- Email: [email protected]
GM crops and the rat digestive tract: A critical review
Environment International 84 (2015) 213–214
Contents lists available at ScienceDirect
Environment International journal homepage: www.elsevier.com/locate/envint
Correspondence GM crops and the rat digestive tract: A critical review
The researchers published their gross pathological findings (Carman et al., 2013), indicating severe stomach inflammation in pigs fed a diet of genetically modified (GM) crops. They conclude, after only macroscopic analysis, that said crops promote severe stomach inflammation in these animals. In their follow-up work on the toxicology of GM foods (Zdziarski et al., 2014), the research group (comprised of many of the same authors, including Dr. Carman, who is the corresponding author on both manuscripts, and Dr. Haynes, who is the histopathologist listed for both studies) criticizes many of the histopathological investigations to date on GM toxicology, yet they notably abstained from such investigation altogether in their only published study on GM toxicology in pigs. Although not the focus of this letter, others have criticized their pig study for not performing any histology. Food Standards of Australia and New Zealand (FSANZ), an independent statutory agency that develops food standards, stated the following in their review in 2013: The presence of ‘inflammation’ was determined by visual appearance (reddening) only, without any microscopic (histological) confirmation. This is not considered a reliable method for establishing the presence of true inflammation, because it relies solely on the colour of the tissue which can vary for many reasons. (Carman and Vlieger, n.d.). In their review, the authors sought to establish standards in the assessment of GM crops on digestive tract health by stating “it is difficult to assess damage to the digestive tract purely on macroscopic grounds (Morini and Grandi, 2010), therefore a histopathological analysis should be part of the investigation.” But, the authors failed to meet the standards mentioned in their review, making their prior study, according to the authors' own words, “…impossible to properly review or repeat…” (Zdziarski et al., 2014). Perhaps this is one reason the authors have chosen not to cite their main finding of severe stomach inflammation in pigs as part of the rationale for their review. It is conspicuous that the authors have excluded from their study rationale their main finding of severe stomach inflammation in tissues of animals fed a long-term diet of GM products. They have cited other work in piglets in their review to propose additional microscopic analyses as part of a comprehensive GM toxicological investigation, but again, the authors attempted no such analysis in their prior study in pigs. By not citing their prior work, they have tacitly acknowledged FSANZ, admitting that the pig study does not meet the standards they have developed in their review. The suggestion that signs of toxicity can be detected reliably through gross pathology, as shown in Carman et al. (2013), is somewhat antiquated, given the increasing technologies available to identify or confirm tissue damage. In fact, one could argue that these technologies
http://dx.doi.org/10.1016/j.envint.2015.07.018 0160-4120/© 2015 Elsevier Ltd. All rights reserved.
have become so widespread in science today that it has allowed scientists to comparatively evaluate potential flaws in these technologies. For example, in a critical editorial, Henson (2005) suggests that “a disconnect between staining results and genetic changes has been observed” when evaluating biomarker expression using immunohistochemistry (IHC), a technique Zdziarski et al. (2014) explicitly favor as part of the toxicological assessment of GM food. Oftentimes, diagnostic interpretations using IHC are made qualitatively (i.e., presence or not of antigen) and subjectively (Matos et al., 2010), with the potential for significant bias especially when staining intensity using semi-quantitative means is the desired goal. So, even as methods of tissue analysis can be highly variable and ultimately non-determinative on their own, Zdziarski et al. (2014) highlight the importance of using such technologies in identifying not only presence of pathology but the severity of pathology, which can vary as well. The authors are advocating that histopathology investigation be pushed to its limits to not only detect but grade adverse outcomes of GM consumption. This is a potentially problematic position and is why other quantitative analyses should also be employed to confirm any inflammatory biomarkers revealed by histopathology investigation. Some of the studies included in the Zdziarski et al. (2014) review report histopathology as well as other quantitative analyses (i.e., cell proliferation ELISA, DNA analysis, etc.) and still determine, from all available evidence, no adverse outcomes. Yet, the authors do not view this heterogeneous approach as being a potential strength in the toxicological investigation into GM products, hence the focus of their review and the overwhelming concentration on the specific histopathological outcomes, as shown in Table 2. These outcomes may not be elaborated to the authors' liking because the results were unremarkable insofar as they did not corroborate any other quantitative analyses. It is, therefore, too simplistic to say that the studies cited in the review are flawed because single histopathological outcomes are absent from the scientific report. It could be argued that some of these studies at least performed histopathology as part of their investigation, an endeavor not attempted by Carman et al. (2013) in their only empirical assessment to date on gut health after long-term GM consumption. The authors of the current study should, therefore, elaborate why they have come to two different methodological standards based on their own observations and those of others cited in their review. Why can't gross pathology be acceptable for all GM toxicological investigations? If not acceptable, the authors should acknowledge that their prior work does not meet these standards and ought to not be considered in any policy-making decisions involving GM foods. Furthermore, attempts should be made going forward to adopt the standards elaborated in their review so that future timely contributions from this group can be given thorough consideration from regulatory bodies like FSANZ. References Carman JA, Vlieger H. Reply to Food Standards Australia New Zealand on GMO diet pig study. Gmojudycarman.org. (Accessed April 25, 2015).
