Dr Clare Sansom, Senior Associate Lecturer in Biological Sciences, writes on the screening of Resistance: not all germs are created equal and panel discussion on antibiotic resistance, which took place as part of Science Week 2017
Antibiotic resistance is one of the most crucial issues facing humanity in the early 21st century, with some commentators even suggesting that it poses as serious a threat to civilization as climate change. It was therefore timely that one of Birkbeck Department of Biological Sciences’ contributions to Science Week 2017, with its strapline ‘Microbes in the Real World’, should tackle the issue. This took the form of a screening of an award-winning feature film from 2014, Resistance (subtitle: Not all germs are created equal) followed by an extensive and lively panel discussion. The four panellists were scientists from the department whose research is geared to the development of antimicrobial drugs: Dr Sanjib Bhakta, a Reader in microbiology; Professor Nicholas Keep, Executive Dean of the School of Science and a structural biologist; and two promising students from Dr Bhakta’s lab: PhD student Arundhati Maitra and MRes student Alina Chrzastek.
Not surprisingly, given the timeliness of the issue and (it has to be admitted) the size of the venue – the tiny Birkbeck Cinema in Gordon Square – the session was over-subscribed. After a short introduction by Dr Bhakta, who used his own research field of tuberculosis to set out the ‘global threat’ of drug resistance, the packed audience were treated to 70 minutes of engaging and at times chilling documentary. The film, by US producers Ernie Park and Michael Graziano or, collectively, Uji Films, uses a combination of archive footage, animation, interviews and personal stories to explain how we have arrived at a point where antibiotics are failing and what we need to do to ‘save antibiotics in order to save ourselves’. Although the film was made in the US and focuses on US policies and case studies, the problem it describes is a global one and it would not have been difficult to find equivalent examples in the UK.
The producers weaved three case studies of patients who had suffered antibiotic-resistant infections engagingly through the footage. We were introduced to a teenage lad who had been exceptionally lucky to survive drug-resistant pneumonia with some disability; a fit, middle-aged man who picked up methicillin-resistant Staphylococcus aureus (MRSA) while surfing and is now seriously disabled; and, most harrowingly, a mother whose 18-month-old baby picked up a new strain of MRSA and died within 24 hours.
The film’s narrators explained that all antibiotics are ‘poisons that kill bacteria but not us’; if they don’t kill the bacteria they make them stronger. Using antibiotics in such a way as to promote this rapidly sets up a ‘Darwinian battleground’ in which weak bacteria are knocked out but strong ones survive. This can happen very quickly because bacteria grow and divide so fast. In the words of scientist and author Maryn McKenna, we had the only effective way of killing bacterial pathogens and squandered it. And we have done this in three main ways: by over-use in the environment, in agriculture and in medicine.
The first two of these are particularly prevalent in the US and some Asian countries and less of a problem in Europe, where regulation is stronger. In the US, antimicrobials are used in everyday household products, sprayed on everything from fruit trees to kitchen counters. And once farmers had realised that constant small doses of antibiotics made livestock grow faster and fatter, even in crowded, unsanitary conditions, they were determined to keep doing so even though it ‘makes as much sense as sprinkling antibiotics on your children’s cereal’. Most US-produced meat and poultry is now contaminated with resistant bacteria, and occasionally this is multi-drug resistant. A Danish hog farmer, Kaj Munck, explained the sensible approach taken in Denmark where antibiotic growth promoters in animal feed were banned in 1995 following an extensive public debate. The Danish pig industry is still profitable, producing 28 million a year: about the same as the state of Iowa.
The beginning of the antibiotic era in human medicine coincided with World War II, when it was seen as a ‘miracle drug’ for curing infected wounds. Over-use, however, started very soon: penicillin was given to overseas sex workers, not to protect them from infection but to prevent their US military clients from becoming infected. The danger of resistance was known as early as 1945, when Sir Alexander Fleming told the New York Times that “in such cases the thoughtless person playing with penicillin is morally responsible for the death of the man who finally succumbs to infection.” Doctors who prescribe antibiotics inappropriately are often not morally wrong, or even thoughtless, but over-anxious to avoid mistakes when the chance of an infection being bacterial is low but not vanishingly so. Readily available, rapid diagnostic tests would go a long way towards preventing this type pf misuse.
