Bio- or natural product based pesticides account for just 11% of the total pesticide market, compared with around 50% of the pharmaceutical sector that is bio-based, according to Ray Lam from Marrone BioInnovations. Speaking at the 2011 annual meeting of the US Society for Industrial Microbiology, he said the potential for biopecticides is huge at a time when harmful pesticides are being phased out and there is increasing pest resistance to existing products. In addition, there are declining numbers of approvals for new synthetic pesticides, due to fewer new leads, escalating costs and increased chemical screening needed to put a product on the market.
The growth rates in biopesticides, however, give an indication of their potential. Lam pointed out that their growth is outpacing that of conventional products, with a current 15.6% compound annual growth rate (CAGR) against 1.3% CAGR for synthetic pesticides. He added that, according to estimates by BCC Research, the biopesticide market will reach $3bn by 2014.
The principal function of any pesticide is to reduce the amount of food lost to pest damage, which is becoming increasingly important as the world’s population continues to grow. Lam estimated that current post-harvest crop losses amount to around $300bn, while losses due to weeds total over $40bn and to sucking insects stand at around $5bn.
As Susan Boyetchko, from the Canadian government agency, Agriculture and Agri-Food Canada (AAFC) explained, several factors are fuelling the need for biological alternatives. These include the banning of chemicals in urban municipalities; the development of pesticide resistance in crop pests; the demand for new products by organic farmers; and the recognition of hidden costs to human health and the environment of synthetic pesticides.
She pointed out that Canada’s public health agency, Health Canada, has classed biopesticides as reduced risk products that are less hazardous to human health and the environment. They therefore represent the next generation of pest control products.
The AAFC provides information, research and technology, and policies and programmes to achieve an environmentally sustainable agriculture, agrifood and agri-based products sector; one that is also competitive, innovative and proactively manages risk. Boyetchko said that within this remit, the AAFC is investing in biopesticide technology to replace synthetic compounds that have been banned or are less effective owing to increased pest resistance.
‘Selection and screening is the easy part of biopesticide development,’ she said, ‘It is the interaction of fermentation, formulation and application technology that is inter-related and the most complicated part....an holistic view is needed for this development.’
Boyetchko believes that the use of integrated pest management tools will lead to the successful adoption of biopesticides, and in addition to their applications for crops, the control of post-harvest/ storage diseases presents a major market.
In its development work, the AAFC uses an approach described by Byetchko as the ‘biopesticide innovation chain’, which takes biopesticide technology from discovery to industrial commercialisation. It begins with the selection of an appropriate target pest with a large market potential and ecological impact, and requires a thorough understanding of pest populations. Every stage of a biopesticide’s development is examined from initial bioprospecting through to optimisation and scale up, which can be achieved through domestic and international collaborations.
Two target pests currently of interest to AAFC are Phytophthora infestans, responsible for late blight in potatoes, and Erwinia amylovora, which causes fire blight in apples and pears. For the latter, the gram-negative bacterium Pantoea agglomerans is being used by the AAFC as a phage delivery system, which has been shown to be as effective as streptomycin in controlling the disease. For the successful development of such natural products, Denise Manker, from US biopesticide developer, AgraQuest, identified an understanding of modes of action and the development of analytical quality control assays as key factors, along with the protection of intellectual property and a focus on safety.
She emphasised that the registered active ingredient in the case of biopesticides is the microbe itself, but a single microbe can yield many molecules through process changes and metabolic pathway engineering. ‘It is the combination of the molecules that gives the effect,’ she said.
One mode of action involves disrupting pest cell membranes by replacing the existing lipopeptides with similar molecules, which cause pores to form in the cell wall, resulting in cell death. Her company’s Serenade product is based on specific strains of Bacillus subtilis, which produce iturins and agrastatins. These molecules are similar to phospholipids in cell membranes and operate synergistically to destabilise the pest cell membrane; individually they are ineffective.
