Supercells key to regeneration

By CHRIS BARTON

Dr Mary Birdsall wears a blue apron, helmet and visor and pulls on long protective gloves to lift the lid on the stainless steel tank. A waft of liquid nitrogen vapour momentarily envelopes her as she withdraws the precious cryogenic cargo.

This is not a sci-fi movie and there is no frozen, severed head. The contents here are very real, but also mysterious - human stem cells collected from the umbilical cords of newborn babies.

These are the cells, said to have regenerative powers, that paralysed actor Christopher Reeve believed would enable him to walk again. The dream, cut short by his death this week, would have seen Superman live again, giving testimony to a super cure.

Back on planet Earth, we're at CordBank, a private cord blood storage facility in Auckland city, and home for 2000 babies' stem cells held for future medical uses. It's a warehouse for suspended hope.

"I think it's for peace of mind," says Birdsall, CordBank's founder. "As people realise the promise that stem cells may hold ... I think that's why parents store their babies' cord blood."

The peace of mind Birdsall talks about doesn't come cheap - $1950 for each baby and then $150 a year, or $2350 for an 18-year storage contract.

At present, stem cells can be used in cord blood transplants for treating diseases that include leukaemia, lymphoma, sickle-cell anaemia and some immune disorders.

The process - still relatively new, with only about 3000 transplants carried out worldwide and about half a dozen a year in New Zealand - is similar to transplanting bone marrow.

The advantage of cord blood stem cells is that they are more "immunologically naive", have less graft-versus-host disease in transplants and are an off-the-shelf product. And unlike the invasive procedure used for bone marrow transplants, they are easily harvested at birth.

But it's the prospect of what stem cells - the building block or seed cells of the body - may do that has the medical world and people like Reeve excited.

"We're in the discovery phase," Birdsall says. "People have recognised that stem cells are enormously valuable. Now we're waiting to see which stem cells hold the most promise."

Early stages of research suggest that stem cells - found in cord blood, bone marrow, the brain, embryos and even body fat - may eventually cure brain diseases such as Parkinson's, Huntington's and Alzheimer's. There is also excitement over what stem cells may be capable of doing to repair damaged tissue in hearts and even spinal cord injuries.

If you believe the hype, stem cells may be a miracle cure-all.

"For the true biological miracles that researchers have only begun to foresee, medical science must turn to undifferentiated stem cells," Reeve told a United States Senate hearing in 2000 on federal funding for stem-cell research. "We need to clear the path for them as rapidly as possible."

Other celebrities followed his lead. Actor Michael J. Fox, who has Parkinson's disease, pushes the stem cell cause, as do the wife and son of the late President Reagan, who also had Alzheimer's. "Science has presented us with a hope called stem cell research which may provide our scientists with answers that have so long been beyond our grasp," Nancy Reagan told the Juvenile Diabetes Research Foundation.

Not everyone is convinced. Reeve's claim that he would one day walk again was not well received by certain scientists and advocates for the disabled, according to an article in the Observer in February: "Some critics attribute his words to a state of denial; others have been more caustic, calling him a spoiled celebrity who raises false hopes."

The cult television cartoon series South Park viciously parodied Reeve's stance in an episode featuring Larry King interviewing Reeve, who illustrates how stem cells help him by taking a foetus, cracking the back of its neck open and sucking out the insides.

It's worth noting that stem cells played no part in Reeve's own remarkable recovery of some sensation in his legs and arms.

That was attributable to his own courage, refusal to accept the finality of his paralysis and a radical exercise regime.

Many in the biomedical community are concerned that the public is being fed unrealistic expectations.

"It's going to be at least five years before we understand how we can utilise stem cells for the treatment of brain disease," says Professor Richard Faull of Auckland University's medical school.

"The concept that these stem cells can form into any type of cell that you want is true in theory, but more basic research needs to be done to understand exactly how we can achieve that in patients."

Faull, who heads a team researching the role of adult stem cells in brain disease, advocates caution and points out that stem cells have been shown to grow tumours.

"To just take undifferentiated cells and put them into the brain or into another organ is doing blind medicine - you have to understand what their biology is and what's going to make them grow into particular types of cells."

Hype is not the only problem.

Combine stem cells with in-vitro fertilisation (IVF) and whole new set of ethical dilemmas emerge.

As Birdsall points out, the two technologies are natural partners and the idea for CordBank was a developed from her work with Fertility Associates.

"It's an ideal thing for someone from my background because I'm involved in an IVF practice so I'm used to liquid nitrogen for storing eggs and embryos - so moving into storing something else in liquid nitrogen is not that big a leap."

The big leap comes when our Government passes the Human Assisted Reproductive Technology (HART) bill and allows pre-implantation genetic diagnosis (PGD) of embryos (see story page B3).

That procedure involves the screening of a test-tube embryo for genetic defects before it gets to the womb.

"PGD in the future means we will know before we put any embryo back into a woman's uterus whether or not it has normal chromosomes."

To some overseas parents, these so-called designer babies are a blessing - not only enabling a child to be born free of a life threatening disease but providing a means for treatment of a diseased sibling through the collection of the designer baby's cord blood .

