科学家警告多抗Bt作物存在风险

2016年1月7日 11:22 阅读 2346

Scientists warn of dangers of multi-toxin Bt crops
科学家警告多抗Bt作物存在风险

翻译：jrry86；原文发表时间：2015年12月7日；原文链接： //www.gmwatch.org/news/latest-news/16583-scientists-warn-of-dangers-of-multi-toxin-bt-crops

Hazards to non-target insects and mammals from multi-trait Bt insecticidal crops are being ignored by regulators, a new scientific review shows. Claire Robinson reports
最新的科学综述显示，多抗Bt抗虫转基因作物对非标靶昆虫和哺乳动物的危害一直都被管理机构忽视。Claire Robinson报道

An increasing number of “stacked-trait” GM Bt insecticidal crops combining several Bt toxins in one variety are coming onto the market. We’re assured that they’re safe. But evidence presented in a comprehensive new review throws this claim into question.
越来越多的将多种Bt毒素整合进同一个品种的多抗转基因Bt抗虫作物正进入市场。我们被告知它们是安全的。但是一篇最新综述（ //journal.frontiersin.org/article/10.3389/fenvs.2015.00071/abstract ）提供的证据使该主张受到质疑。

Stacked-trait GM crops are produced by cross-breeding single or double-trait GM Bt crops. They have been approved as safe based on several assumptions.
将单抗或双抗Bt转基因作物进行杂交就可以产生多抗转基因作物。基于某些假说，这些多抗作物被认定为是安全的。

For example, individual Bt toxins are often thought only to harm a few target insect pests and not to affect non-target and beneficial organisms, like ladybirds and lacewings. Also, regulators accept the argument from the industry and allied scientists that if the single Bt toxins included in the stacked crop are individually deemed safe, a combination of several Bt toxins and other GM traits present in stacked GM Bt crops will also be safe.
例如，通常认为单个Bt毒素只杀死一些标靶害虫，而不影响非标靶昆虫及益虫，如瓢虫和草蛉。并且监管机构也认可（ //www.testbiotech.org/sites/default/files/SmartStax_Bt_Synergies_Testbiotech.pdf ）业界及其联盟科学家的说法，即如果多抗作物中引入的Bt毒素在单独存在时是安全的，则把多个这样的Bt毒素以及其它转基因特性组合在一起，得到的多抗转基因Bt作物也一样安全。

But these assumptions are shown to be false by scientific evidence, the new review shows. The authors, Angelika Hilbeck of the Swiss Federal Institute of Technology and Mathias Otto of the German Federal Agency for Nature Conservation, reviewed the scientific literature for evidence of Bt toxin effects on non-target organisms and for combined effects of several Bt toxins acting together. Then they compared their findings to the regulatory dossiers provided by industry to support approval of stacked-trait GMOs.
但是这篇新的综述显示有科学证据证明这些假设是错误的。文章作者，瑞士联邦技术学院的Angelika Hilbeck和德国联邦自然保护机构的Mathias Otto，综合分析了科学文献中的Bt毒素对非标靶生物的影响以及多种Bt毒素同时作用的协同效应。他们还将研究结果与业界为向监管部门申请批准多抗转基因作物而提供的档案材料作了比较。

Their findings make for sobering reading.
他们的研究结果读起来不容乐观。

Bt toxins don’t only affect certain insect pests
Bt毒素并不仅仅影响某些害虫

First, Hilbeck and Otto addressed the declaration made by industry and regulators that Bt toxins are specific to certain insect pests and no documented cases of non-target effects on beneficial insects exist. They found that the evidence points to the opposite conclusion. Research studies show that individual Bt toxins can have harmful effects on beneficial and non-target organisms. But the industry dossiers submitted to regulators ignore these studies and maintain the fiction that Bt toxins only harm the target insect pests.
首先，Hilbeck和Otto探讨了业界和监管机构所宣称的Bt毒素只针对特定的害虫、而对益虫没有已记录在案的非标靶效应。他们发现有证据指向相反的结论。研究结果显示单个Bt毒素也会对有益的非标靶昆虫产生毒害效应。但是业界提交给监管机构的申请材料却忽略了这些研究，以便维护Bt毒素只伤害标靶害虫的神话。

