Pestic. Sci. 1997, 51, 227È234

Review

Resistance as a Concomitant of Modern CropProtection*

Pierre A. Urech,1” Theo Staub2 & Gu� nther Voss2

1 European Crop Protection Association, Ave E Van Nieuwenhuyse 6, B-1160 Brussels, Belgium2 Novartis Crop Protection Division, CH-4002, Basel, Switzerland

(Received 28 March 1997 ; accepted 21 July 1997)

Abstract : This paper reviews the impact of resistance to fungicides andinsecticides/acaricides on the way crop protection is practised. It is now clearthat resistance can develop to virtually any crop-protection product, in any pest,fungal pathogen or even weed. As a limiting factor in crop protection, it is a factof life. A positive side-e†ect is the precision with which products are used today,with increasing implementation of Integrated Pest Management (IPM) pro-grammes. This is a vital step towards sustainability. This paper describes : pastexperiences ; current status of resistance ; how resistance management inÑuencescurrent crop protection practices ; regulatory aspects ; and the outlook for thefuture. It concludes that EU regulations on resistance management must besimple and workable. Chemicals will continue to have a central role in opti-mising yields from the worldÏs crops, as new tools, including biotechnology,become available for crop protection and resistance management. The crop-protection industryÏs innovations and product stewardship programmes will con-tribute to sustainable agriculture. This will provide continued beneÐts to users,the environment and society.

Pestic Sci., 51, 227È234, 1997No. of Figures : 1. No. of Tables : 4. No. of Refs : 2

Key words : crop protection, resistance, fungicide, insecticide, acaricide, biotech-nology

1 INTRODUCTION

The issue of resistance is little understood in manycircles. For example, the following quotation is from USVice-President Al Gore :1

* Based on a presentation at the Conference “Resistance Ï97ÈIntegrated Approach to Combating ResistanceÏ organised bythe Institute of Arable Crops Research in collaboration withthe SCI Pesticides Group and the British Crop ProtectionCouncil and held at Harpenden, Herts, UK on 14È16 April1997.” To whom correspondence should be addressed.

“Pesticides often leave the most resistant pests behind. . . T hen . . . the resistant pests multiply . . . soon,enormous quantities of pesticides are sprayed on thecrops to kill just as many pests as were there when theprocess began. Only now the pests are stronger. And allthe while, the quantity of pesticides to which we our-selves are exposed continues to increaseÏ

Is Vice-President Gore correct? Is resistance out ofcontrol ? Are crops full of monster pests ? No, and withthe responsible management of resistance it will be pos-sible to ensure that crop protection remains as part of

2271997 SCI. Pestic. Sci. 0031-613X/97/$17.50. Printed in Great Britain(

228 Pierre A. Urech, T heo Staub, Gu� nther V oss

Fig. 1. Design elements of a fungicide use recommendation (from Reference 2).

sustainable agriculture.Members of the European Crop Protection Associ-

ation (ECPA) account for more than 90% of WesternEuropean sales of crop-protection products. As the pan-European voice of the crop-protection industry, theassociation currently has 18 full and associate memberNational Associations and 16 full and associate membercompanies.

ECPAÏs major goals are to :

to the political process leading to newI contributelegislation and regulation ;

sustainable agriculture, in which crop-I supportprotection products remain important elements ;and

Integrated Pest Management (IPM) asI supportpart of our e†orts to protect the environment.

2 PAST EXPERIENCES

Resistance to crop-protection products springs fromnatureÏs reaction to strong and speciÐc selection pres-

TABLE 1The Concept of Fungicide Resistance Managementa

1. DeÐnition of objectives2. Design of procedures and approaches

resistance risk assessmentdesign and test of resistance strategiesdetermination of monitoring methods

3. Co-ordination between manufacturers of products withcross-resistance

4. Implementation of use strategies and monitoring methodsin practice

5. Ongoing over product lifetime : Ðeld monitoring

a From Reference 2.

sure. For fungicides, it Ðrst became a practical problemin the early 1970s with new-generation systemic fungi-cides. For insecticides and acaricides, resistance wasencountered even earlierÈexamples are DDT and thepyrethroids. In each case, widespread use led to build-up of resistance in target diseases and pests, and torapid loss of efficacy. More recently, it has become clearthat resistance can develop to virtually any crop-protection product, in any pest, fungal pathogen oreven weed.

