Flavocide: Taking a new insecticide from leaf to lab

Pest control is on a precipice. Harmful bugs have become increasingly resistant to our insecticides. Meanwhile, misuse of the same treatments are threatening beneficial insects that we need to help us protect and pollinate our crops.

It's clear that a transformation in pest management is needed, and fast.

Fortunately, a collaboration between us and an innovative Australian company could help us to turn over a new leaf.

The buzz on insecticides

Some years ago, the founders of the Australian agtech company, Bio-Gene Technology Ltd, began searching for unique insecticidal compounds contained in Australian plants.

Their search led them to a unique eucalyptus variety that contains an effective pest-fighting class of chemicals: beta-triketones. These natural compounds have evolved to be markedly different from existing insecticides. They kill unwanted pests like mosquitoes, flies and ticks in a unique way, with minimal impact on bees and other beneficial insects.

Bio-Gene recognized that these compounds could play a vital role in pest management. But they knew it would take sophisticated research infrastructure and expertise to harness their potential.

Scaling up with science

Peter May is the Executive Director of Research and Development at Bio-Gene. He said natural extraction is possible for some beta-triketone compounds, but chemical synthesis is more cost-effective for others. This is important for large-scale production and deployment.

"We knew that synthesis would be necessary to achieve our vision, but we would need help. Given CSIRO's stellar reputation, state-of-the-art labs and top-tier scientists, we knew they were the perfect partner," Peter said.

"Together we embarked on a mission: to create a synthetic, nature-identical version of a key beta-triketone and transform it into an efficient, commercially viable, eco-friendly pest control solution."

Adam Meyer, CSIRO Principal Research Scientist and project leader, said the process wasn't straight-forward.

"We went through four distinct projects, refining and improving the processes and product with each phase over five years," Adam said.

"In the beginning our main aims were to reduce the cost and complexity of the manufacturing process while improving the product yield.

"The end result was a brand-new bio-identical product dubbed 'Flavocide,' and a synthesis process that was safe, cost-effective and positioned for large-scale manufacture."

For the Bio-Gene team, one of the project's greatest achievements was finding a way to recover and reuse a significant raw material in the manufacturing process.

"Through recycling, the CSIRO team demonstrated we could recover over 80% of this key ingredient thus improving the sustainability of the process and significantly reducing production costs," Peter said.

He noted our role didn't end in the lab.

"CSIRO's invaluable support included assisting us to obtain grants. We participated in their Kick-Start program, which offers Australian start-ups and SMEs the opportunity to collaborate with researchers to optimize their products and grow their businesses," he said.

"We really appreciated having a partner we could trust and who had access to expertise and facilities to deliver high quality research."

Flavocide offers targeted bug busting

A "mode of action" refers to how insecticides affect pests on a cellular or molecular level. Flavocide's is completely different from other insecticide products.

The new mode of action addresses insecticide resistance, which happens when insects evolve ways to counteract known treatments.

"The fact that pests have never encountered this sort of insecticide means Flavocide will work where other solutions are failing," Peter said.

"This is no small feat. In humanity's ongoing battle against pests, less than forty different specific modes of action have been identified and classified."

Deadly to pests, a lifeline for bees

In addition to the project with CSIRO, Bio-Gene has conducted extensive independent testing using Flavocide.

"Bio-Gene's testing partners found that Flavocide has demonstrated effectiveness in tests against a variety of harmful insect pests including whitefly, aphid, shield bug, mirid, and planthopper species. All of these threaten crops globally," he said.

"Flavocide is also a potent adversary to disease-spreading mosquitos. This includes Anopheles gambiae (which spreads malaria) and Aedes aegypti (which spreads dengue and Zika viruses). And it promises to be an effective means of controlling harmful ectoparasites such as mites, ticks, flies, and lice in animals."

Flavocide could be a powerful enemy for these unwanted pests. In addition, studies commissioned by Bio-Gene indicate it is up to 5,000 times less toxic to bees upon ingestion than existing treatments.

But Peter says it's not just bees that are safer.

"Bees are just ones of the beneficial insects in our ecosystem. We have other allies, like parasitic wasps that prey on pests and protect our crops," he said.

"We have undertaken research which showed Flavocide to be safer than a commonly used insecticide for some key beneficial arthropods that are crucial for high-crop yields.

"Moreover, eco-toxicity assessments found reduced environmental impact of Flavocide in aquatic environments. Indeed, a preliminary test found no detrimental effects on any species from Flavocide use, even at the highest concentrations tested."

Fighting pests to protect public health

Bio-Gene believes Flavocide could also deliver positive health outcomes for humans.

"Flavocide shows great potential to help in the fight against vector-borne diseases like malaria, dengue fever, Zika virus, and even Lyme disease by combating the insects that transmit them," Peter said.

"Collectively, these diseases result in millions of infections and take hundreds of thousands of lives year on year. Indeed, in 2021, malaria alone caused over 600,000 fatalities out of an estimated 247 million cases globally."

Going global

A brilliant idea, coupled with CSIRO's expertise, resulted in an efficient synthesis process and a potentially game-changing product.

Since then, Bio-Gene has gone on to forge overseas manufacturing partnerships to enable production of hundreds of kilograms of Flavocide. This is an important step in further proving the scalability and commercialization potential of the technology.

They have also turned their attention to securing registration and commercializing the product in multiple markets around the world.

This has included large-scale field trials with a key mosquito control product supplier in the U.S. and with other multi-national companies in other market areas. In addition, they have been working with the Grains Research and Development Corporation to progress Flavocide as a grain protectant against stored grain pests. Flavocide will also be registered with the Australian Pest and Veterinary Medicines Authority (APVMA).

But even as the enterprise expands globally, Peter said the relationship with CSIRO endures.

"Bio-Gene continues to maintain a research service engagement with CSIRO and we reach out if we need advice. CSIRO's support to our manufacturing programs has been indispensable, and we will continue to draw on their expertise and experience as we commercialize our technology in public health and plant protection markets."

Provided by CSIRO