The Future of Pest- Resistant Crops:

Transcription

1 The Future of Pest- Resistant Crops: Lessons from the Fight Against Antibiotic Resistance David McAdams Professor of Economics Duke University October 27, 2014

2 A bit about myself 1. Professor of Economics at Duke University 2. Economic theorist specializing in game theory 3. NOT an expert in entomology, ag sciences, 4. Author of Game-Changer: Game Theory and the Art of Transforming Strategic Situations (2014) for which I researched antibiotic resistance from a game-theory perspective this has led to my interest in control-resistant pests

3 Plan for talk Intro: Strategic Ecosystem of Pest Management Is Resistance Inevitable? NO!! The Game Theory of Pest Control Reversing Resistance: Applications

4 What are Games? No Man is an Island, Entire of Itself - John Donne, 1624 A game is any situation with multiple interconnected decision-makers, i.e. in which my decision impacts you and/or your decision impacts me.

5 Strategic ecosystem of pest management PRIMARY GAMES pest and pest population dynamics crowding; mating; dispersal

6 Strategic ecosystem of pest management PRIMARY GAMES pest and pest pest and predator Sucking predators, such as wolf spiders, are better suited to eating rootworms than are chewing insects, such as beetles [because of rootworm larvae s sticky blood]. -- USDA entomologist Jonathan Lundgren predation

7 Strategic ecosystem of pest management PRIMARY GAMES pest and pest pest and predator farmer and pest crop management, e.g. crop rotation; crop cover; scouting; rescue treatment; soil insecticide; etc

8 Strategic ecosystem of pest management PRIMARY GAMES pest and pest pest and predator farmer and pest farmer and farmer pest dispersal

9 Strategic ecosystem of pest management PRIMARY GAMES pest and pest pest and predator farmer and pest farmer and farmer KEY THIRD-PARTIES technology suppliers

10 Strategic ecosystem of pest management PRIMARY GAMES pest and pest pest and predator farmer and pest farmer and farmer KEY THIRD-PARTIES technology suppliers academic scientists

11 Strategic ecosystem of pest management PRIMARY GAMES pest and pest pest and predator farmer and pest farmer and farmer KEY THIRD-PARTIES technology suppliers academic scientists regulators

12 Plan for talk Intro: Strategic Ecosystem of Pest Management Is Resistance Inevitable? NO!! HISTORY OF FAILURE in agriculture and medicine UNFOLDING FAILURE of crop refuges [Bt-resistant WCR] UNFOLDING SUCCESS in medicine [CRE] The Game Theory of Pest Control Reversing Resistance: Applications

13 Old View of Resistance: Highly Unlikely It is highly unlikely that weed resistance to glyphosate will become a problem as a result of the commercialization of glyphosate-tolerant soybeans Monsanto petition to USDA for nonregulated status for soybeans with a RoundupReady TM gene

14 New Reality: It s Already Upon Us! We asked farmers to share their experiences with glyphosate resistance on their farms and we re clearly seeing the problem intensify. Kent Fraser, vice-president of Stratus Agri-Marketing, January 2013 In 2012, 61.2 million acres (and nearly half of all U.S. farmers) were affected, with troubling growth rate of 25% in 2011 and 51% in 2012.

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16 New Reality: It s Already Upon Us! It s now a regional problem. Lance Meinke, UNL entomology professor in March 2014, on rise of western corn rootworm resistance to Cry3Bb1 and mcry3a toxins

17 New Reality: It s Already Upon Us! B. fusca [African maize stalk borer] resistance to Bt maize is now widespread in South Africa. Johnnie van den Berg, North-West University zoology professor, September 2012

18 New Reality: It s Already Upon Us! Field-evolved resistance [to Bt toxins] has been reported now for 5 of 13 major pest species examined, compared with resistant populations of only one pest species in Tabashnik, et al, Insect resistance to Bt crops: lessons from the first billion acres, Nature Biotechnology, June 2013

19 History of Drug Resistance -- TB 19 th century: TB causes 25% of all deaths in Europe 1943: streptomycin (1 st anti-tb drug) introduced 1948: resistance to streptomycin documented 1951: isoniazid (2 nd anti-tb drug) introduced 1955: resistance to isoniazid documented 1950s: pyrazinamide, cycloserine, ethionamide, and rifampin introduced 1970s-1990s: many outbreaks of multi-drug resistant TB 2012: totally resistant TB strains reported in India Similar concerns with staph, gonorrhea, E. coli, etc

20 Isoniazid, hailed six months ago as a wonder drug against tuberculosis, lost some of its glamour today. Dr. Ross L. McLean announced the abandonment of isoniazid alone as a TB treatment because of the appearance in TB patients of organisms resistant to the drug. Adirondack Daily Enterprise, May 22, 1953

21 How Does Resistance Arise So Quickly? Most antibiotics are based on / inspired by substances produced by microbes themselves Microbial warfare has raged for over a billion years Resistance to (say) streptomycin is lodged in the memory of TB bacteria, from when its ancestors battled Streptomyces forebears Mycobacterium tuberculosis (TB) Streptomyces sp.

