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Executive Summary
T ITERALLY HUNDREDS OF SPECIES of insects, plant pathogens, rodents,
and weeds have become resistant to chemical pesticides. Indeed, re-
~sistance to pesticides is a global phenomenon. It is growing in fre-
quency and stands as a reminder of the resiliency of nature. Public health
protection efforts have been frustrated sometimes dramatically-by resis-
tance in populations of insects and rodents involved in the spread of disease
to human populations. Substantial effects of resistance on agricultural pro-
ductivity, however, have been limited so far to a few crops and locations
because nonchemical tactics and alternative pesticides have generally been
available for use.
Although scientists recognized resistance of insects to chemical pesticides
nearly 76 years ago, the problem became widespread in the 1940s during an
era of extensive use of synthetic organic insecticides and acaricides. Research
on the phenomenon of resistance progressed slowly over the next three de-
cades, despite a steadily growing list of documented cases. In the 1970s
three unrelated factors converged, heightening concern around the world and
lending momentum to scientific research focused on the genetic, biochemical,
and ecological factors associated with resistance.
First, entire classes of once highly effective compounds became useless
in many major applications because of resistance. The number and diversity
of pests displaying resistance increased appreciably worldwide, as did the
list of chemicals to which resistance developed. Second, clear limits began
to emerge in the ability of chemists to identify and synthesize effective and
safe alternative pesticides. The stock of available compounds came to be
viewed as a limited resource that could like natural resources be depleted
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2
EXECUTIVE SUMMARY
through poor management. Third, tremendous progress occurred within sev-
eral basic scientific disciplines: scientists experimented with powerful new
tools for elucidating the genetic and biochemical modes of action of pesti-
cides; understanding of the cellular and subcellular mechanisms by which
pests develop resistance grew rapidly; and progress in unraveling the genetics
of resistance led to new insights into the defense systems and vulnerability
of pests. Scientists began to use these new insights with some encouraging
early results to develop more stable and effective pest-control strategies.
The combination of these three factors profoundly influenced the thinking
of most pest-control researchers, practitioners, and manufacturers. Resistance
is spreading at an increasing rate among pests in some crops in virtually all
parts of the world. Hard lessons for pesticide manufacturers have accom-
panied the economic consequences of resistance. Companies now take very
seriously the prospect that resistance may limit the number of years a new
product will have to recover the steadily growing costs incurred in its de-
velopment, testing, production, and registration. In the United States timely
progress in managing resistance is a practical necessity for many farmers
struggling to stay profitable in the face of growing international competition.
The committee believes that slowing or halting the spread of resistance to
pesticides should become a prominent focus in both public and private sectors.
A range of activities needs to be pursued, including research, field monitoring
and detection programs, education, and incorporation of strategies to manage
resistance into international development and health programs. Fortunately,
various individuals and groups involved in pest management have pioneered
the application of some promising new strategies, and more resources and
attention throughout the pest-control industry are being devoted to the ver-
ification and dissemination of data on resistance and methods to manage its
evolution.
The idea and impetus for this project reflect growing concern about re-
sistance and the sense that a more systematic and scientific approach is needed
to deal with this recurrent problem. In this report we take stock of what is
now known about the extent and severity of resistance problems around the
world, limiting the discussion primarily to pests of agricultural importance.
(Resistance in disease organisms and vectors also is extremely important,
but this area has already received considerable attention.) The genetic and
biochemical mechanisms of resistance are assessed and emphasis is placed
on some of the new biotechnological methods used to study resistance.
Application of population biology to the study of resistance is also reviewed.
Papers and dialogue presented at the November 27-29, 1984 conference
suggest that significant advances in understanding the development of resis-
tance can be achieved by researchers in biochemistry, genetics, and theo-
retical population biology collaborating with those in applied pest-management
disciplines. Such synergism and multidisciplinary cooperation may prove
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EXECUTIVE SUMMARY
3
critical in developing, refining, and validating practical management strat-
egies that can be adopted to halt or slow down the emergence of resistance
or otherwise reduce the severity of its impact.
Biotechnology is already providing critical insights into the mode of action
of a few major classes of herbicides and is expected to do the same for other
pesticides. These and other insights that biotechnology can offer may even-
tually make most conventional pesticides obsolete. Under the best of cir-
cumstances, however, such breakthroughs are a decade off for the majority
of major pests and crops. In the meantime (perhaps indefinitely) pest-control
strategies involving some use of chemical pesticides will need to be devel-
oped, implemented, monitored, and adjusted to sustain control that is both
efficacious and affordable. The nature and properties of new pesticides will
also evolve over the next several decades. Most new products will be more
selective, less toxic to mammals, and effective at lower rates of application.
