Landcare Research - Manaaki Whenua

Landcare-Research -Manaaki Whenua

Developing species-selective novel control tools for pest control

Rat eating a fantail chick taken from its nest. Image - Nga Manu Images.

Rat eating a fantail chick taken from its nest. Image - Nga Manu Images.

Most vertebrate pest control has been achieved through the use of acute poisons and first- and second-generation anticoagulants. Collectively, these poisons have varying degrees of success but one common disadvantage – they are all broad-spectrum and pose primary and secondary non-target risks to humans, domestic pets, wildlife, and livestock. Moreover, these poisons variously pose risks through environmental contamination, accumulation in the food chain and a general lack of humaneness. These concerns are likely to become more prominent at the scale at which control would need to be undertaken to achieve Predator-Free New Zealand.

The increased worldwide concern and public disapproval of the use of broad-spectrum poisons for pest control means that regulatory authorities are imposing ever-increasing restrictions on their use. Clearly, there is an immediate, growing, national and worldwide need and opportunity for alternative ‘cleaner’ methods of pest control that provide greater safety at all levels, from governmentally and municipally controlled programmes for environmental protection, to the efforts of individual farmers and citizens to protect their food, crops and homes from pest damage.

Consequently, over the last decade Brian Hopkins and colleagues have progressed research programmes aimed at developing species-selective control tools. Their initial focus has been on developing new agents mainly targeting the rat as this pest is by far the most destructive globally, and its control depends heavily on the use of broad-spectrum anticoagulants.

Despite the millions of dollars spent annually in controlling rats, they still cause billions of dollars of damage worldwide to agricultural crops and stored foods. As vectors of disease, rats also pose serious health risks to humans and domestic animals, and are one of the invasive species most responsible, worldwide, for the loss of native biodiversity. This is especially so in ecologically fragile ecosystems of island environments such as New Zealand. Predation by rats is considered the fourth largest cause of decline of New Zealand’s native animal species.

Brian’s research to date has focused on two approaches. The first is based on peptide/protein differences between species, and the second is based on novel chemistry. These approaches represent a major scientific advance in the development of low-risk pest control tools.

The proteomic approach takes advantage of species-specific differences in the peptide sequence of cell surface proteins that are involved in key physiological processes of the body, e.g. respiration. Agents have been developed that when injected into animals specifically bind to the species-specific protein sequence, resulting in extensive cell death within key organs, e.g. lungs, and leading to an acute and humane death of the animal. To date, experimental agents that kill rats, mice, stoats and possums have been produced. Recent work has focused on optimising formulations of the agents to maximise the potential for oral delivery and minimise the cost of manufacture.

The chemistry approach is based on norbormide (NRB), a compound discovered in the 1960s that is selectively toxic to rats and relatively harmless to other rodents and mammals. In spite of its initial promise, this compound failed commercially due to palatability problems that resulted in sub-lethal dosing, bait aversion, and variable kill rates. All the usual methods to mask problems associated with potential taste affects (e.g. inclusion of a variety of palatable ingredients into bait), or unattractive physicochemical properties (e.g. microencapsulation) failed to increase consumption and efficacy in cage trials. Taking a leaf from the pharmaceutical industry, the team shifted its focus to the use of medicinal chemistry to overcome the inherent problems associated with NRB. Through manipulation of NRB’s chemical structure using a structure–activity relationship, Brian, in collaboration with the Chemistry Department, University of Auckland, designed, synthesised and screened more than 100 novel variants in an attempt to increase the palatability and efficacy of the NRB molecule. As a consequence, Landcare Research has patented several series of novel compounds that show a significant enhancement in rat-selective efficacy, and discussions are ongoing with industry partners for further product development.

Building on these successes, new funding is being sought to extend the range of pest species targeted, through a generic technology ‘platform’ based on genomics. Essentially, techniques commonly used in the pharmaceutical industry for elucidating disease mechanisms will be utilised to confirm the identity of the receptor through which NRB mediates its lethal response. This knowledge will then be used to identify NRB receptor equivalents in other key pest species for the development of alternative species-selective poisons. The same approach can be used to identify other relevant species-specific receptors suitable for as yet unknown orally-deliverable species-selective poisons.

Once validated this platform technology can be extended to a broad range of pest species including pest invertebrates and possibly even weeds, and will hopefully act as a catalyst for a paradigm shift in how pest control tools are designed.

This work was funded by the Ministry of Business, Innovation and Employment and government Core funding to Landcare Research.

Brian Hopkins