22 How Does Resistance Arise So Quickly? Most pesticides are based on / inspired by substances produced by microbes themselves Microbes have been preying on insects for hundreds of millions of years Resistance to (say) Bacillus thuringiensis toxin is lodged in the memory of western corn rootworm. Western corn rootworm (WCR) Bacillus thuringiensis (Bt)

23 Is Resistance Inevitable? Only a matter of time before pests develop resistance to an active ingredient used to control them report by gmo-safety.eu (German Federal Ministry of Education and Research)

24 2012 Some experts say we are moving back to the preantibiotic era. No. This WILL BE a post-antibiotic era. A post-antibiotic era means, in effect, an end to modern medicine as we know it. Things as common as strep throat or a child s scratched knee could once again kill. Margaret Chan, Director-General of the World Health Organization

25 Plan for talk Intro: Strategic Ecosystem of Pest Management Is Resistance Inevitable? NO!! HISTORY OF FAILURE in agriculture and medicine UNFOLDING FAILURE of crop refuges [Bt-resistant WCR] UNFOLDING SUCCESS in medicine [CRE] The Game Theory of Pest Control Reversing Resistance: Applications

26 Regulation of GM Crops The EPA places a high value on the efficacy of Plant Incorporated Protectant crops. To ensure that these very safe methods of insect control continue to be available long into the future, they have to be managed properly to prevent insects from developing resistance to the natural proteins being expressed. - Environmental Protection Agency, January 2013

27 Refuge Requirements EPA requires a corn field that contains insectprotected (or Bt) crops with a single mode-ofaction against corn rootworm to be planted with 20% non-bt corn in corn-growing areas (the U.S. Corn Belt) and 50% non-bt in cottongrowing areas (the U.S. Cotton Belt). - Monsanto website, Learn More about Refuge Requirements: Protecting Against Insect Resistance

28 Illustration: Refuge Requirements source: Monsanto.com

29 The Theory Behind Refuges The concept underlying the refuge strategy: 1. Most of the rare resistant pests surviving on Bt crops will mate with the relatively abundant susceptible pests from nearby refuges of host plants without Bt toxins 2. If inheritance of resistance is recessive, the progeny from such matings will die on Bt crops, substantially delaying evolution of resistance. Tabashnik, et al, Nature Biotechnology, 2013

30 Key Assumptions: Refuge Theory 1. Random Mating [essential] when rare, resistant pests rarely mate w/ each other 2. High Dose [essential] Bt toxin equally lethal to heterozygous progeny of resistant-susceptible pairs and to susceptible pests 3. Fitness Costs of Resistance [optional] resistant and heterozygous pests are at reproductive disadvantage even in the refuge crop

31 Gene-Selection Interpretation Consider the reproductive success of an individual gene ( R ) implicated in Bt-resistance Bt-resistance genetics are not well understood and multiple genes are likely involved This gene will spread if, on average, pests that carry it outperform those that don t. R-R: resistant pest assume x2 advantage S-S: susceptible pest R-S: heterozygous pest

32 Why Random Mating is Essential If R-R pests are likely to mate with each other, resistance will grow explosively R gene enjoys multiple generations in a resistant host sustained x2 resistance advantage

33 Why Random Mating is Essential With random mating, rare R gene transitions (and remains for a long time) in heterozygote R gene enjoys transient x2 resistance advantage and then sustained heterozygote (dis)advantage

34 Why Fitness Cost is Helpful If heterozygous pests have a survival / fecundity disadvantage [on Bt and/or refuge crop], R gene will dwindle while stuck in R-S hosts resistance can actually be eradicated

35 Why High Dose is Essential If heterozygous pests enjoy any survival / fecundity advantage, R gene will again have sustained advantage and grow explosively

36 Why High Dose is Essential If heterozygous pests enjoy any survival / fecundity advantage, R gene will again have sustained advantage and grow explosively until eventually heterozygous matings produce resistant progeny that grow even more explosively

37 Is Random Mating a Valid Assumption? The random-mating assumption can fail in practice, for three sorts of reasons: 1. separation in space 2. separation in time 3. within-type preferential mating

38 Random-Mating Failure(?) African Maize Stalk Borer The females start calling [emitting pheromones] and mating starts within a few hours after moth emergence A single spermatophore is generally sufficient to fertilize all eggs of a female Calatayud, et al, Ecology of the African Maize Stalk Borer, Insects, 2014 Given the role of smell in finding a mate, and the speed of mating, could emergent resistant moths in a field of Bt corn be likely to mate with each other? Random-mating could be very wrong.

39 Random-Mating Failure: WCR Resistant lines emerged approximately 2 3 days earlier than control lines when reared on both MON863 [Bt corn] and the isoline [refuge corn], indicating that selection for Bt resistance resulted in a general increase in the rate of larval development. Oswald, et al, Assessment of fitness costs in Cry3Bb1-resistant and susceptible western corn rootworm, Journal of Applied Entomology, 2012

40 Random-Mating Failure: WCR Western corn rootworm beetles do not always conform to assumptions about random mating and individual movement limited male mating capacity, premating male and female movement patterns and delayed adult emergence from CRW-active maize all may contribute to unexpected or undesirable patterns of WCR reproductive behavior. Spencer, et al, Isolated females and limited males, Entomologia Experimentalis et Applicata, 2013

41 High-Dose Validity: Diamondback Moth = susceptible = resistant = half-breed Fig 1 of Tabashnik, et al, Inheritance of Resistance to Bacillus thuringiensis in Diamondback Moth, 1992

