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转基因玉米致癌论文被撤 编委曾就职孟山都

  法国研究人员2012年在《食品和化学毒物学》杂志上发表转基因玉米致癌论文,已成为部分人士反对转基因食品的重要证据。但杂志出版方爱思唯尔公司28日在美国宣布,由于进一步分析显示论文数据不足以支持其结论,因此决定撤除这篇论文。

  爱思唯尔公司在声明中说,《食品和化学毒物学》杂志对所发表的论文及论文所报告的数据进行了彻底的、长时间的分析,对论文发表的同行评议过程也进行了调查,“没有发现欺诈或对数据有意曲解的证据”,然而,“有理由担忧”论文所提及实验中研究人员使用的实验大鼠数量和类型。

  声明说:“对原始数据的深入调查表明,用如此小规模的样本数据无法得出明确结论”、“考虑到(实验中所用的)斯普拉格-道利大鼠的已知肿瘤高发生率,喂食转基因玉米组所观察到的更高的死亡率及肿瘤发生率的原因不能排除是正常变化”。

  声明说,归根结底,论文的结果“尽管无不妥之处”,但是“没有说服力”,因此这篇论文达不到《食品和化学毒物学》的出版要求。

  声明还说,这篇论文发表后编辑部收到多封来信,对论文描述结果的有效性、实验动物的合理使用表达关切,有些来信甚至称其中存在欺诈,多数来信呼吁撤回这篇论文。这些来信以及支持这篇论文的来信,都已和作者的回应一并发表。

  英国《自然》杂志网站说,这一撤稿举动并不令人意外,《食品和化学毒物学》杂志主编本月初曾要求作者主动撤回论文,并表示如果作者拒绝,杂志方也将予以撤稿。报道还说,论文作者把撤稿形容为“丑闻”,并声称,这是因为杂志任命的一名编委此前曾在转基因农业巨头孟山都公司工作过7年。

  2012年,《食品和化学毒物学》杂志刊登了法国卡昂大学分子生物学家塞拉利尼等人的一份研究报告。该报告称,将100只雄性和100只雌性大鼠分成10组,分别喂食孟山都公司的NK603转基因玉米及其他食物,两年后发现,喂食转基因玉米的实验大鼠出现肿瘤的风险高、寿命短。

  这一结论在全球引起风波。法国国家卫生安全署、生物技术最高委员会和欧洲食品安全局均对塞拉利尼等人的研究展开调查,结果均认为,该研究存在诸多不足,不能作为评估转基因玉米健康风险的有效依据。

  【下面是塞拉利尼团队声明中英对照本。2013-11-28。引用自顾秀林博客】

  我们是FCT一年多前发表的论文的作者,关于农达和耐受农达的转基因生物的事(塞拉利尼等2012)对于同样的质疑,我们已经在同一个刊物上回应过(塞拉利尼等,2013),即:作为正常的科学辩论,仅仅由于实验鼠品系的选择和数量的原因,就判定研究结果“结论不完整”,这是不能接受的。我们坚持我们的结论。我们早已公布了对相同的质疑所做的回答,但至今没有见到对我们的任何回应(塞拉利尼等,2013)。

  We, authors of the paper published in FCT more than one year ago on the effects of Roundup and a Roundup-tolerant GMO (Séralini et al., 2012), and having answered to critics in the same journal (Séralini et al., 2013), do not accept as scientifically sound the debate on the fact that these papers are inconclusive because of the rat strain or the number of rats used. We maintain our conclusions. We already published some answers to the same critics in your Journal, which have not been answered (Séralini et al., 2013).

  关于实验大鼠品系

  同一个大鼠品系,被用在研究致癌性和慢性化学毒理学的美国国家毒理学项目中(King-Herbert et al., 2010)。SD大鼠是常规性用于毒理和致癌效果实验中的动物,其中有孟山都公司的90天实验,被当做批准NK603转基因玉米应用的依据,其他转基因农作物也是这样做的(Sprague Dawley rats did not came from Harlan but from Charles-River) (Hammond et al., 2004; Hammond et al., 2006a; Hammond et al., 2006b).

