Could engineering crops save our food systems?

Modern agriculture faces unprecedented challenges. Climate change is bringing longer droughts and greater risks from pests and diseases. At the same time soil degradation, fertiliser run-off and rising global demand are stretching food systems to their limits. Traditional breeding can’t alter crops fast enough to match the pace. 

Crop plants originally evolved to grow in different wild environments and are not optimised for agriculture. But what if the innate ability of plants to alter their growth and metabolism in response to their environment could be tuned? Can we enhance their ability to take in nutrients, to improve fertiliser uptake and reduce run-off? Could we strengthen their capacity to produce defensive compounds to ward off pathogens and pests?

Enter the rapidly maturing field of synthetic biology. Synthetic biology aims to precisely program living organisms with predictable functions, applying engineering principles such as modularity and standardisation to speed up the design-build-test cycle.

With synthetic biology products now beginning to appear in manufacturing and medicine, UK researchers are making strides in applying the field’s approaches and techniques to plants to address some of the challenges facing agriculture. 

The promise and challenge of synthetic biology

Humans have been engineering the natural world for millennia, ever since we started farming seed-producing grasses and eventually bred wheat. We chose the best varieties of apple to crossbreed for size and sweetness. We bred miniature dachshunds to go down rabbit holes and Great Danes to hunt bears. We domesticated yeast to ferment bread and beer.

But last century, we made huge technical advances, building bioreactors to make antibiotics, vaccines and insulin. We discovered the structure of DNA and how to read its sequences and copy it. 

Armed with this knowledge, in the 1990s, researchers began swapping genes into crops, bringing pest resistance to cotton and herbicide tolerance to soybeans and corn. Sometimes this had unintended consequences, such as when these plants bred with wild relatives or weeds developed resistance to herbicides.

Now these powerful but imprecise techniques have been augmented by genome editing tools – hallmarks of this era of synthetic biology. These techniques, such as CRISPR, allow us to precisely target sections of DNA, to modify, remove or insert individual DNA ‘letters’.

Professor Jim Haseloff at the University of Cambridge is one of the UK’s leading figures in synthetic biology. He believes the future depends on engineering biological systems in ways that let us coexist sustainably with the planet – not just in food production, but also in materials, chemicals and energy.

As Haseloff puts it, biological systems are “inherently modular.” Every gene is made up of four chemicals, bases, that are the ‘letters’ of DNA. “[Evolution] happens through tweaks and changes,” he says. “Step by step, base change by base change.” It is this modularity that allows genes to be rewritten – and in turn the proteins and biological pathways they code for – without collapsing the whole system. 

Living systems evolved to work in this compartmentalised way because it has many advantages. Modules can evolve independently, be repurposed, combined, or even sustain damage without necessarily affecting the overall system. 

For a synthetic biologist, a module is any self-contained, functional unit that performs a specific task. This could be a gene, a network, a metabolic pathway, or even an organ. 

These elements can – in principle – be treated similarly to inanimate modular elements such as those used when constructing a bridge. But while biological systems can be designed, built, tested and learned from, there are caveats to engineering them.

“Most engineering projects outside biology will be driven by a blueprint, where you’ve got a master plan,” says Haseloff. “The connection between components is much more straightforward.”

Biology, on the other hand, is complex and dynamic, with unpredictable obstacles. Because biological systems adapt and evolve, the module a researcher is working with can change unexpectedly. This is, says Haseloff, “the big challenge” of engineering biology.

“If we want to take advantage of the power of biological systems, harness the ability to grow the most complicated structures that we know from simple ingredients like glucose, those are the kinds of problems we have to grapple with.”

Systems challenges

The past decade has seen the first precision-edited crops made commercially available. In the US, there is a soybean gene-edited to produce no trans fats in its oil, and the Sicilian Rouge High GABA tomato, sold in Japan, promises higher levels of the neurotransmitter GABA (which some claim boosts relaxation). 

But as yet, no gene-edited crops on the market are designed to tackle large-scale agricultural challenges. Dr Nicola Patron, a plant synthetic biologist at the University of Cambridge, wants to change this. As well as working to improve the existing abilities of crops to produce antifungal agents in response to infection and growth in response to nutrients, her group is also engineering plants as factories to produce novel products for agriculture. 

Patron aims for her work to result in products, “that genuinely [reduce] the environmental impact of food production, whether that’s a crop that needs fewer fertilisers or a natural product that replaces chemical pesticides.”

In 2023, Patron and colleagues engineered a wild relative of tobacco (a model organism in plant biology) to produce insect sex pheromones.

These chemicals disrupt the breeding behaviour of pests, so could reduce pest numbers on crops, and in turn, reduce our reliance on pesticides that also harm pollinators and predators. Insect pheromones have been used in organic farming practices for several decades, but are currently only available for a small number of insects. Production from living cells could expand this to a wider range of crop pests.

The group has also set its sights on trickier systems engineering problems, such as modifying key traits that are decided by many genes wired into complex networks.