She explained that the intellectual property protection here relates to the specific lipopeptides produced by AgraQuest’s microbe and not by other strains of Bacillus subtilis. Moreover, pest resistance is unlikely to develop because membrane destruction is difficult for pathogens to overcome, and products like Serenade can therefore be used as a protectant.
Nematodes represent a major problem with an estimated 28% of US crop acreage infested, costing over $5bn/year in crop losses, according to Gene Drago from Pasteuria Biosciences, based at the University of Florida’s Sid Martin Biotech Incubator. He said that losses for cotton alone total around $130m/year, while for peanuts, the losses total $82m/ year, and 40% of the US strawberry crop is ruined.
Nematodes are also a major problem on golf courses. Pasteuria Biosciences has developed Econem specifically for the professional turf market for golf courses. The product is based on Pasteuria usgae, which parasitises the nematodes with the release of the organism’s spores when the nematodes die, thereby continuing the protection.
Econem is effective against the Sting and Lance nematodes, according to Drago, and offers ‘virtual elimination’ of nematode populations, resulting in up to four times stronger root growth than in untreated turf. The product has also been shown to increase cotton lint yield and has been used as a seed treatment. Drago added that his company has entered into a technical agreement with agro major Syngenta for further seed treatment development for soya bean.
Marrone is also developing a range of biopesticides. For example, Zequanox, based on Pseudomonas fluoroscens, ruptures the gill cells of mussels but is safe for fish, clams and other similar water species, including mussels that are cultivated commercially as a food product. Mussels are a particular problem in water treatment plants and power plant water supplies. According to Lam, the specific chemical entity responsible for the effect has been identified as γ-dodecalactone.
Originally live P. fluoroscens bacteria were used to clean up the plants, but regulatory authorities in North America require that dead bacteria only should be released into the environment. As a result, development work was required to stabilise the active ingredients and enhance dispersability to produce a product that would be ingested by the mussels. One liquid and two dry formulations have been developed and Marrone is waiting for approval from the US Environmental Protection Agency for a product launch in late 2011 or 2012.
Marrone is also developing a bioinsecticide, MBI 203, based on a species of chromabaterium (sub stugae) licensed from the US Department of Agriculture’s Agricultural Research Station, for the control of sucking insects. The new biopesticide has a broader spectrum of activity than neem and pyrethrums, but is safe for bees.
Another bioinsecticide, MBI 206, which Lam said is similar to Dow’s synthetic product Spinosad, is based on the discovery of a new species of bacterium with a broad spectrum effect on caterpillars, mites, thrips and houseflies.
Marrone is developing two bioherbicides. The first, MBI 005, is a selective product based on Streptomyces sp., aimed at controlling broad leaf weeds, which Lam said improves the efficacy of synthetic turf herbicides. Since the wild strain used is not stable, however, current work is focused on strain development.
The second bioherbicide, MBI 011, is sarmentine, a pyrrolidine compound isolated from a Chinese pepper that can also be manufactured synthetically and has good activity against most grasses and many broad leaf weeds. The compound is unstable when exposed to light, heat and oxygen, however, so work began earlier in 2011 to develop a stable liquid concentrate with a target shelf-life of two years.
Shelf-life and safety both have to be taken into consideration when developing a biopesticide. AgraQuest’s Manker emphasised that natural doesn’t necessarily mean safe because the dose can be the poison. It is essential, therefore, that the chemistry of the individual molecules produced within or by the microbe involved is fully understood. ‘Even the gases, the volatile organics (VOCs), produced by the microbe may have pesticide activity,’ she added.
Manker also explained that because of their novel nature, in some cases the Environmental Protection Agency’s regulatory tests are not applicable, quoting as an example tests for the potential impact on bees. With bee populations crashing around the world, there is great concern that pesticides may be implicated.
Rather than just testing the effect of a new biopesticide on individual bees, therefore, she said her company tests products in real situations, checking not just for toxicity against individual bees but also for the potential effect on the hive itself, which is not currently required by the EPA.
Lam echoed these comments saying that while initial testing usually takes place in the greenhouse, controlled field trials are essential to check efficacy and identify any potentially harmful effects.