Lead researcher Hilbeck commented in an interview, “The notion of a narrow specificity for Bt toxins is not true. Those who talk of narrow specificity base this on a narrow definition of an effect – the ‘quick kill’ effect.
主要研究者Hilbeck在一次采访中评价道，“关于Bt毒素的狭隘特异性的观点是不对的。那些谈论狭隘特异性的人都是基于对'效应'的狭隘定义---即'快速杀灭'效应。

“This is an economic concept: you want a quick kill for economic reasons, to save the crop from pest-induced damage.
“这是一个从经济角度来考量的概念：从经济实用来说，你希望能快速杀死，以挽救作物免受害虫伤害。

“But Bt toxins are not fast-acting toxins. Even in target pests, Bt toxins don’t kill quickly – it takes most susceptible insects a day or more to die. The Bt toxin in GM crops is expressed in the crop plant for months at a time. Residues linger in soil and aquatic systems.
“但是Bt毒素并非快速作用毒素。即使对标靶害虫，Bt毒素也不能快速杀灭，最易受到攻击的昆虫也需要一天或更多天才会死亡。转基因作物中的Bt毒素在作物中会一次性持续表达数月。其残留则长期存在于土壤和水系中。

“Regulatory tests need to look at long-term and sublethal effects, because that is what non-target organisms are likely to be exposed to. Currently these tests are not required. Yet we found a lot of evidence in the scientific literature that non-target organisms such as ladybirds, water fleas, lacewings and even slugs are adversely affected by Bt toxins.”
“监管检测需要审视长期和亚致死作用，因为这才是非标靶生物可能遭遇到的情况。而我们在科学文献中可以找到许多证据证明诸如瓢虫、水蚤、草蛉、甚至鼻涕虫这些非标靶生物，都会受到Bt毒素的不利影响。”

Hilbeck warns that mammals may be affected, too. She mentions a separate newly published review, which concluded that Bt toxins “cannot be considered innocuous, as they have some physiological effects that may become pathological”.
Hilbeck警告说哺乳动物也会受到影响。她提到了另一个新发表的综述，该综述作出结论（ //www.ncbi.nlm.nih.gov/pubmed/26537666 ）说“不能认为Bt毒素是无害的，因为它们会对生理带来一些影响，并可能导致病理反应。”

Hilbeck suggests a direction for future research on non-targets: “We have to extend the definition of ‘effect’ from the economic to the ecological.” She believes that pre-market safety testing should include long-term animal feeding studies with the complete stacked-trait crop. Currently these are not required by any regulator in the world.
Hilbeck为将来对非标靶生物的研究方向提供了一个建议：“我们必须把'效应'这个词的定义从经济角度扩展到生态。”她相信上市前的安全性检验应该包括使用完整的多抗作物来进行长期动物喂养研究。目前世界上还没有任何监管机构作此要求。

“Drastically increased” Bt toxin load
“急剧增加”的Bt毒素含量

Another commonly ignored issue in risk assessment of stacked-trait Bt crops is the large amount of Bt toxins expressed in them – which is far higher than in single-trait Bt crops. Together, the pyramid of different Bt toxins go to make up what the researchers call a “drastically increased” Bt toxin load.
另一个在多抗Bt作物的风险评估中常常被忽视的方面是，多抗作物中表达了大量Bt毒素，远比单抗Bt作物多得多。这些不同Bt毒素堆积而成的金字塔共同导致了被研究者称为的Bt毒素含量的“急剧增加”。

And in spite of frequent claims that Bt crops reduce or eliminate pesticides, stacked-trait Bt crops contain far more insecticide than the amount of chemical insecticide that is supposed to be displaced. For example, SmartStax GM maize contains six different Bt toxins (as well as two herbicide-tolerant traits). The total Bt insecticidal protein production of the crop is estimated at 4.2 kgs/ha, 19 times the average conventional insecticide rate of application in 2010.

