Eighty three delegates met at Syngenta’s Jealott’s Hill Research Station on Wednesday 9 September 2009 to hear seven internationally acclaimed scientists speak about the future of agricultural research. The meeting was organised by the BioResources Group of SCI as a celebration of the work of David Lawrence, the retiring R&D Director of Syngenta and was special in that R&D Directors or senior managers from competing companies in Europe and the USA chose to contribute.
The seed as delivery mechanism
The meeting began with a talk from Martin Battersby (Syngenta Seeds) who addressed ‘The seed: an ideal delivery mechanism for customer benefits’. Four fundamental agricultural technologies have together contributed to the growth in global food production: Seeds; Crop protection; Fertilisers; and Mechanisation (including irrigation). These technologies combine to increase and protect yield and to enhance the quality of the harvested product. The value of seeds has been growing as new customer benefits are built into the genetics of modern crop varieties and hybrids. The value of high-quality high-yielding seed to growers is well known, but benefits delivered through the seed can also meet customer needs throughout the value chain and can be derived from GM approaches and/or 'native trait' discovery coupled with marker-assisted breeding.
Thanks to advances in plant science, seed research today can tackle challenges like creating flavour-enhanced fruit and vegetables – and achieve this more predictably than has previously been possible. In addition to benefits derived from the genetics packaged in the seed, seed treatments can protect the seed in its early stages of germination and growth, bringing benefits which translate into higher yields. But beyond such conventional seed treatment with fungicides, nematicides and insecticides we are now seeing useful incremental 'cropenhancement' effects from the interactions of chemical and genetics. These synergistic interactions provide additional seedling vigour, even in the absence of pests, and result from chemical seed treatments working with the genetics to boost the plant’s performance. This just adds to the value of the seed as a vehicle for effect delivery.
New genes in agriculture
David Fischhoff (Monsanto) in his talk ‘New Genes in Agriculture – Beyond Two Traits and Three Crops’ summarised the first decade and a half of commercial crop biotechnology. This has been very successful with the 2008 global planted area exceeding 300 million acres (140 million hectares). The total added value brought by crop biotechnology in the 12 years since the first trait launch in 1996 has been estimated to be over $44 billion. The first generation of crop biotechnology traits focused on systems for insect and weed control and in the future, the market will continue to demand improved traits for insect and weed control with new products providing multiple modes of action against pests through the combination of up to eight different genes, enhancing the consistency and durability of yield protection for growers.
In soybeans and cotton, the stacking of dicamba herbicide tolerance with glyphosate tolerance can offer effective management solutions for even difficult weeds. The expansion of this technology into crops like sugarcane focuses on supporting emerging demand in these markets. Traits that protect yield potential will continue to be important, but the development of traits that target intrinsic yield improvement and abiotic stress control, such as drought-tolerance and nitrogen utilisation efficiency, can represent a step-change in crop yield performance by improving productivity. For example, development of soybeans containing a trait for intrinsic yield improvement has resulted in an average yield increase of 7.5% over negative isolines across four seasons of testing on two continents. Efforts to deliver this type of trait in corn are also advancing and, as in soybeans, focus on enhancement of yield on a broad-acreage scale. Traits such as these can also play a role in reducing the environmental footprint of agriculture by producing more yield per unit of inputs such as land, energy and water. The World Economic Forum recently predicted that by 2025, water scarcity could affect annual global crop yield to the equivalent of losing the entire grain crops of India and the US combined, representing 30% of global cereal consumption.
Monsanto’s drought-tolerance research in corn works to address different types of drought conditions, such as areas with routine water stress or areas that experience only periodic drought pressure, to develop products with broad applicability. Nutritional quality is also a key focus area for crop biotechnology. The major emphasis for Monsanto has been the development of improved soybean oils with the new Vistive soybean product continuing to offer low linolenic fatty acid levels to help eliminate the need for hydrogenation and the resulting trans fats created in the process. Additionally, it will contain lower saturated fat levels and boost oleic acid content to create an oil profile similar to olive oil. Enhancement of stearidonic acid levels in soybean oil could represent a land-based source of omega-3 fatty acids similar to levels found in fish oil without the resulting flavours. The ability to enter a new frontier beyond two types of traits in three crops has been enabled by advancements in several technologies such as high-throughput genotyping, genome sequencing, functional genomics, plant transformation and RNA interference. The next decade of crop biotechnology traits holds the promise for meeting global demands for food, feed, fibre and fuel.
Molecular genetic variation
John Bedbrook (DuPont/Pioneer) gave a talk entitled ‘Using a Molecular Understanding of Native Genetic Variation to Enhance Crop Productivity’. We were told that maize is one of the most genetically diverse species known and to use this diversity in product development we need to understand the relationship between molecular diversity, as exemplified by DNA sequence, and phenotypes of interest to plant breeders and customers. Several years ago Pioneer embarked upon a large germplasm characterisation project at the single nucleotide polymorphism (SNP) and SNP haplotype level, by sequencing 10,000 genetic loci in >600 inbreds, resulting in the identification of ~50,000 SNPs organised in haplotypes at known locations in the genome.
