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Published online 1 September 2008 | 455, 12 (2008) | doi:10.1038/455012a
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Republicans at odds over human embryo research
Stem cells divide McCain's camp.
By changing one little word, the committee drafting the Republican 2008 election platform calls for banning all human embryo research in the United States, whether publicly or privately funded.
John McCain, the presumptive Republican presidential nominee, is under no obligation to follow the party platform — which is a statement of principle with no binding power — but the change highlights the already noticeable contrast between him and the official party position.
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As I have uderlined also in www.nature.com (http://blogs.nature.com/reports/theniche/2008/04/stemcell_skin_creams_a_san_die.html#comments http://www.nature.com/news/2008/080130/full/451511a.html?q=2#last-comment http://www.washingtonpost.com/ac2/wp-dyn/comments/display?contentID=AR2007041101736&start=41 http://www.nature.com/news/2008/080822/full/news.2008.1060.html?q=2#last-comment ), in my opinion, based on a long, well-established, clinical experience, the central problem in using and utilising stem cells is among scientists mainly overlooked all around the world.In fact, a great lot of money on studying staminal cells, even in amnyotic fluid, accounts for the reason there is a paramount bias in such as researches! As a matter of fact, in performing staminal cell researches worldwide scientists overlook both an inherited mithocondrial cytopathy, I termed Congenital Acidosic Enzyme-Metabolic Histangiopathy and Biophysical-Semeiotic Constitutions (ibidem) See my website www.semeioticabiofisica.it. For instance, accordingly, type 2 diabetes is a major problem in both developing and developed countries, i.e., a real epidaemics. Independent of different countries, in recent decades diabetes prevalence has increased rapidly over time among both developed and developing populations. Surely, genetic factors alone cannot explain these patterns. However, as allows me to state my clinical experience, See URL: an individual, without diabetic AND dyslipidemic biophysical-semeiotic constitutions, can not be involved by type 2 diabets, at all 1-6. Certainly, rapid changes in lifestyle and risk factors such as obesity, unhealthy diets, physical inactivity, tobacco smoking, a.s.o., acting on people with diabetic and dyslipidaemic constitution may cause, AT FIRST, Pre-Metabolic Syndrome, then, over years or decades, metabolic syndrome 2, 6, IGT, and finally type 2 diabetes. In a few words, all around the world, e.g., the war against diabetes mellitus and its well-known and harmful complications, as well as the war against all other serious and common human diseases, is nowadays possible, also utilizing possibly staminal cells of whatever origin, exclusively by means of a primary prevention, which must be perform at the bed-side, i.e., clinically, on a very large scale, using the simple stethoscope. In addition, we must in the future utilize staminal cell, even of amnyotic fluid, of individuals not involved by above-cited biophysical semeiotic constitutions! In other words, in both primary prevention and screening programme for whatever disease, including DM and its complications, and cancer, we need efficacious clinical tools to obtain the best results, avoiding, e.g., to use staminal cell with impaired mitochondria. Really, early diagnosis must certainly be established in asymptomatic patients, who, for example, are evolving slowly towards diabetes mellitus, i.e. long time before disease onset, in order to avoid the well known, severe complications. In fact, to prevent these diabetic complications, including diabetic retinopathy, on very large scale it is extremely necessary that doctors use a clinical tool reliable in diagnosing early diabetes mellitus stages, from initial stages, i.e., biophysical-semeiotic constitutions, and then the Pre-Metabolic Syndrome (ibidem), usefull particularly in selecting appropriate stem cells to be utilized. As I wrote formerly also in PLOS (Stagnaro Sergio. Single Patient Based Medicine: its paramount role in Future Medicine. Public Library of Science, Stagnaro Sergio. Single Patient Based Medicine: its paramount role in Future Medicine. Public Library of Science. http://medicine.plosjournals.org/perlserv/?request=read-response 2005 . http://medicine.plosjournals.org/perlserv/?request=read-response), physicians can fortunately utilize bedside clinical methods reliable in ascertain the truth of articles published in famous peer reviews.
