The time is now to develop new antibiotics, but serious barriers stand in our way
We’re all doomed.
Well, possibly not. But having recently returned from the American Society for Microbiology annual meeting in Denver, Colorado, where thousands of my fellow scientists flocked to present and absorb all the latest research into our tiny ancient enemies, I certainly have a lot to think about.
Large conferences present the whole spectrum of a topic, rather than one specialized niche. So while you attend them in the hopes of learning the latest findings (and gossip) in your own particular area, you are simultaneously exposed to helpful information and inspiration from a wide variety of parallel systems. For example, I work on bacterial pathogens of the urinary tract, but there is a lot to be learned from similar ecosystems in the gut, the mouth and indeed pretty anywhere else on the human body where microorganisms can gain access (even the penis, it transpires – who knew?).
And what struck me was the vast complexity of the problem at hand. Human beings (and their animal companions) have co-evolved with bacteria for millennia, but bacteria always seem to be one step ahead. First of all, we are vastly outnumbered: it’s been estimated that there are five million trillion trillion bacteria on our planet, more than there are stars in the universe. Our bodies themselves harbour a hundred trillion individual bacteria, which is ten times more than the number of human cells that make us up – and there are probably about a thousand different types along for the ride.
But the more we study microbes and how they interact with us, their hosts, the more complicated the picture becomes. I sat back in my chair and was blown away by the many ingenious strategies bugs employ to gain the upper hand. I learned about parasites that invade our cells and then throw up an elaborate shell coated with proteins that, like snipers, go after anything our cells throw at them. I learned about bacteria that spit out toxins that drill holes into our white blood cells to render them inert, or that create syringe-like structures to inject helpful materials into our tissues like an advanced party prepping the ground. I learned about bugs that dock on the surface of our cells and then tickle them, somehow persuading our membranes to obligingly produce welcoming cup-like structures that usher them inside like honoured guests. I learned about bugs that lurk almost dormant inside our cells, feeding themselves by diverting common biochemical pathways like the Krebs cycle to their own benefit.
These strategies are surely just the tip of the iceberg. Given that five million trillion trillion bacteria share our world, we are only scratching the surface of how an infinitesimally small fraction of them actually work.
All of this bacterial diversity is wonderful from the point of view of the biologically curious, but as a species, we really ought to be getting our own backs a bit better. As most people have heard, antibiotic resistance is on the rise. We are rapidly running out of new classes of drugs for diseases that we thought we’d conquered decades ago, such as tuberculosis, some strains of which are now able to completely evade all of our current therapies. Scary examples like this are inevitably going to increase in number and variety. And it’s not just the usual suspect killer diseases – given the risk of infection during routine procedures such as operations and hip replacements, the scope for havoc in the absence of useful antibiotics is even higher. Before antibiotics, people could die from a paper cut.
These worries are not new. In fact, Alexander Fleming, one of the discoverers of antibiotics, was trying to warn people as far back as 1945 – a warning that came true very soon after when soldiers started to develop penicillin-resistant gonorrhoea. I myself have been hearing about the looming antibiotic crisis ever since I trained as a Microbiology PhD student back in the early 1990s. A few months ago Sally Davies, the UK’s Chief Medical Advisor, produced yet another call to arms, calling antibiotic resistance a “catastrophe” akin to climate change and terrorism. But after a brief media flurry in response, it all went quiet again – as it always does.
There’s no quick solution in sight, even though we have a pretty good grasp of why we are rubbish at developing and approving new classes of antibiotics. As outlined recently in a nice piece by Ben Hirschler for Reuters, there’s a major question of incentive. Antibiotics don’t command the same prices as blockbuster drugs for heart disease or cancer, and they aren’t used on a regular basis like, say, prophylactic treatments for stroke. So companies, who quite justifiably need to have a good return on the heart-stoppingly expensive process of developing a new drug in the first place, just can’t afford it – and very few are now bothering. (I know it’s very popular to demonize big pharma for not being more selfless, but anyone who has worked in business – in any sphere, not just in medicines – will easily grasp that without enough return, spending money on something that will not produce enough profits is a one-way ticket to bankruptcy.) Traditionally, selfless research has been performed by academia, but with spending cuts and people losing the art of antibiotic research, there are fewer to do this sort of work. It’s no wonder, therefore, that there hasn’t been a new class of antibiotics discovered since the 1980s – just sporadic variations on the same tired old themes that bacteria have long since sussed out.
Regulation is another big problem. In 2007, the US Food and Drug Administration cracked down after a scandal involving a new antibiotic called Ketek that caused some harmful side effects, and from that point on virtually crippled attempts to approve all new ones. I was talking to a biotech mogul the other day who told me that there’s another problem in the UK – even if a new antibiotic is developed, it goes to the end of the queue, and you’re not allowed to try it until all others have failed. So they rarely get tried at all.
We’re going to need clever science to stay ahead of the bacteria. But we’re also going to need clever policies, and clever financial incentives. We’ve known for a long time that a catastrophe is brewing, so what will it take to finally make us change our approach? Given that it can take more than a decade to develop a new drug from discovery to market, and that the bacteria are unlikely to politely wait around for this to happen, we’d better get cracking.
Jenny Rohn is a cell biologist at UCL, who tweets as @jennyrohn and fights bad-ass bugs for a living