During the 1970s and 1980s, major advances weremade in our understanding of how to detect andmanage resistance. Key contributors were Charlie Delp,Johann Dekker, Keith Brent and Franz-Josef Schwinn.

This pioneering work set up clearly-deÐned pro-cedures and approaches to resistance management2which are illustrated in Table 1 and Fig. 1. After a,sometimes painful, learning phase, the threat of resist-ance has been turned into a challenge. As a result,resistance is now largely manageable, and a positiveside-e†ect is the care and precision with which cropprotection is practised today. This is a crucial steptowards sustainability. Resistance has become part ofIPM.

The scientiÐc and technical aspects of resistance werethe main focus of the Resistance Ï97 conference.However, these are not the only perspectives fromwhich to view resistance. There are also practical, eco-nomic and social implications to be taken into account.This paper concentrates primarily on these aspects.

3 STATUS OF FUNGICIDE RESISTANCE

The current status of fungicide resistance is summarisedin Table 2. Three interesting points are worth high-lighting :

Resistance

asa

concomitant

ofmodern

cropprotection

229

TABLE 2Current Status of Resistance to Fungicides

Resistance Single/ Occurrence of Ðeld E†ectiveness of resistanceProducts/ riska multiple resistance Resistance management strategya

resistance groups ]]]]] steps Practical impact management strategy ]]]]]

Benzimidazoles ]]] Single Use stopped in Stop use where ] Di†icult once resistancemany cases (very resistance has occurred occursstable) Mixtures and

alternationsPhenylamides ]]] Single Rapid loss with Pre-pack mixtures and ]]] Where strictly followed

sole use limited treatmentsPre-pack mixtures per season^stable

DMIs (SBI) ]] Multiple Safety margin Mixtures (cereals) and ]] Problems with reducederoding spray windows and split rates

(bananas, apples)Morpholines ]] Multiple Safety margin Mixtures (cereals) ]] Problems with reduced

eroding and split ratesDicarboximides ]] Single Loss of control Limited treatments ] Few alternatives

after several years per season availableMelanin inhibitors È ? So far none None ÈAnilinopyrimidines (]]]) ? Single So far none Mixtures and ? Little experience

alternationsPyrroles (]]) ? ? So far none Mixtures and ? Little experience

alternationsStrobilurins ? ? So far none Not yet designed ? No experience

a ]]]\high ; ]\low.

230P

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TABLE 3Current Status of Resistance to Insecticides/Acaricides

Products Key pests Riska Region Resistance management activities

Carbamates Rice hoppers ]] S E Asia New products (buprofezine, imidacloprid)Organophosphates Rice stem borers ] S E Asia Use of Ðpronil, creation of transgenic Bt rice?

L eptinotarsa decemlineata ]] Poland IRAC monitoring since 1994Bemisia tabaci ]]] Cotton areas Substitution by buprofezine, imidacloprid,

pyriproxifen, diafenthiuron, pymetrozinePyrethroids Heliothis virescens, ]]] USA Rotations with OPs, carbamates, Bt, introduction of

Heliothis zea transgenic Bt cottonHelicoverpa armigera ]]] Australia One application window per season, Bt cottonL eptinotarsa decemlineata ]] Poland IRAC monitoring since 1994Bemisia tabaci ]]] Cotton areas Same as OPs

Benzoylureas Plutella xylostella ]] Asia-PaciÐc IRAC 1995 : Product alternation including BtChloronicotinyls Various sucking pests ?b IRAC working group envisagedBenzoylhydrazides Various Lepidoptera ?b None yet, deserves close attentionBacillus Plutella xylostella ]]]c S E Asia, Australia Use of parasitoids in maintaining Bt efÐcacy?thuringiensis(Bt) Helicoverpa armigera ?b Australia Under investigation by CSIRO

Heliothis virescens ?b USA Under investigation by IRAC-USClofentezine, Panonychus ulmi ]] EU Successful mixtures with diafenthiuronhexythiazox

Mitochondrial T etranychus urticae ?b USA, EU, Japan Proposal of Rothamsted-IRAC cross-resistance study needselectron transport Panonychus ulmi ?b to be tested in practiceinhibitorsd

a ]]]\high ; ]\low.b Risks are expected to increase with more AIs of same type and mode of action entering the market ;c Cross-resistance to various cry-types in the Ðeld appears to be possible ;d Fenazaquin, tebufenpyrad, fenpyroximate, pyridaben.

