The Much Hyped End to Antibiotics is Nowhere in Sight

Antibiotics are the drugs used to control bacterial infections. Here I'll point out a couple of recent articles relating to antibiotics research, as counterpoints to the prevailing view that we're in danger of running out of antibiotics that work at some unspecified future date. That would be an existential threat to our desired future of extended healthy longevity, were it to happen, but fortunately I think it is a mirage, as are so many of these predictions of doom. As a general rule predictions of doom rely upon people doing nothing to prevent said doom, and that is never the case.

We humans have trouble thinking rationally about progress. We live in an age of profound technological change: it is everywhere, fast enough to see sweeping differences from decade to decade, and yet it is human nature to look at the present state of things and predict a future that is just today with a few of the deckchairs shuffled around. You have to think carefully on a topic to step beyond this instinct, to consider how the fundamental aspects of the picture will change, not just the fiddling details. The moment that you stop paying attention, you'll backslide into making assumptions that are, in essence, based on the belief that nothing important is going to change.

This aspect of our nature gives rise to Malthusian visions of an end to present resources, and a dismal future world that falters because of it. In practice this end never comes to pass because people react to the threat of scarcity, far in advance, by creating new resources and more efficient ways to use existing resources. The moment that price increases due to scarcity emerge as a possibility on the horizon, scores of entrepreneurs start on their varied visions for a better replacement resource. So we have progress, and in our age that is self-evidently continual, rapid, driven progress.

Present popular views on the future of antibiotics are essentially Malthusian in nature: a trend in drug-resistant bacterial species is observed, and if continued it leads to a scarcity of effective antibiotics in the future. That trend is then projected all the way down to zero, to no working antibiotics and a world of rampaging bacterial infections. That grim result will never happen, however, just as any number of other predicted grim results failed to emerge over the past few hundred years. In this case, as always, entrepreneurs both inside and outside the scientific community have been at work for years on varied solutions to bacterial resistance to antibiotics. A few are mentioned here:

Antibiotics Are Dead; Long Live Antibiotics!

We've been hearing the tales of doom for quite a few years now: the breathtaking promiscuity of bacteria, which allows them to mix and match their DNA with others' to an extent that puts Genghis Khan to shame, has increasingly allowed them to accumulate genetic resistance to more and more of our antibiotics. But this pessimism rests entirely on one assumption: that we have no realistic prospect of developing new classes of antibiotics any time soon, antibiotics that our major threats have not yet seen and thus not acquired resistance to. And it now seems that that assumption is unwarranted. It is based on history - on the fact that no new antibiotic class with broad efficacy has been identified for decades. But very recently, a novel method was identified for isolating exactly those - and it seems to work really, really well.

Antibiotics are generally synthesised in nature by bacteria (or other microbes) as defences against each other. We have identified antibiotics in the lab, and thus necessarily only those made by bacterial species that we can grow in the lab. Yet almost all bacterial species cannot be grown in the lab using present day practical methods. Knowing these points, researchers built a device that allowed them to isolate and grow bacteria in the soil itself, with molecules freely moving into and out of the device, thereby sidestepping our ignorance of which such molecules actually matter. And then they were able to isolate the compounds that those bacteria were secreting and test them for antibiotic potency. And it worked. They found a completely new antibiotic that has already been shown to have very broad efficacy against several bacterial strains that are resistant to most existing antibiotics.

And as if that were not enough, here's the kicker. This was not some kind of massive high-throughput screen of the kind we so often hear about in biomedical research these days. The researchers tried this approach just once, in essentially their back yard, on a very small scale, and it still worked the first time. What that tells us is that it can work again - and again, and again.

Viral Soldiers

Researchers on the hunt for more-effective therapies that preserve a healthy microbiome are taking a closer look at the many different viruses that attack bacteria. Bacteriophages (literally, "bacteria eaters") punch holes through the microbes' outer covering and inject their own genetic material, hijacking the host's cellular machinery to make viral copies, then burst open the cell with proteins known as lysins, releasing dozens or hundreds of new phages. The cycle continues until there are no bacteria left to slay. Phages are picky eaters that only attack specific types of bacteria, so they're unlikely to harm the normal microbiome or any human cells. And because phages have coevolved with their bacterial victims for millennia, it's unlikely that an arms race will lead to resistance. This simple biology has led to renewed interest in the surprisingly long-standing practice of phage therapy: infecting patients with viruses to kill their bacterial foes.

While most research is still in the preclinical phase, a handful of trials are underway, and a growing number of companies are investing in the treatment strategy. Phage therapy is receiving as much attention now as it did in the pre-antibiotic era, when it flourished in spite of the dearth of clinical tests or regulatory oversight at the time. "Bacteriophage therapy will have its day again. It sort of had one, before antibiotics came along, but it wasn't well understood then."

On that topic, what to do about the many types of viruses that we don't want to engage with? This is a very different area of research in comparison to the matter of controlling bacterial infection, but again there are numerous promising strategies that look capable of fundamentally changing the picture for the treatment of viral infections. One of those you might be familiar with is DRACO, double-stranded RNA activated caspase oligomerizer, a technology that can in principle control near any type of viral infection by destroying infected cells before viruses can multiply effectively.

Comments

I'm glad work on new antibiotics is finally getting some traction. I think this is one area where public funding/support can be quite important. In the past few decades few new antibiotics have been developed, mainly because they aren't profitable for drug companies, since they're only used once or a few times. (You seem the same problem with vaccines, which is why govts often have to offer incentives to drug companies for their developement)

Though I'm still not quite as bullish as Reason. Antibiotic resistance is a serious problem, and we can't be sure the rate of new antibiotic creation will be fast enough for our needs.(Or if things like DRACO will actually come to fruition) Along with new antibiotic development I think there still need to be more efforts to curtail unnecessary/irresponsible use of antibiotics. I don't think that's Malthusian, it's just good public health policy.

Posted by: KC at January 5th, 2016 4:43 PM

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