而且，尽管频繁宣传Bt作物可以减少甚至消除农药的使用，多抗Bt作物中所含有的杀虫剂远比理论上它们所能取代的化学杀虫剂多得多。例如，SmartStax转基因玉米含有六种（ //www.testbiotech.org/sites/default/files/Background_TBT_ Imports_SmartStax.pdf ）不同的Bt毒素（还具有两种抗除草剂特性）。据估计（ //www.enveurope.com/content/24/1/24 ），每公顷该作物表达的Bt杀虫剂总量为4.2公斤，是2010年常规杀虫剂平均使用量的19倍。

Yet SmartStax stacked-trait maize was approved for EU food and feed imports without thorough safety testing of the whole GM crop containing the complete Bt toxin package in laboratory animals or non-target organisms. In an interview, Hilbeck commented that only the individual isolated Bt toxins that went into developing the stacked-trait crop may have been tested by industry for short-term safety in few insect feeding trials.
可是欧盟在没有彻底评估完整的含有全套Bt毒素的多抗SmartStax转基因玉米对实验动物和非标靶生物的安全性的情况下，仍然批准（ //www.testbiotech.org/en/node/940 ）了其进口，用作食品和饲料。在采访中，Hilbeck评论道，组成多抗作物的多种Bt毒素，只有单个独立的毒素可能经由业界作了少量短期昆虫喂养安全试验。

Combination toxic effects ignored
协同毒性作用一直被忽视

As well as the increased amount of Bt toxins found in stacked-trait crops, there is also the question of whether potential interactions and combined toxic effects of the different GM traits and chemical residues contained in stacked-trait Bt crops could harm consumers and non-target insects. And both GM and non-GM seeds are often treated with neonicotinoid insecticides, which add to the cocktail of known and potential toxins.
除了在多抗作物中Bt毒素含量大幅增加之外，还存在着另一个问题，那就是多抗Bt作物中不同的转基因性状和化学残留是否会相互作用并产生协同毒性，从而损害消费者和非标靶昆虫。同时，转基因和非转基因种子通常都会被涂裹上新烟碱杀虫剂，这更增加了已知的和潜在的毒性因素。

In spite of these biological and chemical “cocktail” risks, Hilbeck and Otto say that most regulators, including the European Food Safety Authority (EFSA), still limit the environmental risk assessment of stacked-trait Bt crops to consider one Bt toxin at a time, in isolation. And that single Bt toxin is tested not as it is expressed in the GM Bt crop plant, but only as a single purified protein produced in bacteria, in testing schemes developed for the regulatory approval of acute toxins like synthetic insecticides.
Hilbeck和Otto说，尽管存在这些生物的和化学的“鸡尾酒”式混合风险，大多数监管者，包括欧洲食品安全局（EFSA），对多抗Bt作物仍然仅仅进行有限的环境风险评估，一次只独立评估一种Bt毒素（译者注：而不考虑它们共存时的叠加协同毒性效应）。并且对每种单独的Bt毒素，也不是检测其在转基因Bt作物中表达时的毒性，而是检测经细菌表达并提纯后的单个蛋白的毒性，这种检测体系实际上是为监管和批准急性毒素（例如合成杀虫剂）而开发的。

The independent research group Testbiotech has previously warned that combination and synergistic effects of the elements in stacked-trait crops are being ignored by regulators.
独立研究小组Testbiotech以前就曾警告（ //www.testbiotech.org/sites/default/files/SmartStax_Bt_Synergies_Testbiotech.pdf ）说监管者忽视了多抗作物中各元素的叠加和协同效应。

That view is backed by first-hand experience of the author of this article at a public meeting of the European Food Safety Authority (EFSA), which issues safety opinions on GM foods and pesticides. A member of the EFSA GMO Panel asserted without qualification that the various GM traits and chemical residues combined in any authorized GMO stacked-trait crop “will not interact”. When challenged, the panel member presented no evidence for this broad claim.
这个看法在欧洲食品安全局（EFSA）的一个公开会议上得到本文作者的第一手经验的支持，而欧洲食安局负责对转基因食品和农药的安全性发布结论。EFSA转基因委员会的一个成员不负责任地声称说，任何经过批准的转基因多抗作物中的各种转基因性状和化学残留彼此之间“不会相互作用”。当受到质疑时，该成员却不能为这个宽泛的论断提供任何证据。

