Stem Cells, Spinal Cords and Blue Skies

Saturday 10 July 2004 1:00PM

The potential of stem cells to repair injured spinal cords or brains damaged by Parkinson's Disease is an exciting one. Hollywood's Christopher Reeve and Michael J. Fox have heightened interest in the prospects of neural stem cells through their own well publicised plights. But an Australian brain surgeon argues that pressure is mounting to trial new biotechnologies in patients before animal studies are really conclusive. Are we cultivating a climate of false hope? This week on All in the Mind, a neurosurgeon, a medical ethicist and a leading stem cell researcher bring us back to earth...


Relevant links and references at the end of the transcript

Natasha Mitchell: Hello Natasha Mitchell with you, good to have your company. Today on the show stem cells, spinal cords and blue skies. What impact does the public debate over biotech have on our expectations of the science?

News Archive: The superman star Christopher Reeve has told a Sydney audience that scientists are on the brink of helping the paralysed walk again.

Dana Reeves: In 1995 my husband Christopher Reeve suffered a devastating riding accident. He paralysed his body but not his spirit.

Christopher Reeve: We can already plan for a day when people who are presently confined to wheelchairs will be able to get up and leave them behind.

7.30 Report (ABC TV) interview from 2003 - Kerry O'Brien: You were quoted as saying no one can say exactly what technologies or avenues of research will lead to cures. So you say, we should err on the side of unfettered scientific enquiry. Isn't that a little bit open ended?

Christopher Reeve: No, it's deliberately open ended. When public policy is being debated I don't think that any particular group, religious or social conservatives, I don't think that they should have a seat at the table. I think that this is a public policy like a decision to go to war, or various other decisions that our elected representatives make. It should be handled in the same way.

Kerry O'Brien: But there are, the society we live in now, the democracies we live in now are so full of interest groups you start limiting those voices, you start tampering with democracies don't you. Even if they come to decisions at times that you don't like.

Christopher Reeve: No, absolutely. Everyone has the right to be heard and I in the States and I'm sure here... and I know there were 50 hours of debate in Parliament before they passed the bill allowing embryonic stem cell research. But the latest poll that I read about a week ago from the Gallup organisation shows that 70% of the American people are in favour of stem cell research from any source. It is primarily that I didn't expect that politics would be such a determining factor in hope. I thought hope would be the product of science and funding.

Christopher Newell: It's interesting that disability is actually central to many of the developments in healthcare and especially science and technology. The problem with reinforcing that 'catastrophe' that can only be cured by high-tech medical science is it totally avoids the broader conversations that we should be having about how science and technology can actually serve disability but within a broader social context. One of the big problems that we had when the stem cell debate was going on in this country in 2002 was that you largely saw people with disabilities being talked about, rather than actually Australians with disabilities being talked with.

Natasha Mitchell: Medical ethicist and disability advocate Professor Christopher Newell and more of his insights later. But you'll remember the media flurry that accompanied Christopher Reeve's visit to Australian shores last year.

The possibility of transplanting stem cells to repair damage to our central nervous system is certainly an exciting one. And people with spinal cord injury and Parkinson's Disease have been pricking up their ears with interest as Hollywood stars Superman and Michael J. Fox adopt their cause and put money towards unchampioned conditions like their own.

But are we expecting too much of stem cell science too soon? As you'll hear later in the show we're a long while off yet when it comes to understanding just how these cells function in the human body.

And in a recent edition of the Medical Journal of Australia neurosurgeons - Professor Jeffrey Rosenfeld, Head of Neurosurgery at the Alfred Hospital and Monash University and Professor Grant Gillett, an ethicist at the University of Otago - argue that pressure is mounting on surgeons to trial new bio-technologies before they're baked.

Jeffrey Rosenfeld: Some of this work is being done prematurely and I cited the example of experimental work being done in Brisbane where people with spinal cord injury in the chronic stage were having their own olfactory nerve supporting cells taken out from their organ or smell at the roof of their nose and it was being cultured in a dish and then it was being transplanted back into their damaged spinal cord - based on some animal work that had been done that showed that these olfactory supporting cells were actually very good cells to try and promote and support the regrowth of nerve fibres in damaged spinal cord in animals.

