Is it safe to say that genetically modified crops are safe?

The author Leng Yue Rushuang comes from the Science Squirrel Association. Discussing articles about genetically modified crops with gentle words and strong arguments. As a person with basic knowledge and a non-boycott of genetically modified crops, I personally appreciate this article and the author Leng Yuerushuang.

The article "A Chaos-Uncertainty of Genetically Modified Crops" by Wu Ju, a teacher of Science Network, is the highest level of all the articles I have seen that question genetically modified crops. Such questioning based on scientific research papers is also necessary to discuss the safety of genetically modified crops. However, in my opinion, some of the points in the article are open for discussion, so I might as well talk about my points of view. If there is anything wrong, please correct me.

Among the current transgenic crops with insect resistance genes, crops with genes that synthesize BT protein account for a large portion [1], which is also the toxin discussed in the text of Mr. Wu Ju. Briefly, BT protein is a type of protein synthesized in bacteria (BT is the abbreviation of the bacterial scientific name), some Lepidoptera (such as moths, butterflies), Diptera (such as mosquitoes), or Coleoptera (such as The larvae of the beetle will eat these proteins and cause perforation of epithelial cells in the digestive tract, affecting a series of physiological activities and dying. A major problem that many people care about BT protein-containing genetically modified crops is-since BT protein can kill these larvae, does the same toxicity cause perforation of human digestive tract epithelial cells?

So far, the answer to the academic community is no, for three reasons. First, the BT protein needs to be dissolved in an alkaline environment and work properly. The environment in the digestive tract of these larvae is alkaline, but the environment of the human digestive tract is mostly acidic, and only a weak alkaline environment appears at the end of the ileum [2] [3] (not a medical professional, if the cited information is wrong Please also correct me). If these proteins are not successfully dissolved, even the larvae of moths and butterflies will not kill [4].

Second, although an alkaline environment is necessary, it is still not enough for the BT protein to exert its activity. In an alkaline environment, these BT proteins need to be "cut with a knife" by proteases before they are officially activated. To make a very inappropriate analogy, some movies cannot be released without cutting a bit of footage. These proteases have a high species specificity. Proteases present in butterflies may not be present in beetles. Only when specific proteases are present, the BT protein will show toxicity.

Third, these BT proteins after "operation" will only start a series of reactions after they bind to the receptors of epithelial cells, perforate the cell membrane of epithelial cells, and eventually lead to the death of larvae. The binding of this protein to the receptor is also highly specific. Let's take the movie as an example that is not 100% fit. If the cut movie is a cartoon, then the children's channel should be sent; if the cut movie is a documentary, then the record channel should be sent. It is precisely because of the indispensable combination of "alkaline environment, specific protease and specific receptor" that the current academic community believes that the BT protein as an insecticide is safe and non-toxic for vertebrates [ 5].

Because of this, in a paper published in 2012, some laboratories have begun to consider the possibility of using BT protein to kill parasites in the human intestine, and have obtained results in mice [6]. In addition, in everyone's mind, organic food has become synonymous with natural food, and seems to be incompatible with genetically modified crops. But in fact, the practice of spraying pesticides containing BT protein in organic farms is quite common and has been used for more than 50 years [7].

After discussing the toxicology and safety of BT protein, I would like to mention the differences between Wu Ju and Mr. Wu Ju. Teacher Wu Ju said in his article that he found in a paper "In this experiment, it was confirmed that Cry protein can bind to the BBMV of cattle and pigs." I personally have reservations about this.

First, one of the main practices of the original experiment was CPT. Briefly, free BT protein is mixed with BBMV and centrifuged at high speed. The original author believes that the BT protein bound to BBMV will sink at the bottom of the centrifuge tube, and then through conventional protein gel electrophoresis and western-blot can test whether the BT protein can bind to BBMV. But this is a very crude method. In this method, proteins are likely to undergo non-specific binding. In one of my CPT experiments, the originally negative control GFP also showed a band after passing through western-blot. The post-analysis showed that GFP can bind to the wall of the centrifuge tube and adsorb to the top! Therefore, in my opinion, Since no picture of whether the negative control protein binds to BBMV is given, this experimental method is not convincing. Secondly, even if the BT protein does bind to BBMV in this experiment, it does not explain anything. The result that Teacher Wu mentioned that the difference is not obvious (3.2 (silkworm) vs. 1.9 (pig) is indeed quite close) is the result of BIAcore, and the same paragraph in the article also shows the western result of co-precipitation, the band of insects and mammals The difference is very obvious, and the final conclusion of that paper is described in Mr. Wu ’s own words, "... saw a report involving the experiment of Cry protein on mammalian small intestinal epithelial cells, saying that Bt protein does not affect the membrane integrity of small intestinal epithelial cells. Sex. "That is to say, the paper's view supports that BT protein is not toxic to humans.

