04 Sep 2018

Superbugs - an Arms Race against Bacteria

William Hall and Anthony McDonnell are the co-authors of Superbugs - an Arms Race Against Bacteria. They were both members of the core team who produced the Review’s seven reports published during 2014 - 2016.

Earlier this year, the Society for Applied Microbiology (SfAM) hosted an event at the British Medical Association (BMA) to celebrate Lord Jim O’Neill’s honorary fellowship.

He gave an entertaining and authentic acceptance speech. In fact, not at all what one might expect from a Lord - or an economist. He spoke without the hollow jargon that politicians of a certain stripe seem to favour.

He cheerfully signed my copy of the book which I’m now reviewing. If that’s not weird, I don’t know what is - but there you have it - full disclosure. O’Neill stepped down from Government, having been Commercial Secretary to the Treasury from May 2015 until September 2016. During that time, and since Spring 2014, he chaired a formal Review into Antimicrobial Resistance (AMR), reporting its final recommendations in May.

Expert trio

William Hall and Anthony McDonnell are the co-authors of Superbugs - an Arms Race Against Bacteria. They were both members of the core team who produced the Review’s seven reports published during 2014 - 2016.

The combined pedigree of the authors is apparent throughout the book. Hall is a public policy professional and McDonnell is a Senior Health Economist. The attention to detail, budgetary calculations and objective overview are nothing if not sobering.

If you’re looking for a rollicking, LOL - laden gallop across the issues, this is not the tome for you. One could argue, AMR is no laughing matter anyway.

Devil in the detail

The book is divided into two sections. The first, focuses on the pressing issues at hand and the second, on potential solutions to drug resistance. What the book does brilliantly is drill down into issues which seem to have become ubiquitous in their repetition, but rarely understood in their complexities and detail.

It’s widely known that there’s little incentive for pharmaceutical companies to produce new antibiotics. Understanding the mechanics of this situation and how best to address it is much less common. This book fills in those gaps with stats, quotes, and stark reality. For example:

‘When asked what she would do with a useful new antibiotic, CMO for England Sally Davies, said that the drug “would need a stewardship program”- that is, that systems would have to be in place to make sure that the antibiotic was only prescribed when absolutely necessary. However, this also means, that when a really useful new antibiotic is found, the company that invests in it cannot rely on high sales for return on investment’

Food for thought

For those unfamiliar with the motivations, legal complexities and economic aspects of pharmaceutical companies, Superbugs is a revelation and a brain drainer. In many ways, the book helps you view the landscape from a pharma’s perspective, even if you don’t agree with their ideology. In that way, it’s a challenging, informative, and troubling read.

‘Phase 3 trials, which can take several years, recruit up to a few thousand patients. Drug companies spend about $10,000 for each patient in a phase 3 trial, and the risks of failure are high. Estimates from the consulting firm ERG on the probability of success for each phase of antibiotic development suggest that the likelihood of ultimately being approved for market at 9 percent for antibiotics in a phase 1, 28 percent for those in phase 2, and 57 percent for those in phase 3.’

See? It’s no fun, but you can’t escape the facts and figures. Superbugs is full of them.

Patience with patients

On top of the fiscal logistics, there’s practical barriers that may not occur to a casual observer. It’s very hard to conduct trials for rare types of drug resistant infections, because finding patients with those strains is tougher than locating patients with more common infections. If someone is rushed into hospital with a suspected rare and potentially fatal infection- what are going you to say?

‘Hang on! Postpone lifesaving treatment- there’s a trial we’d like to you get involved with. Yes, you may lose a limb or two, but think of the antibiotics we might make in the future!’

Due to this particular challenge, researchers wind up enrolling patients who seem likely to be infected but who may not have it at all. It’s a massive gamble. The pay off, in trials of Clostridium difficile infections- is that only about one in four actually turn out to have the condition. Obviously, this is inconvenient, hard to avoid and very costly.

Solutions

Having presented us with all the struggles, costs and regulatory hurdles that potentially stymie research into new antibiotics, the authors present a range of potential solutions that could potentially liberate our protagonists from the steely cocktail of competition, scientific rigour, and microbial evolution. These include; Public Funding for Research, Collaboration among Companies and Harmonization of Regulation and Market Entry Rewards.

The specifics of how these could be put into action are outlined and Superbugs doesn’t skimp on detail, but it’s hard to maintain optimism. Pharma companies collaborating and sharing trial results with each other? For the benefit of the wider community? In an era where charities are fiercely competitive with each other, it’s hard to see pharmas taking a more holistic approach to the business.

In 2002, the 10 US drug companies on the Fortune 500 list had combined international sales of $217bn (£106.6bn). They spent only 14% of that money on research and development, but 31% on marketing and administration. There’s a reason these companies have reputation for being Machiavellian

Watching Trump attempting to dismantle everything his predecessor achieved is a lesson in the foibles of democracy and the unpredictability of the current political climate. Publicly funded research into potential antibiotics is hardly a vote winner, nor immune from the rollercoaster of geopolitics. There’s no doubt that AMR is a crisis, but the solution requires unity, consistency and strategic alliances that aren’t usually a natural fit.

Masterful microbes

‘Superbugs’ is brilliant at presenting the reader with the facts, then delivering some potential solutions. There may be some who quibble with the figures and a few who’ll question the viability of some of the proposals.

However, there’s no doubt that the predicament is a moving target that we can’t afford to miss. This book may not excite pop culture like the Public Health England (PHE) dancing pills advert, but it’s a handy reference tool for policy makers, teachers, health practitioners and anyone who needs to fight this particular corner.

Hard facts

Microbes are a hell of lot better at working together for their own survival than us. They’re the masters of alliance and evolution and continue to dazzle on that front while we wage war, mess up the planet and seek to maintain the ‘market’. Someone’s gonna have to compromise and it won’t be bacteria.

Hall, McDonnell, and O’Neill have tackled the dilemma, largely through an economic prism. If you’re looking for an uplifting escape from existence, this isn’t it. However, if you want a fiscal slap to the head and a clear window onto the scale of the issue, there’s a wealth of wisdom to be found in these pages.

‘Superbugs an Arms Race against Bacteria‘ by William Hall, Anthony McDonnell and Jim O’Neill is published by Harvard University Press