Science, People & Politics, issue four, volume i, II, 5th July (2010)

New hope for medicine: where cells come from

by Helen Gavaghan
Toronto and Hebden Bridge, W. Yorks.

21st and 22nd MAY, 2010.

The news came through at the end of the first day of the Toronto stem cell conference. The J Craig Venter Institute had done it again, successfully pushed the biomedical envelope with the creation of Synthia, a self-replicating artificial bacteria. I learned the news from neurosurgeon, Stephen Huhn, who tossed the newspaper story onto the restaurant table. It landed northeast of my wine glass and sometime between departure of the lobster bisque starter and arrival of the halibut entree.

To my left two more surgeons chatted in what might have been Swiss, whilst across from me Judy Illes, who holds the Canadian chair in neuroethics at The University of British Columbia, displayed consternation when I asked her what she knew about the philosophy of Confucius. She said she didn't know anything.

My question to her was prompted by conversation I had had during the day with the Chinese ethicist, Dr Qui Renzong, an academic attached to the Chinese ministry of health. We shared a table during the conference along with Carole Chebaro, a switched on, smart physiotherapist whose husband has had spinal cord injury for many years. We were a depleted table because Michael Fehlings, the confernece organiser, and James Price, from The Miami Project to cure paralysis, in fact did not join us, though they were listed as seated with us.

Announcement of Synthia's creation was to my mind significant to this conference's purpose but the subject gained no public discussion.

The conference aim was to develop consensus guidelines for the harmonisation of international regulations addressing the use of stem cells as therapies for spinal cord injuries and related central nervous system disorders. Did they succeed? No. I am quite certain of that.

The ethics centred on Western preoccupation with abortion, and not on views from the large portions of the globe where abortion is not the predominant ethical dilemma.

But it was a good place for intense networking, for gaining an overview of the threads of the debate as they are this year and learning that those with important international civil service roles, people like Patrick Celis of the scientific secretariat from the committee for advanced therapies at the European Medicines'7#32;Agency, are approachable and can explain the esoteria of their expertise - in elegant English. The conference make-up showed, too, the fierce commercial and scientific international competivity of the field.

Stem cells are of a sort that can differentiate into other cells of more specific function. The hope is that stem cells will enable failing heart muscles, demylenated nerve cell or neural lesions to be repaired. Pioneer Martin Evans, professor of mammalian genetics at Cardiff University, told the UK Select Committee on Science and Technology this year that he thinks it will be 50 years before they become a significant part of medicine. When they do it seems to me their potential is revolutionary: to enable all human beings to reach a natural life span of a hundred years without any brutalising eugenics and with the prospect of those years of life being years of good physical health.

These seeming magic bullets, the versatile stem cells, fall into different categories. Some have the potential to become any type of cell, others have an obvious narrower range of biochemical options and might only become, say, types of muscle cell or types of nerve cells or types of skin cells or of blood cell. That is, they move from totipotency through pluripotency to multipotency to eventual full differentiation then into specific types of muscle or skin cell etc... The totipotent egg cell or pluripotent muscle stem cell has its biochemical pathway irrespective of whether the egg or muscle stem cell is from an adult or a seven month old. But as we age DNA gets damaged so older stem cells might be of less reliable therapeutic value.

Initial scientific understanding was that the earlier in its prefoetal development an organism is and the earlier in the pathway of biochemical differentiation a stem cell is then the more wide ranging is the potential for stem cells to differentiate into different successful cell types for therapeutic and curative purposes. In an intuitively obvious investigative move, at least in hindsight, some scientists are now following this initial understanding up by manipulating transcription factors so that fully differentiated adult cell lines revert to an earlier form of less differentiated cells. A process known as induced pluripotency. If it works induced pluripotency could take the heat out of the controversy of obtaining stem cells from embryoes of foetal tissue.