Hilbeck and Otto put such claims to the test. They searched the literature for research on the combined and synergistic effects on beneficial and non-target organisms of multiple Bt toxins, or of Bt toxins together with other proteins, chemicals, or plant components. They found a number of studies showing interactions and combined effects, the mechanisms of which are not fully understood.
Hilbeck和Otto对这类论断作了检验。他们搜索了文献中有关多个Bt毒素，或者Bt毒素和其它种类蛋白、化学试剂或植物组分共存时，对益虫和非标靶生物的叠加和协同效应的研究。他们发现好些研究显示出相互作用和协同效应的存在，而对其机理却并不完全了解。

Crucially, in a finding that directly challenges EFSA’s reductionist “one-at-a-time” approach to stacked-trait crops, Hilbeck and Otto discovered that many synergistic interactions in target organisms were not predictable from single trait effects. They occurred when the individual components tested in isolation did not elicit a response at all or elicited only a sublethal response.
关键是，在一个直接质疑EFSA对多抗作物采用简单化的“一次一个”策略的研究中，Hilbeck和Otto发现，在标靶生物中出现的许多协同相互作用，并不能通过单个性状效应而预测出来。单个组分在独立试验中从来没有诱发任何反应，或者即使有反应，也是亚致死的，可在多抗作物中，这些效应却出现了。

Modes of action of Bt toxins getting murkier over time
Bt毒素的作用机理越来越含糊不清

The assumed safety of Bt toxins for non-targets and human and animal consumers largely rests on their claimed specificity to insect pests. But this claim in turn rests on research on a narrow set of target insect pests, studying mostly a single type of Bt toxin.
Bt毒素对非标靶、动物和人类食用者是安全的这个假说，很大程度上依赖于所宣称的对害虫的特异性。但是这种论断本身又依赖于针对单个类型Bt毒素对狭小范围内的标靶害虫的作用的研究。

And as scientific research and knowledge has grown, uncertainty about how Bt toxins exert their effects has increased. Hilbeck and Otto state in their paper that today there is “less scientific certainty” about Bt toxins’ mode of action than when Bt toxin genes were first engineered into GM plants 30 years ago.
随着科研和知识的增加，对Bt如何发挥作用的不确定性也在增大。Hilbeck和Otto在文章中陈述道，相比于30年前Bt 毒素基因首次转入转基因作物时，今天人们对Bt毒素的作用机理“在科学上更加不确定”。

The situation is made even murkier by the fact that one of the most promoted of possible modes of action has been cast into doubt by a case of apparent scientific misconduct. In 2012 it emerged that the researchers who came up with the proposal, husband and wife team Alejandra Bravo and Mario Soberon, had manipulated images in 11 papers. The researchers had offered the images as evidence for their proposed mode of action for Bt toxins. They have at least one patent related to their work.
这一状况又因为一个明显的科学舞弊行为而变得更为混乱，导致一直最被推崇的Bt的可能作用机理受到了质疑。2012年，提出此作用机理的夫妻档科学家Alejandra Bravo和Mario Soberon被发现（ //retractionwatch.com/2012/11/23/university-disciplines-researchers-who-study-toxins-used-in-gmo-crops-at-least-seven-corrections-to-follow/ ）篡改了11篇文章中的图片。他们用这些图片作为他们提出的Bt作用机理的证据。他们还至少拥有一个与此研究有关的专利（ https://register.epo.org/application?number=EP07747214 ）。

The episode resulted in seven journals agreeing to publish corrections and to Bravo and Oberon resigning from chair positions they held at the National Autonomous University of Mexico.
这个插曲导致七份杂志同意发表更正，并使Bravo和Oberon从其担任的墨西哥全国自治大学的主席职位上辞职。

Their model for Bt toxins’ mode of action has been critiqued by a Canadian team of researchers as “difficult to reconcile” with evidence generated by other investigations. The Canadian team concluded, “Many important questions concerning the mechanism by which insect cells are killed by Bt toxins remain just as poorly understood as they were before these models were put forward.”
他们提出的Bt毒素的作用机理模型受到一个加拿大科研团队的批评（ //www.sciencedirect.com/science/article/pii/S0022201112001358 ），认为它难以与其他研究者得到的证据吻合。这个加拿大团队总结到，“很多与昆虫细胞如何被Bt毒素杀死的机理有关的重要问题都还没搞清楚，这与这些模型被提出之前的状况一样。”