42 High-Dose Failure: WCR None of the currently commercialized Bt toxins targeting western corn rootworm achieve a high dose. Petzold-Maxwell, et al, Effect of Bt Maize and Soil Insecticides on Yield, Injury, and Rootworm Survival, Journal of Economic Entomology, 2013

43 High-Dose Failure: WCR Current Bt maize products targeting the western corn rootworm fail to meet the high-dose condition of imposing 99.99% mortality. Petzold-Maxwell et al, Applying an Integrated Refuge to Manage Western Corn Rootworm, Journal of Economic Entomology, 2013

44 High-Dose Failure: African Maize Stalk Borer Results show that resistance of B. fusca to Bt corn is dominant, which refutes the hypothesis of recessive inheritance, [rendering futile the standard] high dose/refuge strategy Campagne et al, Dominant Inheritance of Field- Evolved Resistance to Bt Corn in Busseola fusca, PLOS ONE, July 2013

45 High-Dose Failure: African Maize Stalk Borer Table 1 of Campagne, et al, Dominant Inheritance of Field- Evolved Resistance to Bt Corn in Busseola Fusca, PLOS One, 2013

46 Fitness Cost Failure: WCR Analysis of performance on the isoline maize demonstrated no fitness costs associated with Bt resistance. In addition, resistant lines reared on Bt maize displayed higher fecundity than those reared on the isoline Oswald, et al, Assessment of fitness costs in Cry3Bb1-resistant and susceptible western corn rootworm, Journal of Applied Entomology, 2012

47 Recap: Failure of Refuge Assumptions 1. Random Mating [essential] FAIL resistant WCR emerge days earlier and, with fast mating after emergence, will more-than-randomly mate with one another 2. High Dose [essential] FAIL Bt toxin not 99.99% lethal even on susceptible WCR; heterozygotes likely have survival advantage 3. Fitness Costs of Resistance [optional] FAIL resistant (and perhaps heterozygous) pests actually appear to be at an advantage on the refuge crop

48 WCR Refuge Failure: An Unfolding Story Since the first documented case of Btresistant [Western corn] rootworm in 2009 in Iowa, confirmed and suspected cases have surfaced throughout the Corn Belt. Emily Unglesbee in Rootworm Realities, DTN Progressive Farmer, April 2014

49 Survival of western corn rootworm larvae on (A) Cry3Bb1 maize, (B) mcry3a maize, and (C) Cry34/35Ab1 maize. Gassmann A J et al. PNAS 2014;111: by National Academy of Sciences

50 Additional Protection Doesn t Change the Logic of Refuge Failure New seed technologies that have multiple Bt genes provide additional protection and effectively reduce the likelihood of insect resistance developing. This enabled the EPA to reduce the size of structured refuge from 20% to 5% in corn-growing areas. - Monsanto website, Learn More about Refuge Requirements: Protecting Against Insect Resistance

51 What is Best Refuge Size? Refuge theory is mostly silent on how large refuges ought to be refuge needs (only) be big enough for random mating to be a valid assumption Economics of long-term IPM for western corn rootworm by Onstad et al, Crop Protection, 2014 offers an answer of sorts simulates 15-year economic impact of various practices (e.g. refuge size, refuge rotation, Bt traits), assuming all farmers follow recommended policy

52 What is Best Refuge Size? A selection of findings, Onstad et al (2014): for pyramided Bt corn, block refuges planted in the same location with a field year after year gave the greatest overall profit for the grower if growers relocate their block refuge annually, then a 5% blended refuge gave the greatest return for single-trait Bt corn, 10-20% blended refuges [were better than] block refuges from 5% to 50%

53 Will Farmers Comply? Unfortunately, knowing what practices are best for farmers is not enough, as farmers will tend to choose what is best for them individually, as opposed to what is best for everyone collectively inadequate refuge protection may be a dominant strategy for each farmer this game among farmers is an example of the Tragedy of the Commons

54 Preventing Resistance: Tragedy of the Commons Overgraze Don t Overgraze 2, 2 4, 1 Don t 1, 4 3, 3 In this so-called payoff matrix, 4 / 3 / 2 / 1 represents a player s best / second-best / third-best / worst outcome

55 Individual vs Collective Good One farmer could avoid planting Bt corn or avoid planting a refuge and likely get higher profit if all other farmers plant required refuge and plant expected amount of Bt corn.. Dr. David Onstad, DuPont Agricultural Biotechnology, private correspondence, October 2014

56 Preventing Resistance: Tragedy of the Refuge(?) Rotate Fixed Rotate Refuge 2, 2 4, 1 Fixed Refuge 1, 4 3, 3 In this so-called payoff matrix, 4 / 3 / 2 / 1 represents a player s best / second-best / third-best / worst outcome

57 Plan for talk Intro: Strategic Ecosystem of Pest Management Is Resistance Inevitable? NO!! HISTORY OF FAILURE in agriculture and medicine UNFOLDING FAILURE of crop refuges [Bt-resistant WCR] UNFOLDING SUCCESS in medicine [CRE] The Game Theory of Pest Control Reversing Resistance: Applications

58 The Rise of Nightmare Bacteria CRE are a triple threat, according to CDC director Thomas Frieden: resistant to all or nearly all antibiotics deadly, with mortality rate up to 50% can spread resistance to other bacteria

59 CRE: Impossible to completely contain The challenge is to keep these bacteria from reaching the general population. CRE = Carbapenem-resistant Enterobacteriaceae - Dr. Nancy Snyderman, NBC News, 2013 Carbapenem resistance testing is imperfect. So, some CRE will always escape any attempt at containment.