  Rat strain

  The same strain is used by the US national toxicology program to study the carcinogenicity and the chronic toxicity of chemicals (King-Herbert et al., 2010). Sprague Dawley rats are used routinely in such studies for toxicological and tumour-inducing effects, including those 90-day studies by Monsanto as basis for the approval of NK603 maize and other GM crops (Sprague Dawley rats did not came from Harlan but from Charles-River) (Hammond et al., 2004; Hammond et al., 2006a; Hammond et al., 2006b).

  这里有一个简明的初步的文献清单,表明在同行评审的杂志上SD大鼠被用在36个月的实验如(Voss et al., 2005) or in 24-month studies by (Hack et al., 1995), (Minardi et al., 2002), (Klimisch et al., 1997), (Gamez et al., 2007).,其中有一些文章就发表在FCT上。

  A brief, quick and still preliminary literature search of peer-reviewed journals revealed that Sprague Dawley rats were used in 36-month studies by (Voss et al., 2005) or in 24-month studies by (Hack et al., 1995), (Minardi et al., 2002), (Klimisch et al., 1997), (Gamez et al., 2007).Some of these studies have been published in Food and Chemical Toxicology.

  Number of rats, OECD guidelines

  实验动物数量与OECD实验规范

  OECD 实验规范:第408条,关于90天实验,第452条关于慢性毒性试验,第453条关于综合致癌性/慢性毒性试验,都要求用20只动物为一组(1981和2009的规定都这样要求),尽管可以用10只动物的实验就能取得生物化学参数。我们做的是长期毒性研究而不是致癌性研究,从一开始就不是这样设想的。根据常规10只动物一组已经足够在生物化学水平上进行研究,我们测量的参数数量是非常大的。

  OECD guidelines (408 for 90 day study, 452 chronic toxicity and 453 combined carcinogenicity/chronic toxicity study) always asked for 20 animals per group (both in 1981 and 2009 guidelines) although the measurement of biochemical parameters can be performed on 10 rats, as indicated. We did not perform a carcinogenesis study, which would not have been adapted at first, but a long-term chronic full study, 10 rats are sufficient for that at a biochemical level according to norms and we have measured such a number of parameters!

  在我们的实验中,性激素干扰的参数以及其它参数对于解释一年之后的严重后果是充分的。我们采用的OPLS-DA统计方法是最适宜的。关于肿瘤和动物死亡,时间效果以及每只动物的平均肿瘤数量都必须被纳入分析。在风险研究中出现的每一个迹象,都必须被充分重视。孟山都公司的研究用了同样的大鼠品系,每组仅10只衡量20个参数,就得出同一种NK603转基因玉米“安全”的结论,而且他们的实验只做了3个月 (Hammond et al., 2004)

  The disturbance of sexual hormones or other parameters are sufficient in themselves in our case to interpret a serious effect after one year. The OPLS-DA statistical method we published is one of the best adapted. For tumours and deaths, the chronology and number of tumours per animal have to be taken into account. Any sign should be regarded as important for a real risk study. Monsanto itself measured only 10 rats of the same strain per group on 20 to conclude that the same GM maize was safe after 3 months (Hammond et al., 2004).

  The statistical analysis should not be done with historical data first, the comparison is falsified, thus 50 rats per group is useless

  统计分析不应该先做历史数据,用这个方法做比较研究是错误的,用每组50只动物做研究是无意义。

  采纳历史数据会把健康风险评估变成研究造假,因为食谱中的材料已经受到化学污染(by dibenzo-p-dioxins and dibenzofurans (Schecter et al., 1996)和汞污染(Weiss et al., 2005),镉污染,铬污染等,污染的程度足以改变动物肝脏和肺脏的基因表达,足以扰乱基因分析(Kozul et al., 2008)。以往的食料中还发现农药和增塑剂污染,污染来自箱笼或者水(Howdeshell et al., 2003)。历史数据也有来自可能食用了转基因的动物,很多地方的鼠粮中的确发现了转基因成分。这一切都与污染水平相关,我们已经在实验大鼠和对照组大鼠中检测到这些问题。

  The use of historical data falsifies health risk assessments because the diet is contaminated by dibenzo-p-dioxins and dibenzofurans (Schecter et al., 1996), mercury (Weiss et al., 2005), cadmium and chromium among other heavy metals in a range of doses that altered mouse liver and lung gene expression and confounds genomic analyses (Kozul et al., 2008). They also contained pesticides or plasticizers released by cages or from water sources (Howdeshell et al., 2003). Historical data also come from rats potentially fed on GMOs, some animal pellets in the world do indicate that. All that corresponds to the contamination levels for which we have detected some effects in our treated rats versus appropriate controls.

