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N°97 - January 2007

 

Reprogramming adult stem cells

Reprogramming technique
The "reprogramming" technique initially developed by Shinya
Yamanaka, and then corroborated by Rudolf Jaenisch and James Thomson (see Gènéthique No 96) is really interesting. Having said this, it deals with a research which does no pretend to any clinical application in its current stage, and which requires even other explorations, in particular to clarify the mechanism by which the four transcription factors used by Yamanaka act to determine the totipotency. Thomson’s divergent results (he includes Nanog in his factors) show that the question is not resolved by simply insulating the four "magic factors". The mechanisms of the instauration of totipotency have to be explored, and latter this will maybe allow doing without genetic transfer by retroviral (Yamanaka) or lentiviral (Thomson) vector. The great credit of this research is that it clearly shows the possibility of the cell reprogramming, thus removing the ethic obstacle from the necessary destruction of blastocysts to obtain embryonic cells (EC). Its other great credit is precisely to invite scientists to explore more the mechanisms of totipotentiality.

The objections
Strangely, we did not much highlight that the results from Yamanaka-Thomson only resolve partially the problem raised by a possible clinical application of ES cells: There is still the
carcinogenic risk, which will require the implementation of efficient removing techniques of non-differentiated ES cells; also there is still the problem of an effective control of the differentiation of these cells.
On the other hand, we underlined the risk which determines
the use of c-Myc oncogene as an agent of totipotentiality by Yamanaka. Since then, Yamanaka showed that we can do without c-Myc, and Thomson does not use it. Thus this objection, heavily raised by R. Lanza, found its answer.
The objection raised by Debi Vinnedge (Children of God) regarding
the use of Plat-E cells by Yamanaka (modified 293T cells, initially prepared in the 70’s from foetal kidney cells coming from an aborted foetus) is interesting, but cannot be really take to much seriously in the current state of researches, since it only concerns the "packaging" technique of retroviruses used for the transfer of genes and it is not certainly in the centre of Yamanaka’s protocol. We are not at the clinical stage. It is however good to indicate to the researchers that, if they want to perfectly respect ethics, they should refrain from using as "packaging" cells, vectors of cell lines derived from aborted foetuses. In fact, the techniques available for gene transfer are multiple, and this is not the problem.

Efficacy of the method
The real question is that of efficacy of the method (less than 1% of cells are reprogrammed). Even using the bias of the neomycin resistant gene to develop selectively, in culture, the iPS cells, these are rather rare, which drives Yamanaka to want to develop a bank of these cells (but then we have the problems of immunologic rejection the Yamanaka’s technique allowed resolving if the iPS cells were used in the patient donor of initial fibroblasts). Here again research on totipotentiality mechanisms should allow obtaining a much more efficient technique.

Conclusion
In conclusion, it is a research to support without forgetting adult stem cells and umbilical cord blood cells, which have immediate clinical application. There is still a lot of work to do before thinking about a clinical application of iPS cells. Finally, we should remind the non-ethical character of the use of Plat-E and 293T cells by Yamanaka, initially derived from aborted foetus, as "packaging cell lines" of retroviral vectors.

 

Vincent Humbert’s death: to legitimate euthanasia?

On the occasion of the broadcasting of the telefilm, on 3rd December 2007 "Marie Humbert, l’amour d’une mère", the polemic renewed with the testimony of Hervé Messager, Vincent Humbert’s physiotherapist.

The physiotherapist’s testimony
Hervé Messager cured Vincent Humbert for two years in the heliotherapy centre in Berck-sur-Mer. He states that “from a real fact, we embroidered all which was painful, […] to give an ideology”. “The truth and the opinion were completely manipulated”, he underlines in a message send to all MPs and broadcasted on the website of the association SOS Fin de vie. “Why was Vincent killed? He had already a lot of thing to live […] He was joking, he was laughing. We lied about a lot of things to justify the final act. It was said he was blind: certainly, he had a bad sight, but he saw; it was said he suffered: He did not suffer.” Hervé Messager recognizes that Vincent passed through discouragement and fear phases but he was also happy.