60 and yet WE RE WINNING!! A country-wide CRE outbreak in Israel has been successfully controlled, and CRE has been eradicated from numerous health-care facilities See Containment of a Country-wide Outbreak of Carbapenem-resistant Klebsiella pneumonia by Schwaber, et al, Clinical Infectious Diseases, 2011.

61 and yet WE RE WINNING!! A country-wide CRE outbreak in Israel has been successfully controlled, and CRE has been eradicated from numerous health-care facilities See Containment of a Country-wide Outbreak of Carbapenem-resistant Klebsiella pneumonia by Schwaber, et al, Clinical Infectious Diseases, Hospitals new approach, called Detect and Protect, is not only working but predicted by theory to reverse even prevalent resistance i.e. success doesn t hinge on resistance being rare

62 Why Does Drug Resistance Arise? Drug-resistant and drug-susceptible strains of the same disease are in competition. Drug treatment favors resistant strains IF all strains treated the same [ equal treatment ] RESISTANT DRUG TREATMENT RESISTANT SUSCEPTIBLE SUSCEPTIBLE

63 Game-Changer: Resistance Diagnosis If doctors could identify which strains are drugresistant, treatment could be tailored to put resistant strains at a disadvantage, e.g. ISOLATION RESISTANT RESISTANT DRUG TREATMENT SUSCEPTIBLE SUSCEPTIBLE

64 Detect and Protect (CDC 2012) In June 2012, CDC published guidance on a proven Detect and Protect strategy* that hospitals can use to eradicate CRE: 1. MONITOR to identify cases in your hospital; 2. ISOLATE identified CRE sufferers; and 3. SCREEN patients who are epidemiologically linked to any identified CRE sufferer (e.g. by shared machine) * Guidance for Control of Carbapenem-resistant Enterobacteriaceae (CRE): 2012 CRE Toolkit, CDC Division of Healthcare Quality Promotion, June 2012.

65 Detect and Protect (CDC 2012) 1 st 2 nd 1 st transmission prevented by isolation RESISTANT 2 nd transmission prevented by testing epidemiological links SUSCEPTIBLE 1 st 2 nd susceptible strain takes over general population DESPITE resistant strain s fitness advantage in the hospital environment

66 Plan for talk Intro: Strategic Ecosystem of Pest Management Is Resistance Inevitable? NO!! The Game Theory of Pest Control the games of life burden vs resistance diagnosis and targeted treatment Reversing Resistance: Applications

67 The Games of Life: Microbe A microbe s reproductive success can be disrupted at any phase of its life cycle STAGE 1: HOST INFECTION Examples of disruptive treatment: healthful lifestyle vaccine against flu

68 The Games of Life: Microbe A microbe s reproductive success can be disrupted at any phase of its life cycle STAGE 2: TRANSMISSION BEFORE HOST SEEKS MEDICAL ATTENTION Examples of disruptive treatment: wash hands contact tracing against Ebola

69 The Games of Life: Microbe A microbe s reproductive success can be disrupted at any phase of its life cycle STAGE 3: TRANSMISSION AFTER HOST SEEKS MEDICAL ATTENTION Examples of disruptive treatment: broad-spectrum antibiotics quarantine against Ebola

70 The Games of Life: Pest Likewise, a pest s reproductive success can be disrupted at any phase of its life cycle STAGE 1: HOST FINDING Example of disruptive treatment: crop rotation

71 The Games of Life: Pest Likewise, a pest s reproductive success can be disrupted at any phase of its life cycle STAGE 2: LARVAL GROWTH Examples of disruptive treatment: fostering predators soil / seed insecticide Bt-corn

72 The Games of Life: Pest Likewise, a pest s reproductive success can be disrupted at any phase of its life cycle STAGE 3: MATING Examples of disruptive treatment: staggered planting

73 The Games of Life: Pest Likewise, a pest s reproductive success can be disrupted at any phase of its life cycle STAGE 4: DISPERSAL / EGG-LAYING Examples of disruptive treatment: trap crops

74 Plan for talk Intro: Strategic Ecosystem of Pest Management Is Resistance Inevitable? NO!! The Game Theory of Pest Control the games of life burden vs resistance diagnosis and targeted treatment Reversing Resistance: Applications

75 Burden vs Resistance: Sisyphean Pest Control Every new treatment option allows farmers to get the ball rolling and reduce pest burden but, ultimately, those most resistant to the new treatment survive then thrive and we are left to start all over again with fewer treatment options than before.

76 Burden vs Resistance: Tragedy of the Commons Sadly, understanding the problem is not enough to solve it, as farmers have incentive to use it [as much as possible!] until we lose it inappropriate, overly-broad use is dominant strategy for each farmer this game among farmers is an example of the Tragedy of the Commons

77 Burden vs Resistance: Tragedy of the Commons Farmer #1 Use Other Farmers Use Treatment Preserved? Payoffs Selective Selective Yes Good for all Broad Selective Yes Best for #1; Good for others Broad Broad No Bad for all Selective Broad No Worst for #1; Bad for others Whether or not others take steps to combat resistance, Farmer #1 would prefer not to do so.

