Coevolutionary Governance of Antibiotic and Pesticide Resistance

Human cultures coevolve with human environments through ecoevolutionary dynamics.Increasing biocide resistance is a result of human–environment coevolution (HEC).Coevolutionary governance (CG) is informed by and proactively shapes HEC.Three CG priorities are identified with the aim of limiting biocide resistance. Development of new biocides has dominated human responses to evolution of antibiotic and pesticide resistance. Increasing and uniform biocide use, the spread of resistance genes, and the lack of new classes of compounds indicate the importance of navigating toward more sustainable coevolutionary dynamics between human culture and species that evolve resistance. To inform this challenge, we introduce the concept of coevolutionary governance and propose three priorities for its implementation: (i) new norms and mental models for lowering use, (ii) diversifying practices to reduce directional selection, and (iii) investment in collective action institutions to govern connectivity. We highlight the availability of solutions that facilitate broader sustainable development, which for antibiotic resistance include improved sanitation and hygiene, strong health systems, and decreased meat consumption. Development of new biocides has dominated human responses to evolution of antibiotic and pesticide resistance. Increasing and uniform biocide use, the spread of resistance genes, and the lack of new classes of compounds indicate the importance of navigating toward more sustainable coevolutionary dynamics between human culture and species that evolve resistance. To inform this challenge, we introduce the concept of coevolutionary governance and propose three priorities for its implementation: (i) new norms and mental models for lowering use, (ii) diversifying practices to reduce directional selection, and (iii) investment in collective action institutions to govern connectivity. We highlight the availability of solutions that facilitate broader sustainable development, which for antibiotic resistance include improved sanitation and hygiene, strong health systems, and decreased meat consumption. Humans' role as the strongest evolutionary force on Earth [1.Palumbi S.R. Humans as the world's greatest evolutionary force.Science. 2001; 293: 1786-1790Crossref PubMed Scopus (906) Google Scholar] results in widespread ecoevolutionary environmental change [2.Hendry A.P. Eco-evolutionary Dynamics. 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The term 'coevolution' was originally applied to studies of interdependent Darwinian evolution of pairs, groups, or communities of species [4.Søgaard Jørgensen P. et al.Evolution in the Anthropocene: informing governance and policy.Annu. Rev. Ecol. Evol. Syst. 2019; 50: 527-546Crossref Scopus (19) Google Scholar,12.Ehrlich P.R. Raven P.H. Butterflies and plants: a study in coevolution.Evolution (N. Y). 1964; 18: 586Crossref Google Scholar,13.Vermeij G.J. The evolutionary interaction among species: selection, escalation, and coevolution.Annu. Rev. Ecol. Evol. Syst. 1994; 25: 219-236Crossref Scopus (275) Google Scholar], but with the advent of theory for cultural evolution, the use of the term has been expanded to studies of how culture and genes coevolve within a species [8.Creanza N. et al.Cultural evolutionary theory: How culture evolves and why it matters.Proc. Natl. Acad. Sci. U. S. A. 2017; 114: 7782-7789Crossref PubMed Scopus (145) Google Scholar,14.Feldman M.W. Laland K.N. 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The trajectory of human–environment coevolution is not predetermined but is path-dependent and can proceed along several trajectories, depending on how and whether it is governed by humans. However, coevolution is poorly integrated into current governance theories for studying how societies, at all levels, steer themselves toward desirable ends. To provide a venue for such integration, we introduce the concept of 'coevolutionary governance,' which is the explicit governance of human–environment coevolution [4.Søgaard Jørgensen P. et al.Evolution in the Anthropocene: informing governance and policy.Annu. Rev. Ecol. Evol. Syst. 2019; 50: 527-546Crossref Scopus (19) Google Scholar]. Coevolutionary governance is related to but distinct from adaptive [16.Folke C. et al.Adaptive governance of social-ecological systems.Annu. Rev. Environ. Resour. 2005; 30: 441-473Crossref Scopus (3325) Google Scholar] and other forms of anticipatory governance [17.Boyd E. et al.Anticipatory governance for social-ecological resilience.Ambio. 