Sheffield’s fight against killer bugs

YOU might assume that the biggest killer in 1918 was the war that still raged across large swathes of Europe and beyond. But you’d be wrong.

There was something even more deadly in the air than the hail of bullets and shrapnel on the Western Front – Spanish Flu. It’s estimated that as many as one billion people – half the world’s population – were struck down by the Spanish flu pandemic.

By the time the virus had swept across the planet it had claimed 50 million lives, higher than the total number killed during the entire First World War. The 1918 flu killed more people than any other single outbreak of disease in history, surpassing even the Black Death which laid waste during the Middle Ages.

The discovery of penicillin, the world’s first antibiotic, has since saved countless millions of lives. Antibiotics revolutionised medical care in the second half of the 20th century but increasingly the bugs are fighting back.

Last year, England’s Chief Medical Officer Dame Sally Davies described the growing resistance to antibiotics as a “ticking time bomb” and said the danger should be ranked alongside terrorism on a list of threats to the nation. It’s certainly not one that’s going away and the fear remains that a new more deadly virus could emerge in the future.

What this means is that modern medicine faces a constant battle to try and stay ahead of the threat from pathogens – bacteria, viruses and parasites. It’s a battle that involves the University of Sheffield which has recently unveiled two ambitious projects, called Florey and Imagine, aimed at pushing back the boundaries of our biological understanding and helping to protect us from infectious diseases.

Professor David Dockrell, Florey Project Director, says the challenge is keeping one step ahead of the bugs. “In an era when we face major challenges with resistant bacteria that are hard to treat, and in an era when despite all the advances with vaccines we are still struggling to prevent some of these infections, it seems we have to go back and find a new approach.”

The Florey Project is focusing on studies into Streptococcus pneumoniae, the most commonly identified cause of meningitis and pneumonia. “It leads to several million deaths each year worldwide. It’s a major cause of ill health and one of the four big infections that kill people along with malaria, TB and HIV.” Researchers are also looking at another bacteria called Staphylococcus aureus, source of the MRSA superbug found in hospitals.

Prof Dockrell says that although a lot has been achieved with antibiotics there are a growing number of bacterial infections, like MRSA, that have become resistant to them. Part of their work is looking at why certain bacteria make some people sick and not others. “Most people protect themselves very effectively and understanding what fails in the people who get sick is a fundamental question. We don’t know why one person will get sick when they’re in hospital with an MRSA infection and it’s understanding why that is that will allow us to target treatment more effectively to the right people.”

Researchers working on the university’s Imagine project are using the latest hi-tech microscopes and imaging techniques to help find the answers to these underpinning biological questions.

Professor Simon Foster, who co-heads the Imagine Project, says it has opened their eyes to a whole new miniature world. “It means we can see things we’ve never been able to see before, and what this has shown us is that things are actually much more complicated than we thought.”

But there is still a lot that we don’t know. Which is where the new technology comes in, although as Prof Foster points out their work is about more than just fancy microscopes.

“The most important thing is not the buildings or equipment, it’s the people and we’re attracting new academics and support staff to make Sheffield a world class centre for this kind of research.”

We often think of major scientific breakthroughs being made by inspired individuals, like Isaac Newton or Albert Einstein, but research is increasingly a collaboration involving teams often working in different corners of the world. “Science shouldn’t be a competition it’s about finding things out, so we’re setting up links with key institutions around the world so we can compliment each other,” says Prof Foster.

This can help them tackle the big questions more effectively. “We already collaborate across the disciplines from medicine, through to physics, chemistry and biology and we’re building on that to create international alliances.”

But what about the threat we still face from infectious diseases? “The threat is the same but there’s a perception that infectious disease is beaten because you can go to your doctor and get an antibiotic,” says Prof Foster. “We soon forget that devastating diseases such as TB or polio were prevalent in the UK and now antibiotics and vaccines have completely altered our outlook.”

However, you don’t have to travel far to find reminders of our deadly past. “Go to Sheffield station and look up the far hillside and there’s a monument to commemorate more than 400 people who died following an outbreak of cholera in 1832.”

Today, of course, we have better sanitation and antibiotics but these diseases haven’t disappeared, so could we face a modern day plague in the future?

“Pandemic influenza or other serious viral infections like SARS will happen again,” says Prof Dockrell. “But we’re talking about bacteria. What killed a lot of people who had the 1918 flu was pneumonia caused by bacteria not the virus itself. So with all these viral pandemics it’ll be the sort of bacteria we’ve been talking about that will kill actually people.”

One of the challenges is to find alternatives to antibiotics. “There are some bacteria we don’t have effective antibiotics for and that is a real threat. Which is why we need to find better ways of treating people that are less reliant on antibiotics, or vaccinations and use people’s natural defences against infection.

“Any time we use an antibiotic sooner or later the bacteria becomes resistant to it. We’re constantly having to develop new antibiotics to try and combat the infections and actually the number of new ones are dropping off so we need alternative strategies.”

Prof Foster agrees. “Science has made fantastic advances in the last hundred years but our true understanding of what underpins the life of infectious organisms is somewhat lacking.”

But this shouldn’t be seen as a failure. “It’s just a recognition that what we’re trying to study is something very complicated that has evolved over millions of years.”