Derek Lowe continues to swat down the canard that all the real drug research is done in academic labs, while drug companies unfairly reap the rewards:
I also mentioned recently that I’d come across a good example of an academic compound with interesting activity but no chance of being a drug. Try this one out, from Organic Letters. Yes, there aren’t many other compounds that do what this one does (inhibit the production of TNF-alpha). And no, it’s not going to be a drug – well, at least the odds are very, very long against it.Why so negative? Several reasons. For one thing, this molecule is extremely greasy. This is not a killer in and of itself, but it’s inviting trouble, for the reasons noted here. The second problem is that this thing looks like it’s going to have some trouble dissolving. That’s trouble both from both the thermodynamic (eventual amount in solution) and kinetic (speed of dissolution) senses. That greasiness will be the problem with the former, since a lot of this molecule’s surface area gives water molecules no incentives to join in on anything. And all those aryl rings (along with the symmetric structure) are asking for trouble with the latter. Those features make the structure look like it’ll form a very good, very happy crystal, with its aromatic rings stacked onto each other like ornamental bricks. “Brick” is the very word that comes to mind, actually.
But solubility is only the beginning. The real problem is that quinone functionality in the center of the molecule. In medicinal chemistry, no one wants quinones; no one likes them. They’re just too reactive. It would not surprise me for a minute to learn that this group, though, is the reason for the compound’s activity. It’s probably reacting with some functional group on the surface of the target protein and gumming up the works that way. It’ll do that to others, too, if it gets the chance. There are all sorts of weird little quinones in the literature that hit proteins that nothing else will touch, but none of them are going anywhere.
No, it’s safe to say that any experienced drug-company chemist would draw a red X through this one on sight. Plenty of reasonable-looking compounds turn up with unanticipated problems, so we don’t need to go looking for trouble. That’s not to say that it can’t be a research tool (although I’d be careful interpreting the data from complex systems – there’s no telling how many other things that quinone is going to react with).
But all this brings up another thing that we were talking about around here – how much do drug companies owe academia for working out fundamental biochemistry and molecular biology? What if someone uses this very compound, for example, as a research tool and discovers something about its target that could be used to develop an actual drug? What do we call that?
Well, we call that “science”, as far as I can see. Everything is built on top of something else. In a case like this, the discoverers of this current compound, even if they’ve patented it, do not have a claim on what discoveries might come from it later on.
Megan - I like your overall point, but the quotation doesn't support it very much. Lowe's point is about the legal status of drug research patents - namely, that just because patented research discoveries indirectly lead to profitable drug research, doesn't mean the owner of the research patent has a legal claim to the later profits. His whole point is about legal ownership in a legal system that is designed to spur innovation, and not really a statement about who-is-dependent-on-what.
An example he uses in the rest of the piece illustrates this perfectly - the discovery of the COX-2 enzyme was done academically, and while the discoverers sued for some of the profits for Celebrex and lost (supporting Lowe's point), I don't think anyone would doubt that Celebrex could have been made without the COX-2 discovery first.
I agree with James Tanner that this excerpt doesn't really support Megan's point. I don't pretend to know the percentage of research dollars spent by the NIH vs Big Pharma, but if she were interested in swatting down this so-called canard that seems like a good place to start. An interesting side discussion might be how much pharmaceutical companies spend on research vs how much they spend on advertising.
" An interesting side discussion might be how much pharmaceutical companies spend on research vs how much they spend on advertising. "-Posted by Mike T
I don't think that is very telling. If a company can make more from advertising, they do it. If they can make more from research, they do it. It is not a zero sum game.
What I would like to know more about are the tricks they do to manipulate intellectual property laws. A lot of what they spend on research is actually in attempts to tag new protections onto essentially old drugs. They find a patentable application for an old drug, to extend its protection and keep out generics for another 10 years or so. That too is science. It is counterproductive and wasteful, but it makes the drug companies a lot of money.
With regard to the main thrust of the post, isolated incidents of private research are not very convincing. The people saying that drug companies do no research at all are made of straw.
Most of the cost (and risk) of developing a new drug is in the testing for approval part of the process. Target identification is pretty cheap in the big picture. A large part of the economic role of drug companies is to get together the money and resources to test compounds that may or may not turn out to be marketable.
It's worth noting that subsidizing the basic research that indentifies drug targets would predictably result in less similar research by drug companies. This research is a complement for testing and marketing and drug companies spend on all three until the marginal returns are equal, so when more of any of the three is provided to the drug companies for free, the spending on the other two will go up. This is amplifed by the fact that the total research spending across both the gov't and drug companies has diminishing returns since potential targets get looked at in order of how likely they are to yield something; the public research money only goes to these ends, so the public funding encourages a shift towards other expenditures in the companies.
Which is all very good, but then again pharma is busy offshoring all its research, and about 90% of what they book as research is marketing.
If target acquisition is cheap, then it is only because someone else, like the brilliant and unheard of experiment that was NIH when it was founded, already paid for it.
Eli Rabett you said
Got cite for those two assetions?You seem to have missed the point of the post. Finding targets (whether done by drug companies or by NIH or other publicly funded research) is relatively inexpensive compared to the safety and efficacy testing, which takes a long time and costs a great deal to perform and may or may not end up producing a usable drug. This article gives a good overview of what's involved.
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