78 Burden vs Resistance: Tragedy of the Commons Overgraze Don t Overgraze 2, 2 4, 1 Don t 1, 4 3, 3 In this so-called payoff matrix, 4 / 3 / 2 / 1 represents a player s best / second-best / third-best / worst outcome

79 Burden vs Resistance: Tragedy of the Commons Broad Selective Broad Use 2, 2 4, 1 Selective 1, 4 3, 3 In this so-called payoff matrix, 4 / 3 / 2 / 1 represents a player s best / second-best / third-best / worst outcome

80 Burden vs Resistance: Sisyphean Pest Control Every new broadly-applied treatment option allows farmers to get the ball rolling and reduce pest burden... but, ultimately, those most resistant to the new treatment survive then thrive and we are left to start all over again with fewer treatment options than before.

81 A Loophole for Sisyphus This is the logic behind resistance s seemingly inevitable rise... BUT THERE S A LOOPHOLE IN THIS LOGIC!! as it assumes resistant pests are exposed to the same treatment as susceptible ones

82 Plan for talk Intro: Strategic Ecosystem of Pest Management Is Resistance Inevitable? NO!! The Game Theory of Microbe/Pest Control the games of life burden vs resistance diagnosis and targeted treatment Reversing Resistance: Applications

83 Targeted Treatment: Framework If resistance can be diagnosed either before or after treatment targeted steps can be taken to put resistant strains at a disadvantage PRE-TREATMENT DIAGNOSIS OF RESISTANCE POST-TREATMENT DIAGNOSIS OF RESISTANCE TREATMENT FOLLOW-UP TREATMENT

84 Targeted Treatment: Framework Treatment can be effectively targeted, to disadvantage resistant strains, in two ways: 1. pre-treatment diagnosis if doctor/farmer knows ahead of time that patient/crop is at risk of resistant disease/pest, an effective alternative treatment is prescribed PRE-TREATMENT DIAGNOSIS OF RESISTANCE POST-TREATMENT DIAGNOSIS OF RESISTANCE TREATMENT FOLLOW-UP TREATMENT

85 Targeted Treatment: Framework Treatment can be effectively targeted, to disadvantage resistant strains, in two ways: 1. pre-treatment diagnosis 2. post-treatment diagnosis if doctor/farmer discovers resistance, more intensive follow-up treatment is prescribed PRE-TREATMENT DIAGNOSIS OF RESISTANCE POST-TREATMENT DIAGNOSIS OF RESISTANCE TREATMENT FOLLOW-UP TREATMENT

86 Targeted Treatment: Framework Resistant strains will be at overall reproductive disadvantage as long as 1. pre-diagnosis is possible AND targeted alternative treatment is more effective against resistant strain than standard treatment is against susceptible OR DIAGNOSIS TREATMENT DIAGNOSIS TREATMENT

87 Targeted Treatment: Framework Resistant strains will be at overall reproductive disadvantage as long as 1. pre-diagnosis is possible AND targeted alternative treatment is more effective against resistant strain than standard treatment is against susceptible OR 2. post-diagnosis is possible AND targeted follow-up treatment is more costly to resistant strain than its benefit from resisting the initial treatment DIAGNOSIS TREATMENT DIAGNOSIS TREATMENT

88 Plan for talk Intro: Strategic Ecosystem of Pest Management Is Resistance Inevitable? NO!! The Game Theory of Microbe/Pest Control Reversing Resistance: Applications staph bacteria resistance to methicillin diagnostic game-changer WCR resistance to crop rotation WCR resistance to Bt-crops

89 Methicillin Resistance Methicillin-resistant Staphylococcus aureus (MRSA) is a bacteria that is resistant to many antibiotics. In medical facilities, MRSA causes lifethreatening bloodstream infections, pneumonia and surgical site infections. -- CDC website, 2014

90 Methicillin Resistance Medicine disregarded it. Antibiotics can t control it. MRSA drug-resistant staph may be the most frightening epidemic since AIDS. -- subtitle of Superbug by Maryn McKenna, 2010

91 MRSA: The Challenge [-] Pre-treatment diagnosis costly and timeconsuming [2-3 days + trained technician] initial treatment decision cannot wait [-] Alternative treatments [like vancomycin or isolation] not attractive option for typical patient, as long as most staph is susceptible to methicillin DIAGNOSIS TREATMENT DIAGNOSIS TREATMENT

92 MRSA: The Challenge [+] Post-treatment diagnosis and intensive follow-up treatment is possible but may be too little too late as post-treatment diagnostic delay gives MRSA a lengthened window in which to transmit itself to new hosts [worse still, if those new hosts are easiest to find in the hospital, MRSA gains by evolving into a more virulent form that induces hospitalization] DIAGNOSIS TREATMENT DIAGNOSIS TREATMENT

93 MRSA: Diagnostic Game-Changer In 2007, molecular diagnostic-maker Cepheid introduced a new test to (i) diagnose staph and (ii) diagnose staph resistance to methicillin: The GeneXpert System has taken the TAT of results from 2-3 days down to a few hours. Now we do not have to presumptively isolate patients. This has helped to reduce nursing labor, improve bed management and reduce isolation costs in the ICU. ICU Nurse DIAGNOSIS TREATMENT DIAGNOSIS TREATMENT

