Biocontrol research: understanding what makes possums tick

Possum

Effective management of wildlife and pest species is becoming increasingly necessary throughout the world. Here, in New Zealand, the leading candidate for such management is the brushtail possum (Trichosurus vulpecula), our number one vertebrate pest in both economic and ecological terms. World-leading research being done in this country on new technologies to control possums could eventually have applications for the way other wildlife or pest species are managed here and overseas. But, for now, possums are the prime target.

Threat to trade, environment and tourism

Possums represent the principal wildlife reservoir of bovine tuberculosis (Tb), a major threat to the exporting of our dairy, beef and deer products. Production losses due to possums have been estimated at $40 million/year. That figure does not include intangible environmental and biodiversity values; nor does it include the potential costs to industries such as tourism through any damage to New Zealand's 'clean, green' image.

While conventional control methods – poisons and traps – are effective, the environmental, trade, public acceptance and cost risks associated with poisons may create difficulties for their continued long-term use. New tools are needed that can be used in conjunction with existing methods.

Biological management (biocontrol) offers technologies that may cost-effectively reduce dependence on conventional control methods and was identified as a priority research area by the National Science Strategy Committee for Possum and Bovine Tuberculosis Control. (See "What is biocontrol?" on page 15 for definitions of biocontrols.)

Formation of possum biocontrol centre

In July 2005, the National Research Centre for Possum Biocontrol (NRCPB) was formed through a partnership between the major research providers (AgResearch and Landcare Research) and key end-users: the Animal Health Board (AHB), Department of Conservation, Ministry of Agriculture and Forestry (MAF) and regional councils. The programme is funded by the Foundation for Research, Science and Technology as an outcome-based investment and co-funded by other organisations such as AHB, Otago University and MAF. A major review has been scheduled for 2009, where the continuation of the programme will be determined based on progress up to that time.

The primary objective of the NRCPB is to develop cost-effective and acceptable methods for the biological control of possums, and by working with end-user organisations to integrate these methods into improved strategies for the long-term management of possums in New Zealand. Achieving the NRCPB objectives will help reduce possum numbers along with the use of poisons and the welfare costs of possum management, while increasing the scale of the management effort.

Multi-stranded approach to research

The NRCPB's multi-stranded approach to biological control employs a diverse range of disciplines: reproductive biology, immunology, parasitology, virology, gut physiology, pharmaceutical science, ecology, social science and ethics. The research programme (Figure 1) comprises interlocking components that form a product development pipeline.

  • The programme starts with research to identify targets – either reproductive targets for fertility control or ion transport targets for the development of novel possum-specific toxins. A possum EST database has recently been made available that will assist in this area. An EST is a short piece of DNA that represents a gene that has been turned on. This database will aid in the discovery of new genes and expedite the evaluation of gene function.
  • Next is research to identify potential methods of elivery – either non-transmissible baits or live, genetically modified transmissible agents.
  • Finally, the different methods being developed are tested and refined. This also includes research to define the specifications of biocontrol products (efficacy, coverage, etc) andhow these products might be integrated with (or, in some situations, replace) existing non-biological methods. Modelling, based on field work, forms a major part of this implementation component. Informing each of these activities is a programme of ethical, social and communications research and activity.

Working models

Currently, a major focus is on developing working models that combine physiological targets and delivery systems. These model systems represent methods of fertility control that will either act directly at the target site or indirectly via the immune system, as well as toxins that target unique ion and water transport mechanisms in the possum. For fertility control, target molecules have been identified that, if inhibited, will significantly suppress possum fertility, and proof of concept studies have been completed to demonstrate how these molecules might be inhibited in a biocontrol system. The model systems are discussed below.

Doug Eckery
Associate Professor Doug
Eckery, member of the Science
Management Group, National
Research Centre for Possum
Biocontrol

Oral zona pellucida protein-based vaccines (immunocontraception)

The aim of this research is to develop a fertility control vaccine that inhibits reproduction (immunocontraception) and can be delivered as baits in the field.

The possum egg is surrounded by a protein layer called the zona pellucida (ZP) which is important for fertilisation and early embryonic development. The proteins that make up the ZP are attractive targets for immunocontraception because they are expressed only in the ovaries, are able to stimulate potent immune responses, and there are regions of the protein sequence that are specific to possums.

Vaccination of possums (by injection) against possum-derived ZP proteins significantly reduces fertility. Importantly, vaccination of non-target species (mouse and chicken) against these possum ZP proteins did not affect fertility.

