Launching a new active ingredient – the secrets behind the success
Dow AgroSciences Crop Protection Scientist Mike Loso has spent most of his near 30-year career on a voyage of discovery. Reflecting on the recent launch of Isoclast™ active, Mike suggests that there are 3 key ingredients in the recipe for the successful discovery and launch of a new active ingredient: curiosity, collaboration and perseverance.
‘Having the right mind-set from the beginning is absolutely vital’ Mike contends. ‘You really need to be curious and open-minded – to be willing to pursue lots of ideas knowing that most may not pan out. You must continuously be asking ‘why’ when trying to make sense of experimental observations, particularly trends and outliers. And asking ‘what if’ in formulating and testing new ideas and hypotheses. You are constantly learning and asking ‘why’ – it’s essential to innovating. Interestingly, it’s sometimes the simplest observations that lead to those ‘Aha!’ moments. And they’re the ones that can really change the direction of a project’.
This notion of continuously enquiring minds coupled with scientific rigour was the foundation for the Isoclast breakthrough. The original idea came from a now retired Crop Protection Discovery Research Fellow who was intrigued about investigating small, underexploited chemical fragments, or ‘novel bio-active scaffolds’ as building blocks for larger, novel molecules for screening. Working in collaboration with a small team, he set out to synthesize and test a number of different sets, or ‘libraries’, of target compounds. Despite the lack of bio-activity in the initial sets of compounds, the team persevered in exploring and refining the original idea.
Scientific curiosity and teamwork played a crucial role in the optimization of the lead molecule. As is usual for the development of most commercial crop protection active ingredients, extensive optimization of the initial lead molecule is required to achieve the biological attributes needed for commercialization. For Isoclast, the original lead molecule still lacked the commercial activity necessary for advancement and so a ‘Lead Optimization’ team was brought together to understand and optimize the structural features of the molecule responsible for insecticidal activity.
‘In trying to optimize a lead molecule, we always work with a hypothesis based on observations or insights and generate the experiments that test these hypotheses along the way’, Mike noted. ‘We realized that there was a key interplay between two key parts of the molecule and it was this observation that eventually led to the structural modifications that ultimately became Isoclast™ active’. We also identified that there was no cross resistance to key classes of existing insecticides and so we used a hypothesis based on atom arrangement and charge density and designed an experiment to test it. We concluded that Isoclast is not susceptible to the same metabolic pathways in insects as existing commercial insecticides that operate in the same market area’, he said.
Collaboration and perserverance in the innovation journey are essential. ‘In reducing the original idea to practice, a small team explored and, based on bio-activity analysis, continuously refined various compound libraries and eventually identified a lead molecule with strong aphid activity. Similarly, in the optimization phase, teamwork and tenacious persistence was vital in developing the many hypotheses associated with analogue enhancements and testing protocols. Finally in the development phase, cross-functional teamwork was needed to meet the challenges associated with bringing a molecule through development to the marketplace. These collective contributions gave us both the confidence that we were selecting the right molecule and contributed to building a strong intellectual property estate for Isoclast.’
Continuously asking ‘why’ and what if’ provides the scientific due diligence needed for advancement. ‘Knowing that you have identified the most effective molecule, then subjected it to the most rigorous testing gives you the confidence that it is the optimal option to pursue. The input and ideas from a wide variety of scientists ensure continuous peer-reviews that are an integral part of a rigorous R&D process’ Mike said.
‘The final ingredient for success is perseverance’, Mike suggests. ‘Every project has its hurdles and challenges which is why the input and efforts of a wide variety of scientists and functions is so important to encouraging the push forward, even when progress is slow.’
‘Discovering, developing, and ultimately launching a new active ingredient to the marketplace is an extremely challenging endeavour. But the odds of success can be enhanced by several key factors’. Mike concludes. ‘Have a curious and open mind-set, ensure a collaborative environment with a talented group of colleagues, and have the confidence and perseverance to be able to innovate and overcome obstacles.’