214
Correspondence
Carman, J.A., Vlieger, H.R., Ver Steeg, L.J., Sneller, V.E., Robinson, G.W., Clinch-Jones, C.A., Haynes, J.I., Edwards, J.W., 2013. A long-term toxicology study on pigs fed a combined genetically modified (GM) soy and GM maize diet. J. Org. Syst. 8 (http://www. organic-systems.org/journal/81/8106.pdf). Henson, D.E., 2005. Back to the drawing board on immunohistochemistry and predictive factors. J. Natl. Cancer Inst. 21, 1796–1797. Matos LL, Trufelli DC, de Matos MG, da Silva Pinhal MA. Immunohistochemistry as an important tool in biomarkers detection and clinical practice. Biomark. Insights 2010. 9; 9–20. Zdziarski, I.M., Edwards, J.W., Carman, J.A., Haynes, J.I., 2014. GM crops and the rat digestive tract: a critical review. Environ. Int. 73, 423–433.
Keith Fluegge Institute of Health and Environmental Research, USA E-mail address: keithfl[email protected]. 25 April 2015
Contents lists available at ScienceDirect
Environment International journal homepage: www.elsevier.com/locate/envint
Correspondence GM crops and the rat digestive tract: A critical review
The researchers published their gross pathological findings (Carman et al., 2013), indicating severe stomach inflammation in pigs fed a diet of genetically modified (GM) crops. They conclude, after only macroscopic analysis, that said crops promote severe stomach inflammation in these animals. In their follow-up work on the toxicology of GM foods (Zdziarski et al., 2014), the research group (comprised of many of the same authors, including Dr. Carman, who is the corresponding author on both manuscripts, and Dr. Haynes, who is the histopathologist listed for both studies) criticizes many of the histopathological investigations to date on GM toxicology, yet they notably abstained from such investigation altogether in their only published study on GM toxicology in pigs. Although not the focus of this letter, others have criticized their pig study for not performing any histology. Food Standards of Australia and New Zealand (FSANZ), an independent statutory agency that develops food standards, stated the following in their review in 2013: The presence of ‘inflammation’ was determined by visual appearance (reddening) only, without any microscopic (histological) confirmation. This is not considered a reliable method for establishing the presence of true inflammation, because it relies solely on the colour of the tissue which can vary for many reasons. (Carman and Vlieger, n.d.). In their review, the authors sought to establish standards in the assessment of GM crops on digestive tract health by stating “it is difficult to assess damage to the digestive tract purely on macroscopic grounds (Morini and Grandi, 2010), therefore a histopathological analysis should be part of the investigation.” But, the authors failed to meet the standards mentioned in their review, making their prior study, according to the authors' own words, “…impossible to properly review or repeat…” (Zdziarski et al., 2014). Perhaps this is one reason the authors have chosen not to cite their main finding of severe stomach inflammation in pigs as part of the rationale for their review. It is conspicuous that the authors have excluded from their study rationale their main finding of severe stomach inflammation in tissues of animals fed a long-term diet of GM products. They have cited other work in piglets in their review to propose additional microscopic analyses as part of a comprehensive GM toxicological investigation, but again, the authors attempted no such analysis in their prior study in pigs. By not citing their prior work, they have tacitly acknowledged FSANZ, admitting that the pig study does not meet the standards they have developed in their review. The suggestion that signs of toxicity can be detected reliably through gross pathology, as shown in Carman et al. (2013), is somewhat antiquated, given the increasing technologies available to identify or confirm tissue damage. In fact, one could argue that these technologies
http://dx.doi.org/10.1016/j.envint.2015.07.018 0160-4120/© 2015 Elsevier Ltd. All rights reserved.
