Public confidence in genetically modified (GM) crop studies is tenuous at best in many countries, including those of the European Union in particular. A lack of information about the effects of ties between academic research and industry might stretch this confidence to the breaking point. We therefore performed an analysis on a large set of research articles (n = 672) focusing on the efficacy or durability of GM Bt crops and ties between the researchers carrying out these studies and the GM crop industry. We found that ties between researchers and the GM crop industry were common, with 40% of the articles considered displaying conflicts of interest (COI). In particular, we found that, compared to the absence of COI, the presence of a COI was associated with a 50% higher frequency of outcomes favorable to the interests of the GM crop company. Using our large dataset, we were able to propose possible direct and indirect mechanisms behind this statistical association. They might notably include changes of authorship or funding statements after the results of a study have been obtained and a choice in the topics studied driven by industrial priorities.

Copyright: © 2016 Guillemaud et al. This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

We used the COIs created by ties with GM crop companies as a model of COIs for this study because the best interests of these companies was easy to characterize (efficacy and durability of the crops) and COIs were easy to detect (affiliation of an author to a GM crop company or part of the funding provided by a GM crop company).

The efficacy and durability of Bt crops are defined here as the level of pest control provided by the Bt toxin they produced or by the crop themselves and the sustainability of this pest control over time, respectively.

The details of the protocol of literature inclusion and exclusion are described in the material and methods section.

We investigated the occurrence of COIs in GM crop studies and their association with the outcome of those studies further, by analyzing 672 full-text articles focusing on two topics: the efficacy and durability of GM crops producing Bacillus thuringiensis (Bt) toxins–often referred to as Bt crops–against target pest insects (see the flowchart of article selection in Fig 1 and S1 Table for a list of all the articles, with the associated classifications).

Despite the extraordinary financial, political and ideological stakes relating to genetically modified (GM) crops, we were able to identify only two research studies [ 1 , 2 ] focusing on conflicts of interest (COIs)—defined as “a set of circumstances that creates a risk that professional judgment or actions regarding a primary interest will be unduly influenced by a secondary interest” [ 3 ]—in this field of research. These two studies reported similar frequencies of COIs in research articles on GM crops, but differed markedly in their conclusions. Sanchez [ 1 ] concluded that COIs were not frequent enough to be a serious issue in GM crop studies, whereas Diels et al. [ 2 ] warned that COIs might be a problem because they were significantly linked to study outcomes. Unfortunately, one of these studies was potentially subject to COI itself [ 1 ] (the author’s affiliation was ChileBio, http://www.chilebio.cl , which is funded by companies that develop GM crops) and the other included a limited number of articles [ 2 ] (n = 94).

Materials and Methods

Goal of this study We explored the occurrence of COIs and the association between COIs and outcomes in studies of genetically modified (GM) crops. We focused our analysis on articles evaluating the efficacy or durability of GM crops producing toxins (Cry and Vip proteins) from Bacillus thuringiensis (Bt) against targeted pests. These articles included studies on the main Bt crops developed by Monsanto (e.g. maize and cotton varieties expressing the MON810 and MON1076 events, respectively), Syngenta (e.g. maize varieties expressing the Bt11 event), Dow AgroSciences and DuPont Pioneer (e.g. maize varieties expressing the 59122 event). We used the COI created by the professional affiliation of authors to GM crop companies or the provision of funding for the study by these companies as the model of COI for this study. We considered only COIs linked to GM crop companies because the best interests of these companies were easy to characterize (efficacy and durability of crops) and the presence of such COIs was easy to detect (an author was affiliated to a GM crop company or some of the funding came from a GM crop company). The COIs investigated here correspond therefore to financial COIs. Non-financial COIs [4], also known as intrinsic COIs or intellectual COIs, were not investigated. The goal of this study was 1) to measure the extent of COIs in this field of research, 2) to test the hypothesis that study outcomes for the efficacy or durability of Bt crops are more frequently favorable to the interests of GM crop companies in the presence than in the absence of COIs and 3) to investigate the mechanisms underlying the association between COIs and study outcomes.