Patron’s team is rewiring a network in lettuce, the UK’s most valuable leafy vegetable crop, to help the plant fight fungal diseases. In an ordinary year, farmers lose about 1 in 10 lettuces to fungal disease. Sometimes the loss can be as much as 50% of their crop. The group is fine tuning the plant’s response system, so that lettuce can eliminate disease quickly and easily, without the need for human intervention.

But Patron believes the analogy of genetic circuits being like electronic circuits can be pushed too far. 

“The caveat with synthetic biology is we are putting engineered parts into a biological system. So yes, in some cases, things behave as we expect them to. But inevitably, if you do anything else to that system or to that circuit, your predictions will go off.”

This can happen even in simpler systems such as bacteria, she says. “A circuit will perform at lab scale. But once you start scaling up the growth, the stresses and environmental conditions change the metabolism of that cell. We need new information to be able to predict how cells behave in a wider range of conditions.

“It can be frustrating from an engineering perspective. But as a biologist, it’s actually valuable. When the circuit behaves differently, that tells you something about the system. If you’ve controlled and standardised everything else, any unexpected change helps narrow down the factors influencing the biology.” 

With the ultimate goal for the plants to grow either outside or in a controlled greenhouse, all of this information is critical to ensuring the engineering is robust. It allows synthetic biologists to build up a picture of how the new genes might affect the plant under different conditions – for example, if it was grown in a field and subject to weather variations.

Programming plants

The Advanced Research + Invention Agency (ARIA) is a UK funding agency set up in 2023 to fund high-risk, high-reward ideas. Its Synthetic Plants programme is funding an array of early-stage research projects, many aiming to address challenges in agriculture and food systems. 

ARIA’s programme thesis is that while synthetic biology is bringing new ways of producing drugs and potentially game-changing new therapeutic treatments, it has so far been underfunded and undervalued for the impact it could have in agriculture.

But the organisation sees now as the time to change this. “With advances in genome editing and synthetic biology, it’s now possible to predict and design plant traits more precisely,” says Fabrizio Ticchiarelli-Marjot, a technical specialist in ARIA’s Synthetic Plants programme. 

“Plants make up 80% of Earth’s biomass,” he says. “They’re self-replicating, self-healing and can be deployed at massive scale. We see them as an ideal platform technology – the ‘hardware’ of the natural world.”

One project ARIA is funding aims to insert complex traits, such as disease resistance and resilience to changing climates, into plants’ genomes by building synthetic chromosomes. Chromosomes are long, tightly wound-up DNA strands found in cell nuclei. Depending on the species, plant chromosomes contain hundreds to tens of thousands of genes, plus a lot of baggage. 

Building chromosomes from scratch would give synthetic biologists the ability to deliver multiple genes into a plant at once. And not only that: without all the baggage, they would also theoretically have a greater understanding of and control over the chromosome.

With a team including researchers at the University of Cambridge and startup Phytoform, this project will be the first attempt to create and deploy a functional synthetic chromosome in a plant. The team will use an easy-to-engineer moss as a development platform to build and test the synthetic chromosome. If the project is successful, the next stage will be transferring the chromosome into the potato plant.

Assessing the risks

These projects are designed to help humanity and the natural world. It’s important to ensure they don’t have any deleterious effects such as uncontrolled breeding with wild plants or escape of an unwanted dominant gene.

Like all the researchers, Ticchiarelli-Marjot takes biosafety very seriously. “All our ARIA teams work on biocontainment strategies,” he says. “One of the most effective methods is genome recoding.”
Genome recoding is one way to reduce the chance that engineered genes would function in a wild plant. Synthetic biologists do this by rewriting the genetic code that maps DNA to proteins. The result is that the engineered gene will be unlikely to produce a functioning protein in a wild plant.

In the UK, plant products of synthetic biology are likely to be classed as either genetically modified (GM) or gene-edited (precision-bred) plants, depending on the type of modification. GM plants have been grown commercially for more than two decades. Overall, more than 190 million hectares of biotech crops were planted worldwide in 2019. 

Gene-edited crops are not yet grown commercially in the UK. The Genetic Technology (Precision Breeding) Act 2023 does allow their commercial cultivation, but research trials are still in the early stages. 

Engineered plants are bred and tested in controlled environment rooms under strict regulations and monitoring. Environmental impact assessments must be carried out before release to measure any potential effects on wild relatives.

But if the changes made could have been created through classical selective breeding, no fail-safes are needed. 

For example, if the DNA of an apple variety has a gene from a different apple added to improve sweetness it would not be considered to be genetically modified, because the same result could have occurred through natural cross breeding. 

What’s next?

Biology is not steel or silicon. It adapts, evolves and responds to context in ways that can frustrate tidy assumptions. However, these uncertainties are integral to the field. Synthetic biology is about learning to collaborate with nature, rather than control it. 

This means unexpected behaviour can become a source of insight, instead of a failure. As Patron and fellow synthetic plant biologist, Dr Sarah Guiziou both note, when engineered systems behave differently under real-world conditions, they often reveal new biological principles.

As techniques mature and scale, we will see increasing emphasis on robustness, manufacturability and real-world deployment. At a moment when climate change, biodiversity loss and food insecurity are placing unprecedented strain on planetary systems, combining engineering discipline with biological insight offers a way to expand what is possible.