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Rapid Responses: Rapid Responses published:
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Is there a fundamental bias at the base of cloning?
- Sergio Stagnaro (20 February 2004)
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Potential danger of cloning
- Martin P Mayfield (26 February 2004)
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Re: Potential danger of cloning
- Ian Wilmut (27 February 2004)
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A Matter of Nomenclature
- Sanjeev D Sharma (1 March 2004)
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Sergio Stagnaro, Specialist in Blood, Gastrointestinal, and Metabolic Diseases. Researcher in Biophysical Semeiotics Via Erasmo Piaggio 23/8 16037 Riva Trigoso (Genova) Italy
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Sirs, I should like to express my scientific opinion about human cloning and consequently human cells from cloned embryos in research and therapy. Cloning indicates the possibility to generate two or more organisms, showing the same genetic equipment starting from unique donor. Notoriously, this process is based on the strong statement, claiming that “nucleus”, and I underscore “nucleus”, of every tissue cell of an individual contains its complete genetic endowment, and, therefore, the whole information in order to reproduce an organism. Consequently, it is sufficient and necessary to substitute the “nucleus” of an ovolum with the cellular “nucleus” of tissue specimen cell, and subsequently activate it simulating spermatozoon contact. The individual, who will be born, will show the same genetic endowment as that from whome cellular “nucleus” has been drawn. At this point, development process of embryo will initiate, which will be transplanted in a womb, to perform pregnancy. In my opinion, at the base of such as argument, with which all scientists apparently agree, there is a fundamental bias, i.e., whole DNA is in the “nucleus”. By contrast, it is now-a-days well-known, even to laymen, that exists also the mitochondrial DNA (in almost all cells, of course, but not in all), localized in well-defined cytoplasmatic structures, varying from 400 to 1200 per cell, which represent cellular “lungs”, providing endo-cellular free energy. In addition, mit-DNA codes really 13 “essential” proteins, unavoidable for individual’s life, indepentenly from n-DNA interaction. I have previously (more than 25 years ago) demonstrated “clinically” (1-4) (See web site HONCode 233736, www.semeioticabiofisica.it) that it exists a functional mitochondrial abnormality, that causes the most common and serious human disease, including Type 2 diabetes (5) and malignancy: I termed such as mitochondrial cytopathology Congenital Acidosic Enzyme- Metabolic Histangiopathy (CAEMH). This mitochondrial functional impairment is different, as regards it seriousness, from individual to individual, from tissue to tissue of the same individual, as well as from part to part (from cell to cell) of the same biological system. In a few words, I think that the present concept of human cloning is not an indication of a scientific event, but rather one of desolate and arrogant scientism. 1) Stagnaro S., Istangiopatia Congenita Acidosica Enzimo-Metabolica condizione necessaria non sufficiente della oncogenesi. XI Congr. Naz. Soc. It. di Microangiologia e Microcircolaz. Abstracts, pg 38, 28 Settembre-1 Ottobre, Bellagio 1983 2) Stagnaro S., Istangiopatia Congenita Acidosica Enzimo-Metabolica. X Congr. Naz. Soc. It. di Microangiologia e Microcircolazione. Atti, 61. 6-7 Novembre, Siena 1981 3) Stagnaro S., Istangiopatia Congenita Acidosica Enzimo-Metabolica. Una Patologia Mitocondriale Ignorata. Gazz Med. It. – Arch. Sci. Med. 144, 423 (Infotrieve) 1985 4) Stagnaro S., Polimialgia Reumatica Acuta Benigna Variante. Clin. Ter. 118, 193 (Pub-Med indexed for Medline) 5) Stagnaro S., Diet and Risk of Type 2 Diabetes. N Engl J Med. 2002 Jan 24;346(4):297-298. letter [PubMed –indexed for MEDLINE]. Competing interests: None declared |
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Martin P Mayfield, General Practioner 10 Netherfield Road, Guiseley W Yorkshire LS20 9HE
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Leaving aside the ethical considerations, using cloned embryos with transferred host nuclear material entails some risk which does not appear to have been considered. Human fibroblasts have been shown to have shortened DNA (specifically, loss of telomere from the chromosome tips), which is proportional to the age of the host, in both cultured [Harley et al, 1990] and freshly donated cells [Allsopp et al, 1992]. Shortened telomere length is associated with reduced viability in culture, and has been shown in individuals with congenital premature aging [Allsopp et al, 1992]. DNA analysis of cloned sheep has demonstrated abnormally shortened telomeres [Shiels et al, 1999]. Taking a donor nucleus from the skin, and implanting it into an egg cell to produce an embryo is therefore likely to produce a cloned embryo with a restricted life expectancy, with a time of senescence synchronous to that of the host. In the case of tissue produced in this way to 