The post here the other day on resistant bacterial infections prompted some readers to wonder why the drug industry isn’t doing more to come up with compounds in this field. It’s not like there’s no money to be made, and it’s not like there’s no history of antibiotic research, after all. But since my industry doesn’t have a history of knowingly leaving money on the table (what industry does?), you’d figure that there’s more to the story.
Money aside, there’s a real problem with finding good targets. For as long as I can remember in the industry, the infectious disease field has suffered from a relatively small target landscape. Almost all the known drugs in the area work through just a handful of basic mechanisms, and adding new ones to the list has been very difficult for at least the last twenty or thirty years.
That was supposed to change, in theory, starting about ten years ago. I interviewed around then at a company that was working in the field, and everyone was quite excited about the bacterial genome sequences that were starting to appear. Surely this would open the sluice gates and let that long-delayed swell of new targets come washing down the flumes. Hasn’t happened. Not yet, anyway.
I have the impression that the same problems that have affected the translation of human genomic data to new drugs have been the problem here as well. In some cases, not as many genes came out as some people were hoping for. And of these, the function of many of them was (to put it mildly) obscure. Of the ones whose use was at least partially known, many of them have proved not to be useful targets for killing the bacteria or limiting their growth. And of the ones that made that cut – and we’re down to an all-too-manageable set by now – screening hasn’t turned up much chemical matter for people like me to work on.
In fact, there’s a persistent feeling among many people in the field that bacterial and fungal proteins have a lower hit rate than you’d assume they would. Even enzymes that are fairly homologous to those in higher organisms, so the story goes, don’t turn up as many hits in the screens as expected. I’m not sure if this is true or not, but as folklore it’s pretty well known. The combination of all these factors with the perceived lack of opportunities for profits (even if you do find something) has made for slow going.
In recent years it’s become clear that the medical need has grown to the point that antibiotic research can indeed be financially worthwhile – but there are any number of financially worthwhile drug outcomes that we haven’t been able to realize. (See obesity, Alzheimer’s, and many other therapeutic areas for examples of multibillion-dollar opportunities waiting for a good idea to come along. Resistant bacteria have their name on one more sword stuck in yet another stone.
Update: there's clearly another reason why developing good antibacterials is hard, and it's the same reason we need more of them. Bacteria are well-stocked with efflux pumps to get rid of molecules they don't like (and with other weapons as well), and they evolve so fast that you can watch them do it. I wrote about efflux on the site a while back - another post is well worth doing soon.