But just because that's happened in animals it doesn't mean that it's going to necessarily work in humans and we felt that work had been done prematurely because not enough experimental work had been done to actually confirm and to further document why these grafts might be working or whether they were working at well.

Natasha Mitchell: You're a neurosurgeon, you have patients with damage to their central nervous system and your concern is a major one that surgeons like yourself are under mounting pressure to trial stem cell technology in patients prematurely. Can you spell that concern out, I mean is the pressure a very real one?

Jeffrey Rosenfeld: I think Natasha it is a real pressure, it comes from the patients and their extended family and there's intense pressure in that way because the patients, they'll come and say "Could you please put me down as one of the first patients to have a stem cell transplant"? I've had a number of Parkinson's patients who are desperate to have stem cells put in their brain, they're willing to try anything.

And then we get pressure from the rest of the medical community because of the race to see who the first one is to successfully 'cure' Parkinson's disease. So, like of a lot of medical research, it's intensely competitive. If we know that a group in America is working towards that goal well we might say to ourselves "well why shouldn't we in Australia beat the American to that quest"? Athletics is very competitive so is medical science and that competition and the pressure from the patients does put a lot of pressure on the individual surgeon to try a new treatment and aim for success.

Natasha Mitchell: Well you suggest that also the private industry, private biotech companies looking for a market increasingly for stem cell lines is also a source of pressure.

Jeffrey Rosenfeld: Yes Natasha I really think that that is a third factor which when there are commercial imperatives and pressures which may advantage a hospital or an institution, an institute, an individual practitioner - particularly of he or she has shared in the company. I'm not saying that that always happens but there are those ethical concerns that come into the interaction of private enterprise with pure scientific research and I think that we have to always bear that in mind and try and divorce ourselves from that commercial imperative. And I'm always willing to try new things but they have to be based on firm scientific foundations.

Natasha Mitchell: What do you tell your patients who ask you?

Jeffrey Rosenfeld: What I say to them is that I'd like to wait a little while till more evidence comes in, as soon as I'm satisfied that there is a technique that I feel is safe, reproducible and applicable to their particular condition. And our ethics committee at our particular hospital has looked into this as well so it's not just me saying that we're ready to go, that we do have independent oversight. The ethics committee might say well we're not ready, we don't have enough evidence, we've looked at this very carefully, we've weighed it all up and we won't permit you to go ahead.

And an example of where this sort of surgery went ahead unchecked was when transplantation first started in about the mid 90s for Parkinson's Disease, people were transplanting adrenal tissue from the patient into their brain. Now if you take adrenal medulla which is the - the adrenal gland is the gland that sits on top of the kidney and secretes adrenalin and noradrenaline, if you take the tissue that secrets the adrenalin...

Natasha Mitchell: An important hormone...

Jeffrey Rosenfeld: Yes, it also can make dopamine and that's why it was put into the brains of the patients with Parkinson's Disease but the problem was it didn't work. I mean it didn't survive very well and it didn't really produce dopamine as it was thought to do from the experiments that were done. And so the operation failed but there were many people, measured in the hundreds, who were having these operations in the mid 90s and many were going to Mexico because they were desperate. And the hype was there and the publicity was there but it turned out when it was all analysed scientifically and reviewed very carefully that the results were shocking. And maybe if it had have been more closely controlled it wouldn't have got to that stage.

Natasha Mitchell: Neurosurgeon Professor Jeffrey Rosenfeld. Well, the day before Ronald Reagan died last month a bipartisan letter to President George Bush was signed by 58 of the 100 US Senators. It called for a change in what's perceived to be his restrictive embryonic stem cell research policy so as to combat diseases like Alzheimer's. And recently Christopher Reeve and leading international researchers including Australia's own Alan Trounson did the very same at the UN headquarters. So the pressure is certainly on, especially from patient groups.

Christopher Newell: Patients are absolutely desperate for any form of cure, any form of hope and will quite happily seek medical intervention even when the risks are very high because the tragedy looms so large in our minds. And especially for a few years after you sustain disability it's not unusual for for us to grasp at anything.

