轉(zhuǎn)基因玉米致癌論文被撤 編委曾就職孟山都

　　法國(guó)研究人員2012年在《食品和化學(xué)毒物學(xué)》雜志上發(fā)表轉(zhuǎn)基因玉米致癌論文，已成為部分人士反對(duì)轉(zhuǎn)基因食品的重要證據(jù)。但雜志出版方愛(ài)思唯爾公司28日在美國(guó)宣布，由于進(jìn)一步分析顯示論文數(shù)據(jù)不足以支持其結(jié)論，因此決定撤除這篇論文。

　　愛(ài)思唯爾公司在聲明中說(shuō)，《食品和化學(xué)毒物學(xué)》雜志對(duì)所發(fā)表的論文及論文所報(bào)告的數(shù)據(jù)進(jìn)行了徹底的、長(zhǎng)時(shí)間的分析，對(duì)論文發(fā)表的同行評(píng)議過(guò)程也進(jìn)行了調(diào)查，“沒(méi)有發(fā)現(xiàn)欺詐或?qū)?shù)據(jù)有意曲解的證據(jù)”，然而，“有理由擔(dān)憂”論文所提及實(shí)驗(yàn)中研究人員使用的實(shí)驗(yàn)大鼠數(shù)量和類型。

　　聲明說(shuō)：“對(duì)原始數(shù)據(jù)的深入調(diào)查表明，用如此小規(guī)模的樣本數(shù)據(jù)無(wú)法得出明確結(jié)論”、“考慮到(實(shí)驗(yàn)中所用的)斯普拉格-道利大鼠的已知腫瘤高發(fā)生率，喂食轉(zhuǎn)基因玉米組所觀察到的更高的死亡率及腫瘤發(fā)生率的原因不能排除是正常變化”。

　　聲明說(shuō)，歸根結(jié)底，論文的結(jié)果“盡管無(wú)不妥之處”，但是“沒(méi)有說(shuō)服力”，因此這篇論文達(dá)不到《食品和化學(xué)毒物學(xué)》的出版要求。

　　聲明還說(shuō)，這篇論文發(fā)表后編輯部收到多封來(lái)信，對(duì)論文描述結(jié)果的有效性、實(shí)驗(yàn)動(dòng)物的合理使用表達(dá)關(guān)切，有些來(lái)信甚至稱其中存在欺詐，多數(shù)來(lái)信呼吁撤回這篇論文。這些來(lái)信以及支持這篇論文的來(lái)信，都已和作者的回應(yīng)一并發(fā)表。

　　英國(guó)《自然》雜志網(wǎng)站說(shuō)，這一撤稿舉動(dòng)并不令人意外，《食品和化學(xué)毒物學(xué)》雜志主編本月初曾要求作者主動(dòng)撤回論文，并表示如果作者拒絕，雜志方也將予以撤稿。報(bào)道還說(shuō)，論文作者把撤稿形容為“丑聞”，并聲稱，這是因?yàn)殡s志任命的一名編委此前曾在轉(zhuǎn)基因農(nóng)業(yè)巨頭孟山都公司工作過(guò)7年。

　　2012年，《食品和化學(xué)毒物學(xué)》雜志刊登了法國(guó)卡昂大學(xué)分子生物學(xué)家塞拉利尼等人的一份研究報(bào)告。該報(bào)告稱，將100只雄性和100只雌性大鼠分成10組，分別喂食孟山都公司的NK603轉(zhuǎn)基因玉米及其他食物，兩年后發(fā)現(xiàn)，喂食轉(zhuǎn)基因玉米的實(shí)驗(yàn)大鼠出現(xiàn)腫瘤的風(fēng)險(xiǎn)高、壽命短。

　　這一結(jié)論在全球引起風(fēng)波。法國(guó)國(guó)家衛(wèi)生安全署、生物技術(shù)最高委員會(huì)和歐洲食品安全局均對(duì)塞拉利尼等人的研究展開調(diào)查，結(jié)果均認(rèn)為，該研究存在諸多不足，不能作為評(píng)估轉(zhuǎn)基因玉米健康風(fēng)險(xiǎn)的有效依據(jù)。

