Pesticide Innovation and R&D: Considering How to Conduct Pesticide Molecular Design from Four Perspectives

In recent years, the number of newly registered pesticide varieties in China has been steadily increasing; however, truly innovative compounds with groundbreaking chemical structures remain exceedingly rare. AI‑driven pesticide molecular design holds great promise as a powerful tool for new‑drug discovery and development. Professor Guangfu Yang’s team at Central China Normal University has traversed the entire R&D pipeline—from developing computational tools and identifying lead compounds to advancing into novel drug creation—offering insights into whether the integration of cutting‑edge molecular‑design technologies with traditional R&D represents a revolution or a collaboration, how to strike a balance that fosters their symbiotic coexistence, and what remaining challenges still need to be addressed in pesticide molecular design.

When conducting pesticide molecular design, the first step is to clearly define the desired objectives of the molecular design, which can be considered from four dimensions.

1. From the perspective of the pesticide industry’s own development

The development of any industry or emerging phenomenon follows a gradual process.

Take pesticides as an example: in the early years after the founding of the People’s Republic of China, the pesticide industry was still underdeveloped. The State Key Laboratory of Element‑Organic Chemistry at Nankai University is one of the key birthplaces of China’s pesticide science. In those formative years, the central government entrusted Yang Shixian, then president of Nankai University, with the crucial task of “solving the problem of feeding 400 million people.” Accepting this responsibility, President Yang shifted his research focus from pharmaceuticals to pesticides. At that time, the most pressing need in Chinese agriculture was to address the lack of available chemical inputs. Under Yang Shixian’s leadership, Nankai University swiftly introduced a series of pesticide formulations—including malathion, China’s first organophosphorus insecticide produced on an industrial scale—thereby meeting the agricultural production demands of the era. Back then, labor costs were low, and weed control relied primarily on manual weeding; pesticides were largely limited to insecticides and fungicides, with little demand for herbicides. Moreover, during the early years of the PRC, no formal pesticide registration system had yet been established, public awareness of pesticides was extremely limited, and safety concerns were largely overlooked, with attention focused instead on efficacy. Consequently, the primary R&D objectives were to identify products effective against pests and diseases and to develop scalable industrial manufacturing processes. Such gaps in understanding and a rudimentary regulatory framework inevitably gave rise to numerous challenges throughout the industry’s development.

In 1982, China introduced a pesticide registration system and, in 2017, enacted a revised version of the Regulations on Pesticide Administration, which has since undergone multiple further amendments and refinements. The 2017 revision marked a significant shift, with its guiding principle moving from an emphasis on efficacy to a focus on safety. At the same time, China has progressively banned the production and use of highly toxic pesticides; starting in September 2022, the Ministry of Agriculture and Rural Affairs issued an announcement revoking the pesticide registrations for the active ingredients and formulated products of phorate, methyl isofenphos, isocarbophos, and monocrotophos, thereby prohibiting their manufacture. In March 2023, the Ministry again announced measures to phase out four highly toxic pesticides—phorate, methyl isofenphos, isocarbophos, and monocrotophos. Currently, only six highly toxic pesticides remain available on the Chinese market. Over the past seven decades, China’s pesticide industry has achieved substantial progress, now standing at an advanced global level.

Therefore, when considering any phenomenon, one should first understand its historical development and examine it from the perspective of its evolutionary trajectory.

2. From the perspective of technological progress

General Secretary Xi Jinping has repeatedly emphasized that scientific and technological innovation must adhere to the “Four Orientations,” one of which is to remain at the forefront of global science. Accordingly, when assessing the development of the agrochemical industry, we must consider not only the evolution of agrochemicals themselves but also the broader advances in science and technology worldwide.

In the 1960s and 1970s, pesticide research and development largely followed a straightforward “synthesis–screening” cycle, under which identifying a single new pesticide typically required synthesizing and screening around 1,000 compounds. However, evolving regulatory requirements for pesticide registration and increasingly stringent performance expectations have fundamentally altered the landscape. Today, internationally recognized statistics indicate that developing a new pesticide entails synthesizing and screening approximately 159,000 compounds, incurring costs of about US$286 million, and taking an average of 11.3 years from initial synthesis to market launch. The rising barriers to registration stem primarily from advances in science and technology, which have enabled a more rigorous and comprehensive understanding of pesticide efficacy and safety.

Of course, technological advances are exerting an increasingly profound influence on pesticide research and development. The integration of cutting-edge multidisciplinary technologies—such as high-performance computing, artificial intelligence, big data, and biotechnology—with the pesticide field is becoming ever more seamless, significantly boosting R&D efficiency.

3. From the perspective of agricultural production

We cannot examine pesticides in isolation; rather, we must consider them within the broader context of agricultural production. Pesticides serve agricultural production, yet they are also chemicals that enter the environment. This dual role determines why pesticides are designed, how they should be designed, and what kinds of pesticides ought to be developed.