94 GeneXpert System [Cepheid] The GeneXpert System returns most test results in about an hour, including sample prep... With the GeneXpert technology, labs no longer need rows of equipment and extensively trained staff to access molecular testing. -- Cepheid s website, July 2013

95 2014 Many [are] resigned to the inevitability of antibiotic resistance. But there is hope. Recent advances in genetic testing have created new strategic options that hold the potential to reverse antibiotic resistance and, in doing so, to tame bacterial disease forever. David McAdams in Game-Changer

96 Plan for talk Intro: Strategic Ecosystem of Pest Management Is Resistance Inevitable? NO!! The Game Theory of Microbe/Pest Control Reversing Resistance: Applications staph bacteria resistance to methicillin WCR resistance to crop rotation treatment game-changer WCR resistance to Bt-crops

97 Crop Rotation as Treatment Crop rotation is an effective crop-management strategy against western corn rootworm one generation per year eggs deposited in soil, mostly near corn roots, and cannot move more than 10 to 20 inches Larvae die if they emerge into an unsuitable crop [WCR larvae thrive on corn and cucubits like pumpkin, melon ]

98 Crop-Rotation Resistance Corn rootworms have adapted in two ways to resist the effect of crop-rotation treatment: 1. extended diapause: larvae emerge from eggs after TWO years, not one [northern rootworm] 2. soybean egg-laying: if corn-soybean rotation, larvae emerge into newly-planted corn crop My focus here is on loss of maize-fidelity adaptation that leads to soybean egg-laying

99 Rotation Failure in Illinois

100 Rotation Failure in Illinois The population adapted to soybean spreads km per year, depending on the directions of the prevailing storms and winds. -- Onstad et al, Population Ecology, 1999

101 Rotation Resistance: The Challenge [-] Pre-treatment diagnosis appears infeasible some eggs are laid in soybean fields even by normal WCR hard to detect first rotationresistant pests to arrive from another area rotation-resistant beetles may multiply and disperse to still other areas before detection DIAGNOSIS TREATMENT DIAGNOSIS TREATMENT

102 Rotation Resistance: Treatment Game-Changer [+] Post-treatment diagnosis is straightforward as farmers observe damage to first-year corn DIAGNOSIS TREATMENT DIAGNOSIS TREATMENT

103 Rotation Resistance: Treatment Game-Changer [+] Post-treatment diagnosis is straightforward as farmers observe damage to first-year corn [+] Appropriate follow-up treatments are available one 3-year rotation of corn > soybean > other [with continuous corn refuge in years 3-4] one year of Bt corn monocrop DIAGNOSIS TREATMENT DIAGNOSIS TREATMENT

104 Idea: Corn > Soybean > Other(*) Rotation plus Corn Refuge Consider the following planting pattern, after discovering rotation resistance in year 1: in years 1-3, rotate corn > soybean > wheat(*) in year 4, return to corn > soybean rotation in years 3-4, plant continuous corn refuge (*) Corn > Soybean > Wheat/Red Clover is recommended 3-year sequence (in Wisconsin) in Crop Rotation with Cover Crops, USDA Sustainable Agriculture Research & Education Program

105 3-Year Rotation w/ Corn Refuge YEAR ONE damage discovered on first-year corn low-fidelity WCR are likeliest culprit! CORN SOYBEAN WHEAT

106 3-Year Rotation w/ Corn Refuge YEAR ONE damage discovered on first-year corn low-fidelity WCR are likeliest culprit! eggs likely laid in corn and soybean fields CORN SOYBEAN WHEAT

107 3-Year Rotation w/ Corn Refuge YEAR TWO emerging low-fidelity larvae all die wintering eggs are low-fidelity survivors [few] immigrants from distant fields [few] CORN SOYBEAN WHEAT

108 3-Year Rotation w/ Corn Refuge YEAR THREE 1 st -year-like crop damage WCR laying eggs include: low-fidelity survivors [few] Y2 immigrants [few] Y3 immigrants [more b/c corn is now planted] CORN SOYBEAN WHEAT

109 3-Year Rotation w/ Corn Refuge YEAR FOUR 2 nd -year-like damage [use insecticide this year] most larvae are from year-3 immigrants reboot local population CORN SOYBEAN WHEAT

110 3-Year Rotation w/ Corn Refuge YEAR FIVE emerging larvae (mostly laid near corn) mostly die those that survive are susceptible to rotation corn > soybean rotation effective once more!! CORN SOYBEAN WHEAT

111 Rotation Resistance: Treatment Game-Changer [+] Post-treatment diagnosis is straightforward as farmers observe damage to first-year corn [+] Appropriate follow-up treatments are available one 3-year rotation of corn > soybean > other plus continuous corn refuge in years 3-4 Bt corn [only works if local WCR still susceptible] DIAGNOSIS TREATMENT DIAGNOSIS TREATMENT

112 Idea: Bt-Corn Crop for One Year Consider the following planting pattern, after rotation-resistance is discovered in year 1: in year 2, monocrop Bt corn In year 3, resume corn > soybean rotation

113 Bt-Corn Reboot YEAR ONE damage discovered on first-year corn low-fidelity WCR are likeliest culprit! CORN SOYBEAN BT CORN

114 Bt-Corn Reboot YEAR ONE damage discovered on first-year corn low-fidelity WCR are likeliest culprit! eggs likely laid in corn and soybean fields CORN SOYBEAN BT CORN

