Finding Good Drugs Is Harder Than It Sounds

As NIH director, Elias Zerhouni was a great champion of "translational research" that would get academics into the business of trying to make drugs rather than doing basic research like identifying drug targets.  Now that he's the head of R&D at Sanofi Aventis, he seems to be realizing that discovering drugs is harder than it sounds:

When he arrived at Sanofi, "I thought the solution would be simple," Zerhouni said at a recent R&D press event attended by the Health Blog. He thought the answer to the company's R&D woes was to make it more creative and more nimble, like a small biotech.

But he realized that small biotechs are no more successful than large drug makers at coming up with new drugs. "At the end of the day, there's a gap in translation," he said. . .

At Sanofi, the goal now is to strive for "open innovation," which involves looking for new research and ideas both internally and externally -- for example, at universities and hospitals. In addition, the company is focusing on first understanding a disease and then figuring out what tools might be effective in treating it, rather than identifying a potential tool first and then looking for a disease area in which it could be helpful.

Derek Lowe adds:

With a lot of these things, if you're going to first really understand them, you could have a couple of decades' wait on your hands, and that's if things go well. More likely, you'll end up doing what we've been doing: taking your best shot with what's known at the moment and hoping that you got something right. Which leads us to the success rates we have now.

On the other hand, maybe Zerhouni should just call up Marcia Angell or Donald Light, so that they can set him straight on the real costs of drug R&D. Why should we listen to a former head of the NIH who's now running a major industrial research department, when we can go to the folks who really know what they're talking about, right? And I'd also like to know what he thinks of Francis Collins' plan for a new NIH translational research institute, too, but we may not get to hear about that. . .

I think it's fair to say that industry researchers have a bit of a chip on their shoulder about academics. But I also think it's fair to say that the academics have done a lot to put (and keep) that chip there. The op-ed or magazine piece claiming that the "real" pharmaceutical research is all done in government and university labs, with pharma just swooping in at the end to smack a label on the thing and stack all their money in neat piles, is an evergreen. The truth is that the human body is complicated, finding good drugs is hard, and the regulatory hurdles make it harder every year.  

In general, be skeptical of arguments that there are fabulous savings in money and efficiency to be gained by "eliminating the middleman".  The phrase is a favorite with infomercial hucksters for a reason--it's the sort of thing that sounds really plausible and intuitive.  But in fact, since most people don't like paying more than they have to for their goods and services, and producers do not willingly give up a share of the profits, if there's a middleman in a market, he's usually there for a reason.

Of course, sometimes that reason goes away.  The computers that are replacing travel and real estate agents, for example, are arguably delivering better service at lower cost, and I expect that both professions will eventually reconstitute themselves as consultants for those who want them--advising buyers on neighborhoods and carrying costs, helping sellers file the correct paperwork and set the price.  

But you shouldn't get excited about replacing the middleman unless you understand what function they serve, and have a plausible plan for replacing it.  As G.K. Chesterton once wrote:

In the matter of reforming things, as distinct from deforming them, there is one plain and simple principle; a principle which will probably be called a paradox. There exists in such a case a certain institution or law; let us say, for the sake of simplicity, a fence or gate erected across a road. The more modern type of reformer goes gaily up to it and says, "I don't see the use of this; let us clear it away." To which the more intelligent type of reformer will do well to answer: "If you don't see the use of it, I certainly won't let you clear it away. Go away and think. Then, when you can come back and tell me that you do see the use of it, I may allow you to destroy it."

This paradox rests on the most elementary common sense. The gate or fence did not grow there. It was not set up by somnambulists who built it in their sleep. It is highly improbable that it was put there by escaped lunatics who were for some reason loose in the street. Some person had some reason for thinking it would be a good thing for somebody. And until we know what the reason was, we really cannot judge whether the reason was reasonable. It is extremely probable that we have overlooked some whole aspect of the question, if something set up by human beings like ourselves seems to be entirely meaningless and mysterious. There are reformers who get over this difficulty by assuming that all their fathers were fools; but if that be so, we can only say that folly appears to be a hereditary disease. But the truth is that nobody has any business to destroy a social institution until he has really seen it as an historical institution. If he knows how it arose, and what purposes it was supposed to serve, he may really be able to say that they were bad purposes, that they have since become bad purposes, or that they are purposes which are no longer served. But if he simply stares at the thing as a senseless monstrosity that has somehow sprung up in his path, it is he and not the traditionalist who is suffering from an illusion.

Midlemen are usually performing some valuable service for either customer or producer, or more usually both: price discovery, or bundling, or branding/quality assurance, or knowledge of local markets, or convenience, or some other expertise--something that makes producers willing to give them a cut of the profits.  The proponents of the "real research" story seem to believe that in the case of pharma, that service is simply greed--academics are too busy doing the important research to bother themselves with trifles. 

But if you think carefully about this, it is self refuting.  What it tells you is that translating basic research into a drug involves something that academics aren't doing--something they prefer not to do.  Things like turning their discovery into a product that a) hits the target b) in a dose that doesn't kill the human c) in a form that can be preferably be dosed orally or topically d) can be reliably and cost-effectively synthesized on a large scale and e) doesn't degrade without a team of dedicated lab acolytes on constant watch.  This is maybe not as sexy or fun as academic research (pharma researchers feel free to weigh in here) . . . which would explain why it pays better; it would have to, to attract people into the field.

Unless academics are suddenly going to start doing all that stuff, we're going to need pharma, or some other middleman that looks a lot like pharma.  Don't get me wrong--I think there's plenty wrong in the biotech field, and I'm certainly not suggesting that pharma is some sort of a platonic free-market ideal which has already been led by incentives to the perfected heaven of the invisible hand.  But I also assume that the reason that no one has solved Pharma's current woes is that they're probably pretty hard to solve.