The sum of known and unknown factors about GM Bt toxins lead Hilbeck and Otto to conclude that while stacked GM crops may offer benefits to some farmers, “these benefits may come with serious health and environmental risks” that should be experimentally studied before market approval. They recommend a “comprehensive examination of the systems, organs, tissues and cells” of non-target organisms and animal and human consumers, “especially the gastrointestinal tract, the immune system, the genitourinary tract and the respiratory and nervous systems.” They also call for further studies on the sub-chronic, chronic and immunotoxicological effects of Bt toxins, particularly on humans.
对转基因Bt毒素所有已知和未知因素的总结，使Hilbeck和Otto得出结论，多抗转基因作物也许给某些农民带来益处，但“这些益处伴随着严重的健康和环境风险”，应该在批准上市前加以研究。他们推荐对非标靶生物、动物和人类食用者进行“彻底的系统、器官、组织和细胞检测”，“特别是胃肠道、免疫系统、泌尿生殖道、呼吸和神经系统。”他们还建议对Bt毒素进行亚慢性、慢性和免疫毒性效应研究，特别是针对人类。

—
Review article: Specificity and combinatorial Effects of Bacillus thuringiensis Cry toxins in the Context of GMO environmental risk assessment

Angelika Hilbeck and Mathias Otto
Front. Environ. Sci., 9 November 2015 //dx.doi.org/10.3389/fenvs.2015.00071

Stacked GM crops expressing up to six Cry toxins from Bacillus thuringiensis (Bt) are today replacing the formerly grown single-transgene GM crop varieties. Stacking of multiple Cry toxins not only increase the environmental load of toxins but also raise the question on how possible interactions of the toxins can be assessed for risk assessment, which is mandatory for GM crops. However, no operational guidelines for a testing strategy or testing procedures exist. From the developers point of view, little data testing for combinatorial effects of Cry toxins is necessary as the range of possibly affected organisms focuses on pest species and no evidence is claimed to exist pointing to combinatorial effects on non-target organisms. We have examined this rationale critically using information reported in the scientific literature. To do so, we address the hypothesis of narrow specificity of Cry toxins subdivided into three underlying different conceptual conditions (i) “efficacy” in target pests as indicator for “narrow specificity,” (ii) lack of reported adverse effects of Cry toxins on non-target organisms, and (iii) proposed modes of action of Cry toxins (or the lack thereof) as mechanisms underlying the reported activity/efficacy/specificity of Cry toxins. Complementary to this information, we evaluate reports about outcomes of combinatorial effect testing of Cry toxins in the scientific literature and relate those findings to the practice of environmental risk assessment of Bt-crops in general and of stacked Bt-events in particular.

综述文章：Bt Cry毒素在环境风险评估中的特异性和协同效应

作者：Angelika Hilbeck和Mathias Otto
《环境科学前沿》，2015年11月9日，链接： //dx.doi.org/10.3389/fenvs.2015.00071

摘要：当前最多可表达六种来自苏云金芽孢杆菌的Cry毒素的转基因多抗作物已经取代以前种植的单抗转基因作物品种。多重Cry毒素的叠加，不仅会增加环境中毒素总量，而且带来了在对转基因作物的强制性风险评估中，如何评定毒素之间可能存在的相互作用的问题。但是至今还没有一个针对检验策略或检验程序的可操作性指南。从开发者的角度来说，不需要检验Cry毒素的协同效应，因为可能受到影响的生物范围只聚焦在害虫上，没有证据显示对非标靶生物存在协同效应。我们利用科学文献中所报告的相关信息，对此理论做了严格的审核。为此，我们将Cry毒素的狭隘特异性假说分成隶属的三个概念不同的范畴来讨论（1）对标靶害虫的“功效”，作为“狭隘特异性”的指标，（2）缺乏Cry毒素对非标靶生物不利影响的报告，（3）所提出的的Cry毒素作用方式（或对作用方式的理解的缺乏），也即文献中报告的Cry毒素的活性/有效性/特异性的形成机理。作为这些信息的补充，我们还评估了科学文献中对Cry毒素协同效应检测结果的报告，并将研究结果与Bt作物特别是多抗Bt作物的环境风险评估的实践联系起来。