Resistance as a concomitant of modern crop protection 231

First, the only categories of fungicide which have so farlost substantial market share due to resistance are thebenzimidazoles and dicarboximides. The phenylamides,which have a high inherent risk of resistance, havemaintained a major market share. This was achieved byusing mixtures of phenylamides and conventional pro-tective fungicides, resulting in intervention at di†erentstages of the life cycle of pathogens, with action on bothhaustoria and spores and activity at two di†erent bio-chemical sites within the pathogen. The outcome of thisstrategy was a very stable system. It e†ectively prevent-ed this product category from being lost, and may wellbe a useful case study for planning future strategies.

Second, the majority of recent discoveries in the fungi-cide sector appear to have some risk of resistance. It isindustryÏs experience that only a pro-active and timelyapproach to resistance management ensures continuingefficacy. Appropriate strategies must therefore bedesigned and implemented before market launch, andmonitoring must follow. It is to be hoped that allcompaniesÈincluding their marketing departmentsÈwill co-operate.

Third, the issue of cross-resistance has become lessclear-cut. Initially, it was thought that compounds withthe same biochemical mode of action would induceresistance in the same way. Now, it appears that cross-resistance is not usually represented in every strain offungal pathogen. Non-resistant strains can always befound, even for cross-resistance between benomyl andthiabendazole. The exceptions result from di†erentresistance mechanisms which can be speciÐc for individ-ual fungicides within a group.

4 STATUS OF INSECTICIDE/ACARICIDERESISTANCE

The current status of resistance to insecticides andacaricides is summarised in Table 3. In the 1980s, therewere few new product introductions in these two cate-gories, but, during the present decade, promising newchemistry has been developed along with some newniche products. These are very welcome as additionaltools to help to manage development of insecticide/acaricide resistance. However, the new chemistry alsohas inherent resistance risks. In practice, the latter couldbecome a major threat if many products with a similarmode of action were launched, giving greater marketpenetration.

It is important to note that resistance is not conÐnedonly to chemicals. It has also been reported with bio-logicals such as Bacillus thuringiensis Berliner. This is aworrying trend, given the increasingly widespread use ofBt endotoxin genes in bioinsecticides and transgeniccrops.

It can be concluded that management strategies havetoday generally brought fungicide resistance undercontrol. Insecticide resistance is more complicated, andthe scope for action is more limited. For the future, theInsecticide and Fungicide Resistance Action Com-mittees (IRAC and FRAC) will continue to have a vitalrole in monitoring the situation and reacting as neces-sary.

Today, there is a good empirical knowledge of fungi-cide, insecticide and acaricide resistance. There is alsosome scientiÐc understanding of its basis. As a result,there has been considerable success in the practicalmanagement of resistance. However, it must beaccepted that in-depth scientiÐc knowledge is stilllacking.

5 RESISTANCE AND ITS INFLUENCE ONCROP-PROTECTION PRACTICES

The key threat related to resistance is that of partial ortotal loss of efficacy. This has triggered action in theareas of industry, crop-protection practices, regulationand among stakeholders (Table 4). Resistance is farfrom being a straightforward phenomenon. It does notdepend only on a single factor, but, on the contrary, is acomplex issue which needs a holistic approach. Solu-tions can only be found through integrated thinkingand action, which must take into account the following :

scientiÐc and technical aspects, which are themselveshighly complex ;social factors, with communication and co-operationneeded between all parties, including companies, aca-demia, extension services and farmers ;regulatory requirements ; andliability aspects.

Resistance is also a limiting factor in crop protection.Due to the need for management strategies, it directlyinÑuences tactics and choices in the Ðeld and has a sig-niÐcant inÑuence at the commercial level. On the tech-nical side, in the Ðeld, resistance management strategiesoften prevent full exploitation of the useful properties ofpromising new products. It may not be possible to use asystemic or curative product in a technically optimalwayÈfor example by soil application, or with longintervals between spraysÈin order to avoid resistance.These limitations also have a major impact on the com-mercial attractiveness of new products. Approachessuch as the use of product mixtures reduce turnover,proÐtability and return on investment.

