Safer than ever, right from the start

Something all farmers know is that pests and diseases move fast. Imagine a silent, invisible army moving through fields of golden wheat, lush green corn or rows of vibrant vegetables. In mere days, this stealthy army of pests can transform a bountiful harvest into a farmer's worst nightmare.

Even with the latest and most sophisticated crop protection products to hand, pests can still develop resistance, and new diseases can always emerge. To farmers, it can feel like being locked in an endless arms race with a foe that is constantly adapting and threatening our food security.

So, developing new crop protection products for farmers is an urgent necessity if we are to safeguard food supplies for the future. The solution? A new generation of tools, powered by molecules designed with scientific precision to target these evolving threats.

But here’s the catch: getting these solutions from lab to field is a marathon, not a sprint. This time-intensive process moves from the initial stages of discovering a molecule with potential, designing a product candidate through iterative design cycles to exhaustive in-field testing and safety evaluation studies before eventual regulatory approval.

The whole development journey from a promising molecule to a farmer-ready product can take as long as 12 years, with a price tag that can soar into hundreds of millions of dollars.

On top of that, this kind of innovative discovery carries risks, as long-term safety studies can't be carried out until late in development. An alert at this stage, and cancellation of the product means a staggering loss of money and time. Those years of research spent designing a molecule that didn’t reach farmers could have been better spent elsewhere.

But what if we could change the game entirely?

A team of Syngenta scientists is leading a multi-million-dollar project using new technologies to ensure only molecules with the highest possible safety profile go forward to development, reducing risk and speeding up innovation.

Anthony Flemming, Principal Technical Specialist and one of the leaders on the project, explains that it's about ″using breakthrough technologies to identify potential risks, right from the first moment of discovery.″ Imagine a crystal ball that could see a molecule’s future right at the start before committing a decade of effort and funding. That is what these breakthrough technologies allow Syngenta's scientists to do.

To ensure safety, any product in development already goes through hundreds of different scientific tests, covering everything from how the molecule might perform against its target, to any possible negative impacts it might have on animals, humans or the wider environment.

Naomi Pain, who leads research in predictive sciences, says: ″We do a huge amount of testing to fully understand how a molecule behaves and interacts before it goes for regulatory approval.″

The four 'omics'

The new technologies are known informally as 'omics' – or to be more precise, transcriptomics, metabolomics, cell painting (phenomics) and proteomics.

Each one of these technologies offers the potential to unlock large volumes of high-quality granular data about novel molecules and how they interact with the components of cells, and what the potential outcome of these interactions might be.

This enables scientists to tweak the chemical structures of a molecule to achieve the perfect level of binding to its target and at the same time reduce any potential risk factors. Ultimately, this all helps ensure the safety and efficacy of new discoveries.

First, transcriptomics. This technology is starting to be used widely in pharmaceuticals, particularly in drug discovery and development. It offers a means of measuring the pattern of gene expression changes in a cell that result when the molecule interacts with it. Think of this as listening in to a cell’s internal communications to know which genes are chattering away and which have gone silent when a molecule comes knocking.

Flemming says: ″Understanding this allows us to predict potential downstream consequences.″ Certain changes in gene expression are a clear indicator that a molecule is unlikely to be a good candidate for development.

Syngenta’s own adoption of transcriptomics uses breakthrough sequencing and processing approaches that allow for cost effective, high throughput analysis. This means teams of researchers can assess large numbers of molecules far more quickly, speeding up the process of moving promising chemistry through development.

Next up: metabolomics. This allows scientists to look at the chemical constituents of a cell, and any changes that occur in response to chemical treatment. A cell is like a factory with many dynamic processes happening constantly, like production lines. Metabolomics provides a view of the status of these production lines. Understanding any changes that occur helps to identify potential concerns and select compounds with the most favorable profile.

Cell painting is, as the name implies, painting on a cellular level and results in some eye-catching visuals. In essence it is extremely detailed microscopy. Think of it like the world’s tiniest art studio, where scientists use molecular ‘paints’ to create a vivid and detailed portrait of a cell’s inner workings.

Finally, there is proteomics. Flemming explains it as ″a bit like fishing – you dangle the molecule into the bits of the cell and pull out the constituent part of the cell that stick to it.″ This allows for scientists to know far more precisely what a molecule is doing when it interacts with a cell, and which parts of that cell are being affected.

Four techniques equals more data than ever

To see how these technologies work together, let’s take the example of a very common chemical – ethanol, or as it is more widely known, alcohol. By using these four ‘omics, scientists can get precise data on how ethanol interacts with human biology.

Transcriptomics shows the ways that ethanol causes certain gene signaling pathways to kick into gear to clear the ethanol from the body, among other things. Using cell painting, the damage to cellular membranes caused by ethanol is crystal clear.

With metabolomics you can trace how ethanol breaks down, but you also get to see how ethanol and its byproducts impact the natural chemical processes that are always at work in healthy cells.

Finally, proteomics shows how, when ethanol molecules hit our cells, those cells produce proteins to break down ethanol and get it out of our system.

These techniques used in combination offer precise and unbiased insight into the impact a new molecule can have right at the cellular level.

In contrast to traditional methods of safety testing which can be expensive, time consuming and inefficient, and which depend upon having large quantities of a molecule to test, these techniques can be implemented right at the point of discovering what could well be a new active ingredient that protects crops.

Crucially, with as many as four million data points generated per molecule tested, this new technology allows for a colossal amount of data to be cross-referenced easily by the team from across all these technologies to form a holistic view of the behavior of a molecule and gain insights on any deviation from a 'healthy' profile.

But this internal data is just the start, as Pain says: ″We can also align the data we generate with other data sets to correlate responses seen in cells with whole animal effects. We utilize our own internal data, but also draw on external data from fields like pharmaceuticals.″

Cell painting enables us to examine the internal workings of cells.

As a result, Syngenta scientists are leading the way in using multiomics data at the earliest stages of molecular design, saving years of time and effort.

Pain underscores the impact of this safer by design approach to molecule development: ″We’re not just saving time and money but helping generate and optimize new chemistry that will get more safe molecules to farmers faster than ever.″

These new technologies and ways of working are ″miniaturized, information rich, more efficient and much faster - from a scientific point of view it's a win, win, win,″ she says.

In the end it comes down to this: with farmers needing to produce more food than ever and still reckon with nature's own evolutionary machine, humanity's best hope lies in the brilliant minds and groundbreaking technologies pushing the boundaries of what's possible. The future of our food depends on it.