Medicine's Holy Grail is no soft cell

By EUGENE BINGHAM

Botanist Gottlieb Haberlandt, a pioneer of cell culture, was dead by the time his ground-breaking theory of 1902 was put into practice.

It had taken 50 years for the Austrian's prediction - that cells carried all the genetic information for the whole organism - to be demonstrated in the laboratory. Now cell research has accelerated to the speed of light. Developments in the field have advanced so fast since the late 1990s that the legal and ethical guidelines supposed to be regulating them have been left behind in the space dust.

Scientists are impatiently chasing breakthroughs that could dramatically change the lives of millions of people suffering from numerous disorders.

But stem cell research has caused enormous friction between those who believe its benefits are too good to ignore - such as actors and potential beneficiaries Michael J. Fox (who has Parkinson's) and Christopher Reeve (paralysed from a spinal injury) - and those who see some of its applications as an attack on the sanctity of life - the Pope, another Parkinson's sufferer, for one.

This week, the New Zealand Government announced proposed legislation for assisted human reproduction procedures. The legislation will cover stem cell research if the cells are to be taken from embryos. But there are still no proposals to legislate other aspects of stem cell work. Neither, though, has New Zealand seen any of the controversial work on human embryos or foetuses. It has not been a major issue - until now.

ALONG the green-tiled floor of the wood-panelled corridors in National Women's Hospital is Auckland University's department of obstetrics and gynaecology. Department head Professor Peter Stone has long been interested in foetal medicine and the possibilities of surgery on foetuses within the mother's womb. He has talked to fellow New Zealand clinicians about whether they could take advantage of what stem cell research has to offer, but it was not until he was approached by an Australian group that he had to give the technology serious thought.

The Australians, who are a subsidiary of Dutch biotechnology company Crucell, approached Stone last year asking his department to contribute to work that could lead to breakthrough treatments. The work would involve taking cells from aborted New Zealand foetuses - an ethical hornet's nest in itself - flying them across the Tasman and growing lines of retinal cells, the building blocks used to construct eyes.

An initial proposal was lodged with the Wellington Regional Ethics Committee by the Capital Coast District Health Board but late yesterday the application was withdrawn. It was a move which showed the sensitivity of the issue. Even if the Wellington application had been approved, Stone says the department would have had to think long and hard about its involvement. It would have meant a radical departure from their present lines of research inquiry.

He has the natural caution of a scientist. He talks in great detail about the many complex hurdles the project has to encounter before it could get off the ground. He talks of the funding constraints.

But behind the caution and conservativeness, it is possible to see every cell in his body jumping with excitement at the thought of what he could do. The field of stem cell research converges with his interest in foetal surgery and he can envisage a day when babies identified with abnormalities can be treated months before they are born.

"The Holy Grail, if you like, is that you'd be able to identify the foetus as being affected and while the foetus is in utero, do a transplantation, putting in new cells that you hope will graft," says Stone.

This Holy Grail of medical science is all down to the discovery of the existence of stem cells, the so-called "master cells" that can develop into more than 200 different types of cells in the body including skin, blood, muscle, nerve and bone cells. That they exist is just the beginning. Their possible uses are simply incredible.

Damaged or diseased tissue in patients suffering from Parkinson's, diabetes or serious burns could be repaired or replaced with new tissue grown from master cells.

Scientists are also developing techniques which would allow them to clone a person's genetic material for transplants. No need to worry about a lack of suitable organs or the risk of rejection - just grow a replacement heart, liver, kidney to slot straight in.

And Professor Stone's vision of repairing babies before they are born is more than just a dream. Internationally, several cases of foetal transplants have already been reported.

United States doctors operated on a foetus in his mother's womb when it was discovered he had the genetic disorder Severe Combined Immunodeficiency Syndrome (SCID) - the disease which afflicted the "boy in the bubble" made famous in a Disney movie.

After diagnosing the foetus as having the condition 12 weeks into the pregnancy, doctors transplanted cells taken from the father into the foetus. The parents had already lost a child at seven months old to SCID, but the new baby was born healthy and free of the disease, thanks to the transplant.

In that particular case, the cells were taken from the father's bone marrow. As well as bone marrow, stem cells can also be found in blood taken from the umbilical cord after birth. Early research in the area has favoured the use of cells from more controversial sources - embryos usually created for fertility treatments, and foetuses.

Therein lies the ethical debate; this is where stem cell research intersects with the strong feelings engendered by the pro-life movement.

If foetuses are to be used, they are the product of abortions. The embryos are either "leftovers" from fertility centres or they have been created or cloned especially for the research. In both cases, the embryos are destroyed in the process of harvesting the stem cells.