Natasha Mitchell: Christopher Newell is an Associate Professor in the School of Medicine at the University of Tasmania where he specialises in ethics and disability studies.

He's also one of the nine members of the NH&MRC committee which oversees licensing for human embryo stem cell research here in Australia.

And as someone who's reliant on a wheelchair and an oxygen cylinder himself, Christopher is also a voice for disability advocacy, one of many diverse voices.

Christopher Newell: The challenge I suggest is to actually reclaim balance in our lives and not just to live a life which is totally obsessed with a cure at all costs. Again one of the issues that Christopher Reeve has actually faced in America and in Australia is some people actually want to get on with their lives rather than just actually waiting desperately for some saviour science just around the corner.

What we see is the debate's offering what sometimes can be false hope to people. When the stem cell debate was on you may recall that parliamentarians wept as they spoke about the situation of people with disabilities in their constituencies. And then the legislation was passed and everybody thought 'oh well that's dealt with disability' and then within weeks the same parliamentarians were talking about cutting back on welfare and pensions for people with disabilities and they didn't see any of the contradictions there.

Natasha Mitchell: The contradictions are there obviously but I wonder if someone's a powerful advocate for stem cell research - does that have to be at cross purposes with the human rights and social equity agenda of the wider disability rights movement?

Christopher Newell: No it doesn't at all. Again I'd actually call for balance. One of the disturbing things I found was when I tried to actually talk about a broader agenda about how science serves society rather than giving in yet again to the forces of technological and economic determinism, was that we need those series of conversations about you know what it is to be a civil society, how people with disabilities can actually fit in.

And if we were really fair dinkum about tackling the incidence of disability in society there are a variety of low-tech solutions that we could be focussing on. Many disabilities can either be prevented or actually tackled very effectively with primary health care for example and yet that's not sexy. Also we've failed to recognise that there is a diversity of experience of disability out there. For example, people who are 'capital D' deaf, who come from deaf culture do not want to be cured, they actually identify in a totally different way, not in terms of loss but as part of a beautiful culture with actually a beautiful language in sign language.

Natasha Mitchell: It's very difficult for the wider community to come at that too.

Christopher Newell: Again I'd say that part of the problem that we have is because of the way in which we have these polarised realities. One of the problems we have with the telling of the story of disability and the telling of the story of science by the media is it becomes far too simplistic and we don't actually honour the voices that are actually also speaking.

For example Christopher Reeve is one version of reality with regard to disability but his voice has been disproportionately amplified by a media and indeed I'd suggest that political interests actually appropriated and facilitated his voice to trumpet over everyone else's voice in reinforcing that message of tragedy. And people say "oh, how could you possibly say that?" because of course disability is a tragedy. But people when they're born, for example, with disability it becomes quite normal for them and then they have a very different take on life.

Natasha Mitchell: I guess for those who end up in a wheelchair after a traumatic car accident they might view the debate a little differently though.

Christopher Newell: I think so but then, when you say that, I'm reminded of the 2002 media debate where we had Bob Carr the Premier of New South Wales who orchestrated a media spot outside a spinal cord injury unit and he spoke about a unnamed young woman with disability and said he 'dreams of a day when she'll walk out of the spinal cord unit'. Instead of actually asking her to speak about her experience and you might say 'well she'd probably say some of those sorts of things'. And I think that's fantastic because we need to have the diversity of voices out there as opposed to the tragedy of disability being appropriated by political and economic interests.

Natasha Mitchell: Professor Christopher Newell there and here on ABC Radio National you're tuned to All in the Mind with me, Natasha Mitchell and on Radio Australia and the web as well.

So where is stem research at? How close are we really to the prospect of transplanting neural stem cells to repair damaged spinal cord or perhaps to replace the depleted neurons in the brain of a person with Parkinson's?

And a reminder here that stem cells are what are called 'undifferentiated' cells so they have the potential to develop into any type of cell in the body, like liver cells, or red blood cells for example. And, there are two major types of stem cells - embryonic stem cells - taken from the cell cluster of embryos only a few days old. Or adult stem cells which reside in most of the tissues of our body.

