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?

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

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

This article first appeared in the 30 October 2013 issue of the New Statesman, Should you bother to vote?

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The conflict in Yemen is a Civil War by numbers

Amid the battles, a generation starves.

Ten thousand dead – a conservative estimate at best. Three million internally displaced. Twenty million in need of aid. Two hundred thousand besieged for over a year. Thirty-four ballistic missiles fired into Saudi Arabia. More than 140 mourners killed in a double-tap strike on a funeral. These are just some of the numerical subscripts of the war in Yemen.

The British government would probably prefer to draw attention to the money being spent on aid in Yemen – £37m extra, according to figures released by the Department for International Development in September – rather than the £3.3bn worth of arms that the UK licensed for sale to Saudi Arabia in the first year of the kingdom’s bombing campaign against one of the poorest nations in the Middle East.

Yet, on the ground, the numbers are meaningless. What they do not show is how the conflict is tearing Yemeni society apart. Nor do they account for the deaths from disease and starvation caused by the hindering of food imports and medical supplies – siege tactics used by both sides – and for the appropriation of aid for financial gain.

Since the war began in March 2015 I have travelled more than 2,500 miles across Yemen, criss-crossing the front lines in and out of territories controlled by Houthi rebels, or by their opponents, the Saudi-backed resistance forces, or through vast stretches of land held by al-Qaeda. On those journeys, what struck me most was the deepening resentment expressed by so many people towards their fellow Yemenis.

The object of that loathing can change in the space of a few hundred metres. The soundtrack to this hatred emanates from smartphones resting on rusting oil drums, protruding from the breast pockets of military fatigues, or lying on chairs under makeshift awnings where flags denote the beginning of the dead ground of no-man’s-land. The rabble-rousing propaganda songs preach to the watchful gunmen about a feeble and irreligious enemy backed by foreign powers. Down the road, an almost identical scene awaits, only the flag is different and the song, though echoing the same sentiment, chants of an opponent altogether different from the one decried barely out of earshot in the dust behind you.

“We hate them. They hate us. We kill each other. Who wins?” mused a fellow passenger on one of my trips as he pressed green leaves of the mildly narcotic khat plant into his mouth.

Mohammed was a friend of a friend who helped to smuggle me – dressed in the all-black, face-covering garb of a Yemeni woman – across front lines into the besieged enclave of Taiz. “We lose everything,” he said. “They win. They always win.” He gesticulated as he spoke of these invisible yet omnipresent powers: Yemen’s political elite and the foreign states entangled in his country’s conflict.

This promotion of hatred, creating what are likely to be irreversible divisions, is necessary for the war’s belligerents in order to incite tens of thousands to fight. It is essential to perpetuate the cycle of revenge unleashed by the territorial advances in 2014 and 2015 by Houthi rebels and the forces of their patron, the former president Ali Abdullah Saleh. This demand for retribution is matched by those who are now seeking vengeance for the lives lost in a UK-supported, Saudi-led aerial bombing campaign.

More than 25 years after the two states of North and South Yemen united, the gulf between them has never been wider. The political south, now controlled by forces aligned with the Saudi-led coalition, is logistically as well as politically severed from the north-western territories under the command of the Houthi rebels and Saleh loyalists. Caught in the middle is the city of Taiz, which is steadily being reduced to rubble after a year-long siege imposed by the Houthi-Saleh forces.

Revenge nourishes the violence, but it cannot feed those who are dying from malnutrition. Blowing in the sandy wind on roadsides up and down the country are tattered tents that hundreds of thousands of displaced families now call home. Others have fled from the cities and towns affected by the conflict to remote but safer village areas. There, food and medical care are scarce.

The acute child malnutrition reported in urban hospitals remains largely hidden in these isolated villages, far from tarmac roads, beyond the reach of international aid agencies. On my road trips across Yemen, a journey that would normally take 45 minutes on asphalt could take five hours on tracks across scrubland and rock, climbing mountainsides and descending into valleys where bridges stand useless, snapped in half by air strikes.

Among the other statistics are the missing millions needed by the state – the country’s largest employer. Workers haven’t been paid in months, amid fears of an economic collapse. This is apparently a deliberate tactic of fiscal strangulation by the Saudi-backed Yemeni government-in-exile. The recent relocation of the central bank from the Houthi-controlled capital, Sana’a, to the southern city of Aden is so far proving symbolic, given that the institution remains devoid of funds. The workforce on both sides of the conflict has taken to the streets to protest against salaries being overdue.

Following the deaths of more than 140 people in Saudi-led air strikes on a funeral hall on 8 October, Saleh and the Houthi leader, Abdulmalik al-Houthi, called for yet more revenge. Within hours, ballistic missiles were fired from within Houthi territory, reaching up to 350 miles into Saudi Arabia.

Meanwhile, in the Red Sea, Houthi missile attacks on US warships resulted in retaliation, sucking the US further into the mire. Hours later, Iran announced its intention to deploy naval vessels in the area.

Vengeance continues to drive the violence in Yemen, which is being drawn ever closer to proxy conflicts being fought elsewhere in the Middle East. Yet the impact on Yemeni society and the consequences for the population’s health for generations to come are unlikely to appear to the outside world, not even as annotated numbers in the brief glimpses we get of this war. 

This article first appeared in the 20 October 2016 issue of the New Statesman, Brothers in blood