Christopher Reeve, the former Superman actor who has become an advocate for therapeutic cloning after being paralysed in a horseriding accident, told an Australian conference last year that while the concept may be difficult for people today, he believed they would embrace the technology just as they had with test tube babies.

The Catholic Church's opposition to abortion is well-known. Its views are as strong in relation to the use of embryos.

A paper produced by the church's bioethics think-tank, the Nathaniel Centre, said that from the moment of conception, embryos and foetuses were to be treated with all the human rights available to babies and adults.

Experimentation on them was immoral and did not afford them unconditional respect, said the paper.

"Rather than giving value to their existence, experimentation adds indignity to their death."

New Zealand's ethics committees have found themselves in the middle of this exchange. The Wellington Regional Ethics Committee last month became the first such body in the country to be confronted with this situation when the Australian-initiated application from researchers wanting access to aborted foetus cells arrived.

Chairman John Currie, a Masterton farmer and Presbyterian minister, said the committee had to talk to other ethics committees and advisers from the Ministry of Health about how to handle the application.

"It's at the cutting edge and therefore people have to exercise their minds as to where things fit."

The complexity of the issue is acknowledged in Health Research Council guidelines. They define foetuses and "gametes" (germ cells) as "human materials", meaning that their use is governed by the informed consent of the donors.

Other than that, the guidelines do not go much further than advising: "The legal and cultural issues in relation to use of surplus parts and tissues [eg aborted foetuses, placentas, spare embryos] are complex. In respect of some parts and tissues cultural concerns may need to be considered."

Health Research Council chief executive Bruce Scoggins says the guidelines are appropriate for the level of research going on, but the Government was watching what was happening internationally.

Aside from the ethical vacuum, there is a legal hole. Legislation introduced this week will cover the use of embryos for stem cell research, requiring scientists to obtain ethical approval. Other issues relating to stem cell research will be looked at by a ministerial committee.

The use of stillborns - hence aborted foetuses - are not covered in the law. Foetuses are specifically excluded from the Human Tissues Act, which covers the use of body parts for research, an anomaly identified by the Ministry of Health in its ongoing review of the act.

The deputy director-general of health, Gillian Durham, says the review will go to Cabinet within months and will then be released as a public discussion document. She said it was too soon to say how stem cell research would be covered in the document, but indicated that it was not something that could easily be dealt with in legislation.

"The ethical and technical issues around stem cells are complex and are likely to be covered by more than one piece of legislation depending on the source of the cells and their proposed use."

While the fraught issue of whether embryos and foetuses should be used for stem cell research flares in New Zealand, scientists have made discoveries that could be a way to sidestep the ethical prickle-patch around embryos and foetuses.

Professor Richard Faull, of Auckland University's school of medical sciences, has found that stem cells from the adult human brain are capable of repairing a range of degenerative diseases.

"By tapping into and genetically engineering the adult stem cells from the diseased adult brain, we'd overcome major ethical immunological and technical problems associated with the more controversial area of embryonic stem cell technology."

Professor Peter Browett, an Auckland University bone marrow and cancer specialist, said there was promising research on cord blood and bone marrow stem cells, too.

"Although they mainly develop into the blood cells, under particular laboratory conditions if you put them in the right environment and stimulate them with the right growth factors you can cause them to differentiate into neuronal cells, into cardiac muscle, skeletal muscle."

He described the potential as "huge."

But over at National Women's, Professor Stone believes there are limits to how useful cordblood cells are. 'Of course, they contain all the genetic material of the child." The cells could carry the genetic predisposition to develop into the condition doctors were trying to treat.

"What you're doing with cord blood banking is trying to get some cells and grow them up - like taking a cutting and growing it in the ground," says Stone. "What we're talking about in stem cell therapies is completely different."

Stone compares the branch of stem cell therapy he is interested in to planting a row of healthy yellow roses next to a row of sick red roses. "You're hoping to get in early enough and the individual will accept the yellow rose ... and that the yellow rose overtakes."

Before doctors can think of transplanting cells in this way, they need a source of stem cells. One of the main issues is the problem of consent - the parents of the aborted baby would both need to give their approval to take part in the research and be tested to make sure the foetus is free of infection. All this would need to happen before the abortion.

The other lingering question is why Australian researchers would want otherwise normal, healthy foetuses. Stone says the researchers were interested in New Zealand's well-organised abortion service and that pregnancies can be terminated for a greater range of gestation.

While this type of stem cell work is a leap from the kinds of research in Stone's department, he says it may be a case of collaborating with other departments. He describes it as a potential bridge between people working on genetic disorders and those looking at cancer - the researchers would come at it from different angles but have common ground through the techniques offered by stem cell therapy.

There is nothing unusual in co-operation across disciplines. After all, it is a botanist, Gottlieb Haberlandt, who is credited with helping these doctors reach the brink of the breakthroughs they are dreaming of today.