Pioneer also initiated comparative genomic hybridisation to expand the understanding of diversity to gene copy number variants and expression quantitative trait loci (QTL) mapping (expression level measured by microarray is used as a phenotype), to distinguish cis and trans regulation of gene expression. These tools enable positional cloning of rare genes/alleles from exotic sources followed by marker assisted rapid introgressions and genetic association mapping of genes/alleles responsible for common variants in elite germplasm followed by marker assisted selection in breeding crosses. Pioneer is using these approaches to accelerate the rate of genetic based gains in productivity in maize.
John Pickett (Rothamsted Research) addressed the question ‘How can biocontrol be realistically delivered?’ He considered the role of GM as a major intervention for reducing losses by pests, diseases and weeds. Unfortunately, we were told, the genetic bases from which our current elite crop varieties are derived are far too narrow to allow development, by breeding alone, of sustainable pest and weed control, even if possible for pathogens. However, molecular genetics has moved rapidly and instead of having to rely on the expression only of bioactive proteins and polypeptides, we can now realistically manipulate the biosynthesis of small lipophilic molecules (SLMs) that can more effectively provide the needed protection for our crops and livestock, but potentially with intrinsically more benign mechanisms.
Research has shown that small molecules are released by sucking insects when they are challenged by a predator and that these volatiles attract additional predators as well as causing the aphids to disperse. Is it possible to breed crops that release these alarm pheromones? Cisjasmone has induced natural defence mechanism in plants following insect attack and has even been shown to protect crops from nematode attack. Can such a system be incorporated into crop plants? To date, SLMs have served principally as leads for largely synthetic pesticides. However, because these compounds have modes of action relating to single gene products, resistance by the pests is a major problem. This is compounded by the perception, mostly illinformed, that, as toxicants are mostly neurotoxins, these compounds are intrinsically damaging to the environment and human health.
Therefore, in planning the new generation of GMOs for delivery of pest control, to target the natural SLMs that affect in more sophisticated ways behavioural and developmental processes in the pest organisms by acting by non-toxic modes of action. These are exemplified as insect pheromones and other semiochemicals, but will need to be managed by a further development involving 'switching on' the biosynthesis genes by means of another set of SLMs that act as plant activators or gene switches. In addition, the legume Desmodium uncinatum as an intercrop has been shown to protect crops from Striga attack. The active substance is thought to be a flavone. This represents a new opportunity in weed control currently being rapidly taken up in sub-Saharan Africa.
Phillip Lane (BASF) spoke on ‘The Role of Biological Fungicides in Conventional Agriculture’. Crop productivity can be subdivided into four main aspects – availability, quality, affordability, and predictability – which all make important contributions to ensuring adequate food supply. The grower, the retailer and the consumer all have their own needs and expectations in the crop food chain. If we focus on fruit and vegetable crops, consumers demand safe and healthy produce which looks attractive and has no blemishes. The retailer in turn, requires uniform produce that meets his conditions for size and shape and in addition demands produce with residue levels below the safety levels or even absent. The grower must protect his crop against pest and diseases, meet the requirements of the retailer that he supplies and in addition his produce must be in top physical condition.
The demands on the grower lead to a dilemma with respect to protecting his crop. On the one hand, he is expected to produce a crop that is inexpensive, unblemished and in top physical condition, and on the other it should meet exacting demands for residues from chemicals that he uses to protect against such damage. This is particularly acute in the later stages of the crop, just prior to and during the harvesting periods where many crop protection chemicals cannot be used. If an attack occurs later in the season the grower risks a significant reduction in the value of his crop, and in extreme cases complete crop losses with financially disastrous consequences. The presentation discussed the suitability of biological fungicides as a solution for the grower’s dilemma: The concept of biological fungicides is not new. In general biological fungicides have struggled to compete with chemical fungicides in conventional agriculture due to their generally lower efficacy and narrower spectrum. However, they have the advantages that they are usually rapidly degraded and have low pre-harvest interval and reentry times. Extensive trials data showed that the use of the biological fungicide Bacillus subtilis QST 713 (Serenade) when used in combination (sequentially or in mixture) with conventional fungicides gave excellent disease control and also reduced chemical residues in the crop and contributed to delaying the onset of resistance.
Ralf Nauen (Bayer CropScience) addressed ‘Strategic aims and challenges in insecticide discovery’. He emphasised that the number of insect biochemical target sites of real economic importance is rather limited. These days a substantial effort in labour and costs is necessary in order to obtain a single commercial product, meeting ever increasing demands concerning regulatory factors other than insecticidal efficacy. Due to a falling success rate in agrochemical discovery a steady increase in the number of tested compounds is necessary, but this is also accompanied by a technological evolution in chemical synthesis and screening automation and miniaturisation, allowing higher throughput.