However, teacher Wu Ju also said, "In the toxic effect of Cry protein, the most critical thing is not the binding of Cry protein to the brush border vesicles (BBMV) of small intestinal epithelial cells, but the binding of cadherin-like receptors. , Promote Mg2 + -dependent signaling pathways, thereby causing cell death. " Here, I agree with the first half and disagree with the second half. There are currently two models of specific pathways after binding receptors, Mg2 + is only one of them, and these two models have not been well distinguished [8]. However, this flaw does not conceal Yu. Teacher Wu Ju may have made a typo because he also mentioned later that "in the information he has seen, the Cry protein must come into contact with mammalian intestinal cells, but the toxicology research presents different theories. The first is the receptor-signal theory, that is, after the Cry protein binds to the receptor, the Mg2 + -dependent signaling pathway caused by the receptor activates the intracellular apoptosis signal, thereby killing the cells; the second is the pore-forming protein theory, that is, the Cry protein itself, The receptor promotes hydrolysis, oligomerizes mature proteins, and forms pores in the cell membrane, causing osmotic shock. "

When referring to BT protein receptors, teacher Wu Ju said that they "all come from insects and belong to Cadherin-like receptors. There are a large number of different types of cadherin in mammals, and it is unknown whether they can participate in The cytotoxic function of Bt protein is rarely reported in this regard. " I tried to search in the afternoon. Perhaps the keywords I set were incorrect. There were many papers. However, I did not find a paper that detailedly analyzed whether the mammalian protein can participate in the BT protein toxicity function, so I agree so far "There are few research reports I can find in this regard." But I don't quite agree with Teacher Wu Ju's reasoning. In my understanding, teacher Wu Ju wanted to imply that because there are a large number of different types of cadherins in animals, there may be some receptors that can bind to BT protein, which makes BT protein toxic in humans, causing Uncertainty in security (of course, if Teacher Wu does n’t mean that, then it ’s okay to treat me as nonsense). My objections are as follows: before the BT protein binds to the receptor, it needs to pass the protease "cutting knife" to show activity (see the second article of BT protein toxicology above), even if Teacher Wu asked "Which cell does not have Cadherin? Which tissue does not have alkaline phosphatase? "I still insist that these proteases are specific. If these proteases are not present in the human body, what about these receptors? What's more, there is no such receptor in the academic community. In addition, Teacher Wu also mentioned in the following "For example, Cry1Ab and Cry1Ac, although the sequence similarity is very high, but they may act on the midgut cells of target insects through different mechanisms [11], different receptors have different affinity for different Cry proteins . I agree with this, the receptor is also specific. But in my opinion, although it cannot be said that there is definitely no receptor in the human body that can bind to BT protein, from the perspective of the relationship between humans and insects, before it is found that a certain receptor can bind to BT protein, I tend to I think that this receptor does not exist in the human body (of course, my opinion is not conclusive, and I welcome discussion) I searched for papers related to protease / receptor specificity, and found no evidence to support me or support Mr. Wu, so I opposed In opposition, I cannot say that Teacher Wu is definitely wrong, or that he is definitely right. In order to make Teacher Wu feel at ease, I think that after analyzing whether all proteases in the human body can cleave BT protein and whether all receptors can bind to active BT protein, this question is inconclusive and requires time and more research.

After discussing the toxicology and safety of BT protein, let's take a look at whether the theory of transgenic technology is mature. Teacher Wu said, "The genes transferred into eukaryotes have no corresponding error correction mechanism. If the mutation probability is calculated, the mutation probability of the transferred gene will be higher than that of other parts of the genome." I don't know what is the basis of your saying. The transferred gene needs to be integrated into the genome to work. The transferred gene has become a part of the genome and is no different from other parts of the genome. DNA polymerase has the function of "proofreading" and can check whether there is a misread on the newly copied DNA strand; Photolyse can cut off the polymerized T; Endonuclease can cut off the mismatched bases; Helicase can match the entire segment of mismatched Cut the DNA. Does Teacher Wu think that because the transferred gene originally belonged to prokaryotes, does it not pass through a series of error-proofing facilities in eukaryotic cells? Or because Teacher Wu feels that the transferred gene has no introns, so it does not Enjoying the benefits of eukaryotic cells? I do n’t dare to say anything else, but be aware that there are many plant genes that do not contain introns in the model plant Arabidopsis thaliana ... I think that these genes still enjoy eukaryotes Biological error correction mechanism.