Article selection–first step The flowchart describing the literature included/excluded is shown in Fig 1. We initially selected articles by searching the Web of Science (WoS, ISI Web of Knowledge, Thomson Scientific) bibliographic database. We used a Boolean search term including (1) most crops (e.g. cotton, maize, potato) for which GM varieties producing Bt toxins have been commercialized, and (2) most of the pests targeted by Bt crops (e.g. Diabrotica virgifera virgifera, Ostrinia nubilalis, Pectinophora gossypiella). The exact Boolean search term was: ((TI = (rootworm* OR Diabrotica OR borer* OR Ostrinia OR Diatraea OR armyworm* OR Spodoptera OR stalkborer* OR Busseola OR Sesamia OR bollworm* OR Helicoverpa OR earworm* OR Leafworm* OR Pectinophora OR budworm* OR Heliothis OR "Colorado potato beetle" OR "Colorado potato beetles" OR Leptinotarsa OR Chrysomela OR "Cottonwood beetle" OR "Cottonwood beetles" OR "Diamondback moth" OR "Diamondback moths" OR Plutella OR "Rice leaf folder" OR "Rice leaf folders" OR Cnaphalocrocis OR "Chilo suppressalis" OR "Leucinodes orbonalis" OR "Soybean looper" OR "Soybean loopers" OR "Pseudoplusia includens") AND TS = (maize* OR corn* OR "Zea mays" OR cotton* OR "Gossypium hirsutum" OR soybean* OR "Glycine max" OR potato* OR "Solanum tuberosum" OR poplar* OR Populus OR eggplant* OR "Solanum melongena" OR brinjal* OR tomato* OR "Lycopersicon esculentum" OR rice OR "Oryza sativa" OR broccoli* OR "Brassica oleracea" OR tobacco* OR nicotiana) AND TS = ("bt" OR cry* OR bacillus OR toxin*) AND TS = (transgenic* OR GMO* OR GMP* OR "genetically modified" OR "Bt crop" OR "Bt plant" OR "Bt tree")) OR (TS = ("western corn rootworm" OR "Diabrotica virgifera" OR "European corn borer" OR "Asian corn borer" OR "Southwestern corn borer" OR "Ostrinia nubilalis" OR "Ostrinia furnacalis" OR "Diatraea grandiosella" OR "Diatraea saccharalis" OR "Sugarcane Borer" OR "fall armyworm" OR "Spodoptera frugiperda" OR "African maize stalkborer" OR "Busseola fusca" OR "Sesamia nonagrioides" OR "Mediterranean corn borer" OR "Australian bollworm" OR "Helicoverpa punctigera" OR "Helicoverpa zea" OR "Spodoptera littoralis" OR "Corn earworm" OR "Cotton Leafworm" OR "Pink bollworm" OR "Cotton bollworm" OR "Pectinophora gossypiella" OR "Helicoverpa armigera" OR "Tobacco budworm" OR "Heliothis virescens" OR "Colorado potato beetle" OR "Leptinotarsa decemlineata" OR "Chrysomela tremulae" OR "Chrysomela scripta" OR "Cottonwood beetle" OR "Diamondback moth" OR "Plutella xylostella" OR "Rice leaf folder" OR "Cnaphalocrocis medinalis" OR "Striped stem borer" OR "Chilo suppressalis" OR "Leucinodes orbonalis" OR "Fruit Borer" OR "Shoot Borer" OR "Soybean looper" OR "Pseudoplusia includens") AND TI = (maize* OR corn* OR cotton* OR soybean* OR potato* OR poplar* OR eggplant* OR brinjal* OR tomato* OR rice OR broccoli* OR tobacco*) AND TI = ("bt" OR cry* OR bacillus OR toxin*) AND TS = (transgenic* OR GMO* OR GMP* OR "genetically modified" OR "Bt crop" OR "Bt plant" OR "Bt tree"))) We searched the WoS database on September 11, 2015. Using the above search term and limiting the query to articles published in English between 1990 and 2015, we recovered 1,227 articles. Two of us (DB and TG) then independently screened the titles and abstracts of these 1,227 articles, to eliminate those beyond the scope of our survey. Articles that were classified either with uncertainty by at least one of us (4.6%) or differently (7.9%) were jointly discussed to reach a consensus. We excluded 307 articles which dealt with various subjects, including assessments of the effects of Bt crops on non-target organisms, GM crops producing toxins other than those from Bt (e.g., toxins from spiders, lectins) and Bt crops developed by academics rather than by GM crop companies.