However, the latest version of the Mode of Action Classification scheme of the Insecticide Resistance Action Committee (IRAC, www.irac-online.org) lists 26 insecticidal target-sites, including 11 nerve and muscle targets, 7 growth and development targets, 6 respiration targets, one midgut target and 8 compounds with unknown or uncertain mode of action. This is worse because at least 80% of global insecticide sales account from compounds binding to just four different target-sites, all involved in insect neurotransmission. The latest chemical class of insecticides with outstanding economic impact in the agrochemicals industry comprises the neonicotinoid insecticides, acting agonistically and with high selectivity on insect nicotinic acetylcholine receptors, and introduced in 1991. Novel target-sites with fairly recent market introductions of new chemical classes are the ryanodinesensitive intracellular Ca2+ release channels and acetyl CoA carboxylase.
These new chemical classes (diamides and ketoenols) show not only excellent potential against resistant pests, but also some other outstanding properties such as IPM suitability (both classes) or ambi-mobile translocation behaviour in crop plants (ketoenols). Dr Nauen cleverly showed the limitations of the currently available insecticides by describing the situation in Germany for the control of hop aphid (Phorodon humuli) with reference to the IRAC mode of action list. When biological activity, resistance and regulatory clearance were taken into account there was only one compound available to hop growers to control aphids! (The German regulatory authorities have realised the seriousness of the problem and have granted clearance for use in hops of the recently banned OP insecticides.)
The major challenge in modern applied entomology is the management of insecticide resistance. Whereas some of the world’s most destructive insect and mite pests have developed resistance to many established chemical classes of insecticides, newer classes of insecticides introduced for their control usually provide good activity. These modes of actions need to be conserved by implementing resistance management strategies for sustainability, both of the insecticidal efficacy and crop production. This is considered of utmost importance, and is reflected in the development scheme of a new insecticide by considering strategic plans for life-cycle management as early as possible.
Innovation: past and future
The final presentation was given by David Lawrence (retiring Syngenta R&D Director) and he addressed ‘Innovation: past and future’. We were told that overall, the agrochemical industry is managing to develop significant new AIs, despite the fact there has been major consolidation and reducing investment in the industry. This success contrasts with that in the pharmaceutical industry, where the number of new drugs approved has fallen despite significantly increased R&D spend. However, there have been major changes in the discovery process over the last 30 years. He reviewed the success of different approaches to agrochemical innovation and concluded that despite advances in scientific understanding and massive automation, lead generation still depends on individual creativity, though 'factory' approaches to biology and chemistry have greatly helped in optimisation. Transgenes have made a huge commercial impact through GM crops, primarily maize, soybean and cotton. However, given the investment over several years, the rate and diversity of transgene innovation is surprisingly low, and as yet it is hard to define a model for success.
Recently, the focus for transgene innovation has shifted from pest control to agronomic traits, such as drought and heat stress tolerance and nitrogen-use efficiency. Largely coincidentally, it has been found that a significant number of ingredients developed as pesticides also directly increase plant yield (many Syngenta’s products!). In this light, the failed industry attempt to develop chemical plant growth regulators in the 1970s and 1980s was re-examined, and attempts made to draw lessons from this of relevance to transgene innovation, and the renewed ambition to extend plant performanceenhancing chemicals. Over the same period of review, the global population has continued to increase and affluence has changed and increased consumption. This, combined with predictions of increasing climatic volatility and the need to transition to a lower carbon economy, has made food security a major, visible global challenge. Overcoming this challenge will require continued innovation.
There were also seven posters:
Agrochemicals with Bioenergetics-related Modes of Action: Inhibitors of Respiration or Photosynthesis from Janet Phillips (Syngenta)
A Method For Detecting the Actions of Neonicotinoids on Spontaneous Neuronal Activity in the CNS of an Aphid from Melissa Peter and Jim Goodchild (Syngenta)
Agro-process intensification using agromicrobioreactors as soil additives from Galip Akay and David Burke (Newcastle University)
The application of LCMS as a replacement for radioisotopic labelling in ligand binding studies from Andrew Crosswaite, Melissa Peter, Mark Drossopoulus, Dave Portwood, Mark Seymour and Fergus Earley (Syngenta)
A method for detecting the actions of neonicotinoids on spontaneous neuronal activity in the CNS of an aphid by Melissa Peter and Jim Goodchild
Using Drosophila genetics to support insecticide invention in the agrochemical industry from Lucy Firth, Anthony Flemming, Marcus Guest, Julia Hill, Jenny Pennack, Melissa Peter, Wendy Terry and Jim Goodchild (Syngenta)
Caenorhabditis elegans: a novel system in agrochemical discovery from Anthony Flemming (Syngenta)