It would not matter as much if antibiotics became ineffective if there were other molecules ready to take their places. However, the current antibiotic pipeline is weak, with few drugs coming through. Pharma companies can spend at least a decade and a billion dollars on developing a single drug, so it makes more sense to work on drugs like statins that patients must take every day. We must begin to encourage and reward companies that bring forward antibiotic ‘drugs of last resort’ rather than best-sellers. In short, the film concluded, the problem of antibiotic misuse is a classic example of ‘the tragedy of the commons’; one individual’s over-use of antibiotics may be neutral or even beneficial, but if everyone does it there will be a huge problem. To win the arms race against bacteria we may need to redesign all the processes through which we discover, use and protect antibiotics, and to ‘use our wits to keep up with their genes’.
Bhakta introduced the panel discussion with a short explanation of the molecular mechanisms through which bacteria acquire resistance to antibiotics. Bacteria evolve quickly, and almost all have acquired some resistance either intrinsically, through mutations, or by acquiring resistance genes directly from other species. This is an inevitable process but we have some control over how quickly it occurs: good antibiotic stewardship is as important as innovative science for winning the ‘arms race’ described in the film.
Bhakta’s group at Birkbeck is interested in tackling the problem of resistance through discovering new compounds with novel modes of action and by aiming to ‘re-purpose’ some over-the-counter medicines that are already in use for other indications. Drugs in this category will have already been shown to be safe and are therefore quicker and cheaper to develop. Keep summarised the role of structural biology in antibiotic discovery as one of determining the structure of bacterial proteins that might be vulnerable to attack by drugs and identifying compounds that can bind to and inhibit them. We are now often able to see directly how these structures are changed by mutations that increase (or decrease) resistance.
Bhakta chaired the discussion that followed, which was extensive and wide-ranging, taking in politics and economics as well as science and medicine. Several questions touched on the role and responsibilities of the pharmaceutical industry, which is reluctant to invest in drugs that will only be used for short periods. More drug discovery than ever before is taking place in academic labs and small companies, often working together; Maitra, whose Birkbeck Anniversary PhD studentship is part-funded by Wellcome, highlighted the role of the Trust in promoting links with industry. Re-purposing drugs that have already been used clinically is much cheaper than developing a molecule from scratch. MRes students in Bhakta’s lab, including Chrzastek, are testing common anti-inflammatory drugs against Mycobacterium tuberculosis and have found some potentially useful activity although the mechanism of action is still to be explored.
Other questions focused on the need for strict antibiotic control measures. In many European countries, including the UK, antibiotics are only available on prescription and cannot be used as growth promoters in animal feed. This ‘best practice’ needs to be replicated worldwide, but it will be an uphill struggle. Bhakta told the audience that he often visits countries in south and east Asia where resistance is prevalent and has seen antibiotics available over the counter there. In countries without strong, publicly-funded healthcare systems there are often incentives for doctors to over-prescribe drugs including antibiotics. And even where this is not an issue, patients need to be educated to think of antibiotics as drugs of last resort rather than demanding them for every upper respiratory tract infection.
It was perhaps inevitable that someone would ask the ‘Brexit question’: in this case, is there a danger that we would reverse some of our ‘best practices’ when we are no longer bound by EU regulations? Encouragingly, Bhakta doubted that anyone would want to get rid of rules with such clear benefits. He felt that the now inevitable move of the European Medicines Agency, which regulates all medicines marketed in the European Economic Area, from London – and the confusion about how the UK drug market will be regulated – does present a danger, to our strong research base. And however the politics develops the international collaborations that UK-based doctors, scientists and entrepreneurs have built up over decades must be maintained.
In October, BIMI hosted the University of Pittsburgh’s annual lecture with a special talk by Adam Lowenstein’s on David Robert Mitchell’s film It Follows (2014). Shot and set in Detroit, Michigan, the film’s environmental implications often take a backseat to the thrill of its monsters, killings, and gore. Lowenstein’s talk, entitled ‘A Detroit Landscape with Figures: The Subtractive Horror of It Follows’, places the film firmly within the contemporary political and social climate of Detroit, a city that has, in recent years, become synonymous with scarcity and desolation.