2015; 44: 149-161Crossref Scopus (108) Google Scholar] in that it recognises to a larger extent, anticipates, and explicitly analyses these interdependent ecoevolutionary dynamics in its attempt to guide human societies toward identified goals [4.Søgaard Jørgensen P. et al.Evolution in the Anthropocene: informing governance and policy.Annu. Rev. Ecol. Evol. Syst. 2019; 50: 527-546Crossref Scopus (19) Google Scholar]. We highlight the value and insights of coevolutionary governance through two classical examples of human–environment coevolution: that of human antibiotic and pesticide use and the evolution of resistance to these compounds. In this paper, we refer to these compounds collectively as 'biocides.' Modern health systems and production of food, fuel, and fibre are reliant on biocides for controlling unwanted microorganisms, arthropods, and plants with which human societies have coevolved [5.Carroll S.P. et al.Applying evolutionary biology to address global challenges.Science. 2014; 346: 1245993Crossref PubMed Scopus (170) Google Scholar,10.Folke C. et al.Social-ecological resilience and biosphere-based sustainability science.Ecol. Soc. 2016; 21: 41Crossref Scopus (491) Google Scholar]. However, biocide resistance is an increasing risk, with multiple resistance to antibiotics, insecticides, and herbicides on the rise [5.Carroll S.P. et al.Applying evolutionary biology to address global challenges.Science. 2014; 346: 1245993Crossref PubMed Scopus (170) Google Scholar,18.Review on AMR Tackling drug-resistant infections globally - final report and recommendations.https://amr-review.org/sites/default/files/160518_Final%20paper_with%20cover.pdfDate: 2016Google Scholar]. Antibiotic resistance is associated with hundreds of thousands of deaths per year [19.Laxminarayan R. et al.Access to effective antimicrobials: a worldwide challenge.Lancet. 2016; 387: 168-175Abstract Full Text Full Text PDF PubMed Scopus (667) Google Scholar], and insecticide and herbicide resistance is a potential threat to food, fuel, and fibre security that also entails economic losses for farmers and health risks from exposure to increasing pesticide use [5.Carroll S.P. et al.Applying evolutionary biology to address global challenges.Science. 2014; 346: 1245993Crossref PubMed Scopus (170) Google Scholar,20.National Academies of Sciences, Engineering, and Medicine, Committee on Genetically Engineered Crops Genetically Engineered Crops: Experiences and Prospects. The Natonal Academies Press, 2016Google Scholar,21.Carrière Y. et al.Governing evolution: a socioecological comparison of resistance management for insecticidal transgenic Bt crops among four countries.Ambio. 2020; 49: 1-16Crossref PubMed Scopus (41) Google Scholar]. Not only are levels of resistance to a much wider array of compounds now much higher, but for both antibiotics and pesticides, there are declining prospects for developing more conventional compounds in the next decades [22.Living with Resistance project Antibiotic and pesticide susceptibility and the Anthropocene operating space.Nat. Sustain. 2018; 1: 632-641Crossref Scopus (55) Google Scholar]. Simultaneously, the next decade will be critical for meeting a set of interconnected global environmental and societal challenges captured in part by the 17 Sustainable Development Goals (SDGs; https://sustainabledevelopment.un.org/sdgs) put forth by the United Nations [5.Carroll S.P. et al.Applying evolutionary biology to address global challenges.Science. 2014; 346: 1245993Crossref PubMed Scopus (170) Google Scholar]. Rising resistance levels are evolutionary consequences of widespread practices employed to control pests and pathogens [1.Palumbi S.R. Humans as the world's greatest evolutionary force.Science. 2001; 293: 1786-1790Crossref PubMed Scopus (906) Google Scholar,5.Carroll S.P. et al.Applying evolutionary biology to address global challenges.Science. 2014; 346: 1245993Crossref PubMed Scopus (170) Google Scholar,8.Creanza N. et al.Cultural evolutionary theory: How culture evolves and why it matters.Proc. Natl. Acad. Sci. U. S. A. 2017; 114: 7782-7789Crossref PubMed Scopus (145) Google Scholar,22.Living with Resistance project Antibiotic and pesticide susceptibility and the Anthropocene operating space.Nat. Sustain. 2018; 1: 632-641Crossref Scopus (55) Google Scholar] (Figure 1), and resistance is therefore unlikely to be solved through quick fixes. Rather, it represents the dual challenge of governing coevolution between human culture and species targeted for control with strategies that cofacilitate broader goals of sustainable development [5.Carroll S.P. et al.Applying evolutionary biology to address global challenges.Science. 2014; 346: 1245993Crossref PubMed Scopus (170) Google Scholar,8.Creanza N. et al.Cultural evolutionary theory: How culture evolves and why it matters.Proc. Natl. Acad. Sci. U. S. A. 2017; 114: 7782-7789Crossref PubMed Scopus (145) Google Scholar,10.Folke C. et al.Social-ecological resilience and biosphere-based sustainability science.Ecol. Soc. 2016; 21: 41Crossref Scopus (491) Google Scholar,23.Jørgensen P.S. et al.Use antimicrobials wisely.Nature. 