When proponents of destructive human embryonic stem cell research such as Rep. Mike Castle say of those who oppose such research that they ?don't even understand the advances that have been made in embryonic stem-cell research,? would it be asking too much for some examples of these advances? In the past year alone, scientists have succeeded in reprogramming ordinary body cells into ?induced pluripotent stem cells (iPSCs)? that are virtually identical to embryonic stem cells, without harming any human embryos. Commenting on this, James Thomson, who was one of the first to isolate human embryonic stem cells and to produce iPSCs said ?human embryo stem cell research will be abandoned by more and more labs"(Boston Globe 9/21/07). Researchers have further developed some 20 disease specific stem cell lines for 10 different diseases using iPSCs, perhaps allowing them to study how these diseases develop. More recently, scientist succeeded in transforming one type of specific adult stem cell directly into another while still inside a living creature, in this case, mice. Earlier this year, a report in the Journal of the American Medical Association (JAMA) examined hundreds of studies that were conducted between January 1997 and December 2007, and found that therapies using adult stem cells can treat heart disease and autoimmune disorders, including diabetes, MS and lupus. To date, the peer-reviewed literature, publishing actual results with patients, shows that adult stem cells have provided therapeutic benefits to human patients for 73 diseases and conditions. Not one human patient has been treated with an embryonic stem cell, and in over 26 years of research using embryonic stem cells in animal models, researchers have yet to develop a successful treatment in mice for any disease that could be used as a model to undertake the first steps for a clinical trial with human patients. So the next time proponents of destructive human embryonic stem cell research are quoted talking about all the ?advances? that have been made with such research, perhaps whoever the reporter is might do readers a favor and ask them to give some examples.
"Not one human patient has been treated with an embryonic stem cell, and in over 26 years of research using embryonic stem cells in animal models, researchers have yet to develop a successful treatment in mice for any disease that could be used as a model to undertake the first steps for a clinical trial with human patients." Thanks to fanatics like yourself who would rather see a clump of cells flushed down the toilet rather than used in medical experimentation for the benefit of all mankind, rather than only those who hold your particular religious belief .
Gene, I have to disagree with you on numerous points. To start, you point out the discovery of iPS cells. The actual discovery of the 4 or so genes (the actual number of genes needed and in which combination is still being researched and debated) used to induce pluripotency is only possible due to the research in embryonic stem cells. Without ES cell research, there would be no iPS cell. iPS is most definitely ONE OF THE ADVANCES IN EMBRYONIC STEM CELL RESEARCH. And while there are now many disease model iPS lines, we still don't know enough developmentally to utilize them. Any basic developmental research is going to come from ES cells, not iPS cells. And until we get that info, those disease lines aren't worth anything. Also, you mention that adult stem cells have been used clinically with some success. Using heart disease as an example, bone marrow and skeletal muscle stem/progenitor cells have been used in some clinical trials to treat myocardial infarction. To date, the use of these adult cell therapies have shown only short term benefit. Over the long term studies, there is no statistical benefit compared to control patients not receiving adult cell injections. In the animal models of adult cell injection into the heart, long term studies show the same results, with the added result of these cells not being found histologically (we can take this to mean that they don't survive) in the heart. In all likelihood , these injected adult cells secrete cytokines important in angiogenisis and anti-apoptosis for a short duration of time, but they don't survive, couple with host myocardium and act as working myocardium. They get the same results whether they use adult stem cells, skeletal muscle, or fibroblasts. I believe that many adult stem cell animal studies/clinical trials have found similar results in other organs and tissues. The autoimmune diseases such as lupis (I do not include type I diabetes in this category since the problem is both autoimmune and the loss of a non-regenerative tissue) due to the nature of bone marrow stem cells and their engraftment properties. Therefore, I don't think adult stem cells are appropriate for many clinical applications. In this regard, ES cells may still be what provides a relevant clinical therapy. I am not here to say that adult stem cells don't have any clinical relevance for certain tissues and organs, but I don't think that they will prove useful in many situations and ES cells may show to be more appropriate in the end. In my last argument, I just want to point out the mistake in using the argument of "time researched=clinical therapy". Last time I checked, we haven't cured cancer yet. Basic research takes variable amounts of time, and these are complex problems that will most likely result in complex solutions.