　　【下面是塞拉利尼團(tuán)隊(duì)聲明中英對(duì)照本。2013-11-28。引用自顧秀林博客】

　　我們是FCT一年多前發(fā)表的論文的作者，關(guān)于農(nóng)達(dá)和耐受農(nóng)達(dá)的轉(zhuǎn)基因生物的事（塞拉利尼等2012）。對(duì)于同樣的質(zhì)疑，我們已經(jīng)在同一個(gè)刊物上回應(yīng)過(guò)（塞拉利尼等，2013），即：作為正常的科學(xué)辯論，僅僅由于實(shí)驗(yàn)鼠品系的選擇和數(shù)量的原因，就判定研究結(jié)果“結(jié)論不完整”，這是不能接受的。我們堅(jiān)持我們的結(jié)論。我們?cè)缫压剂藢?duì)相同的質(zhì)疑所做的回答，但至今沒(méi)有見(jiàn)到對(duì)我們的任何回應(yīng)（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).

　　關(guān)于實(shí)驗(yàn)大鼠品系

　　同一個(gè)大鼠品系，被用在研究致癌性和慢性化學(xué)毒理學(xué)的美國(guó)國(guó)家毒理學(xué)項(xiàng)目中(King-Herbert et al., 2010)。SD大鼠是常規(guī)性用于毒理和致癌效果實(shí)驗(yàn)中的動(dòng)物，其中有孟山都公司的90天實(shí)驗(yàn)，被當(dāng)做批準(zhǔn)NK603轉(zhuǎn)基因玉米應(yīng)用的依據(jù)，其他轉(zhuǎn)基因農(nóng)作物也是這樣做的(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).

　　這里有一個(gè)簡(jiǎn)明的初步的文獻(xiàn)清單，表明在同行評(píng)審的雜志上SD大鼠被用在36個(gè)月的實(shí)驗(yàn)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).，其中有一些文章就發(fā)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

　　實(shí)驗(yàn)動(dòng)物數(shù)量與OECD實(shí)驗(yàn)規(guī)范

　　OECD 實(shí)驗(yàn)規(guī)范：第408條，關(guān)于90天實(shí)驗(yàn)，第452條關(guān)于慢性毒性試驗(yàn)，第453條關(guān)于綜合致癌性/慢性毒性試驗(yàn)，都要求用20只動(dòng)物為一組(1981和2009的規(guī)定都這樣要求)，盡管可以用10只動(dòng)物的實(shí)驗(yàn)就能取得生物化學(xué)參數(shù)。我們做的是長(zhǎng)期毒性研究而不是致癌性研究，從一開始就不是這樣設(shè)想的。根據(jù)常規(guī)10只動(dòng)物一組已經(jīng)足夠在生物化學(xué)水平上進(jìn)行研究，我們測(cè)量的參數(shù)數(shù)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!

　　在我們的實(shí)驗(yàn)中，性激素干擾的參數(shù)以及其它參數(shù)對(duì)于解釋一年之后的嚴(yán)重后果是充分的。我們采用的OPLS-DA統(tǒng)計(jì)方法是最適宜的。關(guān)于腫瘤和動(dòng)物死亡，時(shí)間效果以及每只動(dòng)物的平均腫瘤數(shù)量都必須被納入分析。在風(fēng)險(xiǎn)研究中出現(xiàn)的每一個(gè)跡象，都必須被充分重視。孟山都公司的研究用了同樣的大鼠品系，每組僅10只衡量20個(gè)參數(shù)，就得出同一種NK603轉(zhuǎn)基因玉米“安全”的結(jié)論，而且他們的實(shí)驗(yàn)只做了3個(gè)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

