Superbugs vs Mankind

Stephen Armstrong meets biomolecular scientist Richard James

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We're huddled in his car driving into the Derbyshire hills on a cold December morning as Professor Richard James outlines his vision of an apocalypse. "Nine per cent of all patients acquire infections in UK hospitals, some of which are superbugs," he explains. "They're responsible for around 5,000 deaths a year. The percentage of blood infections that are methicillin-resistant is over 40%. And it's going to get worse."
"Methicillin-resistant Staphylococcus aureus, or MRSA, can only be treated with vancomycin, but there are already strains that have become immune," he continues. "Now we have community MRSA, which exists outside hospitals. It produces a toxin that eats your flesh, attacking cells in your lungs. The mortality rate is about 50% even in young, healthy athletes. Imagine if that acquires vancomycin resistance. They say that if bird flu transfers to humans we'd get 50,000 deaths in the UK. Well, if we had an epidemic of vancomycin-resistant community MRSA, millions would die. Millions. We'd be returning to the era when the treatment for TB was fresh air."

He quotes a research director at GlaxoSmithKline who said that once we run out of antibiotics, if we cut our finger on Monday we'd be dead by Friday. This seems ridiculous, until he tells the story behind the old medical joke, "The treatment was a success, but the patient died." In 1940, when doctors finally managed to isolate penicillin, they tried it on Albert Alexander - a 48-year-old London policeman who had cut himself while shaving and infected his chin. Initially the penicillin worked, but they hadn't prepared enough of it so the infection returned. Five days later Albert was dead.

It's this that James is struggling to prevent. He sometimes describes himself as an expert in biological warfare, but his official title is director, centre for biomolecular sciences, head of the school of molecular medical sciences at the University of Nottingham. He's spent almost 30 years - from PhD student to head of school - trying to understand our single-celled foes. When he hears the mantra that cleaner hospitals will reduce infections, he all but clutches his head in his hands. In his view, no matter how clean our hospitals become, we have almost lost the war. Unless new antibiotics are discovered, he believes, we may have to close all our hospitals in the next five years or so.

"Between 1940 and 1970 - the golden age of antibiotics - we developed thousands of the drugs," he explains. "And then we squandered them. We fed antibiotics to chickens and cattle. We handed them out to people with a cold. Each time you try to kill bacteria, you're forcing them to select for survival. Now we've basically bred bugs that flourish in a hospital environment and they're just waiting to bite. You've got sick people in there, people having transplants taking drugs to suppress their immune systems, HIV patients, the elderly and the young. And yet nothing is being done."

The problem is, drugs companies have pretty much abandoned the field. After $800m (£456m) was spent developing the last new antibiotic - linezolid - in 2000 only to find resistance developing within 12 months, it was hard to see where the profits would come from. Along with small academic teams in the UK, Europe and the US, therefore, James is racing to create new drugs on small research grants before vancomycin-resistant MRSA spreads. Compared to the £8bn spent combating foot and mouth, the funding is tiny. "We can find money for BSE and train safety," he says. "Recently Gordon Brown announced a £50m stem-cell project in the UK. Whereas in February 2005 the Department of Health offered just £1m for a [healthcare infections research] programme and have yet to announce which of the many applications have been funded."

I need a drink after this, so we pause for a pint at the Monsal Head Hotel, where he points out, with a grin, that our beer represents the beneficial side of microbiology. This pub is a favourite place for James. He's a keen walker and often comes here with his wife. "I like this scale of nature because I can see its splendour. In the lab it's at the molecular level so you can't see it in action, but when you work out how it's done you think - that's wonderful. You have to admire what nature can do."

It wasn't a love of nature that started him on this road, however, but a love of sport. He was the first in his family to go to a grammar school, where he played rugby and football, choosing to study biology almost as an afterthought. Halfway through his degree, however, the research side gripped him; he spent most of the 1970s trying to understand how bacteria divide and took a teaching job at the University of East Anglia, where, during an under-graduate practical, two of his students uncovered a completely new form of bacteriocin - a chemical produced by bacteria to kill competitors.

Around this time, antibiotic resistance was starting to alarm researchers. It became clear that bacteria could carry little packets of DNA in bundles called plasmids. Plasmids could be exchanged between bacteria when they rubbed up against each other, and it was plasmids that stored antibiotic resistance. In other words, immune bacteria could pass on their immunity simply by touch. The public, meanwhile, remained in blissful ignorance.

Then his enemy did something that left him almost breathless. In Sweden there was an experiment to overcome resistance by rotating antibiotics every six months. Bacteria can't afford to carry dead weight. It slows them down. Anything that isn't being used, therefore, is pushed out of the cell. The Swedes figured that as resistance tends to be carried on plasmids and as useless plasmids are expelled, by the end of six months resistance to the previous drug would have disappeared.

"It seemed to be working," James explains. "But some plasmids developed genes that killed their host if they were ejected." He shakes his head in awe. "If you had said to a military tactician, 'Design something that would make bacteria even more dangerous,' I don't think they could have come up with that. We're not fighting guerrillas taking pot shots here. This is a sophisticated army with astonishing weapons. And each time we develop something new, they develop a defence for it."

We drive to the village of Eyam - the site of a strange skirmish in this long-running campaign. In 1665 the Black Death arrived there via some flea-infested cloth. In an attempt to protect nearby towns and cities, the villagers made an extraordinary sacrifice: they quarantined themselves. No one could leave and no one could enter. Over the ensuing two years, more than 260 out of 350 died, but the plague was contained. Curiously, one of the survivors was the undertaker, who had handled every infected corpse. Researchers into Aids recently traced his descendants and found that they possessed unusual cell walls that made them immune to both bubonic-plague bacteria and HIV.

Eyam remains practically unchanged today. It's streets are almost identical to the ones the plague victims staggered through. In sharp contrast, James's office is in a sleek, modern building next door to the university's medical school. It's here that his 1979 undergraduate practical is starting to bear fruit. His team has begun to isolate versions of the bacteriocin and has discovered some that kill MRSA. He also has colleagues looking at a Soviet-era Russian attempt to use viruses that attack bacteria as a sort of counter-infection. They believe that enzymes used by those viruses to destroy bacteria cell walls could be employed as a new generation of antibiotics. These are ancient natural chemicals, so they're hoping it'll be tough for bacteria to develop resistance to them.

At the same time, the centre is looking at ways of switching off something called quorum sensing. Bacteria enter our bodies and don't attack until they know there's enough of them to cause damage. His colleagues have molecules that will switch off the attack signals; because these don't actually kill the bacteria, the bugs don't need to develop resistance to survive. "It's all very hopeful," he says. "We've even got chemists in the building to make the stuff. All we need is more money."

James sighs and spreads his hands. "What's the tipping point going to be?" he asks rhetorically. "Let's say we had a big epidemic of vancomycin-resistant MRSA that killed 50,000 people. There'd be hell to pay, but by then it's too late. People ask if I'm an optimist or a pessimist and I say, 'In between, but verging on the pessimist.' If I were betting on a race between superbugs and us developing the drugs... well, right now I'd be betting on the bugs."