I also have some different views on the impact of the genetic modification on the plant genome proposed by Teacher Wu.

Teacher Wu raised three questions. First, "Whether the position of its insertion will cause frameshift mutations due to upstream and downstream nucleotides, resulting in malfunction of the promoter or termination of the terminator". My answer is that there is no frameshift mutation in the promoter and terminator because they do not encode. If Mr. Wu said the promoter and terminator refer to "start codon" and "stop codon", the question is whether the gene can successfully start transcription and stop translation, then this problem is only by extracting genomic DNA and sequencing It can be solved, but it takes only two days before and after me.

Second, "Does the insertion of countless artificial genes disrupt the plant genome structure and cause the original genes to be misexpressed? This produces undesirable or even toxic substances." My answer is that genetically modified crops generally require confirmation of single copy insertion. In fact, we pursue single-copy insertion because multiple copies are likely to cause co-suppression and lead to silence, so single-copy insertion is usually the most expressed. The innumerable copy insertions cannot pass the R & D level first, because they are usually useless waste, let alone used for production. As for the wrong expression of the original gene, this is possible, but it can also be solved by extracting genomic DNA and sequencing. But now, research on gene expression has begun to consider the three-dimensional structure of chromosomes, and this three-dimensional structure is likely to be changed. No one knows whether it will have an impact or what impact it will have.

Third, "Due to the network relationship of the cell components mentioned above, whether these foreign proteins will have a great impact on the normal metabolism of cells, increase or decrease secondary metabolites and are not suitable for human consumption." This is a very good question. Due to the complexity of the regulatory network, it is not only impossible to move the whole body at once, but it is very common. For example, if you put a plant that was standing upright for 10 minutes, the RNA level inside might change. But I do n’t think that talking about change will seem to cause much harm. In my opinion, breeding good traits from generation to generation or hybrid crops, the changes in the gene regulation network inside are not necessarily less than those caused by genetic modification. As for the specific impact of these changes, of course, specific problems should be analyzed. In fact, each new genetically modified crop is still subject to these two tests when it is evaluated for safety. And the "uncertainty" of other breeding methods is even smaller than that of GM (this "even" may not be true, such as how to prove that the "uncertainty" of mutation breeding is smaller than that of GM?), Because they are not tested Therefore, the uncertainty of listed products may be higher than that of genetically modified products.

In addition to these differences, I still agree with some of Wu Ju's other opinions. For example, I agree that GM technology should not be abandoned in the laboratory (of course, this is not possible, or biology will not be able to develop), and I also agree that strict safety testing needs to be done before the GM food is marketed. In view of teacher Wu Ju's saying, "I should encourage people who like to eat more, so as to verify the uncertainty of genetically modified foods on the human body." As long as the genetically modified foods provided are real and effective, I am willing to act as such a pioneer.

The time and level are limited. The discussion ends here. The format of the reference materials is not unified. Please understand. If there are omissions and errors in the text, please also point out.

Note. I always support "metaphor can not replace reason". Therefore, the metaphor in the article is just for easy understanding, and the logical relationship with the ontology may not be strictly one-to-one.

References

[1] 30 years of transgenic practice-Ministry of Agriculture Safety Management Office of Agricultural GMOs, Institute of Biotechnology, Chinese Academy of Agricultural Sciences, Chinese Society of Agricultural Biotechnology

[2] Intraluminal pH of the human gastrointestinal tract, Fallingborg J, Dan Med Bull. 1999 Jun; 46 (3): 183-96.

[3] Intestinal luminal pH in inflammatory bowel disease: possible determinants and implications for therapy with aminosalicylates and other drugs, SG Nugent, D. Kumar, Gut 2001; 48: 571-577 doi: 10.1136 / gut.48.4.571

[4] Bacillus thuringiensis: Mechanisms and Use, A Bravo and M Soberon, Comprehensive Molecular Insect Science. 2005, Elsevier BV, Amsterdam, pp. 175–206

[5] Bacillus thuringiensis: a century of research, development and commercial applications, Georgina Sanahuja, Raviraj Banakar, Richard M. Twyman, Teresa Capell, Paul Christou, Plant Biotechnology Journal (2011) 9, pp. 283–300

[6] Bacterial pore-forming proteins as anthelmintics, Yan Hu and Raffi V. Aroian, Invert Neurosci (2012) 12: 37–41

[7] http: //

[8] Current models of the mode of action of Bacillus thuringiensis insecticidal crystal proteins: A critical review. Vincent Vachon, Raynald Laprade, Jean-Louis Schwartz, Journal of Invertebrate Pathology, 2012

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