　　統(tǒng)計(jì)分析不應(yīng)該先做歷史數(shù)據(jù)，用這個(gè)方法做比較研究是錯(cuò)誤的，用每組50只動(dòng)物做研究是無(wú)意義。

　　采納歷史數(shù)據(jù)會(huì)把健康風(fēng)險(xiǎn)評(píng)估變成研究造假，因?yàn)槭匙V中的材料已經(jīng)受到化學(xué)污染(by dibenzo-p-dioxins and dibenzofurans (Schecter et al., 1996)和汞污染(Weiss et al., 2005)，鎘污染，鉻污染等，污染的程度足以改變動(dòng)物肝臟和肺臟的基因表達(dá)，足以擾亂基因分析(Kozul et al., 2008)。以往的食料中還發(fā)現(xiàn)農(nóng)藥和增塑劑污染，污染來(lái)自箱籠或者水(Howdeshell et al., 2003)。歷史數(shù)據(jù)也有來(lái)自可能食用了轉(zhuǎn)基因的動(dòng)物，很多地方的鼠糧中的確發(fā)現(xiàn)了轉(zhuǎn)基因成分。這一切都與污染水平相關(guān)，我們已經(jīng)在實(shí)驗(yàn)大鼠和對(duì)照組大鼠中檢測(cè)到這些問(wèn)題。

　　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.

　　在歷史數(shù)據(jù)中，2年SD雌性大鼠罹患乳腺纖維瘤的為13%~62%(Giknis, 2004)，但在我們的實(shí)驗(yàn)中對(duì)照組的發(fā)病率要低得多，這才是真正的對(duì)照，而我們的實(shí)驗(yàn)鼠發(fā)病率比對(duì)照組高很多，這使得我們的研究結(jié)果有顯著性。動(dòng)物的死亡率也是這樣。

　　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 雙重標(biāo)準(zhǔn)

　　遵循同一個(gè)邏輯把塞拉利尼的實(shí)驗(yàn)和孟山都公司的實(shí)驗(yàn)做一對(duì)一的比較，如果前者被認(rèn)為不足以顯示危害，那么后者也不能認(rèn)為證明了安全。

　　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.

　　以往的研究發(fā)現(xiàn)凡是顯示轉(zhuǎn)基因農(nóng)作物有負(fù)面效果的，都會(huì)被監(jiān)管者從實(shí)驗(yàn)到統(tǒng)計(jì)方法做嚴(yán)格的重審，凡是聲稱轉(zhuǎn)基因農(nóng)作物安全的研究，都被照單接受。只要是沒(méi)有報(bào)告負(fù)面效果的研究，都被接受為“安全”的證明，無(wú)論他們的研究方法有何種不足(被認(rèn)為無(wú)關(guān)緊要)。

　　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.

　　來(lái)自(Snell et al., 2012) 的一份文獻(xiàn)概覽研究可以說(shuō)明這個(gè)傾向。如作者在摘要中這樣說(shuō)，“在這里的24項(xiàng)研究的結(jié)果都不建議存在任何健康危害問(wèn)題…”即所有被審閱的研究都被按“票面價(jià)值”被接受和通過(guò)了。然而在文章中卻指出，研究報(bào)告的作者們留下了無(wú)數(shù)缺陷，同他們指責(zé)塞拉利尼論文的問(wèn)題類似，或者更嚴(yán)重。例如24篇中16篇(67%)文章沒(méi)有交代對(duì)照組飼料是否與實(shí)驗(yàn)用的飼料屬于同基因品種(他們的解釋只是“沒(méi)有采用”)。許多篇文章連討論所用的方法都沒(méi)有介紹。此外還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，F(xiàn)CT應(yīng)該把Hammond 等人關(guān)于耐受農(nóng)達(dá)轉(zhuǎn)基因玉米的那些論文全都撤回。那些論文貌似都是真正的科學(xué)討論，發(fā)表它們只是為了給孟山都提供權(quán)威證據(jù)。

　　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 參考文獻(xiàn)

　　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 modi?ed 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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