18.04.2019
The drugs don’t work
The huge problem of antimicrobial resistance and antibiotic shortages is greatly exacerbated by the profit motive, argues James Linney
One of the most critical challenges facing modern medicine is increasing antimicrobial resistance (AMR). This is a process that leads to previously treatable bacterial infections evolving their own defences against the actions of antibiotic medications, resulting in far more serious and potentially fatal outcomes for those infected.
Despite the growing incidence of AMR, we have seen the drying up of new antibiotic research and development by pharmaceutical companies over the past few decades. As we will see, the problems of AMR and the lack of any effective solutions is a case study in how the drive for profit can create an acute health crisis of global proportions that could have potentially catastrophic consequences.
On the whole, bacteria get a lot of unfairly bad press - most of our relationships with the trillions of bacteria that live on or in our bodies are symbiotic. Within our gut, for example - where there are huge numbers of bacteria cells - the thousands of different species of bacteria help contribute to the breaking down of food and the regulation of weight, as well as playing a crucial role in our immunity. This balanced collaboration is the result of millions of years of evolution. Bacteria can become pathological (disease-causing) if their numbers are able to grow excessively or they manage to get to certain areas of our body usually best kept sterile - for example, the heart, lung and bone tissue or circulating blood.
Although the earliest accounts of germ theory have been attributed to the Italian scholar, Girolamo Fracastoro, in 1546, it was not until the second half of the 19th century - thanks largely to Louis Pasteur and Robert Koch - that empirical evidence soon led to the development of vaccinations. It is hard to overstate how these discoveries revolutionised medicine. Diseases that had for millennia terrorised humanity, such as rabies, polio and smallpox, were now preventable. It took another 70 years - helped by Alexander Fleming and his mouldy petri dish - before penicillin, the world’s first antibiotic, was isolated; and it was soon being manufactured on an industrial scale - just in time to be given to soldiers injured on the battlefields of World War II.
This was a game-changer. It was now possible to not just prevent infectious diseases, but to cure someone over whom the pathogen already had a strong hold. Penicillin is within the class of B-Lactam antibiotics - it is derived from the Penicillium fungi that inhibit the synthesis of the cell wall of some common bacteria. Over the next 40 years there were many more new classes of antibiotics isolated, and within each class dozens of different antibiotics were manufactured. Optimism was riding high and it was felt that it was only a matter of time before all the serious bacterial infections would be contained or eradicated for good.
Defences
However, in the 1980s two things happened that allowed the bacteria to strike back: they started developing their own defences against the new drugs; and the manufacture of antibiotics dried up (the most recent class was developed in 1987).
Antibiotic resistance is to an extent an inevitable, evolutionary process - random mutations in bacteria allow for some advantageous defence against the action of the antibiotic and hence they can propagate, whilst others are killed. However, the enormous overuse of antibiotics in farming and medicine is the catalysing process creating the emergence of many types of bacteria that are now resistant to multiple different antibiotics - the so-called ‘superbugs’. Most countries use far more antibiotics in farming than they do to treat humans: for example, in the US 70% of such use is in farming.1 The same antibiotics that we depend on to defend us from potentially fatal diseases are en masse nonchalantly employed to prophylactically keep livestock disease-free or to help increase their size - inadvertently creating worldwide factories for the manufacture of lethal, multi-resistant bacteria that leak out into the environment and into our food chain.
In medicine too antibiotics are overused - largely because globally most people cannot afford access to doctors or diagnostic tests that would help ensure they were used more appropriately. It is much cheaper to just prescribe or buy broad-action antibiotics (which kill lots of different types of bacteria) in the hope that you see off the harmful ones - along with all the other useful gut bacteria. This is a process that kills all but the drug-resistant bacteria and, with all their competition being nuked by the antibiotics, they can happily flourish. Hence the development of very difficult-to-treat bacterial diseases in hospitals, such as MRSA (multi-resistant staphylococcus aureus) and Clostridium Difficile. These are just two of the more well publicised resistant bacteria, but there are now hundreds of them. For example, sexually transmitted diseases that it was once thought would be eradicated by drugs have developed resistance - gonorrhoea, chlamydia and syphilis are increasingly becoming more difficult to treat.
Ask any doctor and they will attest to previously common infections - of the urinary tract and skin, pneumonias, etc - becoming more resistant to treatment, so requiring the use of stronger (intravenous) and rarer antibiotics. Last year a Lancet study found there were around 33,000 annual deaths in European Union countries attributable to antibiotic resistance.2 Worldwide there are about such 700,000 deaths annually - a figure that is growing: it has been estimated that by 2050 this will increase to 10 million deaths a year.3 This could mean a future where having an operation, undergoing chemotherapy, giving birth or simply cutting your finger whilst gardening could result in untreatable, potentially fatal infections.