Many will be chemical analogs of naturally occurring chemicals that control
some physiological aspect of development in pest species. Nevertheless,
effective management of the propensity of pest populations to develop re-
sistance will remain a practical necessity.
A second major focus of the symposium and this report is the critical
requirement for dealing with resistance now and in the foreseeable future.
Resistance is a phenomenon that typically develops rapidly. A pest population
just beginning to display resistance may respond favorably to a change in
management tactics for only a relatively brief period after detection. Resis-
tance can progress within just a few seasons or even within a season to
a point at which dramatic changes in control strategies or cropping patterns
become necessary. If this narrow window is not exploited, the battle can
soon be lost.
Two other conclusions surfaced at the symposium and workshops: (1) pest
populations that are already resistant to one or more pesticides generally
develop resistance to other compounds more rapidly, especially when the
compounds are related by mode of action to previously used pesticides, and
(2) most pests can be expected to retain inherited resistance to pesticides for
long periods. Hence primary reliance on chemical control strategies over the
long run will depend on a steady stream of new compounds with different
.
modes of action that can also meet regulatory requirements and economic
expectations an unlikely prospect in many pest-control markets.
Throughout the United States and around the world new strategies are
being formulated to slow or reverse the onset of resistance during this window
of time between the detection of resistance and its often rapid evolution in
severity to an unmanageable state. A necessary first step, treated at length
in this volume, is the development and use of rapid, reliable methods to
detect low levels of resistance in pest populations. Immunology, biochem-
istry, and molecular genetics are expected to play a major role in developing
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EXECUTIVE SUMMARY
these methods. Methods also are needed to monitor the spread and severity
of a resistance episode over time and space in order to gain an accurate sense
of the size of the window and how rapidly it is closing.
Data stemming from new assay methods used in resistance detection and
monitoring efforts would be extremely valuable in the development of active
strategies to manage pesticide resistance. The thinking underlying the use of
such strategies is closely related to the philosophy and principles of integrated
pest management (IPM). Put simply, management of resistance is an attempt
to integrate chemical and nonchemical control practices through a range of
tactics, singly or in combination, so that the frequency of resistant members
of pest populations remains within a manageable, economically acceptable
level.
Management of resistance offers great promise as a complementary ex-
tension of IPM. The tools and knowledge needed to structure and analyze
opportunities to manage resistance are very similar to the information needs
of scientists developing, applying, monitoring, and adjusting IPM strategies.
Application of theoretical concepts from population biology and the use of
general and specific models may provide important new capabilities in pre-
dicting the outcome of different sets of pest-management tactics. On the other
hand, we see little justification in maintaining the polite fiction that pesticide
resistance is solely a technical problem that can be readily overcome with
the right new pesticide or an adjustment in the way conventional pesticides
are used. For even a single crop or clinical situation, the design, execution,
monitoring, and long-term implementation of a pesticide-use program is a
major endeavor. Even with careful monitoring, timely research, and enlight-
ened product stewardship, the efficacy of many pesticides will prove im-
possible to sustain except in a very limited sense and in isolated applications.
Problems loom ahead as we are forced to deal with the practical conse-
quences of resistance episodes. These problems must be faced and will
invariably command the attention of most scientists engaged in pest-control
research. Experience has taught us that resistance episodes will flare up like
forest fires, sometimes unexpectedly and other times not surprisingly.
As scientists and institutions gain expertise and devote additional resources
to contend with threatening resistance occurrences, it is critical that steps
also be taken, steadily and collectively, to develop a deeper understanding
of resistance. New institutional mechanisms and a shared commitment are
vitally needed so that the lessons learned in each resistance episode are not
lost. Only by learning systematically from mistakes can we hope to avoid
making the same mistake elsewhere, or in other crops or for different pests
or pesticides. Much of the knowledge needed will be gained more quickly
if new forms of collaboration, and closer ties can be forged between applied
and academic biology. A concerted effort by research administrators to un-
derwrite such collaboration and overcome well-entrenched barriers will
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EXECUTIVE SUMMARY
s
be an important step toward identifying practical solutions to pesticide re-
sistance problems.
Resistance is a potentially powerful, pervasive natural phenomenon. The
development and severity of resistance to pesticides is controlled primarily
by human action. Ignorance or a lack of concern in dealing with resistance
can set the stage for explosions in pest populations leading to crop failure
and reversals in the effectiveness of public health protection programs.