115 Bt-Corn Reboot YEAR TWO Bt corn monocrop IF local WCR lack Btresistance, they are effectively controlled eggs laid by local survivors & immigrants CORN SOYBEAN BT CORN

116 Bt-Corn Reboot YEAR THREE IF local WCR lack Btresistance, emerging larvae mostly immigrant reboot of population corn > soybean rotation effective once more!! CORN SOYBEAN WHEAT

117 Plan for talk Intro: Strategic Ecosystem of Pest Management Is Resistance Inevitable? NO!! The Game Theory of Microbe/Pest Control Reversing Resistance: Applications staph bacteria resistance to methicillin WCR resistance to crop rotation WCR resistance to Bt-crops treatment game-changer diagnostic game-changer [more speculative]

118 WCR Bt-Resistance Since the first documented case of Btresistant [Western corn] rootworm in 2009 in Iowa, confirmed and suspected cases have surfaced throughout the Corn Belt. Emily Unglesbee in Rootworm Realities, DTN Progressive Farmer, April 2014

119 Bt-Toxin Resistance: The Challenge [-] Pre-treatment diagnosis appears infeasible not possible to detect Bt-resistant immigrants Bt-resistant beetles may multiply and disperse to still other areas before detection DIAGNOSIS TREATMENT DIAGNOSIS TREATMENT

120 Bt-Resistance: Treatment Game-Changer [+] Post-treatment diagnosis is straightforward as farmers observe damage to Bt-corn [+] Appropriate follow-up treatments are available corn > soybean rotation DIAGNOSIS TREATMENT DIAGNOSIS TREATMENT

121 Idea: Reboot by Rotating Soybean Consider the following planting pattern, after Btresistance is discovered in year 1: in year 2, plant soybean and non-bt corn [use soil insecticide on non-bt corn to limit damage] in year 3, rotate soybean and non-bt corn [do not treat with insecticide] in year 4, return to monocrop Bt corn

122 Reboot by Soybean Rotation YEAR ONE damage observed on Bt corn crop evidence of Bt-resistance CORN SOYBEAN BT CORN

123 Reboot by Soybean Rotation YEAR TWO given Y1 infestation, use pesticide in corn fields wintering eggs are mostly local [Bt-resistant] CORN SOYBEAN BT CORN

124 Reboot by Soybean Rotation YEAR THREE pests less numerous now wintering eggs now a mix of surviving locals [few] and immigrants [more] CORN SOYBEAN BT CORN

125 Reboot by Soybean Rotation YEAR FOUR population rebooted with immigrants return to Bt-corn P.S. This strategy doesn t work if immigrants are already Bt-resistant CORN SOYBEAN BT CORN

126 Plan for talk Intro: Strategic Ecosystem of Pest Management Is Resistance Inevitable? NO!! The Game Theory of Microbe/Pest Control Reversing Resistance: Applications staph bacteria resistance to methicillin WCR resistance to crop rotation WCR resistance to Bt-crops treatment game-changer diagnostic game-changer [more speculative]

127 Dispersal Forecasting The model predicts the spread of western corn rootworm infesting soybean based on the mean storm pattern and windsupported flight. -- Onstad et al, Population Ecology, 1999 Note: The focus of this paper is on spread of rotation-resistant WCR, but the methods could be adapted to model dispersal flows in the overall system... not just the spread of pioneers.

128 Using Dispersal Forecasts As a pre-treatment diagnostic, a forecast of dispersal risk e.g. you have 25% chance of resistant infestation could prompt: more careful scouting preemptive protective measures Such measures could help stop the spread of resistance in its tracks

129 Using Dispersal Forecasts As a pre-treatment diagnostic, a forecast of dispersal risk e.g. you have 25% chance of resistant infestation could prompt: more careful scouting preemptive protective measures Such measures could help stop the spread of resistance in its tracks BUT will farmers act on such early diagnostics? waiting until year 2 of an infestation may be more economical, though neighbors are harmed

130 Acting on WCR Intelligence: Tragedy of the Commons [Again] Wait Act Early Wait 2, 2 4, 1 Act Early 1, 4 3, 3 In this so-called payoff matrix, 4 / 3 / 2 / 1 represents a player s best / second-best / second-worst / worst outcome

131 Empowering Farmers to Avoid the Tragedy of the Commons The good news is that game theory offers several different ways to avoid commons tragedies: legal requirements [e.g. fishing catch-limits] my view: neither feasible nor desirable here

132 Empowering Farmers to Avoid the Tragedy of the Commons The good news is that game theory offers several different ways to avoid commons tragedies: legal requirements [e.g. fishing catch-limits] local collective governance [e.g. natural resources districts in water management] my view: interesting but probably not realistic P.S. Elinor Ostrom won 2009 Nobel prize for work documenting the effectiveness of this approach

133 Empowering Farmers to Avoid the Tragedy of the Commons The good news is that game theory offers several different ways to avoid commons tragedies: legal requirements [e.g. fishing catch-limits] local collective governance [e.g. natural resources districts in water management] incentives [e.g. bottle deposits for recycling] my view: most promising near-term approach incentives could be provided via existing channels, such as crop-insurance subsidies [incentive from gov t] and stewardship agreements [incentive from Bt seed provider]