Under influence?
Marie Humbert seems to have been influenced by militant associations for the ″right to die″. Vincent was not tetraplegic, as it was stated, but he suffered a double hemiplegia, which means that his cortex was affected and his mental faculties largely impaired. How then could he write a letter to President Jacques Chirac? “He did not use the French language with such subtlety. Behind what it was said about the undeniable truth of his state, I discovered sophisms which could not come from him, as the relation between the President’s right of pardon and the claim for a right to death.” It is also unlikely he could write the book we credit him, Hervé Messager specifies.

Physician or veterinary?
In her book “Pour tous les Vincent du monde(1), Marie Humbert claims to insert euthanasia exception in criminal code. “As my son often told me when he implored me to access his demand, when a dog is dying, we bring it to the veterinary who takes care of putting an end to its ordeal.” The proposal of the law called “Vincent Humbert’s law” is inspired by Belgian legislation: “over there, people are not afraid anymore to die since this law was adopted as they are sure they will not suffer unnecessarily…”, Marie Humbert says. What about the confidence climate which must prevail between patient and health providers whose role is also to support them when they are discouraged?

Parallel with VPT
We find in Marie Humbert, or in those who write for her, the same arguments and errors than those invoked 35 years ago to claim the abortion legalisation, pretending that euthanasia is already in France a reality which it is urgent to frame: Marie Humbert affirms that “in the intensive care unit, half of patients die after decision of limitation or discontinuation of active care and we can estimate that a proportion of 10 to 20% of these medical decisions are injections with death purpose”. Over 180,000 ill patients who die every year in France in an intensive care unit, she insinuates that 9,000 to 18,000 patients would be victims of active euthanasia… Rather than to accept the underhand generalisation, she claims the law takes into account the extreme cases “where the duty of humanity would not be assimilated to a criminal act”. We remember that before the national Assembly of 26th November 1974, Simone Veil exclaimed: “we cannot close the eyes about the 300,000 abortions which, each year, mutilate women of this country”. The INED (National institute for demographic studies) estimates reasonably this figure from 40 to 60,000…


1. Pour tous les Vincent du monde - Une histoire d’amour, Marie Humbert, Ed. Michel Lafont, Août 2007.


 

La mort apaisée – Chronique d’une infirmière en soins palliatifs – E. and M. Gagnet 1


Accompanying until the end
How to accompany a close relative until the death when we and he first know, that he suffers an incurable disease? With sensitivity and delicacy, Elise Gagnet tells the story of several ends of life through her daily nursing experience in a palliative care unit. Without taboo, sometimes with humour and a great humanity, she deals with all the questions arising during this painful period and, through these columns, answers the questions from patients, families and health professionals.

The alleviated death
Offering the patients the maximum comfort for their last moments, alleviating the pain, giving the time, so precious at the end, to say goodbye, to make peace with themselves and their relative, promises a more alleviated death.

The support from a team
Force is required to support so many daily pain and mourning. The team must doubly love live so that patients can enjoy it until the end. The solidarity and the dialog within the health care team are more fundamental than anywhere else, to never let a nurse alone faced with her own anxiety, her own fear of death. Here, the treatments are decided by the whole medical team. Psychologists, orderlies, nurses, all are here to help the physician in choosing the more adapted treatment and the best way to give it.

Feel like dying?
If Elise Gagnet evaluates to one out of three, the patients who said, in moments of intensive pain or anxiety, they wanted to die, if some implore: “give me an injection so that I can die…“, she testifies that reminding the prohibition and the legality is a mean to initiate the dialog with the patient, to force him to the wall. The demand always disappears when the patient is physically and psychologically alleviated. “It is not the fear from the law which refrains me from giving death, but the deep conviction other solutions exists.
When the human contact wins out over the technique, beyond the therapy, offering his time and his patience helps the families exhausted by a heavy and difficult health management. It is possible to give back the man its final dignity. This luminous book is the testimony.


1. La mort apaisée – Chronique d’une infirmière en soins palliatifs, Elise et Michaëlle Gagnet, Ed. de la Martinière, Octobre 2007.

 

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