Clearly then, even if antibiotic use is dramatically reduced, we are going to need new and more effective drugs. Not an easy task, given that most antibiotics originate, like penicillin, from naturally occurring organisms - the overall stock of which has been vastly depleted through deforestation and climate change. Unfortunately, drug companies have shown little appetite for researching and developing new antibiotics. The diminishing amount of return on the necessary investment has meant that there is no incentive to improve on the drugs we already have. Why spend money developing drugs that are notoriously costly and technically hard to manufacture, when they would be used very sparingly as a last resort - and only then for short courses (usually five-seven days)?
Add to this the unpredictable nature of antibiotic resistance: a company might spend 10 years getting a new agent to market, only to see the targeted bacteria develop resistance, rendering the drug redundant. No, much better to develop drugs that are needed by lots of people and have to be taken daily for years - ideally for life - as in the treatment of diabetes, heart disease or depression. As an illustration, global sales of all types of antibiotics (both for farming and medical use) equate to about $45 billion a year - compare this to the single drug, Humira, manufactured by AbbVie and used in the treatment of rheumatoid arthritis, which is worth about $20 billion alone.
There have recently been efforts made to try to entice pharmaceuticals to develop new drugs. To this end the UK government commissioned economist Jim O’Neill, the former chairman of Goldman Sachs, to “analyse the global problem of rising drug resistance and propose concrete actions to tackle it internationally”.4 The resulting 2016 publication, the Review on antimicrobial resistance, suggested pharmaceutical companies should be rewarded for innovation with a $1 billion payment for any new antibiotic. Other suggestions have been to allow longer patents, give tax breaks for drug companies developing antibiotics or simply raise the price of antibiotics, so that they are as costly as cancer-treating chemotherapy drugs. All of which are blatantly beyond inadequate - all they would do is abet the enrichment of drug companies, whilst further shifting the burden of AMR to the less well-off countries (where overcrowding, poor sanitation and lack of access to medical care already means they are the worst affected).
Nationalisation
Since the 2016 report little has changed - apart form the quickening of the pace of AMR. The indifference of the pharmaceutical companies to the possibility of a world without effective antibiotics, and all the horrors that would result, seems to have taken O’Neill by surprise. He has said:
…nearly three years after our review came out, there’s endless talk, but there’s no progress in waking up the pharmaceutical industry to want to do this. So, by default, I find my mind thinking, why not explore the idea of some public utility that’s got public-purpose ownership of it? Just take it away from them and take it over.5
A partial nationalisation of drug companies’ research and development is far more sensible than his earlier suggestions. In fact, this is a more radical policy than Jeremy Corbyn has suggested - when the topic came up in the last Labour leadership contest, John McDonnell stated that Labour does not favour the nationalisation of the pharma industry, which instead should be “better managed and more effective”.6 There is an inherent contradiction between the raison d’être of drug companies (to create wealth for their owners) and the need to provide safe, effective treatments for everyone according to their need. We have no interest in better managing the status quo - we must look for far more radical solutions.
Calling for the nationalisation of the entire pharmaceutical industry is a supportable policy and one we should be fighting for the Labour Party to adopt. However, we must have no illusions in nationalisation as a solution. For a start the pharmaceutical industry is one of the most powerful industries in the world, yielding all the political influence that comes with this. It would not just stand by and leave the NHS - easily its biggest customer - unscathed. Secondly, nationalising it in the UK would likely mean at some point putting it in the hands of the Tory Party, who can be trusted with it about as much as they can the NHS.
Ultimately the challenge of AMR brings into focus our long-term goal - the socialisation of the entire pharmaceutical and healthcare industry, so that it is run democratically for the benefit of all. Of course, a prerequisite for this is a strong and vibrant working class movement. This is something which, given the time pressures involved - exerted not just by AMR, but by the even bigger threat of climate change, to name just one - has never been needed more urgently.
Notes
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www.theguardian.com/environment/2018/jun/19/how-much-does-big-pharma-make-from-animal-antibiotics.↩
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www.thelancet.com/action/showPdf?pii=S1473-3099%2818%2930605-4.↩
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www.bbc.co.uk/news/health-47719269?intlink_from_url=https://www.bbc.co.uk/news/topics/c008ql15151t/antibiotics&link_location=live-reporting-story.↩
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www.theguardian.com/politics/2016/jul/25/john-mcdonnell-jeremy-corbyn-uk-pharmaceuticals-industry.↩