Resistance can and must be attacked in a variety of ways. Some scientists
and pest-control practitioners will focus on the need for changes in farmers'
pest-control practices; some will develop methods to detect and monitor
resistance; and others will attempt to find improved institutions to coordinate
management of resistant pest populations among various groups of farmers,
other pesticide users, and pesticide manufacturers. Some scientists will pursue
fundamental work on identifying the molecular and physiological bases of
resistance. Progress at one level will help at other levels in understanding
the ways organisms manage to overcome external threats like those posed
by pesticides. To progress most swiftly and efficiently COmm~'nio.~tinn anal
· a_ . .. . .. ..
__J ~4,~
~nrorma~on a~ssem~nat~on are critical needs not adequately met either by
public or private institutions.
RECOMMENDATIONS
Basic and Applied Research
Each of these research areas will require moderate or substantial increases
in funding, either from new or redirected sources of funds, or both. Some
of the needed research can and probably will be undertaken by the private
sector. Additional public funding should be supplied through peer-reviewed
programs such as USDA's Competitive Grants Program.
The following recommendations are not listed in order of priority.
RECOMMENDATION 1. More research is needed on the biochemistry, phys-
iology, and molecular genetics of resistance mechanisms in species repre-
senting a range of pests. Molecular biology, including recombinant DNA
technology, should be helpful in isolating and characterizing specific mech-
anisms of resistance.
The information provided by these investigations is essential to develop tactics
to counter resistance, rapid new techniques to monitor and detect the extent of
resistance, and novel pesticides (considered in more detail in Chapters 2, 3, and
51.
RECOMMENDATION 2. The discovery and exploitation of new "target sites"
for novel pesticides should be a key focus as research efforts are initiated
that combine traditional research skills with the new biotechnologies.
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EXECUTIVE SUMMARY
The number of modes of action of pesticides in current use is limited and, as
a result of resistance, the number of functional pesticides is decreasing for some
pests. Pesticide control will remain a necessity in many circumstances, and new
compounds will be needed (Chapter 1~. The methods of contemporary biotech-
nology should be very useful both in the identification of these target sites and
for the production of new pesticides (Chapter 21.
RECOMMENDATION 3. Standard methods to detect and monitor resistance
in key pests need to be developed, validated, and then applied more widely
in the field.
Resistance detection and monitoring techniques are essential to early warning
systems and in establishing the extent and severity of resistance (Chapter 41.
These methods are critical for advancing and evaluating programs to manage
resistance (Chapters 3 and 51. Agricultural producers, pesticide manufacturers,
and applicators will benefit from better methods to monitor resistance.
RECOMMENDATION 4. Concepts and insights stemming from population
biology research on pesticide resistance should be used more effectively to
develop, implement, and evaluate strategies and tactics to manage resis-
tance.
Population biology theory has been useful in a retrospective manner in ex-
plaining past resistance episodes. It can also be useful in a predictive manner,
for the development of optimum operational schemes to manage resistance for
each pest-control situation (Chapter 31;
RECOMMENDATION 5. The development and testing of a system of resis-
tance risk assessment needs to be pursued.
The ability to forecast accurately the likelihood of resistance may allow for
the extension of the effective life of pesticides and offer insight into how the
use pattern of a pesticide should be changed to slow the development of resis-
tance. Experts in resistance risk assessment may eventually be able to recognize
previously undocumented or unforeseen resistance episodes in time to develop
alternative control strategies that halt the evolution of resistance (Chapter 4~.
RECOMMENDATION 6. Increased research and development emphasis should
be directed toward laboratory and field evaluation of tactics for preventing
or slowing development of resistance (Chapter 5~.
RECOMMENDATION 7. Efforts should be expanded to develop IPM systems
and steps taken to encourage their use as an essential feature of all programs
to manage resistance (Chapter 51.
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EXECUTIVE SUMMARY
Implementation of Detection and Monitoring Techniques for
Key Pests and Maintenance of Practices to Manage Resistance
7
RECOMMENDATION 8. It is critical to determine for resistant populations
the level of tolerance to the pesticide and the relative fitness of the resistant
versus the susceptible portion of the pest population.
This information is essential to the development of a sound program for
managing the resistant population (Chapter 31.
RECOMMENDATION 9. Resistance detection, monitoring, and management
organizations should be formed at the local or regional level and assume
greater responsibility for education, coordination, and implementation of
activities to deal with resistance problems.