2016; 537: 159-161Crossref PubMed Scopus (36) Google Scholar]. After reviewing the emerging global dynamics of biocide use and resistance, we identify priorities for coevolutionary governance of biocide resistance and then focus on the challenges of promoting them in the context of the SDGs. We believe that coevolutionary governance has the potential to help promote successful transformations to sustainability in the Anthropocene biosphere by, for example, stimulating the evolution of norms and technology for sustainability. The global dynamics of resistance evolution can be characterised by the scale, intensity, and composition of biocide use, as well as the spatial extent of resistance gene exchange. Over the past 30 years, antibiotics, insecticides, and herbicides have undergone major changes in these four aspects and present both unique and shared governance challenges (Figure 2). For all three biocides, scale of use – indicating global selection for resistance – has increased markedly since monitoring began (Figure 2A,D,G). Only conventional insecticide use has started to decline as transgenic crops producing the insecticidal Bacillus thuringiensis proteins (Bt crops) replace conventional insecticides and as integrated pest management (IPM) is implemented [20.National Academies of Sciences, Engineering, and Medicine, Committee on Genetically Engineered Crops Genetically Engineered Crops: Experiences and Prospects. The Natonal Academies Press, 2016Google Scholar,24.Birch A.N.E. et al.How agro-ecological research helps to address food security issues under new IPM and pesticide reduction policies for global crop production systems.J. Exp. Bot. 2011; 62: 3251-3261Crossref PubMed Scopus (145) Google Scholar]. Global trends in biocide use intensity imply changes in local selection for resistance and are highly divergent between the three types of biocides. Human antibiotic use (monitored mainly via pharmaceutical sales) has increased by 36% since 2000 [25.Klein E.Y. et al.Global increase and geographic convergence in antibiotic consumption between 2000 and 2015.Proc. Natl. Acad. Sci. U. S. A. 2018; 115: E3463-E3470Crossref PubMed Scopus (1400) Google Scholar] (Figure 2B). Although similar global scale monitoring is lacking in important high-use environments such as communities and hospitals as well as animal farming, available regional data show that antibiotic use for animals varies widely among countries [26.Van Boeckel T.P. et al.Reducing antimicrobial use in food animals.Science. 2017; 357: 1350-1352Crossref PubMed Scopus (290) Google Scholar]. Conventional insecticide sales per agricultural area have dropped more than 10% over the past 5 years and are now below levels from the 1990s (Figure 2H). In contrast, herbicide sales per area have increased by 70% (Figure 2E). These diverging trends are in part explained by adoption of transgenic crops: Insecticidal Bt crops helped reduce use of conventional insecticides [20.National Academies of Sciences, Engineering, and Medicine, Committee on Genetically Engineered Crops Genetically Engineered Crops: Experiences and Prospects. The Natonal Academies Press, 2016Google Scholar], whereas glyphosate-resistant crops encouraged a 15-fold increase in the use of glyphosate, driving the herbicide trend [27.Benbrook C.M. Trends in glyphosate herbicide use in the United States and globally.Environ. Sci. Eur. 2016; 283Crossref PubMed Scopus (945) Google Scholar] (Figure 2D,F,I). Biocide use can become uniform through widespread adoption of successful compounds, but the large area across which selection occurs also makes such biocides vulnerable to resistance. The adoption of transgenic crops has homogenised selection pressures through increasing uniformity of pesticide use and of pest management in general. Today transgenic crops make up more than 30% (glyphosate-resistant crops) and 15% (Bt crops) of the planted area of certain crops, such as corn, cotton, and soybean, worldwide (Figure 2F,I) and more than 90% in some of the largest-producing countries [28.International Service for the Acquisition of Agri-biotech Applications (ISAAA) Global Status of Commercialized Biotech/GM Crops: 2016. ISAAA, 2016Google Scholar]. Similarly, as low- and middle-income countries (LMICs) have seen economic growth, their use of antibiotics has increased dramatically, leading to a global convergence in antibiotic use [25.Klein E.Y. et al.Global increase and geographic convergence in antibiotic consumption between 2000 and 2015.Proc. Natl. Acad. Sci. U. S. A. 2018; 115: E3463-E3470Crossref PubMed Scopus (1400) Google Scholar]. Resistance can spread rapidly in highly connected systems. Historical efforts to govern antibiotic resistance have, for good reasons, largely focused on managing local and regional use and less on governing international spread. However, intercontinental spread of antibiotic resistance is increasingly well documented for some of the most worrying resistance genes in gram-negative pathogens, which are reported as endemic in a growing set of countries (Figure 2C) [22.Living with Resistance project Antibiotic and pesticide susceptibility and the Anthropocene operating space.Nat. Sustain. 2018; 1: 632-641Crossref Scopus (55) Google Scholar]. Although there are still few reports of intercontinental spread of insecticide and herbicide resistance, common exchange of plant and insect pests among continents similarly imperils pesticide susceptibility (see [22.Living with Resistance project Antibiotic and pesticide susceptibility and the Anthropocene operating space.Nat. Sustain. 