134 Insurance Subsidies Already Influence Crop Selection On August 14, 2008, the USDA s Federal Crop Insurance Corporation Board of Directors approved reductions in crop insurance premiums for producers who elected to plant certain qualifying transgenic maize hybrids, including many Bt hybrids. - U. Illinois entomologist Michael Gray in Relevance of Traditional Integrated Pest Management Strategies for Commercial Corn Producers in a Transgenic Agroecosystem: A Bygone Era?, Journal of Agricultural and Food Chemistry, 2011

135 Insurance Subsidies Already Influence Crop Selection 19% [of surveyed farmers] indicated that this government program did influence their decision to use a Bt hybrid. - Michael Gray in Relevance of Traditional Integrated Pest Management Strategies A Bygone Era?, Journal of Agricultural and Food Chemistry, 2011 Insurance subsidies could (and arguably should) depend on farmers proactive steps to limit risk of resistance emerging much as installed fire alarms reduce home insurance costs.

136 An Incentives Issue: Who Watches the Watcher? To induce farmers to take proactive steps to halt / reverse Bt resistance, a third-party may be needed to monitor farmers actions [ watch ] and provide financial or other incentives [ pay ]. EPA or providers like Monsanto are natural candidates, given their desire to preserve Bt tech BUT EPA and Monsanto have their own incentives raising a host of new strategic issues to consider

137 Summary: Key Points (1/3) Is resistance inevitable? NO: with wisely-deployed diagnostics and targeted treatments, we can continually and permanently stamp out resistance wherever it rears its head BUT YES: if we adopt a universal (untargeted) treatment, we should always expect resistance to eventually arise

138 Summary: Key Points (2/3) Why is Bt-resistance becoming prevalent? farmers have widely adopted a flawed refuge strategy (promoted by EPA) that is essentially guaranteed NOT to preserve Bt-susceptibility I ve brainstormed some alternative strategies to illustrate the diagnostic + targeted treatment framework but we need to harness knowledge and creativity of farmers and other experts to identify workable solutions

139 Summary: Key Points (2/3) Why is Bt-resistance becoming prevalent? farmers have widely adopted a flawed refuge strategy (promoted by EPA) that is essentially guaranteed NOT to protect Bt-susceptibility farmers face a tragedy of the commons in which individual incentives conflict with the greater good any diagnostic game-changer [that helps farmers monitor resistant pest dispersal] will require cooperation

140 Summary: Key Points (3/3) What does the future hold for Bt crops? IF Bt monocropping becomes/remains universal, total resistance WILL eventually arise and our ability to control pests with Bt technology will be lost forever

141 Summary: Key Points (3/3) What does the future hold for Bt crops? IF Bt monocropping becomes/remains universal, total resistance WILL eventually arise and our ability to control pests with Bt technology will be lost forever BUT I ve also suggested how Bt technology can work in a complementary fashion to strengthen traditional integrated pest management e.g. targeted Bt treatment can help reverse rotationresistance

142 Final Word: Is Bt-Corn Worth Saving? In healthy agro-ecosystems, there is usually limited need for these types of pest control, and in most cases, that need can be met through breeding at much less expense Why should farmers be saddled with these unnecessary costs when cheaper technologies will work in the large majority of cases? In a sensible agriculture system, it is not clear that [Bt-Corn] is really needed, or worth the cost. - Doug Gurian-Sherman, Union of Concerned Scientists

143 Of Course!! Why Throw Out a Treatment Option?!? but What We Really Need is to Revive Supervised Control After WWII, entomologists such as Vernon Smith proposed the concept of supervised control chemical / biological treatments determined by active monitoring; no routine / automatic approach see e.g. The integration of chemical and biological control of the spotted alfalfa aphid: The integrated control concept, Smith et al, Hilgardia, 1959

144 Of Course!! but What We Really Need is to Revive Supervised Control After WWII, entomologists such as Vernon Smith proposed the concept of supervised control chemical / biological treatments determined by active monitoring, no routine / automatic approach see e.g. The integration of chemical and biological control of the spotted alfalfa aphid: The integrated control concept, Smith et al, Hilgardia, 1959 Widespread adoption of this integrated pest management (IPM) approach assured the continued effectiveness of synthetic insecticides.

145 Will Supervised Control Return in Time? That sensible agriculture system [IPM] doesn't exist anymore. It is possible to grow corn in a much lower input system than we do now [but] farmers are not just farmers anymore. Most are getting on in years and have jobs 'in town'. Today's farmer is balancing farm work with another job. The current system is streamlined to save the farmer time and allow them to accomplish both. Asking them to do more to get less or the same doesn't add up. - Professor Joseph Spencer, U. Illinois Prairie Research Institute, private correspondence, October 2014

146 Is High-Productivity System a Tragedy of the Commons Trap? Perhaps lower yields would increase profits because supply would be lower [at which point] farmers would be happy to [invest more time in a more sensible agricultural system]. - Joseph Spencer, private correspondence, Oct 2014 High-Yield Sustainable High-Yield 2, 2 4, 1 Sustainable 1, 4 3, 3

147 Can Farmers Escape to Sustainability? 2014 Game-Changer lays out five sorts of escape routes from the Prisoners Dilemma: 1. Invite regulation 2. Merge 3. Enable retaliation 4. Build trust 5. Leverage relationships Which we choose may determine the future of American farming

148 THANK YOU!!