Alec, you still fail to supply an example of an advance using human embryonic stem cells. You cite the advance in reprogramming somatic cells to iPSc?s, but if you mean that this advance happened based on prior research using HUMAN embryonic stem cells, you are wrong. Japan?s Shinya Yamanaka is one of the two scientists, each working independently, credited with the iPSC breakthrough. Yamanaka himself has said that human embryonic stem cells (hESCs) were not crucial to his work. Before his breakthrough in reprogramming human somatic cells to a pluripotent state, Shinya Yamanaka's work in reprogramming utilized mice, not human, embryonic stem cells and he used the same method for human iPSC production. In an interview with Nature, Yamanaka made this clear: "Neither eggs nor embryos are necessary. I've never worked with either" (7 June 2007, p 618). Moreover, it was precisely Yamanaka?s ethical concerns to avoid lethal experiments with human embryos that led to his breakthrough. Recalling looking at a human embryo through a microscope several years earlier, Yamanaka said: ''When I saw the embryo, I suddenly realized there was such a small difference between it and my daughters?''I thought, we can't keep destroying embryos for our research. There must be another way'' (?Risk Taking in His Genes;? The New York Times, 11 December 07). Because human embryonic stem cell research was NOT the basis for the iPSC breakthrough, that breakthrough should not be considered an advance in that field. Rather, it is more properly viewed as an advance for those avenues of stem cell research that do not require the destruction of human embryos, which is why it has been greeted so enthusiastically by those who have ethical concerns about such destruction. You also say that ?we still don?t know enough developmentally to utilize? iPS cells for disease modeling,? to justify the continued necessity of hESCR. Yet this is precisely what cloning pioneer Ian Wilmut (who cloned Dolly the sheep) is doing with iPS cells. Wilmut has publicly announced he was abandoning cloning research to instead focus on work with iPS cells, beginning with using these cells for disease modeling and progression. It seems doubtful that Wilmut would abandon cloning, a field he pioneered, to instead pursue research that is ?worthless." Finally, in none of the peer reviewed studies that I referred to do the authors state merely that they are about to "test" whether adult stem cells may benefit patients or that they have begun "enrollment" in clinical trials. Rather, all these studies (including those on breast cancer and heart damage) are reports of completed trials in which patients with these conditions benefited. We don?t know if all these trials will automatically translate into safe, reliable, and widely available clinical therapies. But that does not argue for denying or belittling benefits in the use of adult stem cells that published approaches have already provided to some patients, benefits that remain lacking from any approach using embryonic stem cells. "Time researched=clinical therapy" may be a faulty argument but it is an argument I never made. There is no doubt that much work needs to be done before the therapeutic potential of adult stem cells is fully realized. But pointing out current shortcomings in the use of adult stems cells in treating patients does not count as an example of a real advance for hESCR, as shown when you write hESC?s ?may still be what provides a relevant clinical therapy? and ?may show to be more appropriate in the end.? Then again, they may not and so far they have not. Nor does it change the fact that right now, research using adult stem cells is much further along than research using human embryonic stem cells in reaching our shared therapeutic goals, and the original question of where are all the therapeutic advances claimed for hESCR still goes begging.
