Here's something a bit out of our field, but it might be disturbingly relevant to the drug industry's current situation: Clay Shirky on the collapse of complex societies. He's drawing on Joseph Tainter's archaeological study of that name:
The answer he arrived at was that (these societies) hadn’t collapsed despite their cultural sophistication, they’d collapsed because of it. Subject to violent compression, Tainter’s story goes like this: a group of people, through a combination of social organization and environmental luck, finds itself with a surplus of resources. Managing this surplus makes society more complex—agriculture rewards mathematical skill, granaries require new forms of construction, and so on.
Early on, the marginal value of this complexity is positive—each additional bit of complexity more than pays for itself in improved output—but over time, the law of diminishing returns reduces the marginal value, until it disappears completely. At this point, any additional complexity is pure cost.
Tainter’s thesis is that when society’s elite members add one layer of bureaucracy or demand one tribute too many, they end up extracting all the value from their environment it is possible to extract and then some.
Readers who work in the industry - particularly those at the larger companies - will probably have just shivered a bit. To my mind, that's an eerily precise summation of what's gone wrong in some R&D organizations. Shirky talks about internet hosting companies and the current dilemmas of the large media organizations, but there's plenty of room to include the drug industry in there, too. Look at the way research has been conducted over the past thirty years or so: we keep adding layers of complexity, basically because we have to - more and more assays and screens. It used to be (so I hear) all about dosing animals. Then you had cell cultures, then cloned receptors and enzymes came along (we're heading out of the 1970s and well into the 1980s now, if you're keeping score at home). Outside of target assays, the Ames test came along in the 1970s, and there were liver microsomes and isolated P450 enzymes for stability, Caco-2 cells for permeability, hERG assays to look out for cardiac tox, et cetera. You can do the same thing for the development of animal models - normal rodents, then natural inbred mutations, then knockouts, humanized transgenics. . .you get the picture.
As I say, we have very little choice but to get more complicated, because our knowledge of biology keeps expanding. But while this is going on, everyone keeps thinking that all this new knowledge is (at some point) going to start making things easier - a future era known, informally, as "when we really start figuring all this stuff out". It hasn't happened yet. If you're someone like Ray Kurzweil, you expect this pretty soon. I don't, although I hold out eventual long-term hope.
Shirky's message for the media companies is that their high-value-added lifestyles are being fatally undermined. We're not facing the same situation in this industry - there's no equivalent of free YouTube stuff eating our lunch, and I'm not expecting anything in that line for a long time, if ever. But the complexity-piling-on-complexity problem is real for us, nonetheless. If the burden gets too heavy, we could be in trouble even without someone coming along to push us over.