Altering Insect Brain Chemistry

Michael E. Adams, assistant professor of entomology, Division of Toxicology and Physiology, Department of Entomology, University of California, Riverside, CA.

Changing the brain chemistry of insects so they become disoriented and unable to function or reproduce, is an area of insect control that shows considerable promise today.

Insects continue to be a major problem in agriculture. Diverse control tactics are now being devised in the basic and applied sciences to manage pest populations. With the development of emerging biotechnologies, both chemical and biological elements could well be incorporated into the design of safer and more selective control agents.

Chemical Control Can Be Dangerous

Enthusiasm for synthetic organic insecticides in insect control has yielded to realization that they are strong, yet often dangerous medicine in the long term. Heavy insecticide pressure on genetically rich insect populations has led to resistant strains which are more difficult and expensive to control. Undesirable environmental and health trade-offs associated with chemical intensive agriculture also are becoming apparent. As a result, the number of safe, yet effective insecticides available to growers is decreasing rapidly in spite of the fact that chemicals often serve as the only reasonable way of dealing with unpredictable pest outbreaks. Insecticides will continue to be an essential option in integrated control strategies, and the development of newer, safer insecticides remains an important goal in agricultural research.

At the same time, there is an increased recognition that more traditional methods for insecticide discovery are too costly and time-consuming to be successful in the future. More sophisticated searching strategies are needed.

How Are Insecticides Discovered?

The evolution of today's major agricultural insecticides can be traced from two main origins. Some have their genesis in the botanical folklore of earlier cultures; for example, pyrethrum from chrysanthemum flowers, nicotine from tobacco, rotenone from Denis, and physostigmine from the Calabar bean. These naturally occurring substances provided model structures for many of the synthetic organic insecticides introduced since World War II, including the pyrethroids and the carbamates.

Other classes of insecticides were discovered purely by accident in exploratory synthesis programs geared initially for purposes other than insect control. These valuable discoveries gave rise to DDT, the organophosphates, and more recently, the formamidines and the avermectins.

Most modern day insecticides, therefore, have been modeled after existing botanicals or from lead structures discovered by chance. Efforts in agricultural chemistry have been primarily devoted to improving these structures, rather than being directed by any real knowledge of the inner-workings of insect pests. The obvious challenge becomes that of understanding and exploiting the unique features of insect life processes for the development of more selective control strategies.

Current research is demonstrating that many aspects of insect brain chemistry may provide clues for achieving selectivity at the physiological level.

The Insect Brain

The nervous system of insects, like that of all other animals, integrates and coordinates the functions of many organ systems in the body. Its component nerve cells relay information through the transmission of chemical signals called neurotransmitters. These endogenous brain chemicals are released in minute amounts between cells to regulate nervous activity and to store information.

The most effective of today's crop protection insecticides are nerve poisons acting to upset the delicate regulation of neurotransmitters within the brain. Unfortunately they are general toxins affecting brain chemicals common also to nontarget organisms, hence the high risk associated with their use. The goal of future insecticide development is to focus on the unique aspects of insect-specific physiological processes, thereby increasing the margin of safety for non-target animals. Because the insect brain is involved in critical, high-level coordination functions, it is a promising target for future insecticides.

In insects, the brain is a central command post which programs developmental, reproductive, metabolic and behavioral states at the appropriate times throughout the body. The brain does this by issuing chemical messages called neurohormones from specific nerve cells, which, in turn, orchestrate the precisely timed liberation of blood-borne hormones from glands. Their structural and physiological properties set them apart from the neurotransmitters, making them unique targets for future insecticides.

Can the brain as a control center be "short-circuited" through the disruption of neurohormone messages? The discovery and structure elucidation of insect neurohormones are proceeding now at a rapid rate and set the stage for answering such a question.

Critical Insect Brain Chemicals

Insects are highly specialized animals, and many aspects of insect physiology are by nature unique in the animal kingdom. A few examples illustrate the types of unique processes which may be vulnerable to future insecticides.

An obvious distinguishing feature of insects is their hard outer shell or exoskeleton. To grow and change form from larva to adult, a multi-step developmental process known as molting occurs in which the insect emerges from its outer shell several times on its way to becoming a reproductive adult. The timing and form of each new growth stage is programmed by two brain neurohormones which trigger the release of developmental hormones from specialized glands. The neurohormone, "PTTH," released from the brain causes the secretion of the molting hormone from the prothoracic gland. A second neurohormone, "allatotropin," activates the secretion of juvenile hormone from the corpus allatum, a pituitary-like gland directly behind the brain. By regulating the relative levels of juvenile hormone and molting hormone in the blood, the brain determines whether the insect continues its development as a larva or if it is to undergo metamorphosis to the adult form. It is likely that any disruption of the PTTH or allatotropin commands from the brain would prove lethal to the developing insect.

Another vital function associated with the molting process is the hardening and darkening of the exoskeleton. For a time immediately following the shedding of the old cuticle, the insect is soft and vulnerable. To speed the hardening of the new cuticle, the brain sends a neurohormone signal called bursicon to the integument where it catalyzes the appropriate biochemical reactions. Inhibition of bursicon release from the brain would effectively prolong the helpless, vulnerable state the insect finds itself in just after the molting process.

Reproductive processes also are driven by brain neurohormone commands. For example, reproductive females attract males through the release of volatile pheromones into the air from specialized abdominal glands. The brain initiates pheromone release by issuing a recently discovered neurohormone to activate the glands. Egg maturation also depends on a newly discovered neurohormone command from the brain.

Such examples show the importance of critical brain neurohormones that serve as high level command signals to the glandular system. These result in hormonally induced physiological states in the insect. It is the goal of researchers today to devise methods of altering these brain chemicals for the purpose of controlling pest insects.

Altering Insect Brain Chemistry

The basic idea involves changing the level of a particular brain chemical, either to cause overabundance or depletion and to thereby disrupt coordination systems vital to insect survival. The most direct method would be to flood insect systems with chemical analogs that mimic the actions of particular brain chemicals. The conventional insecticide nicotine acts this way on neurotransmitter receptors in the nervous system. An alternative method involves inhibition of enzymes regulating the levels of neurotransmitters in the nervous system, exemplified by the anticholinesterase insecticides.

These conventional insecticides operate in precisely the way we have envisioned for those of the future, namely to upset delicate levels of brain chemicals. But the conventional insecticides have the disadvantage of being very toxic to humans and non-target organisms as well as to insects. Efforts are now under way to direct future control agents toward brain chemicals, neurohormones, which serve as command signals for hormonal triggers in the insect endocrine system. By focusing on insect-specific neurohormones, it is hoped that problems of general toxicity to nontarget organisms will be avoided.