On the other hand, thinking in terms of resistancemanagement has positive side-e†ects. It adds an extradimension to product stewardship and ResponsibleCare activities in crop protection. There is increasingly

232 Pierre A. Urech, T heo Staub, Gu� nther V oss

TABLE 4Impact and SigniÐcance of Resistance in Crop-Protection Practices

T hreat of lost efÐcacy due to resistance

Crop-protectionIndustry practices Regulations Stakeholders

Product stewardship and Limitations to full Need for workable Collaborationresponsible care also for exploitation of resistance risk F Industryresistance matters biological properties assessment scheme for F Farmers

R&D investments need Need for diversity in product registration F Public servicespayback control measures F Academia

Liabilities : no damage F ConsultantsCommercial limitations Basic researchdue to resistance Resistance monitoringmanagement accepted Support of strategy

Togetherness needed implementation

B B B B

DeÐned approaches and More sustainable crop- Industry to make Resistance as holisticprocedures protection systems proposal issue

V oluntary action and Resistance as an Collective action neededagreements example of practical ResistanceÈan integral

Establishment of RACs IPM part of crop protectionand subgroups

careful use of novel molecules, along with more innova-tive approaches to crop protection, involving mixturesand alternating applications of various products. Theseapproaches form part of IPM programmes ; they have apositive impact on the environment, and provide furtherimpetus for optimal product use. They also support thetrends in EU agricultural policy towards sociallyacceptable, environmentally friendly and economic agri-culture.

By accepting a leadership role in this issue and bytaking rapid voluntary action, industryÈalong withother institutions and academiaÈhas signiÐcantlyshaped resistance management. The need to take resist-ance seriously has been accepted. This is an essentialstep towards a sustainable future for crop protectiontechnology.

The e†ort put into developing and implementingresistance management strategies has another usefulbeneÐt in that it proves to critics of industry, such ascertain non-Governmental Organisations that industrycan keep its own house in order. Overall, resistance hasbeen, and continues to be, a major challenge toindustry. It is a high priority for companies, and amajor inÑuence on how crop protection is practised. Asa central aspect of modern crop protection, it remainsextremely important.

6 REGULATORY ASPECTS

A concern of our industry is the tendency for over-regulation at EU level. Compared with the situation in

the USA we are already heavily regulated, and this ishaving a negative impact on new product registration.Forty new compounds were registered in the USA in1995, and 58 were approved in Japan between 1992 andJune 1996. In contrast, in the EU, none have been regis-tered since July 1993.

The EU is also lagging behind in terms of time takento register new active ingredients. In the USA, theminimum time to register a new active ingredient is 24months, and in Japan, 18 months. Since Directive91/414 came into force more than three years ago, not asingle new active ingredient has been registered at EUlevel.

Additional burdensome and costly EU regulations forcrop-protection products must therefore be avoided. Wewould like to see a harmonised approach across allOECD countries ; this is also our objective for resist-ance aspects.

The EU Registration Directive (91/414/EEC) saysthat efficacy data should include “information on thepossible occurrence of the development of resistance.Ï Ifresistance is likely, a management strategy must be sub-mitted. The directive sets a framework, but a resistancerisk assessment scheme and detailed data requirementshave not yet been worked out and agreed. Industry sup-ports the implementation of 91/414, but we have a clearvision of how resistance matters should be dealt withand wish to see a simple, workable system. Experienceshows that resistance can be managed using basicstudies which industry routinely carries out on new pro-ducts. Such studies are not excessively complex, costly

Resistance as a concomitant of modern crop protection 233

or time-consuming, and all the main factors to be takeninto account, including inherent product characteristicsor management approaches, are well understood.

In terms of regulation for resistance aspects,industryÏs position is that data requirements should bedescriptive, qualitative and straightforward to interpret,which would simplify evaluation by EU member states.They should cover cross-resistance, inherent risks innew products, and resistance management strategies.

Industry will make a proposal based on its extensiveexperience in resistance management. From this, aresistance risk assessment scheme within 91/414 shouldbe : simple, in order to cope satisfactorily with complexmatters ; applicable to all types of products ; rapid, notdelaying market introduction ; easy to implement ; ahelp to member states ; and based on voluntary actionrather than command and control.