So another therapeutic approach is in fact to find ways to promote the growth of our own existing adult stem cells, which are constantly replacing our damaged or dead cells already.

Jeffrey Rosenfeld: The potential is very good and there's a lot of active research being done at the moment to try and activate these adult stem cells, not only in animals but people are starting to think about maybe doing this in humans. And that you could possibly take a biopsy of someone's brain and identify the stem cells, grow them in a dish outside the person's body and culture them and make them multiply with different growth factors in a laboratory, and then once you've got the numbers...

Natasha Mitchell: ...pop them back

Jeffrey Rosenfeld: ... pop them back in again. Now that's still science fiction as far as I know but people are looking at doing that and they're starting to do it in animal work and I think in the future that will be a strategy that we use in human disease as well.

Perry Bartlett: Animal models have shown some ability to overcome certain aspects of Parkinson's Disease but I have to tell you we've been able to do that for many, many years by various other things in experimental animals. So, it's a little like a lot of animal studies, for example stroke, we've been able to minimise the amount of damage in stroke in animal models but we really haven't been very successful in humans doing that.

Natasha Mitchell: Professor Perry Bartlett is Foundation Chair of Molecular Neuroscience at the University of Queensland and directs Queensland's new Brain Institute.

He's world renowned for amongst other achievements heading up one of the first teams to prove that neural stem cells actually exist in the brain and to isolate them, a discovery that has really radically changed our impression of the organ.

Perry Bartlett: In the animal models of Parkinson's which are, again, somewhat contrived we can show effects of transplantation but that's not surprising cause we've been able to do that for a long while. Now, in the case of the spinal cord repair, which probably gets even more publicity, it's still unclear exactly what the stem cells that would be transplanted into the damaged spinal cord would actually do. I think there's a misconception around that somehow ...

Natasha Mitchell: You pop them in and off they go...sprout...

Perry Bartlett: You pop them in, and somehow they join ...Well, you see the problem in spinal cord injury is not the loss of nerve cells it's the loss of connectivity between the nerve cell that lies somewhere up near your brain or in your brain and the muscle down...activates and that long cord is in the spinal cord. So what really is missing here is the ability to regrow the damaged process or the axons on the nerve, not to replace nerve cells. There's a little bit of naivety about what this approach would do.

What is missing at the moment is really unequivocal data to show that stem cells or the cells that they take from nose which are called olfactory ensheathing cells which some clinical trials have started, actually cause the reconnection of the damaged nerve cells. So to summarise many, many years of work a number of things can show improvement in an animal walking after damage to the spinal cord but very few of these have ever shown that this improvement is walking ability is due to the reconnection of nerve cells, in fact I'd go so far to say none of them have shown that. So it's a very interesting thing in animals, you can get some recovery in walking which is generated locally, that is there are reflex circuits that don't require input from the brain down the spinal cord for you to get some walking capacity.

Natasha Mitchell: So it might have nothing to do with the stem cells, it might just be in response to localised surgery...

Perry Bartlett: Well it could be that the stem cells are releasing a factor that help promote this. I've been an advocate for a long while and saying, well, let's be realistic - if the data doesn't show that we're promoting connection but there is some clinical improvement let's focus on why that might be happening.

Jeffrey Rosenfeld: One of the problems is that the spinal cord injury is chronic when the patient has the transplant. In other words it's all scarred up, it's very different from a transplant in an animal which is a week or two after the injury, or a few days after the injury, you can't compare the two. Because here we asking the graft to actually somehow promote the regrowth of nerve cells across the scar and we've got no guarantee at the moment that the nerve cells will grow across the gap and reconnect with the cells beyond the injury. Just to think that you could put cells in, just stem cells and that they would magically transform into spinal cord tissue - that's a very tall order.

Natasha Mitchell: But that discussion's been had in the public sphere especially around someone like Christopher Reeve and his Foundation for Paralysis.

Jeffrey Rosenfeld: Well the thing is that stem cells have a sort of a magical connotation, that they're all powerful, they're the magic bullet that's going to solve all problems in biology. Maybe that's stretching the point but you see what I mean - that stem cells themselves have such a hype about them that one might think that just putting the cells in is enough. But the biology of spinal cord injury is so complicated, it's even more complicated than a stroke in the brain and people have already tried to transplant embryonic cells into stroke victims, they've implanted embryonic cells into Parkinson's Disease patients, with some success. But spinal cord injury is even more complicated than that and it's not going to be solved by just injecting a few cells.

