England's chief medical officer on why the drugs don't work

Large-scale resistance to antibiotics is inevitable, yet new antibacterials aren't emerging. Why?

New Statesman
Who decides which drugs are made, and which ones we have access to? Image: Getty

The Drugs Don’t Work: a Global Threat
Sally C Davies, with Jonathan Grant and Mike Catchpole
Penguin Specials, 112pp, £3.99

Professor Dame Sally Davies, England’s chief medical officer, likens the impending crisis in antimicrobial drug resistance to global warming. In both instances scientists foresee a problem and can offer solutions. In neither case is our response anywhere near sharp enough, Davies fears. Acting on antibiotic resistance should be the easier of the two; no one has a vested interest in denying the risk. Why then are we stumbling towards a selfmade but preventable calamity?

Alexander Fleming is credited with discovering antibiotics. In the summer of 1928, while working at St Mary’s hospital in London, he went on holiday and left an open plate of bacteria behind. Returning to work, he found a fungus growing on the plate that had killed the bacteria with a chemical that he named penicillin. In 1930s Oxford, Howard Florey and Ernst Chain produced enough penicillin to prove its healing ability. The penicillin production programme that followed during the Second World War is a classic tale of ingenuity under adversity. By engaging American pharmaceutical companies, the Allies were able to cure soldiers of otherwise fatally infected wounds.

Bugs create chemicals to kill other bugs as part of an aeons-old microbial arms race, so drug-hunters turned to soil microbes to help fight a range of diseases. Streptomycin, discovered in America in 1943, even cured tuberculosis, one of mankind’s greatest afflictions. Today, however, roughly a third of the world’s population still carries TB. Of the nearly 9,000 cases reported in the UK in 2011 hundreds of sufferers were resistant to at least one drug. Half a dozen cases carried incurable, “extensively drug-resistant” strains of TB. Cholera, leprosy, typhoid fever and syphilis all remain global scourges. Just last year several people in Edinburgh died after inhaling legionnaire’s disease-causing bacteria. Dozens of Germans died in 2011 after eating beansprouts contaminated with E coli.

Luckily, for now at least, we can still treat most bacterial infections, but some bacterial cells can yield over a billion progeny in just 24 hours. Genetic mutations stimulating drug resistance are inevitable. Cases of penicillin resistance appeared almost immediately: methicillin, a more stable derivative of penicillin, enjoyed only a few years of success before resistance emerged. Methicillin-resistant Staphylococcus aureus (MRSA) now kills hundreds in British hospitals every year.

Yet new antibacterials aren’t emerging. The reasons for this are primarily economic. Antimicrobial agents are usually given in shortterm doses. Compare that to statins, taken by affluent westerners with high cholesterol over decades. Most antibiotics are also off-patent, which has driven prices down. The estimated $1bn it costs to develop a drug inflates the cost of new medicines. Cash-strapped health services will use cheaper, old drugs until their utility is all but gone.

Davies fears that time might come quickly. Resistance genes are flourishing out there and bacteria are remarkably happy to share their genes. The widespread imprudent use of antibiotics has created perfect conditions to select those resistance genes and global air travel can carry resistant bugs around the world in hours.

Davies offers possible solutions. Fifteen years ago the pharmaceutical industry had largely abandoned diseases of the poor – malaria, tuberculosis, sleeping sickness, bilharzia and so on. An anti-sleeping sickness drug, called eflornithine, was even about to be withdrawn because sufferers couldn’t pay for it. When eflornithine was shown to prevent unwanted hair growth, however, pharmaceutical companies fell over themselves to produce it. Economics dictated that a drug could be made to “treat” unwanted facial hair but not to save lives. New models were needed to combat diseases of the poor. Groups such as the Medicines for Malaria Venture and Drugs for Neglected Diseases Initiative emerged to help promote drug development. A decade on, the first new drugs are poised to appear. The pharmaceutical industry itself, though, is in crisis and shedding staff at an alarming rate.

If a pestilential Armageddon really is upon us, a cynical company might gamble on huge profits, getting new antimicrobials ready for when the competition fails. But the economic models won’t shift until the evidence becomes overwhelming. Davies also talks of incentivisation – a £50m prize to develop a new antibiotic, for instance. Given development costs, $1bn would be more realistic. Yet even that’s a snip compared to the taxpayers’ bank bailouts. Surely saving life trumps life savings. Whatever it takes, though, action is needed now. The big pharmaceutical companies continue to abandon their anti-infective programmes and with them goes the expertise and capacity that will be needed when the crisis hits.

Michael Barrett is Professor of Biochemical Parasitology at the University of Glasgow