have become so widespread in science today that it has allowed scientists to comparatively evaluate potential flaws in these technologies. For example, in a critical editorial, Henson (2005) suggests that “a disconnect between staining results and genetic changes has been observed” when evaluating biomarker expression using immunohistochemistry (IHC), a technique Zdziarski et al. (2014) explicitly favor as part of the toxicological assessment of GM food. Oftentimes, diagnostic interpretations using IHC are made qualitatively (i.e., presence or not of antigen) and subjectively (Matos et al., 2010), with the potential for significant bias especially when staining intensity using semi-quantitative means is the desired goal. So, even as methods of tissue analysis can be highly variable and ultimately non-determinative on their own, Zdziarski et al. (2014) highlight the importance of using such technologies in identifying not only presence of pathology but the severity of pathology, which can vary as well. The authors are advocating that histopathology investigation be pushed to its limits to not only detect but grade adverse outcomes of GM consumption. This is a potentially problematic position and is why other quantitative analyses should also be employed to confirm any inflammatory biomarkers revealed by histopathology investigation. Some of the studies included in the Zdziarski et al. (2014) review report histopathology as well as other quantitative analyses (i.e., cell proliferation ELISA, DNA analysis, etc.) and still determine, from all available evidence, no adverse outcomes. Yet, the authors do not view this heterogeneous approach as being a potential strength in the toxicological investigation into GM products, hence the focus of their review and the overwhelming concentration on the specific histopathological outcomes, as shown in Table 2. These outcomes may not be elaborated to the authors' liking because the results were unremarkable insofar as they did not corroborate any other quantitative analyses. It is, therefore, too simplistic to say that the studies cited in the review are flawed because single histopathological outcomes are absent from the scientific report. It could be argued that some of these studies at least performed histopathology as part of their investigation, an endeavor not attempted by Carman et al. (2013) in their only empirical assessment to date on gut health after long-term GM consumption. The authors of the current study should, therefore, elaborate why they have come to two different methodological standards based on their own observations and those of others cited in their review. Why can't gross pathology be acceptable for all GM toxicological investigations? If not acceptable, the authors should acknowledge that their prior work does not meet these standards and ought to not be considered in any policy-making decisions involving GM foods. Furthermore, attempts should be made going forward to adopt the standards elaborated in their review so that future timely contributions from this group can be given thorough consideration from regulatory bodies like FSANZ. References Carman JA, Vlieger H. Reply to Food Standards Australia New Zealand on GMO diet pig study. Gmojudycarman.org. (Accessed April 25, 2015).
214
Correspondence
Carman, J.A., Vlieger, H.R., Ver Steeg, L.J., Sneller, V.E., Robinson, G.W., Clinch-Jones, C.A., Haynes, J.I., Edwards, J.W., 2013. A long-term toxicology study on pigs fed a combined genetically modified (GM) soy and GM maize diet. J. Org. Syst. 8 (http://www. organic-systems.org/journal/81/8106.pdf). Henson, D.E., 2005. Back to the drawing board on immunohistochemistry and predictive factors. J. Natl. Cancer Inst. 21, 1796–1797. Matos LL, Trufelli DC, de Matos MG, da Silva Pinhal MA. Immunohistochemistry as an important tool in biomarkers detection and clinical practice. Biomark. Insights 2010. 9; 9–20. Zdziarski, I.M., Edwards, J.W., Carman, J.A., Haynes, J.I., 2014. GM crops and the rat digestive tract: a critical review. Environ. Int. 73, 423–433.
Keith Fluegge Institute of Health and Environmental Research, USA E-mail address: keithfl[email protected]. 25 April 2015