Natasha Mitchell: Even if we did get neural stem cells to the stage where they could be tested say in people with Parkinson's Disease or spinal cord injury you raise another ethical dilemma of how you then test for the placebo effect in these sorts of trials. And actually the possibility of the placebo effect in say people with spinal cord injury almost seems counter-intuitive.

Jeffrey Rosenfeld: Placebo effects always have to be considered when new treatments are being administered and you have to know how many is placebo and how much is the actual direct effect of the treatment, in this case the graft of stem cells.

Natasha Mitchell: I guess there's some real ethical challenges for giving Parkinson's patients or people with spinal cord injuries a placebo?

Jeffrey Rosenfeld: Very much so, I mean there have been some sham operations where patients have had wholes drilled in their skull and their scalp opened and injections of embryonic cells. That's one group but the other group had the burr holes made in their skull but they didn't actually have the cells put in their brain.

Natasha Mitchell: Incredible.

Jeffrey Rosenfeld: And that was to try and see in fact what the placebo effect was.

Because we do know that with Parkinson's Disease, for instance, if you stimulate the person and give them a very active rehabilitation program you can actually improve the Parkinson's Disease just simply by that activity, by that placebo effect if you like...

Natasha Mitchell:

Jeffrey Rosenfeld: ... of looking after them more than what they're used to. And so you have to always bear that mind and say well how much of their improvement is due to the graft and how much is due to all the extra input that they're getting or the trauma of the graft, it's very complicated.

Natasha Mitchell: Professor Jeffrey Rosenfeld who's Director of Neurosurgery at the Alfred Hospital and Monash University. And back to Professor Perry Bartlett, Director of Queensland's Brain Institute.

How do you see neurosurgeon Jeffrey Rosenfeld's recent commentary that surgeons like himself are feeling the pressure to trial new biotechnologies, like stem cell technologies to an extent, in patients before the technologies are fully baked in animals studies? I mean is his a realistic concern?

Perry Bartlett: I think it's a realistic pressure and it's an interesting pressure.

There is, we've just formed an international consortium to try and get all these spinal repair associations in the world together to try and optimise if clinical trials went ahead that there would be standardisation of reporting and outcomes because one of the real problems is you get some trials with one or two patients and you get these reports. Now one or two patients is very anecdotal and whether you get some indication or improvement you never quite know what are the standards, what are the starting points. So even just to get set in place a rigorous clinical trials program is something very important.

Now Jeff's right, there is incredible expectation out there amongst patients and the expectation is that we should go forward if there's any signs of improvement in animal models. So what I've said is there are some signs of improvement in animal models but it's really not based on the gold standard of what we would like to see, that is, regrowth and reconnection which would lead to long term recovery.

But I very much understand and respect the viewpoint of people in wheelchairs who are now very well informed about what's going on, very much serve on some of the committees that drive this, and who say 'well you know, sometimes things happen and you don't necessarily have to know the reason in animal models'. And you know, sometimes that's right, things are empirically at work and you don't quite know why they work.

Natasha Mitchell: But are there risks in early transplantation into humans?

Perry Bartlett: Well I think the risk in embryonic stem cell-derived material is enormous. Put to one side for a moment the ethical considerations but what keeps getting lost in this debate is that embryonic stem cells in fact always form tumours in animals so the only way that you can overcome that in terms of using them to transplant is either use them by cloning from the individual, which is something that probably won't be allowed in the near future, or to make sure that they are permanently unable to divide.

So in essence what you have to transplant into an animal is something that is a mature neurone, a mature nerve cell. Now I have to tell you you just can't transplant a mature nerve cell, it just dies straight up. So the dilemma I see in this field if using this source is this - overcoming of the tumour problem - and of course the immune problem as well which has been discussed a lot.

Natasha Mitchell: So cells are rejected when they're popped in cause they're not their own.