Gene, With regards to Yamanaka, I believe that the title of a correspondence letter he co-authored in Cell Stem Cell says it best, ?New Advances in iPS Cell Research Do Not Obviate the Need for Human Embryonic Stem Cells,? (Insoo Hyun, Konrad Hochedlinger, Rudolf Jaenisch, and Shinya Yamanaka. Cell Stem Cell. 2007 Oct 11;1(4):367-8.) And Yamanaka has in fact been associated with work on hESCs. In his landmark paper reporting the derivation of hiPS, they compared their hiPS gene expression to hESC gene expression throught RT-PCR, Western blot, and q-PCR (Cell. 2007 Nov 30;131(5):861-72). This work was done in a lab to which he is associated at the Gladstone Institute in San Francisco where he holds an academic appointment. I would also like to point out that something as simple as culture conditions for hiPS is based on previous work in hESCs (as culture conditions for mESCs are not the same as hESCs). In addition, while the same factors used in the derivation of miPS worked for the derivation of hiPS, it first needed to be demonstrated that these transcription factors were important in the pluripotent state of hESCs. His work directly piggy-backed on the work of others regarding hESCs. So while he may have ethical concerns, based on his recent publications I would say that he still believes that hESC research is necessary. Also, Ian Wilmut and James Thompson have signed and endorsed an ISSCR (International Society for Stem Cell Research) letter calling for the continuance of all forms of stem cell research (James Thompson actually co-authored the letter, and you will note that he was the other scientist accredited with the iPS breakthrough), as have 606 other scientists to date (http://www.isscr.org/ScienceStatementEndorsers.cfm). And just to be clear, to my knowledge, Ian Wilmut is working on deriving iPS and somatic nuclear transfer stem cell lines for disease models. He is not directly working on the development of the tissues from these lines (http://www.scrm.ed.ac.uk/group_Ian_Wilmut.html). There is also widespread acknowledgement in the field that the tissue created from any ES like stem cell is very early in development and very poorly characterized, and I stand by my comment that we developmentally don?t know enough yet to utilize iPS disease models. As for advancements in hESC technology and science, I would like to highlight 3 recent examples from the cardiac field. In September 2007, Charles Murry reported on increased survival of transplanted hESC derived cardiomyocytes when injected into a rat ventricular infarct model with a ?pro-survival cocktail? his lab created (Laflamme, et al. Cardiomyocytes derived from human embryonic stem cells in pro-survival factors enhance function of infarcted rat hearts. Nat Biotechnol. 2007 Sep;25(9):993-4). They also go on to report that there was a partial remuscularization of the heart due to engraftment along with an improvement in Left-ventricular end-diastolic dimension, Left-ventricular end-systolic dimension, and fractional shortening compared to controls. In a pre-clinical study carried out by Lior Gepstein, results similar to those of Murry?s are observed (Caspi, et al. Transplantation of human embryonic stem cell-derived cardiomyocytes improves myocardial performance in infarcted rat hearts. J Am Coll Cardiol. 2007 Nov 6;50(19):1894-5). And finally, Gordon Keller earlier this year reported on the derivation of a cardiovascular progenitor cell from hESCs, and when injected into mice improved ventricular injection fraction (Yang, et al. Human cardiovascular progenitor cells develop from a KDR+ embryonic-stem-cell-derived population. Nature. 2008 May 22;453(7194):524-8). While clinical studies are going on with adult stem cells and cardiac infarct, the corresponding animal studies show no long-term cell survival, and the improvement in cardiac function is believed to be largely from a paracrine affect. I am not belittling this benefit, because it is a significant breakthrough. However, the paracrine affect is not the overall goal of regenerative medicine. What is desired is actual working myocardium In terms of getting donor stem cells to actually couple with host myocardium and contributing to working myocardium, I would claim that to date ES and adult stem cells are pretty much at the same stage. It is also important to acknowledge that hESC research is in a pre-clinical stage and that the field is in its infancy. The animal studies must come first, and then the clinical studies to follow. In one last argument, any stem cell derived from, say, umbilical cord blood or bone marrow only generates enough cells to sufficiently engraft a child under the age of 8 without genetic manipulation. Until the field figures out how to increase these cell numbers ex vivo, the treatment for any disease in individuals beyond the adolescent ages is out of consideration (Claudio G. Brunstein & John E. Wagner. Vox Sang. 2006 Oct;91(3):195-205.) I am going to end by saying that any argument for adult stem cells over ESCs is certainly niche specific. In some niches, adult stem cells may prove to be the clinically most relevant, whereas in other niches hESCs will prove to be the most clinically beneficial.