The problem for CordBank is that even when PGD happens here, donating privately stored cord blood isn't allowed.

CordBank stores stem cells in accordance with the 1956 Health Act which allows for private blood storage for autologous use only - that is, only for use by the babies from whose umbilical cord the blood was taken.

Birdsall would like to see a law change to allow immediate family to gain therapeutic benefit from stored stem cells.

The Ministry of Health says a law change isn't necessary because cord blood transplants are available in the public system through the importation of matched cord blood from overseas' cord banks.

In the case of designer babies, the ministry says parents could - in exceptional circumstances - have cord blood to treat a suffering sibling collected by the Blood Service, which has a state-sanctioned monopoly on blood donation.

"Should we have a scenario where we have a sick sibling for whom the cord blood stem cells would be a suitable match, then we would have to ask the Minister of Health for an exemption," Birdsall says.

At present there is no public cord blood bank here.

The Ministry says there is insufficient demand, but is considering a proposal from the Leukaemia and Blood Foundation of New Zealand.

CordBank says it would be keen to provide such a facility, whereby babies' cord blood is donated by parents and made available to patients here and worldwide.

Critics of the designer baby process say it turns children into donor commodities.


"For me it's an ethical issue," British fertility expert Lord Winston told the Herald in September.

"You are subjecting an embryo to removal of cells for DNA analysis that is of no benefit to that embryo.

"That is having a medical procedure without any informed consent."

But the ethical dilemmas concerning adult stem cells - the type found in cord blood and occurring naturally in body organs and tissues - are nothing compared with the maelstrom swirling around embryonic stem cells.

These are primordial cells formed soon after fertilisation that may grow into any type of cell in the human body, but can be obtained only through the destruction of days-old embryos.

As well as supplying an almost unlimited supply of cells for transplant, embryonic stem cells appear to have more regenerative potential and versatility.

In experiments with rats, scientists have shown that embryonic stem cells did not just latch onto a wounded heart the way adult stem cells do, they actually became heart muscle cells that beat in time with the rest of the organ.

Others have persuaded human embryonic stem cells to make dopamine-producing neurons - the brain cells that die in Parkinson's disease patients.

But Faull says that while such results are very encouraging and exciting, the jury is still out on whether this is going to be a potential therapy.

"In double-blind clinical trials the outcome has not very positive.

"It has shown you can put cells into the brain and in some cases they cause a remarkable improvement. In other cases they don't."

In the United States, some pro-life and religious groups, including the National Right to Life Committee and the Conference of Catholic Bishops, equate research on embryonic stem cells with murder. President Bush agrees and has restricted federal money for research into embryonic stem cells, a step that Democratic presidential nominee John Kerry promises to reverse if elected.

He says that Bush has "made the wrong choice in sacrificing science for extreme right-wing ideology.

Reeve argued for many when he said researchers should take more risks and speed up the process for allowing new medical procedures.

Those like him are less concerned with ideology or the finer points of medical ethics. They just want to get better. And while federal funds are off limits, privately funded stem cell research continues unabated - a point not lost on Californians now debating a US$3 billion ($4.4 billion) proposal to fund a new stem cell research institute.

A July NBC-Wall Street Journal poll showed more than 70 per cent of United States voters - and 58 per cent of Bush supporters - approve of using embryonic stem cells for research.

But the debate is further muddied by the issue of therapeutic cloning - the process, necessary to match tissue types, of making embryonic stem cells with the same genetic composition as the patient.

It's a far from perfect science.

Researchers in South Korea announced in February they had harvested stem cells from human embryos they had created by cloning, but they began with 176 human eggs and ended up with one embryo that yielded stem cells.

Enthusiastic supporters argue the technique could provide "replacement parts" that would not be rejected by a patient's immune system.

Cloning aside, the research requires discarded embryos from which to harvest stem cells.

"My feeling is more people would tend to be comfortable with using spare IVF embryos as opposed to bringing new embryos into existence quite specifically for research purposes," says Otago University anatomy professor Gareth Jones, arguing that embryos in an IVF programme were brought into existence in order to give rise to new life but for various reasons a certain number are not required.

"Contrast that with bringing embryos into existence quite specifically for research purposes.

"Many people see the goal as rather different - they are being used as a means to an end."

If this is beginning to sound like an abortion debate, that's because it involves many of the same questions - questions about when and where life begins.

The HART bill now before Parliament establishes, for example, that practitioners must not allow in-vitro embryos to develop beyond 14 days.

It also says that in-vitro embryos may not be stored for more than 10 years.

For some of the 5000 to 7000 stored embryos in New Zealand that amounts to a death sentence.

"In the lab, which is where we are, we get excited with fertilisation," says Birdsall.

"When you look down the microscope and you see a fertilised egg you know that some of those fertilised eggs are going to become children."

So how does she feel about discarded embryos?

"When I have a couple who want to discard their embryos, a part of me thinks, 'Oh my goodness - how can you discard this incredibly precious thing that we've all worked so hard in creating?'

"But that's not my choice to make."

And should those discarded embryos be used for research?

"I see enormous value in embryonic stem cells - so if people choose to donate their embryos for the creation of embryonic stem cell lines with the appropriate informed consent, I'm perfectly OK with that."