2018; 1: 632-641Crossref Scopus (55) Google Scholar] for examples). Priorities for governing coevolution can be derived from analysing the structure of selection and connectivity in human–environment systems. Here we focus on the overarching challenge of shifting away from the escalating coevolutionary dynamics of alternating increases in biocide use and biocide resistance. We propose three priorities for shifting cultural evolution toward achieving that goal (Figure 1B). The first is to promote cultural evolution of mental models and social norms that reduce unnecessary biocide use. The second is to diversify practices to reduce directional selection on the basis of systematic evaluation of new technology as well as principles underlying past practices. The third priority is promoting collective action to govern connectivity from the local to the global scale, which will help reduce the spread of resistance. A range of case studies illustrate the implementation of these priorities for biocide resistance in the context of production systems and health systems (Figure S1 in the supplemental information online). Mental models and social norms play an important role in determining which solutions are applied to a problem [29.Fehr E. Fischbacher U. Social norms and human cooperation.Trends Cogn. Sci. 2004; 8: 185-190Abstract Full Text Full Text PDF PubMed Scopus (861) Google Scholar,30.Nyborg K. et al.Social norms as solutions.Science. 2016; 354: 42-43Crossref PubMed Scopus (341) Google Scholar] and can become engrained as part of emergent world views or ideologies [31.Dentzman K. Jussaume R. The ideology of U.S. agriculture: how are integrated management approaches envisioned?.Soc. Nat. Resour. 2017; 30: 1311-1327Crossref Scopus (11) Google Scholar]. Norms are embedded in cultural and historical contexts, underpin legal systems of action, can evolve with changing conditions, and may arise around novel opportunities such as those afforded by new technologies. The multigenerational state shifts in practice brought about by industrially produced biocides and transgenic crops can make agricultural communities and broader society more likely to assume that new pesticide technologies will continue to replace current ones, should widespread resistance become a problem [32.Dentzman K. et al.Techno-optimism as a barrier to overcoming herbicide resistance: comparing farmer perceptions of the future potential of herbicides.J. Rural. Stud. 2016; 48: 22-32Crossref Scopus (33) Google Scholar]. The importance of this change in perception is supported by modelling showing that the time horizon of farmers is important for how likely they are to implement resistance management strategies [33.Frisvold G.B. et al.Positive and normative modeling for Palmer amaranth control and herbicide resistance management.Pest Manag. 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Evaluating opportunities for integration of new as well as old technologies and practices is a priority for meeting the challenge of systematic diversification. Although focus is often on new technological opportunities, the advances of modern medicine and agriculture can sometimes lead us to forget the practices of the past that, in combination with new technological capabilities and scientific insights, can help build critical resilience [10.Folke C. et al.Social-ecological resilience and biosphere-based sustainability science.Ecol. Soc. 2016; 21: 41Crossref Scopus (491) Google Scholar]. Signs of systematic prioritisation of diversity are emerging. The diversity provided by some experienced-based practices in agriculture was adopted under the name of IPM in the middle of the 20th century (Figure S1A in the supplemental information online). IPM can help reduce pesticide use (Figure S1A1 in the supplemental information online) and is often mandated in industrialised agriculture to reduce resistance as well as pesticide health risks [24.Birch A.N.E. et al.How agro-ecological research helps to address food security issues under new IPM and pesticide reduction policies for global crop production systems.J. Exp. Bot. 2011; 62: 3251-3261Crossref PubMed Scopus (145) Google Scholar] (Figure S1A5 in the supplemental information online). Especially for transgenic Bt crops but also for other insecticides, the old tradition of planting refuges where insecticides are not used has been key to slowing resistance evolution [21.Carrière Y. et al.Governing evolution: a socioecological comparison of resistance management for insecticidal transgenic Bt crops among four countries.Ambio. 2020; 49: 1-16Crossref PubMed Scopus (41) Google Scholar]. Likewise, in human health, recent events associated with antibiotic use have necessitated re-evaluating established practices. For example, the origin of the important antimalarial drug artemisinin in Chinese traditional medicine demonstrates the value of historical uses for expanding the repertoire of current medicines [37.Klayman D.L. Qinghaosu (artemisinin): an antimalarial drug from China.Science. 