Professor Stephen Wallace, creating magic with microbes

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In a parallel universe, Stephen Wallace is an accomplished concert pianist. As the end of high school approached, Stephen was regularly performing in concerts and competitions up and down the country and was poised to take the next step with a diploma in music performance.  He loved playing piano, but his other great love was science, and it was this passion he ultimately chose to channel all his energies into. Now Professor of Chemical Biotechnology and the winner of numerous awards for his pioneering work at the intersection of synthetic chemistry and synthetic biology, we may be deprived of Stephen’s musical talent but we all stand to gain from his sustainability-focused discoveries.

Stephen was much more enamoured with biology and physics at school, until his interest in chemistry was piqued by seeing the critical role it played in forensic science as portrayed in TV shows like CSI. “I hate telling people this is the reason I went into science!” he says.

But it was seeing that link between a fundamental understanding of molecules and the impact it could have in the real world was really enticing to me.

Stephen decided to study Advanced Higher chemistry in his final year of high school. Run through Herriot Watt University and structured to emulate the first year of university science courses, it involved completing an intriguing year-long project called Identification of the Unknown. Stephen was sent a vial of white powder in the post (“not something that would be allowed now!”) and tasked with figuring out its molecular composition. Stephen was permitted to use lab equipment at Herriot Watt’s campus to perform chemical analyses and spectroscopy on the powder.

Using a load of new techniques to find out the specific molecular composition of a complete unknown just blew my mind. That was me hooked.

Stephen went on to study Medicinal and Biological Chemistry at the University of Edinburgh, where his love of chemistry deepened. In the fourth year of his MChem degree he opted to do a 12-month industry placement with global pharmaceutical company GSK. The experience was pivotal for Stephen, who had been oscillating between pursuing a career as an industrial scientist or as an academic researcher. His placement allowed him to be creative with science in a way that he hadn’t been since his time as a musician, but he also found that working in an environment driven by financial incentives had its drawbacks. Projects that weren’t delivering as expected would come to an abrupt halt, which was frustrating for Stephen and thwarted his natural curiosity.

One aspect of his industry placement that still resonates was GSK’s patient insight seminar series, which would bring disease sufferers together with scientists working on the drugs intended to help them.

It was harrowing, but GSK were wise to establish it because it incentivises scientists to not only focus on targets or specific lab results, but on how their work can have real impact. It’s a lesson that has followed me through my career.

After his MChem, Stephen completed a PhD in organic chemistry at the University of Oxford under Professor Martin Smith. He learned a lot, especially how to question everything he’d been taught, and this new perspective made him lean towards applied science, where he would be more able to explore the what ifs and the whys of his research. He embarked on a postdoctoral fellowship under Professor Jason Chin at the prestigious MRC Laboratory of Molecular Biology (LMB), which was designed to provide academics from a physical sciences background with a better grounding in biology. While there, Stephen read a paper by Berkeley chemist Professor Jay Keasling that, combined with his expanding biology expertise, would go on to shape his academic career. Keasling’s paper spelled out the urgent need for a full-scale decoupling from fossil fuels, and called for scientists to innovate more sustainable methods of chemical manufacture using microbes.

Around 70% of medications used to treat disease are made from oil. Until I read Keasling’s paper I hadn’t realised how much we rely on this natural feedstock that’s running out. The idea of programming microbes as I was already doing at the LMB, but to create more elegant and sustainable technologies for the chemical industry, was a complete epiphany.

With new purpose, Stephen applied for a Marie Curie International Fellowship at the Harvard University lab of Professor Emily Balskus, whose innovative work manipulating microbial chemistry through non-enzymatic reactions was deeply inspiring to him. Although Stephen’s partner Phil moved with him to Boston to complete his own fellowship at Harvard Medical School, the intensity of their respective programmes and the demands on their time meant that they saw each other very little over those two years.

Towards the end of this second post-doc, which he completed at the University of Cambridge under Professor Steve Ley, Stephen saw a biotechnology lectureship advertised at the University of Edinburgh that seemed uniquely suited to him. At his interview he pitched his vision for a lab that would harness the combined expertise of synthetic chemists and synthetic biologists to genetically programme microorganisms capable of producing important industrial chemicals from sustainable feedstocks and waste.

I wanted to create a lab where chemists and biologists could unify their efforts to work together and in a more sustainable way.

Stephen went from Edinburgh alumni to staff member in 2017, and he established his multidisciplinary lab that same year. The Wallace Lab is now a pioneering innovator in sustainable chemical synthesis, and a rarity in what is still a burgeoning field. The secret to its continued success? Playful curiosity. “I think it's really important for an academic researcher to avoid getting blindsided by what you want to happen and instead following what does happen,” he says.

All the most exciting research, both from our lab and in my career up until this point, has come from those strange, unexpected observations that are then followed up.

Following the science in unexpected directions has yielded some astounding results for Stephen and his group, and from one project several further breakthroughs have been made. Working with colleague Dr Joanna Sadler, Stephen found that genetically-engineered E. coli bacteria can convert PET – a huge waste burden for our planet - into the food and cosmetic ingredient vanillin. These lab-engineered bacteria can also transform PET into adipic acid - a major chemical ingredient in the production of nylon, cosmetics and pharmaceuticals that is currently made from oil and responsible for ten per cent of global emissions of nitrous oxide. Most recently, Stephen made the discovery that one of the intermediaries en route to adipic acid is the precursor to a molecule used to treat neurological diseases. A world first, Stephen is now collaborating with industry and a dementia charity to develop the first microbial process that will produce this essential medication from plastic waste, instead of from oil.

It's incredibly exciting. Plastic waste is viewed very negatively, and rightly so, but instead of recycling plastic into more plastic that still damages the environment, we can instead turn it into something that will benefit human health. When dementia patients take medicines containing this molecule it's transformed into dopamine, which is the happy hormone. So the process is taking plastic waste that's killing ocean life and turning it into something that makes humans happy.

These processes sound magical, but they stand to have a very real impact on our world. By working with various partners from across the pharmaceutical and manufacturing industries and the third sector who share the Wallace Lab’s aims, Stephen is producing industrial chemicals from waste and renewable feedstocks, and is empowered to help build the green chemical industry that is crucial to achieving net zero.

2023 has been a big year for Stephen by any metric. In addition to validating the commercial viability of various medicines converted from PET, the University’s School of Biological Sciences recently appointed him Professor of Chemical Biotechnology and he has been awarded two prestigious honours. In April he was awarded The Colworth Medal by The Biochemical Society in recognition of outstanding research by a biochemist within 10 years of PhD completion, and in June the Royal Society of Chemistry granted him the Norman Heatley Award for the development of chemical tools and microbial biocatalysts for sustainable synthesis. With all that going on and no shortage of ambition for future projects you could forgive Stephen for taking things easy away from work, but this isn’t in his nature. Instead he and Phil have recently bought their first home, and Stephen's made a significant purchase that serves as a statement of intent: a piano.