A human blastocyst. The stage of life at which the stem cells are extracted from the embryo.
Credit: British government
It's one of those moments in history, when the advance waters of science are crashing up against the rock wall of the reigning establishment.
Like when Galileo was imprisoned for his views on the Solar System or when Sir William Jenner was denounced for tackling smallpox - in both cases, by the Church. In Jenner's case, they took issue with his daring to interfere in the sacred business of life and death; even the medical establishment of the time derided Jenner's claims as hype.
It is a moment like when Australian researchers Robin Warren and Barry Marshall had to struggle against the medical establishment to advance their conviction that ulcers were not the inevitable result of bad genes and bad eating habits, but were the result of a curable bacterial infection.
As Marshall told the press club on 27 July 2006, all ground-breaking discoveries, it seems, have to struggle. He and Warren have now been recognised with a 2005 Nobel Prize for Medicine.
Today the issue of embryonic stem cell research and its most contentious offering, therapeutic cloning, has challenged country after country to decide where it stands. Over the next few months, Australia's government will make its decision.
Embryonic stem cells are derived from surplus embryos from fertility clinics. These few-day-old embryos would be thrown away in the normal course of events but are instead dissected to derive their stem cells. These embryos are at such a primitive stage, that any one of their cells is more likely to become part of a placenta than part of a person.
Embryonic stem cells have captured the global imagination because of their primordial power. While every other cell is limited by the number of progeny it can produce or the types of cells it can make, the embryonic stem cell is limitless: it will proliferate indefinitely, and it can form any cell of the body. For the millions who ail or die because of degenerating tissues, embryonic stem cell therapy, with its promise of a limitless source of replacement tissue, offers the real possibility of an overhaul.
However the tissue grafts derived from embryonic stem cells would still seem foreign to the body, like that from any donated heart, lung or pancreas. Therefore, just as transplant patients now have to wait for a reasonably matched donor and then take a lifelong course of anti-rejection drugs, they would have to do the same for a graft from embryonic stem cells.
But what if those embryonic stem cells could be perfectly matched to a particular patient? That's the promise of therapeutic cloning, a technique where the embryonic stem cells would be derived from an embryo which is a clone of the patient. The technical moniker somatic cell nuclear transfer captures the essence of how the technique works.
Every human being is a colony of three trillion somatic cells (somatic cell just means a cell of the body). And every one of the somatic cells is running a "program" so to speak: it may be the skin program, or heart program or brain program or bone program and so on. A programming metaphor works very well. The hard disk is a dark, round structure at the centre of each cell, called the nucleus. Every one of the three trillion somatic cells is a copy of the single original cell that the person started from - the fertilised egg. That egg carried an identical nucleus to every skin cell, but back then it was freshly installed - and ready to run each and every program. By the time it grows up, the nucleus of a skin cell is only able to run the skin program.
But what if the skin cell nucleus could be rebooted? It can. Transfer the skin nucleus into a human egg (whose own nucleus has been removed) and it will return to its original operating program and once again act as the original fertilised egg did - dividing and forming an embryo. But this embryo would have only a transient existence. After five days, its development would be ended by harvesting its stem cells. The resulting embryonic stem cells would be a perfect match to the skin cell donor. And they could be used to provide a tissue graft that would never be rejected.
And this technique has already been achieved in mice.
In 2002, George Daley at the Children's Hospital in Boston and colleagues at the Massachusetts Institute of Technology used the technique to cure a mouse with bone marrow failure by providing it with a perfectly matched bone marrow graft. A nucleus from a cell at the tip of the mouse's tail was rebooted to develop as an embryo, which provided embryonic stem cells. Those embryonic stem cells were guided to form healthy bone marrow, which was grafted back into the mouse. End result: the mouse's bone disease was cured with its own cells, sparing it the need to use anti-rejection drugs or the possibility of a fatal rejection.
People are not so lucky. According to transplant specialist Miles Prince at the Peter McCallum Institute for Cancer Research in Melbourne, only two thirds of those who need a bone marrow graft will ever find a matching donor. Of these lucky ones, 15 per cent will die because the graft is never a perfect match and will attack their tissues, a term clinically referred to as graft versus host disease. So much for the argument that adult stem cells - the type contained in bone marrow grafts - make embryonic stem cell research unnecessary. There is no reason why the mouse's successful therapy with its own cells could not be translated into people. Indeed in June 2006, George Daley received a licence to attempt therapeutic cloning to derive matched bone marrow cells for a human patient.
Australia would also be a perfect place to attempt the technique. Therapeutic cloning was pioneered at Melbourne's Monash University in 2000. And Andrew Elefanty's current research at Monash is steadily refining the technique of guiding embryonic stem cells to form primitive blood cells that could be used for a bone marrow transplant.
