Antimicrobial Resistance (AMR) is an inevitable global crisis that has been on the rise since the 1960s and threatens to reverse decades of medical advances. Now, the problem of AMR is escalating. Resistant strains of diseases are becoming more abundant, and some of these diseases (such as gonorrhoea) are on their last effective mode of treatment. If such species acquire more resistance and the last-line antibiotics fail, the disease in question becomes untreatable.
Despite resistance occurring more rapidly, antibiotic development has drastically slowed resulting in a situation where there are not enough antibiotics in development to combat this growing resistance. This is a crisis that affects people from all walks of life. Antimicrobial agents – which kill or stop the growth of microorganisms – are essential for preventing and treating infectious diseases, such as tuberculosis. These antimicrobial agents are currently in use for organ transplants, caesarean births, wisdom tooth extractions, to prevent infection during chemotherapy, and so on.
As a society, we have become so reliant on modern medicine that it is hard to imagine a world where simple infections and routine operations can kill – yet this is the future we face if action is not taken.
“If antibiotics no longer work, it would signal the end of modern medicine. It is now not enough to simply cut antibiotic use – we urgently need to find new ones to win the war against the superbugs that are resistant to multiple drugs.”Professor Dame Sally Davies, UK Special Envoy on Antimicrobial Resistance
In 2014, it was estimated that drug-resistant diseases were responsible for 700,000 deaths worldwide every year. This number is set to rise to 10 million per year by 2050 if action is not taken. Despite the need for new antibiotics, many of those currently in use are generations old. Since the last original class of antibiotics was discovered in the 1980s, the field has spent over 30 years in what’s known as a ‘discovery void’. Yet, there is a lack of motivation from pharmaceutical companies when it comes to developing new antibiotics, given that the cost of development for one drug is estimated to be over a billion pounds.
Moreover, when the resultant drug successfully reaches the market, the profit is often insufficient to offset the cost of development. Many large pharmaceutical companies have subsequently dropped out of the market despite the fact that, by 2050, AMR is projected to have caused 300 million premature deaths. Many of these companies are instead pursuing the development of drugs for more commercially lucrative, chronic diseases such as cancer. These drugs would be taken over a much longer duration than antibiotics (which are typically taken for 5-14 days). Therefore, a greater volume of the drugs can be sold, and more profit obtained.
Whilst it is easy to point the finger at such companies, the pharmaceutical industry is ultimately a business and, like most businesses, it can’t be investing in something that doesn’t offer a return. Antibiotics are unique in the sense that their use must be restricted in order to avoid over-prescription, as this can contribute to these drugs acquiring resistance. However, this need to safeguard antibiotics limits the volume that can be sold and makes for terrible business. Given the value of antibiotics to society, there is a strong need to create financial incentives for pharmaceutical companies. To break the link between profitability and volumes sold, a global system of market entry rewards (MER) for new antibiotics has been proposed where companies could be offered up to $1.6 billion for bringing a new drug to market. The specifics for any such market entry rewards are still very much in the works.
This is of course highly relevant to the main issue of today: the coronavirus outbreak was impossible to predict and yet thankfully tackled with a rapid, collaborative response which required huge sums of money. The production of COVID-19 vaccines was a global effort that represents what science can do at its best. In comparison, the threat of AMR was entirely predictable and yet, between 2003 and 2013, less than 5% of venture capital investment in pharmaceutical research and development was for antimicrobial production. The cost of launching a pre-emptive response during that decade would have been significantly lower than responding today, now that AMR threatens to become a true public health emergency.
This urgency to react to visible, immediate threats rather than predictable ones is understandable, yet COVID-19 is a prime example of the huge economic repercussions that come with being unprepared. Moreover, AMR has the potential to surpass COVID-19 in terms of deaths and economic cost, demonstrating that reluctance to act doesn’t make the problem go away. In this instance, it only means that more lives will be lost, and eventually, more tax-payer money will be spent in trying to combat a problem that has been staring us in the face for decades.
Thankfully, the academics here at the University of Leeds are addressing the growing problem of AMR as a matter of urgency. I had the pleasure of speaking to Professor Alex O’Neill who is the co-lead of the cross-Faculty Steering Group on Antimicrobial Resistance. Professor O’Neill’s major concern is what will happen in the next 20 years, a period in which “resistance will continue to intensify whilst we have no new drugs waiting in the cupboard”. He went on to inform me that “because of the length of the drug development process, at the point we decide we have reached a sufficiently serious crisis and [when] there needs to be more investment to bring new antibiotics forward, we will be something like a decade away from new drugs reaching patients. If we leave it too late to act, the results will be catastrophic.”
O’Neill has taken matters into his own hands as his lab is currently working on the discovery of new antimicrobial agents. This work, however, is not without its challenges. Professor O’Neill explained to me that in an academic setting, not only is he faced with scientific challenges, but also practical ones. O’Neill has struggled in “assembling and maintaining teams of individuals with the necessary diverse scientific expertise” as well as the challenge of “continually striving to secure funding for an activity that does not – in terms of delivering new drugs – appear to be a good bet for investment”.
When asked if he was hopeful that his lab would be able to discover a new antimicrobial agent, Professor O’Neill remained honest and realistic stating that “the vast majority of compounds don’t make it; that in turn means that the vast majority of those working in antibiotic discovery will not discover a drug that makes it into the clinic”. Despite this, his lab is focussed on systematically innovating their way around key challenges that have been holding back the field of antibiotic discovery. Therefore, even if O’Neill’s lab does not directly discover a new drug, it will nonetheless be “contributing new knowledge to inform and improve the process in the future”. Ultimately, Professor O’Neill views AMR as an “addressable problem” but only if we can “get to a point where we keep it to an absolute minimum and slower than the pace at which new drugs are introduced”.
By Ella Spittall
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