1985; 228: 1049-1055Crossref PubMed Scopus (2040) Google Scholar]. More broadly, our rapidly developing knowledge and technological expertise give reason for reconsidering opportunities for mastering practices beyond pharmacotherapy, practices that once were considered unsafe and undesirable. A rapidly shifting perspective in Western medicine is in the understanding of the multiple and complex roles of microorganisms in human–microbe interactions and the risk that antibiotics disrupt these symbioses [38.Søgaard Jørgensen P. et al.Changing antibiotic resistance: sustainability transformation to a pro-microbial planet.Curr. Opin. Environ. Sustain. 2017; 25: 66-76Crossref Scopus (16) Google Scholar]. Microorganisms are increasingly recognised as a contribution rather than principally as a threat to human health. Resistant coinfections of virulent new strains of Clostridioides difficile (formerly Clostridium difficile) in patients previously treated with antibiotics infect 450,000 and are involved in 30,000 deaths in the USA annually [39.Lessa F.C. et al.Burden of Clostridium difficile infection in the United States.N. Engl. J. Med. 2015; 372: 825-834Crossref PubMed Scopus (1696) Google Scholar]. These infections can be treated with faecal transplants that restore the gut microbiome to a healthy state (Figure S2 in the supplemental information online). Decisions about whether to use a pesticide or administer an antibiotic tend to be taken in consultation with crop consultants and fellow farmers or with doctors and family, respectively. There is increasing evidence that trust, participation, coordination, and regulation are important for effective resistance management. For instance, high levels of competition can undermine trust between doctors and patients and lead to antibiotic overprescribing in areas of the USA with high densities of health care providers [40.Klein E.Y. et al.Influence of provider and urgent care density across different socioeconomic strata on outpatient antibiotic prescribing in the USA.J. Antimicrob. Chemother. 2015; 70: 1580-1587Crossref PubMed Scopus (27) Google Scholar] (Figure S1B1 in the supplemental information online). Building trust through engagement and local monitoring may help overcome perceived barriers of collective action in the adoption of IPM (Figure S1A1–A4 in the supplemental information online). At the regional or national level, taxing particularly harmful pesticides can help lower their use and encourage IPM (Figure S1A5 in the supplemental information online). Similarly, the regulation and monitoring of non-Bt refuge requirements in the USA and Australia have been important for these countries' relative success compared with countries such as Brazil and India, where resistance has evolved rapidly [21.Carrière Y. et al.Governing evolution: a socioecological comparison of resistance management for insecticidal transgenic Bt crops among four countries.Ambio. 2020; 49: 1-16Crossref PubMed Scopus (41) Google Scholar]. The potential international significance of such decisions is illustrated by the recently documented intercontinental transfer of insect pests that could be carrying insecticide resistance genes [22.Living with Resistance project Antibiotic and pesticide susceptibility and the Anthropocene operating space.Nat. Sustain. 2018; 1: 632-641Crossref Scopus (55) Google Scholar]. As the global spread of resistance increasingly undermines national efforts, the need is growing for new types of international institutions (i.e., accepted formal or informal practices) [23.Jørgensen P.S. et al.Use antimicrobials wisely.Nature. 2016; 537: 159-161Crossref PubMed Scopus (36) Google Scholar]. In a time of consolidated seed production, there remain opportunities for such institutions to govern global dynamics by eliminating perverse incentives. For example, use of single-toxin and multitoxin Bt crops that share common toxins facilitates the evolution of resistance to multitoxins. Incentives for rapidly withdrawing single-toxin crops when multitoxin crops become available will help limit resistance [41.Tabashnik B.E. Carrière Y. Surge in insect resistance to transgenic crops and prospects for sustainability.Nat. Biotechnol. 2017; 35: 926-935Crossref PubMed Scopus (333) Google Scholar]. In the absence of international legally binding instruments that regulate biocide use and harmonised surveillance, targeted interventions are of high importance. Following the international spread of plasmid-borne colistin resistance, likely from China, a diverse array of organisations engaged with the Chinese government to lobby for restricting use of colistin as a growth promoter [42.Walsh T.R. Wu Y. China bans colistin as a feed additive for animals.Lancet Infect. Dis. 2016; 16: 1102-1103Abstract Full Text Full Text PDF PubMed Scopus (164) Google Scholar]. However, for successful reduction of antibiotic use and resistance, governments need to implement their national action plans fol