This Cambridge Life

Since childhood Stephen Baker says he had a grim fascination with poo. He caught the bug for microbiology and spent 12 years in Vietnam researching bacteria that cause diarrhoea. Stephen thinks that antibiotic-resistant bacteria is likely to be humanity’s biggest killer in the future. But says that if we keep doing the science, we have hope.

Infectious diseases are everywhere! We’ve learnt quite a lot more about them given the events of the last couple of years. Now everyone’s an infectious disease expert. This experience has shown how devastating they can be when they circulate. 

I've always been more interested in the applied rather than the mechanistic aspects of science. I realised that if I was going to learn more about the complex infectious diseases I was interested in, I should go somewhere where I would have more exposure to these diseases, rather than studying them in a laboratory in the UK. 

Luckily an opportunity came up to go and work in Vietnam. I initially said I would go for three years but ended up staying for 12. The unit in Ho Chi Minh City became a bit of a hub for research across Southeast Asia – we had collaborators in Thailand, Cambodia, Lao, India, Nepal, and Pakistan, and on other continents.

I was particularly interested in a bacteria called Shigella sonnei which causes an infection called shigellosis, a type of diarrhoea containing blood. Shigella remains a common disease internationally with over 260 million cases a year, and an estimated 200,000 deaths as a result.

A severe case of shigellosis is treated with antibiotics but we discovered that every three to four years the bacterium would go through a cycle of gaining resistance to more and more antibiotics. In the space of 12 years, we followed this whole process from the emergence of resistance to key antibiotics to resistance to almost all antibiotics. Infection with this bacterium is now practically untreatable.

During this process we used genomics to identify and measure a specific mutation that had given rise to resistance of a key antibiotic. We found that this mutation had emerged only once in an organism in South Asia in 2008 and then, just like dropping a stone into a puddle, it had radiated outwards across the world. We picked it up in Vietnam, Bhutan, the UK and the US in the space of a few years. 

Antimicrobial resistance (AMR) is a worldwide challenge that is estimated to kill 10 million per year by 2050 unless we find ways of stopping its progression. It will affect everyone. We’re not far off the position where conditions for which you’d go into hospital for will no longer be able to be treated with any available antibiotics.

As shown by SARS-Cov2, infectious diseases do not respect borders. We can import them easily on our person and transmit them to other people. If we develop chemicals to kill these organisms, they will develop resistance – this is a natural phenomenon. 

I would suggest that the magnitude of the problem and the way it’s being handled is very similar to climate change. People know this has the potential to be devastating to humanity in the coming years, but they can’t quite get organised to work out what should be done about it. 

And yet AMR is a process that can be slowed down. We can do this by using antibiotics less, by using different varieties of antibiotics and by mixing things up. This will buy us some time.

Antibiotics are a 20th-century technology that have served us well, but we need to think: “what’s next?”. In the long term we need to gain a greater understanding of how we can prevent AMR, develop new ways to kill microorganisms and come up with better strategies to prevent disease. We need to see investment to accelerate these research programmes. We need a 21st-century solution. 

Cambridge University will soon launch the Cambridge International Infection Initiative (Ci3). The vision is to create two-way alliances with scientists working in Low- and Middle- Income Countries (LMIC), where the burden of infectious disease is greatest. We want to use the University’s expertise and infrastructure to support their research priorities. 

The centre of gravity in terms of finance and science has massive inequalities, we’ve seen this with the distribution of COVID-19 vaccinations. Wouldn’t it be fantastic if Cambridge had some role in readjusting that imbalance? What if, in 20 years’ time, there were individuals in various LMIC who had developed their research interests at Cambridge University, and then gone on to create and produce the next generation of drugs and vaccines against bacteria and viruses?

The reason we can be optimistic about the future is because of science. The moment we stop funding and carrying out essential research we have a problem. We still face big challenges in the form of economic and political will but I’m confident science will come up with the solutions we need.

Stephen Baker is a Director of Research in the Department of Medicine at the University of Cambridge, a Wellcome Senior Research Fellow and a Fellow of Wolfson College.

This profile is part of This Cambridge Life – stories from the people who make Cambridge University unique.

Words: Charis Goodyear. Photography: Lloyd Mann.