A reader sends along this account of some speakers at last year's investment symposium from Agora Financial. One of the speakers was Juan Enriquez, and I thought that readers here might be interested in his perspective.
First, the facts. According to Enriquez:
Today, it costs 100,000 times less than it once did to create a three-dimensional map of a disease-causing protein
There are about 300 times more of these disease proteins in databases now than in times past
The number of drug-like chemicals per researcher has increased 800 times
The cost to test a drug versus a protein has decreased ten-fold
The technology to conduct these tests has gotten much quicker
Now here’s Enriquez’s simple question:
"Given all these advances, why haven’t we cured cancer yet? Why haven’t we cured Alzheimer’s? Why haven’t we cured Parkinson’s?"
The answer likely lies in the bloated process and downright hostile-to-innovation climate for FDA drug approvals in this day and age...
According to Enriquez, this climate has gotten so bad that major pharmaceuticals companies have begun shifting their primary focus from R&D of new drugs to increased marketing of existing drugs — and mergers and acquisitions.
I have a problem with this point of view, assuming that it's been reported correctly. I'll interpret this as makes-a-good-speech exaggeration, but Enriquez himself has most certainly been around enough to realize that the advances that he speaks of are not, by themselves, enough to lead to a shower of new therapies. That's a theme that has come up on this site several times, as well it might. I continue to think that if you could climb in a time machine and go back to, say, 1980 with these kinds of numbers (genomes sequenced, genes annotated, proteins with solved structures, biochemical pathways identified, etc.), that everyone would assume that we'd be further along, medically, than we really are by now. Surely that sort of detailed knowledge would have solved some of the major problems? More specifically, I become more sure every year that drug discovery groups of that era might be especially taken aback at how the new era of target-based molecular-biology-driven drug research has ended up working out: as a much harder proposition than many might have thought.
So it's a little disturbing to see the line taken above. In effect, it's saying that yes, all these advances have been enough to release a flood of new therapies, which means that there must be something holding them back (in this case, apparently, the FDA). The thing is, the FDA probably has slowed things down - in fact, I'd say it almost certainly has. That's part of their job, insofar as the slowdowns are in the cause of safety.
And now we enter the arguing zone. On the one side, you have the reducio ad absurdum argument that yes, we'd have a lot more things figured out if we could just go directly into humans with our drug candidates instead of into mice, so why don't we just? (That's certainly true, as far as it goes. We would surely kill off a fair number of people doing things that way, as the price of progress, but (more) progress there would almost certainly be. But no one - no one outside of North Korea, anyway - is seriously proposing this style of drug discovery. Someone who agrees with Enriquez's position would regard it as a ridiculous misperception of what they're calling for, designed to make them look stupid and heartless.
But I think that Enriquez's speech, as reported, is the ad absurdum in the other direction. The idea that the FDA is the whole problem is also an oversimplification. In most of these areas, the explosion of knowledge laid out above has not yet let to an explosion of understanding. You'd get the idea that there was this big region of unexplored stuff, and now we've pretty much explored it, so we should really be ready to get things done. But the reality, as I see it, as that there was this big region of unexplored stuff, and we set into to explore it, and found out that it was far bigger than we'd even dreamed. It's easy to get your scale of measurement wrong. It's quite similar to the way that humanity didn't realize just how large the Earth was, then how small it was compared to the solar system (and how off-center), and how non-special our sun was in the immensity of the galaxy, not to mention how many other galaxies there are and how far away they lie. Biology and biochemistry aren't quite on that scale of immensity, but they're plenty big enough.
Now, when I mentioned that we'd surely have killed off more people by doing drug research by the more direct routes, the reply is that we've been killing people off by moving too slowly as well. That's a valid argument. But under the current system, we choose to have people die passively, through mechanisms of disease that are already operating, while under the full-speed-ahead approaches, we might lower that number by instead killing off some others in a more active manner. It's typically human of us to choose the former strategy. The big questions are how many people would die in each category as we moved up and down the range between the two extremes, and what level of each casualty count we'd find "acceptable".
So while it's not crazy to say that we should be less risk-averse, I think it is silly to say that the FDA is the only (or even main) thing holding us back. I think that this has a tendency to bring on both unnecessary anger directed at the agency, and raise unfulfillable hopes in regards to what the industry can do in the near term. Neither of those seem useful to me.
Full disclosure - I've met Enriquez, three years ago at SciFoo. I'd be glad to give him a spot to amplify and extend his remarks if he'd like one.