Resistance monitoring activities are most effective when they are conducted
by the people immediately concerned with the problem and most familiar with
the specific situation of pesticide use (Chapters 4 and 6~. Building wherever
possible on existing initiatives (including NBIAP, the National Biological Impact
Assessment Program, organized by the U.S. Department of Agriculture), new
institutional mechanisms are needed to coordinate the efforts of different sci-
entists working at the local and regional levels on specific crops or pest-control
needs.
RECOMMENDATION 10. Continuous monitoring programs should be used
to evaluate the effectiveness of tactics to manage resistance.
Information derived from monitoring programs is essential to evaluate the
effectiveness of tactics to manage resistance (Chapters 3 and 41. Continuous
monitoring can help protect growers from excessive losses and provide pesticide
manufacturers with an early warning that product efficacy may be in jeopardy.
RECOMMENDATION 11. Federal agencies should support and participate in
the establishment and maintenance of a permanent repository of clearly
documented cases of resistance.
A bank of information on the incidence of resistance to pesticides will be
needed for the rational choice of compounds by users, the planning of programs
to manage resistance, and the development of new compounds by industry. This
data bank should be broad-based and include information about the incidence
and level of resistance for specific pests, the affected geographic regions, and
cross-resistance with other pesticides (Chapter 41.
RECOMMENDATION 12. Departments of agriculture within each state, in
considering whether to request emergency use permits to respond to pest-
control needs that have arisen because of resistance to another compound,
should seek advice on whether the conditions governing the emergency use
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EXECUTIVE SUMMARY
permit are consistent with validated tactics for the management of resis-
tance. The U.S. Environmental Protection Agency, in approving such re-
quests, should also consider the consequences for managing resistance,
especially when cross-resistance is thought to be a possibility.
RECOMMENDATION 13. After consultation with the EPA; university, state,
and federal researchers; and industry trade associations, the U.S. Depart-
ment of Justice should consider issuing a voluntary ruling that clarifies the
antitrust implications (if any) of private sector initiatives to combat resis
tance.
Such a ruling would alleviate concerns over possible antitrust prosecutions
following efforts by private companies working jointly to prescribe directions
for use on labels of competing pesticide products. Such jointly developed use
directions are sometimes needed to slow the onset of resistance to a family of
pesticides or to a single compound sold by different companies (Chapter 6~.
RECOMMENDATION 14. The public sector should become more involved in
the development of required residue chemistry and other data for minor
crop uses. State and federal agencies should consider applying the JR-4
program concept in developing data needed to gain registrations of pesticides
with nonagricultural minor uses.
Such efforts will help ensure availability of efficacious pesticides for use on
minor crops and for nonagricultural uses such as chemical sterilants and roden-
ticides (Chapter 61.
RECOMMENDATION 15. Activities to manage resistance should not override
environmental health and safety responsibilities, which should remain the
highest priority mission of regulatory agencies. Appropriate groups, such
as the Cooperative State Research Service, the Cooperative Extension Ser-
vice, the Public Health Service, and professional societies, should take lead-
ership roles in organizing work and educational groups within state, regional,
and national IPM programs to implement efforts to manage resistance
(Chapter 6~.
It is necessary for some organizations to take a leadership role including the
establishment of new funding sources and mechanisms to help galvanize re-
search pertinent to management of resistance and to initiate new collaboration
on projects essential to scientific progress on many key fronts (Chapter 61.
RECOMMENDATION 16. A considerable effort should be put into the de-
velopment of pest-control measures that do not rely on the use of chemical
pesticides.
Control of pest populations by combining in cycles the use of old and novel
chemical pesticides, as they become available, is unlikely to be a viable long
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EXECUTIVE SUMMARY
9
term strategy. There is no biological or evolutionary justification for the prop-
osition that pest populations will return to sensitive states in relatively short order
following the termination of the use of specific pesticides that brought on resis-
tance. Moreover, experience suggests that novel and safe new pesticides will
not always appear on the market when needed to replace compounds that have
lost their effectiveness due to resistance.
* * *
We are growing familiar, through unfortunate experiences, with the devel-
opment of resistance. We can and should learn from these lessons. It has become
apparent that the phenomenon of resistance demands clear, thoughtful, and sys-
tematic actions to prevent the loss of valuable pesticides that can contribute
greatly to meeting food needs. The day is approaching when effective, affordable
alternatives simply will not be available. Then, adjustments that could at times
be extremely costly will have to be made in how and where we produce food.
Important changes in attitude, commitment, and priority are needed now if we
are to slow and eventually reverse the spread of resistance. This report offers
guidance on logical steps to get the process under way.
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Representative terms from entire chapter:
pest populations