But, as the conference heard, induced pluripotency reveals many pitfalls centring on particular genetic loci. So even though induced pluripotency would eliminate a number of the ethical dilemmas voiced by some groups the technique is not a scientific panacea.

This was the inaugural conference of what the Canadians - the city of Toronto, Province of Ontario and Canada - hope will be a series that turns stem cell therapy into a medical and commercial success for Canada. It was organised by Michael Fehlings, who holds the Krembil Neurocentre chair at Toronto Western Hospital, and an advisory board. He and his students provided a professional if slightly unusual intellectual structure for the event, bringing scientists, ethicists, patients, surgeons and physicians together. I was there to speak in the policy and ethics section of the conference and as a UK journalist and editor without expertise in stem cells, though it is a subject I have covered specifically for the Bulletin of the World Health Organisation nearly 10 years ago and as part of other news stories since.

The format meant we touched only on the tip of a lot of icebergs but that many of those present learned dimensions of the debate they had not known before. Does your injury cause you pain? I asked one wheel chair bound delegate who has learned to live with his injury and who does not want to participate in experimental clinical trials. The patient's answer was yes.

How do you manage your patient's pain, I asked Dr Greg Hawryluk, an MD working on his Ph.D under Professor Fehlings' supervision? The patient I had spoken with was not Dr Hawryluk's, but as Dr Hawryluk jotted down his email address for me he explained that there is a two year wait to get an appointment at the local pain clinic in Toronto. In an unanswered written question I submitted to one panel I asked what effort was being made to characterise the specific nature in detail of human spinal cord injuries and to correlate that with understanding of pain. I do not know why the moderator did not pass the question - which was relevant to the discussion - to the panel, but I later asked Michael Fehlings and he said one of his group was exploring what functional magnetic resonance imaging could tell them about injuries.

The whole two days was of this structured formal/informal pattern and a whirlwind of activity. Coffee in our hotel lobby at 6 am, coaches directly to the conference centre and "incarceration" in the plush surroundings of the MaRS Collaboration Centre. Registration and sessions began at 7 am on both days. On the first day I homed in on an empty table and started chatting about how difficult it can be to find the person at the right level in an organisation to know what is going on. The object of my chatter introduced himself as Thomas Okarma and he assured me he did know what was happening at Geron. So I believed him when he said later in the day that even before the Food and Drug Administration had put his company's phase-1 clinical trial on hold the company had begun a deep investigative dive into the DNA of their potentially therapeutic stem cell product. And I believed him when he said the work had cost $45 million. I had his attention for only a few moments and did not know then of the experimental protocols he was going to describe. It might be also that he knew what I did not then know - of the paper due out about Synthia. My own fault for not keeping up with embargoed press releases.

What I had intended to say in the 10 minutes alotted to me during the final session of the first day was derailed by presentations from Thomas Okarma, president and CEO of the Geron corporation and by an Indian group using dogs as experimental animals. Dr Okarma gave us a scientific overview of why the FDA had put their trial - the first human phase-1 clinical trial in the US for spinal cord injury - on hold.

I found myself half listening and half changing the notes of my own talk as Dr Okarma spoke and as the day proceeded. My aim had been to convey the essence of the House of Commons Select Committee report on bioengineering published 25th March this year, to give the report's political context and to select information relevant to the audience from the report.

I did do that - the chief facts being that the UK views bioengineering as commercially significant and had, since the report's publication, moved from a labour government to governance by a centre right coalition with a centre left opposition.

In the end I was less polished than I had intended. Mainly because the photographs presented by Thomas Okarma of the rats on which his company experiments and those of dogs that were the subject of Indian experiments were shocking. They showed clearly what lies behind the bland words in scientific papers of shock to the spine. What is meant is that the animal's spine is deliberately broken and the animal lives on incontinent and dragging its rear limbs. Since human beings with broken spines are in pain, I suppose the animals must be also. One photograph showed the explosion of bulbous bloody tissue from the spine of one dog following a deliberately caused spinal injury which was so extreme that the animal was too unfit to experiment on, and had to be put down.

