The new age of insecticide discovery-the crop protection industry and the impact of natural products

Highlights

• Since 1990-a new age of insecticide discovery.

• Since 1990 more new classes of insecticidal chemistry than the prior 50 years.

• Last two decades output of new insecticides has been relatively constant.

• Natural products remain an important component in the discovery of new insecticides.

Abstract

Improvements in food production and disease vector control, to feed and protect an expanding global population, require new options and approaches for insect control. A changing and an increasingly stringent regulatory landscape, shifts in pest spectrum due to changes in agronomic practices, and insect resistance to existing insecticides, all contribute to the challenges of, and need for, developing new insect control agents. The nature of insecticides emanating from discovery R&D-based companies in the European Union, Japan, and the United States have evolved from a concentration on a few classes of insecticides and modes of action (MoA), to a far more diversified collection of insecticidal molecules that embody many new, or under-utilized MoAs. Since 1990 there has arguably been a new age of insecticide discovery, with more new classes of insecticides introduced, with greater economic impact, than the prior 50 years combined. Although there has been an on-going evolution and consolidation in the size and shape of the crop protection industry, for the past two decades the output of new insecticides has remained relatively constant. The diversity of approaches employed in the insecticide discovery process (competitor inspired, bioactive hypothesis and natural products) has contributed to the discovery of these new classes of insecticides. Insecticide discovery is today a global enterprise, that armed with new tools and capabilities, will continue to build and provide the future insect control products to meet global grower and consumer demands.

Introduction

The discovery of new tools to control pest insects has been a critical need for centuries and continues today with the requisite of feeding an expanding global population (Godfray et al., 2010) and addressing the longstanding threats from insect borne diseases. Although there are many techniques and technologies for pest insect control including biological control, transgenic plants, host plant resistance, cultural controls, and increasingly biopesticides (Gunther and Jeppson, 1960; National Academy of Sciences, Insect-Pest Management and Control, 1969; National Academy of Sciences, 1972; Gross et al., 2014; Sparks and Lorsbach, 2017a), for many crop-pest-geography scenarios insecticides remain a critical component. Early solutions included natural products (NPs) such as nicotine and pyrethrum (Table 1), along with inorganic options such as sulfur and the arsenicals (Shepard, 1951; Casida and Quistad, 1998). A major transformation in pest insect control began during the 1940s and 1950s, with the introduction of synthetic organic insecticides such as DDT, organophosphates (OPs), cyclodienes, and N-methylcarbamates (Table 1). The late 1940s through the 1960s has been referred to as the “golden age of insecticide discovery” (Gubler, 1983; Achilladelis et al., 1987; Casida and Quistad, 1998), as highly effective, reliable and affordable pest insect control became commonplace. However, during this same time period, there was an expanded rise in insecticide resistance (Fig. 1). The rise in resistance, coupled with increasing concerns about mammalian and environmental toxicology of the available insecticides fueled the introduction of integrated pest management (IPM), and the quest for more selective insecticides that during subsequent decades resulted in numerous new additions to the existing insecticide classes (Table 1).

During the last 50 years, the crop protection industry has been successful in improving many attributes of new insecticides including improving the insecticide selectivity and lowering use rates (Sparks, 2013). Although the environmental profiles for new insecticides have improved over the past several decades, further improvement around attributes related to environmental impact continue to be an essential goal, driven in large part by increasingly stringent regulatory requirements, and public expectations for more environmentally friendly options (Lamberth et al., 2013; Sparks, 2013; Corsi and Lamberth, 2015; Maienfisch and Stevenson, 2015; Sparks and Lorsbach, 2017b; Kalaitzandonakes and Zahringer, 2018; Nishimoto, 2019). Likewise, insect resistance to the available insecticides (National Academy of Sciences, 1969; Menn and Henrick, 1985; Hodgson and Kuhr, 1990; Lamberth et al., 2013; Sparks and Nauen, 2015; Sparks and Lorsbach, 2017b; Kalaitzandonakes and Zahringer, 2018) also continues to be another key driver, with the numbers of cases of resistance continuing to rise (Fig. 1) (Whalon et al., 2008; Tabashnik et al., 2014; Sparks and Nauen, 2015; Tabashnik and Carrière, 2017). Thus, new insecticides, ideally possessing new MoAs and further improvements to environmental profiles are needed to provide new options for insecticide resistance management (IRM) programs (Sparks and Nauen, 2015; Roush, 1989; Thompson and Leonard, 1996; Elbert et al., 2007; Nauen et al., 2019; Insecticide Resistance Action Committee (IRAC), 2019) and provide growers with new options that to meet or exceed current and future environmental standards.