Classification by the type of conclusion The outcomes of the 920 articles retained for the analysis were classified as ‘favorable’, ‘neutral’ or ‘unfavorable’ to the financial interests of at least one GM crop company. This classification was done independently by two of us (DB and TG) and was based exclusively on the titles and abstracts of the articles, with no knowledge of the authors’ names and affiliations or of funding sources. This classification was also preformed independently of the classification on the basis of study topic. Articles that were classified either with uncertainty by at least one of us (11.2%) or differently (19.6%) were jointly discussed to reach a consensus. Articles were classified on the basis of the general tone of the title and abstract and the formal conclusions given in the abstract, on the basis of the following criteria: Favorable if the article reported that: One or several of the Bt crops tested provided a satisfactory level of control of the targeted pests; The susceptibility of the targeted pest populations to Bt toxins was high and/or remained unchanged over time (i.e. indicating an absence of evidence for the selection of mechanisms of resistance to the Bt toxins produced by Bt crops); Laboratory selection did not yield individuals sufficiently resistant to develop on Bt crops; Biotic and abiotic factors (relating to the pests and/or the plants) provided favorable conditions for the management of Bt resistance in targeted pests (e.g. Bt crops produced high doses of toxins, Bt resistance was recessive and/or associated with fitness costs, non-Bt crops (called refuges) were planted in sufficient quantities and sufficiently close to Bt crops); Pest populations resistant to a particular Bt toxin were controlled by another toxin or by other methods for which there was no cross resistance; Several Bt toxins acting via different receptors (i.e. decreasing the risk of cross-resistance) could be successfully combined in Bt crops through pyramiding. Neutral if the article reported: Theoretical models exploring the influence of virtual biotic and abiotic conditions on the selection of Bt resistance in targeted pest populations; The development of monitoring tools for following the susceptibility of targeted pest populations to Bt crops; The baseline susceptibility of pest populations before the cultivation of Bt crops targeting those populations; Receptors for Bt toxins and/or mechanisms or genetic changes conferring resistance to these toxins in the targeted pest populations. Unfavorable if the articles reported that: One or several Bt crops did not provide a high level of control of the targeted pests, potentially jeopardizing the efficacy of the Bt resistance management strategy; The susceptibility to Bt toxins decreased and/or Bt resistance developed in the targeted populations (in either laboratory or natural conditions); Resistance to one Bt toxin in the targeted pest populations jeopardized the successful use of other toxins to control those populations (i.e. the occurrence of cross-resistance); Biotic and abiotic factors (relating to the pest and/or the plant) created unfavorable conditions for the management of Bt resistance in the targeted pests (e.g. Bt crops did not provide high doses of toxins, Bt resistance was not fully recessive and/or was not associated with fitness costs, non-Bt crops (i.e. refuges) were planted in insufficient quantities and/or too far away from Bt crops).

Article selection–second step We were able to retrieve PDF files containing the whole content of the article for 893 of the 920 articles classified by the type of conclusion. These 893 PDF files were screened independently by two of us (DB and TG) to check again the relevance of the papers for this study. Articles that were classified either with uncertainty by at least one of us (5.4%) or differently (5.7%) were jointly discussed to reach a consensus. We identified 672 of these articles as relevant (S1 Table).

