This is a solid article by Jeffrey Flier (open-access in the Journal of Clinical Investigation) on the roles of academia and industry in drug discovery. Which is a topic that refuses to go away. I am prepared to swear that before starting this blog I had no idea of how many people are convinced that the drug industry does little or no research, and that academic labs discover all the drugs.

I will gladly send anyone unfamiliar with the real situation to this new article, because I think it does an excellent job of laying out just who does what in this business. Short answer: it’s a team effort, of course, and we all do different (and valuable) things. As Flier puts it, “Most fundamental biologic insights have resulted from work by academic scientists. . .“, but the view that all industry does is monetize academic discoveries “reflects a limited understanding of the work carried out by the pharmaceutical and biotech industries“. I could not agree more. When someone says that industry doesn’t do research, etc., I just want to ask them what I’ve been up to for. . .well, thirty years this fall. I hope that this article proves especially valuable because it’s coming from someone in academia – my own arguments on the subject, while vigorous and heartfelt, are surely taken as tendentious special pleading by the people whose views I’d most like to change. That link, though, will take you to over ten years of said arguments, for what that’s worth.

For even more chapter and verse, here’s the Congressional Research Service (PDF) in a recently updated report on the National Institutes of Health. I especially recommend the section starting on numbered page 37 on the balance between academia and industry, and a few pages later on publicly funded research and drug development:

Since over 50% of NIH funding supports basic research, NIH funded research is, to a greater extent, indirectly involved—by generating scientific knowledge and innovations that aid in pharmaceutical development. For example, important basic advances in research, such as recombinant DNA, can lead to the development of whole new classes of drugs. NIH also supports the education and training of biomedical scientists, some of whom then work for the pharmaceutical industry. It is therefore difficult to quantify and assign credit for the role of NIH funding in the development of a given drug.

The CRS goes on to reference several previous attempts to quantify how many drugs can be directly attributed to public-sector research, such as the 2011 study that estimated the 1990-2007 share at about 9%. The overall picture is identical to Flier’s paper above (note: that’s because it’s right):

Rather than directly leading to a new drug, NIH-funded researchers are more often indirectly involved in drug development by producing scientific research and innovations that contribute to the knowledge base and available methods for the pharmaceutical industry.

Exactly. Here’s another such study that appeared last year from a group at the Center for the Integration of Science and Industry at Bentley University, which found (from one direction) that NIH-funded basic research contributed in some way to every single one of the 210 FDA-approved drugs from 2010-2016, but (from the other direction) that “>90% of this funding represents basic research related to the biological targets for drug action rather than the drugs themselves“. Both of those conclusions sound correct from my experience as well. The basic research funded by the NIH and others is absolutely crucial to finding drugs. But the applied research in industry is absolutely crucial, too. Both of these things can be true at the same time, and both of them are.

Here’s another excellent look at the issue, from a professor at Stanford’s law school (Lisa Larrimore Ouellette). She specializes in patent law as it applies to translational research, and her conclusions are completely in line with what’s described above. Her post also addresses the returns on investment to the public seen from NIH research, whether everyone is “paying twice” or not when such research is commercialized, and what the various incentives really are for publicly- and privately-funded drug research. I strongly recommend anyone interested in these issues read it; it’s exceptionally detailed and clear-headed. Part of the frustration in talking about such issues, in fact, is dealing with people who have not thought about these issues in any detail, who may not realize that many of these issues even exist, but are nonetheless passionately convinced that they have grasped all they need to know.

I think that some of the confusion about where drugs come from originates from people who don’t understand how research works in general. Some of them appear to have a mental landscape consisting mostly of thieves and victims, with everything and everyone being assigned as one or the other. But if Research Group A, back in the 1980s, identifies a particular enzyme in cells, and Group B in the 2010s uses genetic variants of it in the human population to propose that it’s unexpectedly important in some disease, and Group C screens their company’s compound collection and develops a small-molecule drug against it and takes it into clinical trials after many twists and turns, here’s the thing: none of these people are ripping any of the others off. They’re all doing science, and this is how science works. Group A was using techniques first invented by others and refined by still more people, and Group B were using sequencing technologies that they didn’t invent, either, and Group C built on both of their efforts to do things that neither Group A nor Group B were capable of. This is what we do.

Outside that issue, another source of the confusion is that even if people have some understanding of how research works in general, they may not understand drug research in particular. This has come up over and over again here, but (put shortly) identifying a potential target, or coming up with a hypothesis about a disease, is not discovering a drug. To use the example above, Group B did not discover a drug. Many people seem to think that the steps from what those folks did to having a pill on the pharmacy shelves are rather routine and even trivial, but again: that’s what I’ve been working on since 1989, and believe me, neither of those adjectives apply. Group C, for example, might have found nothing in their screen, or they might very well manage to eventually take a compound into human patients and find (surprise!) that Group B’s proposal doesn’t work out as a therapy, or that such compounds also do other things that make them unusable. Happens about 90% of the time, actually – and I mean that completely literally: ninety per cent of the time things fail in the clinic. Just getting to patients at all from the Group B proposal level is no small achievement itself, and all that does is set you up for the chopping block I’ve just described.

So this post will be what I refer people to when the whole “Where Do Drugs Really Come From” issue comes up again, as it surely will. I have included my own self-serving Big Pharma Shill perspectives, I have included the views of the former dean of Harvard’s Medical School, those of an academic team at Bentley, those of a professor of intellectual property at Stanford, and those of the Congressional Research Service. As far as I can see, we’re pretty much on the same page. Anyone who has a different take on the subject will do themselves and the rest of the world a favor if they will first sit down and read these to see if their views hold up. On the other hand, if you have a different take on the subject but don’t want to engage with these other sources, please do the rest of the world a favor by doing something else with your time entirely.