I have no expertise in ethics so cannot probe the question more deeply than to ask myself what depth of pain, violation irrespective of pain and of objectifying degradation of an animal is acceptable in the name of medicine and pharmaceutial regulations. Breeding animals for this purpose shows us clearly where natural selection stops and eugenics begins. The former is driven by pheromones, perception of what is pleasing, by the ecological niche and desire. The latter by imposition by external parties of what should happen to an animal which strays from its ecological niche or has a genetic complement and/or biochemistry that makes it attractive as a commodity or biological mechano set. Circumstances in which the realities of flesh and blood are overlooked for the "greater" good of medicine. Though I asked one of those with a broken spine if he was in pain I genuinely forgot to ask him if he thought the way we had been shown that science and medicine were treating animals was acceptable. To my mind what I saw was not acceptable. And I ended up departing from my script - only for a phrase or two - but saying things I had no intention of saying and not having known I thought those thing. To bring myself back to a cooler rational place I fastened on to the fact that one of the Indian surgeons had said in his presentation that there was a need in his country for more collaboration between clinicians and scientists. Somehow I dragged out of my memory an initiative of the Wellcome Trust nearly a decade earlier to explore exactly this issue and told the Indian surgeon who had raised the point. And I urged delegates to be conscious in their dealings with the UK that there is a battle between UK science advisors and government as to the advisor's role in the machinery of government.

My fellow speakers in the policy and ethics section broached the vexed subjects of culture, ethics in government, in this case China but in a way accessible to a Western audience, and stem cell sourcing. Timothy Caulfield, chair in health law and policy at the University of Alberta, has studied the cultural significance and meanings and iconography being acquired by the words stem cells. He showed photographs of the creams and potions being promoted. I was not sure from what Professor Caulfield said whether that newly occupied marketing niche is yet a threat to Clinique, Estee Lauder or manufacturers of glucosamine suphate, but judging by professor Caulfield's presentation it is up there, at least in the promotional stakes.

What I did not know was that even as I spoke the world of science had moved on and the dimensions of the ethical debate and the policy issues I was reporting were shifting beneath my feet. As I wrote in the intro: the J. Craig Venter institute had done it again. Pushed the boundaries. Created an artificial organism. Perhaps Synthia will one day act as an experimental animal instead of the traumatised rats and dogs of today's science. Will the possession of pain receptors in an artificial organism be sufficient to lead to a ban on research on Synthia, or will the J. Craig Venter Institute need to develop consciousness for their artificial organism before outrage is expressed. Will that consciousness have the moral equivalence of a human being?

Experts wanting the medical details had better contact directly Michael Fehlings, surgeon and physician, Toronto Western Hospital.

Declaration of interest: My air fare and hotel bill were paid for by the conference organisers.

In addition, as a victim of medical incompetence and of criminality under the UK Mental Health Act since 2004 I am an opponent of the UK Mental Health Act, and I asked neurosurgeon, Stephen Huhn, if any of the people who have undergone experimental procedure for his company, StemCells, have ever been diagnosed with psychotic mental illness. If they have, then irrespective of whether or not they actually ever have had such an illness, and if US law is like UK law, the right of autonomy of those patient to say no will have been compromised. That patient may have been treated with ridicule and derision as I was, and found them self the victim of others' lurid projections and unjustifiable fear of the consequences if they say no to medical intervention. There would in some States in the US be a real danger of a neurosurgeon finding himself on death row if an operation went wrong.

ABOUT Helen GavaghanIn addition to currently editing Science, People & Politics I have been the editor of the weekly international weekly business-to-business newsletter (with daily electronic output), Clinica, which serves the international medical devices and diagnostics market, technology news editor and Washington correspondent for New Scientist, the biomedical research policy correspondent on retainer for Nature, Washington correspondent for Le Journale Internationale de Medecine and UK correspondent for Biofutur.


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