Perry Bartlett: Yes, they're not their own. You know those two questions are still the major hurdle.

Christopher Newell: But do I think that there are potential for stem cell research, I think when we look at the literature we see enormous potential.

But then we, might I dare to suggest, we need also to realise that spinal cord injury, for example, is one particular aspect of a great story to do with disability. We need to realise that if we focus on spinal cord injury and particular neurological conditions then we actually ignore a variety of other disabilities that will not necessarily be attended to. And we also ignore the fact that no matter what we do we will still actually have the incidence of disability and we need to actually make sure there's not just cure but care as well.

The situation of many people with disabilities in the community is appalling and no particular scientific breakthrough is really go to address some of those fundamental issues. And largely we've actually forgotten about so many people with disabilities when we just focus on the saviour science delivering us tomorrow, because tomorrow never quite comes.

Natasha Mitchell: Professor Christopher Newell there from the University of Tasmania. And before him Professor Perry Bartlett, Director of the Queensland Brain Institute.

And for more from the cutting edge of science don't miss 'Pig Parts', on Background Briefing tomorrow morning looking at the extraordinary endeavour to develop animal organs and cells to treat diseases like Parkinson's and diabetes. It's a very interesting area indeed. Or catch it online at which by the way is where you'll find us too, just look for All in the Mind under programs for all our transcripts, real audio and our email address for comments which are always welcome.

My thanks today to producer James Carleton and sound engineer Steven Tilley, I'm Natasha Mitchell back with you next week - take care.


Professor Jeffrey V Rosenfeld
Department of Neurosurgery
Alfred Hospital and Monash University
and University of Papua New Guinea
Associate Professor Christopher Newell
School of Medicine
University of Tasmania
Professor Perry Bartlett
Director, Queensland Brain Institute
University of Queensland


Viewpoint: Ethics, stem cells and spinal cord repair
Jeffrey V Rosenfeld and Grant R Gillett
Medical Journal of Australia 2004; 180 (12): 637-639
Christopher Reeve, utilitarianism and human rights
Christopher Newell
Access: The National Disability Issues Journal (Australia)
Christopher Reeve responds to Dr. Newell
Christopher Reeve
Access: The National Disability Issues Journal (Australia) June/July 2002
Focus on Stem Cells
Nature (Journal) 20 June 2002
Uniting the Nation? Disability, stem cells, and the Australian Media
C. Goggin & C Newell
Disability and Society, Vol 19, No. 1, January 2004
Stem Cell Therapies: A Tale of Caution
Edward Byrne and David W Howells
Medical Journal of Australia 2003; 179 (3): 164-166
Special Issue: Olfactory Ensheathing Cells: Therapeutic potential for spinal cord regeneration.
Issue Edited by Kathryn Jones
The Anatomical Record (Part B - The New Anatomist): Volume 271B, Issue 1, Pages 39-85 (March 2003)
Stem Cells: Scientific Progress and Future Research Directions
National Institutes of Health (NIH) - USA
Department of Health and Human Services. June 2001
A detailed report on the many dimensions of stem cell research
Australian Apartheid?: Encountering Disability in Society
Gerard Goggin and Christopher Newell
UNSW Press, 2004 (forthcoming)

Further Information

National Institutes of Health (USA) resource for stem cell research
Health Insite Background to Stem Cell Research
Australian Federal Government health gateway
Cloning Around With Stem Cells
The Lab - ABC Science Online web feature by Daniella Goldberg (first published 16/12/2001)
Scientists Divided Over Stem Cells
ABC Science Online news story (Anna Salleh - 5 April 2002)
NHMRC (National Health and Medical Research Council) - Guidelines for Embryo Research in Australia
With links to reports and legislation
Stem Cell Research - Separating The Hype From Reality
ABC Radio National Health Report Feature (Norman Swan - 9 April 2001)
National Stem Cell Centre (Australia)
Christopher Reeve and Bob Carr dehumanise disability - stem cell research not the best solution.
Opinion piece published in 'On Line Opinion' (January 27 2003), by Erik Leipoldt, Christopher Newell and Maurice Corcoran.


Natasha Mitchell
Natasha Mitchell / Mike Woods