Cracking nature's code: UK leads the charge in engineering biology

Jim Ajioka wants everyone to know about engineering biology: “It’s going to matter to the planet. And to the United Kingdom – a lot – because we are better at it than almost everywhere else,” he says.

The co-founder of biotechnology company Colorifix, and associate professor at Cambridge University, has a point. Because whether it’s cancer, climate, pollution or pathogens, engineering biology has answers, potentially worth trillions.

In its National vision for engineering biology, the Department for Science, Innovation and Technology (DSIT) quotes an estimate that the technology could have a global economic impact of up to US$4tn a year over the next two decades.

And the UK government is keen to get on board.

Defining it as “the design, scaling and commercialisation of biology-derived products and services that can transform sectors or produce existing products more sustainably”, the government has announced a £2bn investment in the technology over the next 10 years.

Science’s ability to modify DNA has developed so much that ‘synthetic’ biology – as it is often called – promises to revolutionise how we produce the medicines and materials we rely on. Engineering biologists are using plants and microbes, and mammalian cells, to find ‘pathways’ to produce entirely new medical treatments. And others are modifying microbes for new fuels, industrial processes, materials and foods.

With several of the world’s best universities, the UK can boast more than its fair share of these discoveries. The challenge now is to turn pathways into industrial-scale production and home-grown success stories, competing against rivals with bigger budgets, and markets.

In Norwich, Anne Osbourn, professor of biology and group leader at the John Innes Centre, has set up HotHouse Therapeutics, a firm that can rearrange plant genes to create ‘recipes’ for new molecules. Based on Osbourn’s own award-winning research, the firm can identify molecules that might become new drugs and develop them to the point of clinical trials, before partnering with larger pharmaceutical companies to bring them to market.

“The traditional routes to discovery of new drug leads have been drying up,” Osbourn says. But, thanks to evolution, plants and microbes are streets ahead of humans when it comes to making complex molecules. Plants, she says, “can make huge swathes of chemistry, most of which we haven’t yet discovered”. These can be interrogated for potential drug leads. “The hit rate is around 300 times higher than it would be for a traditional synthetic chemistry library,” she says.

Susan Rosser, professor of synthetic biology at the University of Edinburgh, and her colleagues are working on engineering mammalian cells to find new pathways to treatments and drugs. She says that applications include the development of ‘biologic’ drugs ­– “complex proteins that are produced by engineered cells”. The market for such drugs, which include breast cancer treatment Herceptin, has a predicted size of US$620bn in the next 10 years.

Engineering mammalian biology can also play a role in the cell and gene therapies (CGT) that will command an even larger market. Rosser says CGT is “transforming the treatment paradigm of a range of life-threatening and rare diseases”. In gene therapy, disease-causing genes can be replaced, inactivated or modified, relying on viral vectors to carry the ‘genetic cargo’ to the right cells.

“Engineering biology,” Rosser explains, “can be used to optimise the manufacture of [these] viral delivery systems, to engineer the therapeutic genetic cargos and to develop genetic control systems to ensure that the therapeutic gene is switched on in the right tissue, at the right time and at the right level.”

But it’s the field’s potential to address our impact on the environment that might be causing the most excitement. Stephen Wallace, professor of chemical biotechnology, also at the University of Edinburgh, once worked with petrochemicals, but now finds ways to replace them. He is engineering microbes to produce the “small molecules”, currently derived from fossil fuels, that make most pharmaceuticals, cosmetics, colours, flavours, fabrics and many materials.

Wallace and colleagues designed a pathway to use E. coli bacteria to valorise plastic waste into the vanilla flavouring vanillin. “So you’re not just fermenting sugar into compounds, you can actually reduce waste that would otherwise be sent to landfill or incinerator.”

When Ajioka and his then PhD student Orr Yarkoni visited Nepal as part of team developing sensors for heavy metal contamination in ground water, they discovered that industrial textile dyeing was polluting rivers, endangering wildlife and public health.

The pair knew synthetic biology could create colours, but had to figure out how to apply and fix them to materials. Their company, Colorifix, perfected its technology and now has backers including global fashion retailer H&M. Its dyeing solution uses much less water, and energy, and emits less carbon than industrial dyeing. But must compete in an industry where ‘green’ is assumed to mean red on the bottom line.

The path from lab to factory to viable business, Ajioka says, is “not just a valley of death, it’s lots of valleys of death”. Ajioka and others in the industry were consulted in the development of the DSIT vision, which sets out a government to-do list for the sector starting with the establishment of an engineering biology steering group populated by academic, startup and industry leaders.

The strong message from the vision’s consultees was that fostering UK hubs might provide the best route to growth. These include – of course – the golden triangle: London, Oxford and Cambridge. But thanks in part to a need for lab space and cheaper housing, Ajioka’s Colorifix is based in Norwich.

The East Anglian city ­– like Edinburgh, Bristol and Manchester – has world-class research facilities and infrastructure. These are built around a few key presences at the Norwich Research Park, including three institutes of the Biotechnological and Biological Sciences Research Council: the John Innes Centre, the Earlham Institute, and the Quadram Institute. As well as the Sainsbury Laboratory, the Norfolk and Norwich University Hospital and the University of East Anglia. Colorifix is among 30 or so businesses located there, too, including others using engineering biology.

The University of Edinburgh provides the focus in the Scottish capital. It boasts the UKRI-funded Edinburgh Genome Foundry (EGF) ­­­– a world-leading, fully automated DNA design and assembly platform – and the UK Centre for Mammalian Synthetic Biology (UKCMSB). Rosser says the UKCMSB’s £13m funding helped establish it as one of the largest communities of mammalian engineering biology research in the world. And is “vital for the UK to maintain and expand this community to remain internationally competitive”, she says.

Osbourn points out that engineering biology is an intrinsically creative and multidisciplinary field. Already involving biology and chemistry, it increasingly also requires data science as it crunches through genomic data, and AI to predict molecules likely to have useful properties. Osbourn’s lab includes experts in computation and bioinformatics, artificial intelligence-based machine learning, and of course biologists and chemists, she says.

There is a need to grasp our technological advantage while we still have it

Naturally, this entails a regulatory focus for DSIT. The department has created the Engineering Biology Regulators’ network, bringing together 13 regulators from seven government departments to understand how technologies can reach market safely. This follows the passing of the Genetic Technology (Precision Breeding) Act last year.

But after a series of controversies over genetically modified foods­­ – often fuelled by misinformation ­– everyone working in engineering biology is aware they also need to address public concern about genetic engineering.

Ajioka points out that their product, like many, uses genetic modification but is not itself GM. While Rosser says that research shows people “are very open to a treatment for a life-threatening or life-altering disease. Far more so than for a consumer product or engineered food.” This point might also inform the wider debate – where ecological damage and rising temperatures mean society must face trade-offs in how it uses technology.

For the UK, though, there is also a need to grasp our technological advantage while we still have it. Ajioka – originally from the US, but now more than 30 years into life in the UK – says he’s seen too many examples of UK intellectual capital escaping these shores. And this represents too good a UK success to squander.

He says: “We have a lot of smart people. And a lot of motivated people that come from all over the Earth to come here. It’s like, ‘God, don't screw that up.’”

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