'repair' pathology -e.g. pancreatic cells to cure type I diabetes- senescence of the repair at the same time as the donor-recipient might not be considered a great problem, unless there is a period of accelerated telomere loss at the stage of embryo growth, in which case, the original fault is likely to re-emerge. In the case of an embryo used to produce a child, this could be disastrous: if the donor nuclear material is taken from a forty year old (not an unreasonable scenario in assisted fertilisation), the cloned individual would be born with a life expectancy reduced by forty years. It will be recalled that Dolly the Sheep died a premature death from premature aging, and the reason for this should be fully understood before a human is unnecessarily exposed to the risk of being cloned into an artificially shortened life. Martin Mayfield
Allsopp RC, Vaziri H, Patterson C, Goldstein S, Younglai EV, Futcher AB, Greider CW, Harley CB: Telomere length predicts replicative capacity of human fibroblasts. Proc.Natl.Acad.Sci.USA 89: 10114-10118; 1992. Harley CB, Futcher AB, Greider CW: Telomeres shorten during ageing of human fibroblasts. Nature 345: 458-460; 1990. Shiels PG. Kind AJ. Campbell KH. Waddington D. Wilmut I. Colman A. Schnieke AE. Analysis of telomere lengths in cloned sheep. [Letter] Nature. 399(6734):316-7, 1999 May 27 Competing interests: None declared |
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Ian Wilmut, Professor Roslin Institute, Roslin, Midlothian, EH25 9PS
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It is clearly very important before any use of cells derived from cloned embrbyos to ensure that they are appropriate for their purpose, including an asessment of life span of the cells. However, there are a number of misunderstandings in the letter. First, Dolly did not die of premature aging. She was euthanised because she had a virally induced lung tumour. There is no method of detecting the infection before the tumour develops nor any treatment for the disease. Secondly, it seems that in the vast majority of cases telomere length is fully restored in cloned animals, including in sheep. It is not clear why this was not the case on Dolly. One possibility is that the type of cell used as nuclear donor influences telomere length, but this hypothesis remains to be tested. Competing interests: I own shares of the Geron Corporation who have also supported some of our research |
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Sanjeev D Sharma, Consultant, Obstetrician and Gynaecologist Southport and Ormskirk NHS Trust, Southport, PR8 6PN
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Ian Wilmut's leader "Human cells from cloned embryos in research and therapy" (BMJ, 21st Feb 2004) brings the current research in this area up to date, and it is not only appropriate but timely as well. The somatic cell nucleus transfer technology which led to the birth of Dolly the sheep was the most remarkable development since the birth of Louise Brown using an in vitro fertilisation technique. However, Ian Wilmut makes the huge assumption that the hearts and minds of the "consumers" have been won, which is very far from the truth. Not only the ordinary people but even the professionals find research in this area unsettling. The difference between reproductive and therapeutic cloning is lost in the debate in the lay press. Cloning as a term has disconcerting connotations for most non-scientific people. Somatic cell nuclear transfer is a mouthful but describes the process much more accurately and takes us away from the dreaded word. It would be in everybody's interests to be precise in their description of their work and reiterate the difference between therapeutic and reproductive aspects of the research. Another area which causes distress among people is the creation and use of embryos to develop stem cells. There is instinctive emotional abhorrence of any research which specially creates embryos and discards them once they are no longer needed. Two things might make this acceptable; one would be some use of stem cells which can be shown to have made a real difference to patients' suffering. Patients would not only accept but actively support the research if it can be shown to tangibly make a difference to their lives. Another thing would be some other way of developing stem cells - eg, from adult cells. Even though stem cells are best obtained from embryos at this stage, there is no reason why in the future, with more understanding, adult cells could not be reprogrammed to develop into our stem cells of choice. The recent report of the development of stem cells from cloned embryos may be a small step just now, but with developments in structural genetics and molecular biology, this small step could be the first towards a complete revolution in medicine. In the meantime, however, it would be in everybody's interests if the scientists and clinicians involved in the research take the lay-people with them, making the science easier and addressing their fears and concerns. For without the people, we might have revolutionary new modality but nobody to use it on. Competing interests: None declared |
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