In the past, it was often believed that pharmaceutical R&D represented a more sophisticated and cutting-edge field than agrochemical R&D—a view that is, in fact, highly one-sided. Agrochemical research shares many similarities with pharmaceutical research, yet it also possesses its own distinct characteristics, which can be summarized by five key features:

1) Diversity of target pests and diseases

Agricultural production faces a wide array of pest species, each exhibiting substantial variation in morphology and developmental patterns. Taking insect pests as an example, since crops often suffer from multiple pest infestations simultaneously, there is a strong demand for insecticides with broad‑spectrum activity. However, insects differ markedly in their feeding habits and reproductive strategies, and their physiological characteristics also vary considerably across different life stages. When designing insecticidal molecules and applying these agents, it is essential to account for these differences; achieving broad spectrum efficacy remains a major challenge in the molecular design of insecticides.

2) Diversity of protected objects

Pesticides are used to protect a wide variety of crops, including both annual and perennial plants, as well as field and paddy crops, and encompassing both food and cash crops. Crops differ significantly in their growth cycles and physiological characteristics. For crops with long growth cycles, it is desirable that the pesticide have a relatively long metabolic half-life, thereby maximizing its efficacy over time. In contrast, for crops with short growth cycles, the pesticide must be rapidly metabolized by the plant to ensure that residue levels remain within regulatory limits at harvest. Consequently, from the perspective of the target crop, different agricultural commodities impose distinct requirements on the properties of the pesticide.

3) Biodiversity of Environmental Organisms

Biodiversity is an intrinsic property of the natural world. Pesticides are released into the environment, and while they control agricultural pests, they must also ensure the safety of humans, livestock, and beneficial organisms. In recent years, the environmental toxicological and adverse effects of pesticides have attracted widespread global attention; several pesticide formulations that were once widely used worldwide have been banned one after another due to such risks. For example, the bee toxicity of neonicotinoid insecticides has drawn significant public concern in recent years, leading to the successive bans of imidacloprid, thiamethoxam, and other related compounds. Therefore, achieving selectivity between harmful and beneficial organisms and minimizing the environmental impact of pesticides are fundamental scientific considerations that must be addressed at the outset of pesticide molecular design. Even if a new pesticide demonstrates excellent efficacy, it cannot obtain regulatory approval unless it passes an environmental and ecological safety risk assessment.

4) Biodiversity of the environment and ecosystems

After pesticides are applied to crops, they must withstand exposure to wind, sunlight, and rain; their photostability and resistance to wash‑off by rainfall are critical determinants of efficacy. Once pesticides enter soil and groundwater, their environmental fate, the safety of their metabolites, and their environmental half‑life all influence their ecological safety—factors that, in turn, determine whether a pesticide can obtain regulatory registration. For this reason, the same active ingredient may exhibit markedly different performance across diverse ecological settings. Given the diversity of environmental organisms and ecosystems, pesticide registration studies must include environmental toxicology assessments, evaluations of environmental fate and metabolism, and risk assessments of environmental safety—evaluations that are not required in pharmaceutical research. In this respect, the safety assessment for pesticides is more stringent.

5) Cost-effectiveness of use

In pharmaceutical R&D, safety and efficacy are the primary considerations, with production costs rarely taken into account. By contrast, pesticide development must factor in cost, as farmers’ willingness to bear the expense of agricultural inputs is limited. Once the cost of applying a pesticide exceeds the actual economic returns from crop production, it loses its market viability. Consequently, the economic feasibility of production costs is another key distinguishing feature of pesticide R&D compared to pharmaceutical R&D.

4. From the Perspective of Academic Innovation

From a practical standpoint, companies are not particularly concerned with whether a product is a me‑too or a first‑in‑class innovation; what truly matters to them is whether the new product can effectively address real‑world production challenges and resolve key market pain points. Only such agrochemicals will enjoy strong market acceptance. The fundamental purpose of pharmaceutical R&D is to meet unmet clinical needs, and the same holds true for agrochemicals: their development aims to tackle unresolved pest‑ and disease‑control requirements in agricultural production. A good agrochemical is one that meets these needs, and a product that addresses critical, high‑impact demands stands the best chance of becoming a blockbuster.

From an academic research perspective, agrochemical scientists strive to identify entirely new targets and novel chemical structures, as this embodies academic innovation. However, the challenges of discovering truly novel targets and effective new scaffolds remain substantial. Even when both target and structure are entirely new, such compounds do not necessarily translate into blockbuster products. Moreover, from a regulatory standpoint, registering products based on entirely new targets and structures entails greater risks, given the many unforeseen factors involved. Therefore, a revolutionary shift in pesticide molecular design and R&D is imperative, while at the same time preserving and building upon time-tested, proven approaches. At present, many companies and research teams still rely on conventional synthetic‑screening‑based R&D paradigms. If a team possesses deep industry expertise and employs highly distinctive screening strategies, even traditional methods can yield promising new pesticides; thus, it is not accurate to dismiss conventional approaches outright. The ultimate goal of scientific and technological innovation is to address real‑world problems—more tools and methodologies generally lead to higher efficiency. Of course, integrating diverse technical pathways to deliver tailored solutions can also help meet a broader range of societal needs.

Source: ZhiGeng TechCube