In Britain, Ian Wilmut, who cloned Dolly the sheep, has also been issued a license to try the technique of therapeutic cloning. Wilmut's goal is to use a skin cell from a patient with motor neuron disease to make embryonic stem cells that carry the predisposition to the disease. These cells will be guided to form motor neurons and as they replay their life history in the culture dish,, the scientists will be watching them for the first telltale signs of the disease. No one can say exactly what the scientists will learn or whether they will find some new drugs to halt the disease. But one thing is for sure, these cells will provide something unique and new for the study of a hopeless disease: instead of patients in hospitals, cells in petri dishes.
More such licenses have been issued in the USA and Britain. And in seven U.S. states - as well as New Zealand, Canada, Singapore, China, South Korea, Israel, Sweden, Belgium, Finland and Spain - regulatory legislation has been put in place to allow the same.
So what about Australia?
In 2002, Australia passed a law that banned all human cloning, whether the intention was to copy a human being or merely to copy their cells. It was a statutory requirement to review that law after three years, and that task fell to former federal court Justice John Lockhart and his team of five: lawyers, scientists, doctors and ethicists. One of the scientists was Barry Marshall who picked up his Nobel Prize shortly after his appointment to the committee.
Lockhart's report took a vexed and distorted debate and used the tools of reason and justice to straighten it out. Perhaps its greatest value was to clarify what a democratic government should not be doing: it should not be taking sides in a contest between values: on one side those who value a primitive embryo above medical research, on the other those who value medical research above the primitive embryo. Lockhart also pointed out the furphy of attempting to contest the merits of embryonic stem cell research versus adult stem cell research. Research by definition deals with the unknown: what is the logic of placing bets on which research will score the most runs on the board?
The role of government then is not to take sides but to arbitrate. Instead of a sledgehammer ban, the law should be crafted into a fine regulatory tool. Where there was wide community consensus, as in the repugnance towards cloning for reproductive purposes, the report said the ban should remain. But where the community was divided, as it was over the potential medical benefits of therapeutic cloning, the brick wall should be replaced by a hurdle. Individual research projects should be evaluated on a case by case basis, by ethics committees and a government licensing committee. Some proposals would fall by the way-side, others might make it over the hurdle. Indeed this is the type of regulatory system that was installed in 2002 to control research over human embryos. So far nine licenses of limited duration have been granted for embryo research.
For several months after Lockhart's report came out in December of 2005, there was little overt response from the scientific community. Perhaps they were chastened by the excoriating experience of scientists like Alan Trounson who took a public beating for his advocacy in the 2002 debate. For most, the issue of therapeutic cloning probably had little relevance to their immediate research agendas. Perhaps many simply trusted that the recommendations of the Lockhart report would at the very least, be openly debated in parliament.
But as of June this year, the worst fears were realised. After a vote of the cabinet of the ruling Liberal-National coalition government, Australian Prime Minister John Howard announced Lockhart's recommendations would be shelved. The announcement not only produced a revolt on Howard's backbench; it has seen Australia's most eminent scientists stand up and be counted: Nobel prizewinners Barry Marshall and Peter Doherty; cancer researcher and 2006 Australian of the Year, Ian Frazer; emeritus professors like Sir Gustav Nossal, Roger Short and Bob Williamson, and most recently Australia's chief scientist, Jim Peacock.
With the strength of scientific opinion against him and the Liberal Party's backbench rebelling, Howard allowed discussion of the topic in the party room on 15 August 2006. That afternoon the media announced that Howard had agreed to a conscience vote on the issue: Liberal parliamentarians - from cabinet to backbenchers - would not have to toe the party line, and could vote as their hearts and minds dictated. It was a result that took everyone by surprise given that only a week before, the messages coming from his office were still distinctly hardline.
At first, Howard's announcement seemed hollow. He promised a conscience vote, should a bill appear before parliament. But where was the bill? Pundits doubted that the legislation being drafted by Natasha Stott Despoja, a senator from the minority Australian Democrats party, would ever see the light of day. Most such private member's bills never do, since the government chooses what bills are to be debated.
But within a week, Howard's hollow parry met a substantial riposte. Former Health Minister Kay Patterson announced she would draft the necessary bill. Liberal Party backbencher and family doctor Mal Washer - who played a key role in convincing the prime minister to reconsider his position - believes Patterson's bill will have the necessary support both to be introduced to parliament and very likely to pass.
As he told a recent radio interviewer, "I think we'll have more people vote for this bill than we had for RU486," referring to a recent conscience vote that eased restrictions on the use of the abortion drug. In early September, Howard's party will resume their discussions, and presumably address Patterson's proposed bill
Let us hope they will be guided through this difficult terrain by Australia's best scientists, ethicists and judges and - if we are to believe opinion polls - a majority of the community who support medical research. If not, then whose advice are they following?
Elizabeth Finkel is a Melbourne science writer, contributing editor to COSMOS magazine, and the author of Stem Cells: Controversy on the Frontiers of Science.