The last point is of particular relevance. Currenttrends in the USA and in certain European marketsÈsuch as the UK and GermanyÈare to move away fromcommand and control and towards voluntary agree-ments. Excessive regulation always leads to implemen-tation problems in EU Member States, and a lack ofefficiency. Environmental legislation and 91/414 areprime examples of this. While voluntary or negotiatedagreements might not always go as far as legislationand regulation, they have a higher rate of successbecause of their relative ease of implementation. Thiswould be the best approach for resistance management.

In the policy arena, proposals will be made this yearon reforming the EU Common Agricultural Policy(CAP). Part of the 40 billion ECU which support EUagriculture each year will shift from production-basedsubsidies to Ðnancial support for sustainable, environ-mentally sound technologies and practices. IPM andresistance management have a good chance of quali-fying for such funding.

7 OUTLOOK

Industry is committed to advancing understanding ofresistance. A combination of scientiÐc, marketing andcommunications approaches will be needed. From ascientiÐc viewpoint, there are Ðve areas to improve ourscientiÐc base further in the fungicide sector :

Resistance build-upÈThe contributing factors havebeen identiÐed, but there is relatively little under-standing of how they are interrelated. Information isneeded in such areas as : the changes which occur atthe molecular level when resistance develops ; popu-lation dynamics and genetics of resistant or less sensi-tive strains and epidemiology and Ðtness of resistantor less sensitive strains.Cross-resistance aspectsÈmore details are required.Resistance strategiesÈthese are still largely empiricaland not science-based.

ScientiÐc prediction of resistance occurrenceÈas aconsequence of the three above factors, predicting theoccurrence of resistance is still in its infancy.Biotechnology will have a major impact throughtransgenic crops and improved diagnostic methods todetect and monitor resistance.

From a marketing standpoint, additional tools arenow becoming available for crop protection and resist-ance management. The various options are as follows :

Transgenic disease- and pest-resistant cropsÈresistance may also be an issue here. For example,plants which produce toxins throughout the seasonmight pose challenges not yet experienced withchemical crop-protection products. Possible tolerancebreak-down and cross-resistance must be investi-gated.Novel chemistry which does not lead to cross-resistance.Biological products.Products which activate plantsÏ natural resistancemechanismsÈthese appear to have a low resistancerisk.

Only cautious integration of these approaches willensure that resistance remains within control. This willalso help ensure a sustainable future for crop protec-tion. The best strategy will be to combine biotechnologywith chemistry, and not to play one o† against theother.

8 COMMUNICATION

This continues to be vital in resistance management. Ithas two key aspects, in that internal dialogue withincompanies is needed to ensure that the need for short-term Ðnancial gain is balanced against the longer-termfuture of products. Also necessary is dialogue betweenall groups involved. Industry needs to share its experi-ences with academia, extension services and consultants.The resistance action committees have an importantrole to play in furthering this dialogue and industrycontinues to seek further collaboration with otherparties.

9 CONCLUSIONS

Resistance, as a limiting factor in crop protection, is afact of life, and industry has voluntarily takenresponsibility for its management and wishes to retainthis leadership role. EU regulations on this topic mustbe simple and workable ; industry will shortly bemaking speciÐc proposals on resistance risk assessmentand data requirements.

The need for resistance management has a positiveinÑuence on the care with which crop protection ispractised. It goes hand-in-hand with tools like Good

234 Pierre A. Urech, T heo Staub, Gu� nther V oss

Agricultural Practice and Integrated Pest Managementin ensuring sustainability.

In future, increasing numbers of tools will be avail-able for managing resistance. Chemicals will continue tohave a central role in optimising yields from the worldÏscrops for the future. The crop protection industryÏsinnovations and product stewardship programmes willcontribute to sustainable agriculture and this willprovide continued beneÐts to users, the environmentand society as a whole.

REFERENCES

1. Gore, A., Earth in the Balance, p. 52, quoted in Avery,D. T., Saving the Planet with Pesticides and Plastic (1995),page 210.

2. Urech, P. A., Management of fungicide resistanceÈashared responsibility. Proc. 3rd Internat. Conf. Plant Prot.in the T ropics, Malaysia (1990), III, pp. 105È9.