Why Miracle Drugs Are (Almost) Never as Miraculous As They Seem

Derek Lowe

We swim in a sea of hype, of what people would like for us to believe. This is not new, as the electoral graffiti on the walls of Pompeii and such incidents as the South Sea Bubble show, but our technology allows it greater scope than ever. Politics, the arts, finance: there's hardly a field of modern human activity that isn't saturated with promotion and pitchmeisters, most all of them going full yammer, 24 hours a day. I can't help but think that a hunter-gatherer tribesman, brought into modern society and somehow protected from a complete nervous collapse, would end up being amazed at sheer number of things that people would be trying to persuade him of.

And if you think that science is any different, you really should get out and meet some more scientists. The hype varies, depending on what sort of science we're talking about, but since the labs are staffed with modern humans, hype is what you get. In academia, the competition for grant money and prominent journal publication breeds exaggeration as to the importance of research programs, their past successes, and their future chances. The worst of these cross over the line into fraud, some of which makes the headlines, but even the honest stuff (the huge majority) is best-foot-forward all the time. You learn, after a short time doing research yourself, to mentally adjust for the titles of papers, presentations, and (most especially) press releases. The latter should be flipped through as quickly as possible, in preference to the actual publication that they're boosting.

But industrial research has no high horse to get up on. We have analysts to please and shareholders to enrich, and many of these people are not especially patient. There are, after all, plenty of other places to put one's money. As for my own field, there are few ways to spend one's money more surely than trying to bring a drug to market. The failure rate in the clinic is over 90%; the failure rate before you even get to the clinic is no better. A few years ago, the Wall Street Journal estimated that all of the biotechnology industry, taken together, had been a net loss for investors. This despite your Genentechs, your Amgens, your Biogens and what have you - the scores of startups that burned money for years and never were able to generate a return made up for these and more. Trying to get strangers to come in off the sidewalk and finance this process is no small challenge. It's not surprising that a bit of wishful thinking is involved.

The hype is strong for individual companies and drugs, most especially when one small company has only one drug that it can afford to develop. Such companies are like test planes with experimental jets: they're diving straight at the ground from great heights, hoping to get up enough airspeed to get the engine to ignite and to be able to pull up in time. The hype can be strong around entire technologies as well. When I was starting out in the business, antisense DNA was the hot topic, looking fit to put everyone else out of business if it worked out as advertised. It has not. Then, over the last ten years, RNA interference has at times looked like a similar game-changer, for similar reasons. But while it still has a lot of potential, it's also encountered the usual difficulties and convolutions that any new field has, and no one still knows how much of that potential will ever be reached.

Stem cells have had the same problem. The potential there is, again, huge. All that stuff you read about replacement body parts, fixing injured spinal cords and heart muscles, reversing childhood diabetes and Parkinson's disease - none of that is impossible, as far as anyone knows yet. But hardly any of it is possible yet, either. We're just getting into the first steps in the first diseases, and we hardly know anything about what we're doing, compared to what there is to know. There's no manual; we have to find everything out the hard way. We get to work out what cells to use, how to treat them, how to get them where they need to be, how to make them grow into the right tissues and not (say) into galloping metastatic cancers. . .that's a real possibility, that last one, and it's not the only nasty outcome, by a long shot. In the end, we're going to know an awful lot more than we do now about the growth programs of human cells, but every bit of that knowledge is going to be hard-won. I have not seen this perspective emphasized in many articles about stem cells in the popular press.

So, next time you see one of those headlines about a medical breakthrough or a wonder drug, do the same math that the people in the research world do. Divide by five. Divide by ten, or maybe by a hundred, to get the real number. Breakthroughs really do happen, and great things really do get discovered, but not every trading day.