  在历史数据中,2年SD雌性大鼠罹患乳腺纤维瘤的为13%~62%(Giknis, 2004),但在我们的实验中对照组的发病率要低得多,这才是真正的对照,而我们的实验鼠发病率比对照组高很多,这使得我们的研究结果有显著性。动物的死亡率也是这样。

  2-year historical data mammary fibroadenoma rate from Charles River SD females ranged from 13 to 62% (Giknis, 2004). We obtain a lot less in our controls, the real comparators, a lot more in treated rats. This makes our results significant, like for deaths.

  Double standards 双重标准

  遵循同一个逻辑把塞拉利尼的实验和孟山都公司的实验做一对一的比较,如果前者被认为不足以显示危害,那么后者也不能认为证明了安全。

  A factual comparative analysis of the rat feeding trial by the Séralini’s group and the Monsanto trials clearly reveals that if the Séralini experiments are considered to be insufficient to demonstrate harm, logically, it must be the same for those carried out by Monsanto to prove safety.

  以往的研究发现凡是显示转基因农作物有负面效果的,都会被监管者从实验到统计方法做严格的重审,凡是声称转基因农作物安全的研究,都被照单接受。只要是没有报告负面效果的研究,都被接受为“安全”的证明,无论他们的研究方法有何种不足(被认为无关紧要)。

  Basically, all previous studies finding adverse effects of GE crops have been treated by regulators with the attitude: only those studies showing adverse effects receive a rigorous evaluation of their experimental and statistical methods, while those that claim proof of safety are taken at face value. All studies that reported no adverse effects were accepted as proof of safety regardless of these manifest (but deemed irrelevant) deficiencies of their methods.

  来自(Snell et al., 2012) 的一份文献概览研究可以说明这个倾向。如作者在摘要中这样说,“在这里的24项研究的结果都不建议存在任何健康危害问题…”即所有被审阅的研究都被按“票面价值”被接受和通过了。然而在文章中却指出,研究报告的作者们留下了无数缺陷,同他们指责塞拉利尼论文的问题类似,或者更严重。例如24篇中16篇(67%)文章没有交代对照组饲料是否与实验用的饲料属于同基因品种(他们的解释只是“没有采用”)。许多篇文章连讨论所用的方法都没有介绍。此外还有其他被指出的缺陷。

  The review by (Snell et al., 2012) illustrates this issue. In the abstract, the authors state "Results from all the 24 studies [reviewed] do not suggest any health hazards [...]" – taking all those studies at face value. Yet in their review, the authors find numerous weaknesses of similar or greater severity [than those] raised for the Séralini group's paper. For example, of the 24 studies they evaluated 16 (67% of all studies) did not mention using the isogenic line as control (interpreted as having not used them), many did not describe the methods in any detail, and according to the reviewers had other deficiencies too.

  基于完全相同的原因,FCT应该把Hammond 等人关于耐受农达转基因玉米的那些论文全都撤回。那些论文貌似都是真正的科学讨论,发表它们只是为了给孟山都提供权威证据。

  FCT should retract the Hammond et al. paper on Roundup tolerant maize for all these reasons, published for Monsanto’s authorization, or consider that each of these papers is part of the scientific debate.

  References 参考文献

  Gamez, R., Noa, M., Mas, R., Mendoza, N., Pardo, B., Menendez, R., Perez, Y., Gonzalez, R.M., Gutierrez, A., Marrero, G., Goicochea, E., Garcia, H., Curveco, D., 2007. Long-term carcinogenicity of D-003, a mixture of high molecular weight acids from sugarcane wax, in Sprague Dawley rats: a 24 months study. Food Chem Toxicol 45, 2352-2358.