The bacterial ghost delivery system is being investigated as a way to orally deliver a vaccine. This involves genetically modifying a harmless strain of bacteria to express possum ZP in their cell walls. The bacteria are then killed and the non-living empty bacterial shells or 'ghosts' are given to the possum. The possum's immune system recognises the bacterial ghosts as foreign and produces antibodies against them. At the same time, the possum is tricked into producing antibodies against ZP, causing a contraceptive effect. Researchers have recently shown that immunisation by the eye/nose route, using bacterial ghosts expressing possum ZP, significantly reduced possum fertility.

Oral hormone-toxin conjugates

The aim of this research is to target a population of cells that is essential to reproduction and to destroy those cells through the use of toxins that are linked to specific hormones. Two populations of cells are being targeted: gonadotroph cells in the pituitary gland and the eggs in the ovaries. Both cell types represent finite populations of cells that, if destroyed, would result in permanent sterility.

Fertility control using hormone-toxin conjugates utilises a hormone that binds specifically to receptors on the target cells. After the hormone binds to the receptor, the hormone and linked toxin are taken into the cells causing only those cells to die.

One hormone being investigated is gonadotrophin-releasing hormone. It is made by the hypothalamus and acts on specific cells in the pituitary gland that make essential reproductive hormones. Because hormone-toxins will act directly on target cells, they provide an alternative approach to fertility control that does not rely on the immune system. A critical component of this research is the development of methods to deliver these conjugates in baits (oral formulation). The use of polymerised nanoparticles is one technology currently being investigated to deliver bioactive molecules to specific sections of the gut, protect them from degradation and increase their uptake across the gut wall.

Oral gut ion transporter system toxins

Inducing water secretion into the gut can be a very effective and humane way to kill mammals. This research aims to identify and target mechanisms of water secretion for the development of possum-specific toxins.

In placental mammals, the secretion of chloride drives intestinal fluid secretion. Uncontrolled stimulation of intestinal secretion, as occurs with scours or secretory diarrhoea, rapidly kills animals.

In contrast, fluid secretion in the possum, a marsupial mammal, is driven by bicarbonate secretion. Therefore, if the components of this mechanism can be targeted in a possum-specific manner, stimulation of intestinal bicarbonate secretion has potential as a possum-specific means of control.

At present, the primary target is cystic fibrosis transmembrane conductance regulator (CFTR) which is a transporter protein found in the cells lining the intestine. Researchers are screening compounds for their ability to irreversibly switch on possum CFTR, but that have no effect on CFTR in placental mammals or birds. Other transporter proteins have also been identified and are being investigated as additional and/or alternative targets.

Transgenic possum-specific nematode (or virus) expressing proteins inhibitory to possum fertility

Possum biocontrols will initially be delivered in the field as non-transmissible baits. Ultimately, the use of a live, transmissible vector to spread biocontrols may be the most cost-effective way to control possums over large and/or inaccessible areas, many of which are currently not under any form of control. The aim of this research is to develop transmissible delivery systems using possum-specific nematodes or vir uses as vectors.

To date, two strains of a possum enterovirus have been identified and work is being done to understand the biology, pathogenesis, epidemiology and potential usefulness of these viruses. However, at present, the most promising candidate for a transmissible vector is the possum-specific nematode, Parastrongyloides trichosuri. Important progress has been made in the ability to genetically engineer this nematode so that it can stably express a biocontrol protein. A significant milestone was reached when it was demonstrated that a recombinant antigen delivered by a transgenic nematode could elicit a specific immune response in possums. Research to study possum immune responses to transgenic nematodes is being supported by MAF.

Social and ethical dimensions addressed

Any possum biocontrol will involve a new technology being applied to complex ecological and social systems. An essential component of the NRCPB is research addressing the social and ethical dimensions of these proposed new technologies. The aim of this research is to inform and encourage public discussion, identify and address societal concerns and, if required, indicate where research should be modified.

An ideal biocontrol needs to be both technically feasible and publicly acceptable. Public acceptance of these technologies will be a key determinant of success. Studies describing the range of concerns held by the public indicated that none of the methods currently being investigated were unacceptable. However, there were criteria that had to be met for them to be acceptable, including mechanisms to ensure effectiveness and safety and processes for public consultation and involvement.

Hence, the NRCPB has prepared a proactive communication strategy, using the different insights provided by examination of diverse ethics and beliefs, where importance of acknowledging and considering the issues and uncertainties of biocontrol are recognised. This strategy aims to encourage public participation through critical reflection and dialogue.

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Page last updated: 30 April 2008