."

For example, it may be possible to determine whether the disease is genetic, epigenetic, whether it's caused by a multiple gene effect or by a combination of epigenetics, environment and genetic factors, he says. Such stem cell lines could also be used for cell-based assays to test new drugs. "You might get a whole new drug strategy for slowing diseases down or in fact preventing them from being expressed," says Trounson.

The second benefit relates to the therapeutic potential of customising stem cell lines to a particular patient. Deriving cells, such as pancreas or blood cells, from a person's own tissues makes it less likely that the person's immune system would reject these cells if later treated with them.

"It could help with areas like diabetes in terms of where the pancreas is malfunctioning; in areas like Parkinson's where the dopamine neurons have gone wrong in the brain; in motor neuron disease in which the neurons that control voluntary movement progressively die and then you look at replacements for these cells; and in areas like new heart muscle and blood cells and in spinal injury," says Knott.

However, Dr Peter McCullagh, a retired senior fellow at the Australian National University's John Curtin School of Medical Research, says it is "sad" to see people clinging to the false hope of embryonic stem cells. "Patients are dependant and vulnerable individuals," says McCullagh, and medical practitioners should be "damned careful" about statements they make that are likely to influence a patient's behaviour.

Others are also dubious about the promise offered by embryonic stem cells. "We still haven't really clearly seen the benefits of embryonic stem cell research and therapies," says the Sydney Catholic Archdiocese's Vout. "We still don't have a single human treatment. There haven't even been any human trials."

Instead, Vout suggests that scientists should focus on adult or mature stem cell research.

Adult stem cells

Griffith University neurologist Prof Alan Mackay-Sim has spent the last five years investigating adult stem cells in neural regeneration, and has won widespread kudos for his work. He believes that it may not be necessary to "go to the trouble" of SCNT for the purposes of studying diseases.

"I think that the potential for adult stem cell work is lost in all of the hype about embryonic stem cells," he says. "A lot of generalisations are made about the so-called shortcomings of adult stem cell research, automatically assuming that embryonic stem cells can do everything you ask of them and adult stem cells can't."

Mackay-Sim argues that with cell therapies, for example, if you have the appropriate cell, such as beta cells from the islets of the pancreas, then a stem cell may not be needed. "You don't necessarily need to have any kind of stem cell therapy if you can grow them from another cell type," he says.

And the fact that adult stem cells may not be as pluripotent as embryonic stem cells is irrelevant, he says, if they make the right kind of cell for a particular application. "The full potential of either adult stem cells or therapeutic cloned stem cells is not really well explored," he says.

Right-to-life spokeswoman Woolf says that embryonic stem cell scientists should be asked to divert their activities to mature stem cell research. "There are massive advances being made in adult stem cells," she says.

But Tuch says that all avenues, both adult and embryonic stem cells, should be explored. "The Diabetes Transplant Unit has been able to make insulin producing cells using both adult and embryonic stem cells," he says. "At this stage we don't know which one of those options is going to be the best option. But if we don't explore all avenues we could find ourselves discovering in several years times that, in fact, it isn't the best way to go, and we will waste time otherwise."

What defines an embryo?

The great ethical divide between the different view points on SCNT mainly rests on the definition of an embryo and what rights it should be afforded.

Trounson believes that a nuclear transfer embryo is not a "normal embryo". "First of all, it doesn't have much developmental competence -- less than one per cent ever go to term," he says. "And they're never intended to go back into the uterus. So these are cells for research rather than embryos in a reproductive sense."

But Pike, of the Southern Cross Bioethics Institute, disagrees. "Despite some attempts to claim that what's being produced is not an embryo, we have to acknowledge that a cloned embryo would indeed be an embryo," he says.

Pike believes human embryos ought to be afforded respect, and such respect would not allow embryos to "be destroyed in research programs". In particular, he sees SCNT as a process that "involves the destruction of embryos, ones that have been deliberately created defective".

Tuch sees SCNT research differently. "We are creating an embryo that is being used specifically and solely for the purpose of creating cell lines," he says. "It is not a natural phenomenon, and you certainly wouldn't want to go about creating a being from it.

"Potentially it is possible, but you wouldn't want to do that because of the genetics involved. The arrangement of chromosomes in embryos created by this method is not the same as what occurs normally."

Interestingly, while the scientific community is seemingly united in its condemnation of so called 'reproductive cloning', Vout says that despite the Catholic Church's strong ethical objections to cloning, reproductive cloning would be preferable to therapeutic cloning.

"At least with cloning to produce children the intention would be to create human life: to nurture it, to bring it to birth," she says. "But in therapeutic cloning we're creating human life solely for the exploitation of that human embryo. We're creating a human embryo, a living human being, to destroy it, to use it as a means to some other end."

Woolf has similar views. Although she is not in favour of reproductive cloning, seeing it as an expression of "massive egotism", she says, "at least it allows the clone to live".

However, Elefanty says that given the current social and legislative position in Australia it is "unfair to argue that every embryo has the same rights as a person". He points out that in Australia, women have the right to choice, with abortion being permitted as required.

Australian legislation also allows assisted reproductive technologies; and frozen excess embryos -- created in vitro for this purpose -- are required to be destroyed after five years. Organ transplantation from patients who are still alive, albeit brain dead, is also accepted in Australia.

"We're not operating in a vacuum," Elefanty says. "We're not doing anything contrary to what is already agreed to in legislation. We're not making or advocating [completely] new laws, we're working within what, as a society, has been decided."

Strong principles

Although Australia's federal legislation on stem cells as enacted in 2002 allowed embryos to be created for the purpose of infertility treatment, Pike points out the legislation contained a "fairly strong principle" that "no embryos should be deliberately created for research".

He says that if the ban on therapeutic cloning or SCNT in Australia is lifted, "we will be suspending yet another principle that we have previously seen as an important one."

However, scientists such as Tuch believe that limiting embryonic stem cell techniques will "limit people's ability to produce and be creative in trying to solve problems". "You have to explain to me why countries like England, Spain, Israel, Korea, China, Singapore, and so forth, all basically think it's appropriate," he says.

If the ban on SCNT continues, some argue that Australia will see some of our best and brightest scientists leave to pursue careers elsewhere. "We have the ability," says Tuch, "but if you stifle our capacity then you will certainly lose people overseas."

"Australia considers itself a leader in scientific knowledge and breakthrough research," says Knott. "We wouldn't want to fall behind in that position."

Woolf is dubious, though. She says, "We keep saying that we're going to miss all these opportunities in world trade. No one specifies what we're actually missing."

Trounson, however, says that SCNT should be allowed in Australia because it offers "such a huge opportunity to make discoveries, particularly about complex disease states. "This is really something that we can't ignore."

The AusBiotech 2005 conference features a session on stem cell science as therapy, on Wednesday, November 23. Chaired by Hugh Niall, of the Australian Stem Cell Centre, it features South Korean researcher Woo-Suk Hwang -- whose lab this year made key discoveries in embryonic stem cell research -- and Megan Munsie of company Stem Cell Sciences.

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