Classification by topic The 672 articles retained were classified into two categories on the basis of the topic considered: the ‘Efficacy’ or ‘Durability’ of the GM crops studied. This classification was done independently by two of us (DB and TG) and was based on titles and abstracts only, blind to the names and affiliations of the authors and to sources of funding (see below). Articles that were classified either with uncertainty by at least one of us (25.1%) or differently (4.3%) were jointly discussed to reach a consensus. Papers assigned to the Efficacy category reported data on: Plant toxicity; Control of the targeted pests; Yield performance; The baseline susceptibility of targeted species; The efficacy of new toxins; New methods of toxin combination; The economic advantages of GM plant use. Papers assigned to the Durability category reported data on: The selection of target pest strains resistant to Bt toxins in the laboratory; The initial frequencies of Bt resistance alleles within natural populations of the targeted pests; The detection of Bt resistance within natural populations of the targeted pests; Changes in the efficacy of Bt crops over time; Resistance characteristics (number of genes involved, inheritance, dominance, epistasis, pleiotropy) of the targeted pests; The development of strategies for limiting/preventing the evolution of Bt resistance (e.g. the high-dose/refuge strategy) of the targeted pests; Tests of the assumptions underlying such strategies.

Classification by funding source and author affiliation We also analyzed the authors’ professional affiliations and the funding sources (see below) of the 672 articles retained for the analysis. This analysis was again performed independently by two of us (DB and TG) blind to the classification of the article for topic and study outcome, as described above. Articles that were classified either with uncertainty by at least one of us (2.1% and 13.7% for authors’ affiliations and the funding sources, respectively) or differently (5.5% and 10.1% for authors’ affiliations and the funding sources, respectively) were jointly discussed to reach a consensus. For each paper, we recorded: The presence or absence of authors professionally affiliated to a GM crop company. This was established by screening the address of each author appearing in the authors’ affiliation section of the article; For publications co-authored by academics and one or more authors professionally affiliated to a GM crop company, whether the senior author worked for a GM crop company or was an academic researcher. The senior author was identified as the corresponding author for the paper; Whether the sources of funding were declared. In cases in which the funding sources were declared, we distinguished between funding from GM crop companies (partial or complete) and funding from other sources (governmental agencies, non-profit organizations, foundations, universities, etc.). Using this information, we determined, for each article, whether there was: An affiliation COI, defined as the presence of at least one author from a GM crop company on the paper; A funding COI, defined as at least partial funding for the study from a GM crop company. Overall, a paper was considered to display COI if it displayed either an affiliation or a funding COI.

Leading authors For each article, the leading author was identified as the author present on the largest number of papers from among the 672 papers considered in this analysis. If several authors of a given paper had been authors on the same number of articles in our list, the leading author was identified as the first in alphabetic order. We identified 193 leading authors in total (mean number of papers per leading author = 3.48, median = 14.4, minimum = 1, maximum = 53, 5th percentile = 1, 95th percentile = 15)

Statistical analysis The associations between (i) the presence/absence of COI and study outcome, (ii) the presence/absence of COI and the topic of the article, and (iii) the topic of the article and its outcome, were assessed in Fisher’s exact tests, with the function fisher.test of R [5]. For a given article, the effect of its topic (i.e. efficacy or durability) on its number of citations (TC), as recorded on September 11, 2015 in the WoS, was evaluated with a mixed linear model, using the lmer function of R. The data were normalized by log(TC+1) transformation. The number of authors was included as a fixed effect and the identity of the leading author of each article was treated as a random effect. The age of the paper (i.e. 2015 minus the year of publication) was also considered as a fixed effect. For a given author and a given topic, we evaluated the effect of COI on study outcome, by a generalized linear mixed model approach, with the glmer function of R (library lme4). The topic of the article and COI were considered as fixed effects and the identity of the leading author was treated as a random effect. The outcome of the study was considered as a binary variable with levels ‘favorable’ and ‘other’ (containing both ‘neutral’ and ‘unfavorable’ categories). We used the Akaike information criterion (AIC) [6] to select the best model.