  Giknis, M.L.A.a.C., C.B., 2004. Charles River Laboratories. Compilation of spontaneous neoplastic lesions and survival in Crl:CD (SD) rats from control groups.

  Hack, R., Ebert, E., Leist, K.H., 1995. Chronic toxicity and carcinogenicity studies with the insecticide endosulfan in rats and mice. Food Chem Toxicol 33, 941-950.

  Hammond, B., Dudek, R., Lemen, J., Nemeth, M., 2004. Results of a 13 week safety assurance study with rats fed grain from glyphosate tolerant corn. Food Chem Toxicol 42, 1003-1014.

  Hammond, B., Lemen, J., Dudek, R., Ward, D., Jiang, C., Nemeth, M., Burns, J., 2006a. Results of a 90-day safety assurance study with rats fed grain from corn rootworm-protected corn. Food Chem Toxicol 44, 147-160.

  Hammond, B.G., Dudek, R., Lemen, J.K., Nemeth, M.A., 2006b. Results of a 90-day safety assurance study with rats fed grain from corn borer-protected corn. Food Chem Toxicol 44, 1092-1099.

  Howdeshell, K.L., Peterman, P.H., Judy, B.M., Taylor, J.A., Orazio, C.E., Ruhlen, R.L., Vom Saal, F.S., Welshons, W.V., 2003. Bisphenol A is released from used polycarbonate animal cages into water at room temperature. Environ Health Perspect 111, 1180-1187.

  King-Herbert, A.P., Sills, R.C., Bucher, J.R., 2010. Commentary: update on animal models for NTP studies. Toxicol Pathol 38, 180-181.

  Klimisch, H.J., Deckardt, K., Gembardt, C., Hildebrand, B., Kuttler, K., Roe, F.J., 1997. Long-term inhalation toxicity of N-vinylpyrrolidone-2 vapours. Studies in rats. Food Chem Toxicol 35, 1041-1060.

  Kozul, C.D., Nomikos, A.P., Hampton, T.H., Warnke, L.A., Gosse, J.A., Davey, J.C., Thorpe, J.E., Jackson, B.P., Ihnat, M.A., Hamilton, J.W., 2008. Laboratory diet profoundly alters gene expression and confounds genomic analysis in mouse liver and lung. Chem Biol Interact 173, 129-140.

  Minardi, F., Belpoggi, F., Soffritti, M., Ciliberti, A., Lauriola, M., Cattin, E., Maltoni, C., 2002. Results of long-term carcinogenicity bioassay on vinyl acetate monomer in Sprague-Dawley rats. Ann N Y Acad Sci 982, 106-122.

  Séralini, G.E., Clair, E., Mesnage, R. Gress, S., Defarge, N. Malatesta, M. Hennequin, D. Spiroux de Vendômois, J. (2012) Long term toxicity of a Roundup herbicide and a Roundup-tolerant genetically modified maize. Food and Chem. Tox. 50:4221-4231

  Séralini, G.E., Mesnage, R., Defarge, N., Gress, S., Hennequin, D., Clair, E., Malatesta, M., Spiroux de Vendômois, J. (2013) Answers to critics: why there is a long term toxicity due to NK603 Roundup-tolerant genetically modified maize and to a Roundup herbicide. Food and Chem. Tox. 53:461-468

  Schecter, A.J., Olson, J., Papke, O., 1996. Exposure of laboratory animals to polychlorinated dibenzodioxins and polychlorinated dibenzofurans from commerical rodent chow. Chemosphere 32, 501-508.

  Snell, C., Bernheim, A., Berge, J.B., Kuntz, M., Pascal, G., Paris, A., Ricroch, A.E., 2012. Assessment of the health impact of GM plant diets in long-term and multigenerational animal feeding trials: a literature review. Food Chem Toxicol 50, 1134-1148.

  Voss, C., Zerban, H., Bannasch, P., Berger, M.R., 2005. Lifelong exposure to di-(2-ethylhexyl)-phthalate induces tumors in liver and testes of Sprague-Dawley rats. Toxicology 206, 359-371.

  Weiss, B., Stern, S., Cernichiari, E., Gelein, R., 2005. Methylmercury contamination of laboratory animal diets. Environ Health Perspect 113, 1120-1122.

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