Derek Lowe of In the Pipeline has a post up on the use of animals in research within the drug company milieu. It is worth a read.
We watch with all the tools of our trade - remote-control physiological radio transmitters, motion-sensing software hooked up to video cameras, sensitive mass spectrometry analysis of blood, of urine, and whatever else, painstaking microscopic inspection of tissue samples, whatever we can bring to bear. But in the end, it all comes down to dosing animals and waiting to see what happens. That principle hasn't changed in decades, just the technology we use to do it.
Now, if you don't read Lowe that regularly you might want to skim through a few recent posts and you are almost inevitably going to run up against his formulation of the "90%" problem. His most recent musings on this topic concern convincing the (health-care reform engaged and politicizing) public that making effective medications is really hard stuff and the evul BigPharma companies work their tails off on the development side to get to drugs which can be marketed. All joking aside, I think his point is that 90% of drugs fail...at multiple levels of the development process!
This consideration I find critical for some aspects of the animals-in-research discussion.
Back to the original post I linked, we recognize that within BigPharma the toxicity testing is a hugely important part of medication development.
But we also give the drug candidates to healthy ones, at higher doses and for longer periods of time, in order to see what else the compounds might do that we don't expect. Most of those effects are bad - I'd casually estimate 99% of the time, anyway - and many of them will stop a drug candidate from ever being developed. The more severe the toxic effect, the greater the chance that it's based on some fundamental mechanism that will be common to all animals. In some cases we can identify what's causing the trouble, once we've seen it, and once in a great while we can use that information to argue that we can keep going, that humans wouldn't be at the same risk. But this is very rare - we generally don't know enough to make a persuasive case. If your compound kills mice or kills rats, your compound is dead, too.
I've lost count of the number of compounds I've worked on that have been pulled due to toxicity concerns; suffice it to say that it's a very common thing. Every time it's been something different, and it's often not for any of the reasons I feared beforehand. I've often said here that if you don't hold your breath when your drug candidate goes into its first two-week tox testing, then you haven't been doing this stuff long enough.
"Testing", as opposed to "research" can sometimes be easier for ARA types to attack and indeed they work very hard to conflate cosmetics testing with all animal use, both testing and research. Since we academic types don't really do "testing" quite so much we don't have the best perspective to argue why, for example, toxicity testing of promising new compounds is so important and how it works.
This is why Derek Lowe's comments are important. It is only from within the drug-development perspective that we can obtain these numbers about just how many compounds have been found very promising at the non-animal stages and how many have been ruled out at the non-animal stages. Ultimately it is important to communicate what proportion of highly promising candidates based on stage N-1 data/rationale are ruled out by Stage N. And just how many stages of screening (for 90% hit rate?) come before anything gets tested in an animal.
It might be of further interest to examine the proportion of compounds which are ruled out by the animal toxicity (and efficacy) testing . This is because one of the favorite lies of the ARA wackaloon perspective is to argue that if drugs continue to look promising after animal tests but ultimately end up failing in clinical trials this proves that animal research is ineffectual. This is wrong because if animal research prevents 90 drugs which would have been toxic or ineffective in human trials, identifies 8 as safe/effective which fail in humans and only 2 which end up clinical successes, this sounds pretty dang effective to me. The ARA perspective claims 80% failure for this scenario. In fact, an interpretation of 92% successful deployment* of animal models is more accurate.
From what I can tell, my numbers here are wildly optimistic. Fractions of a percent of compounds end up as human therapies. But these data are hard to come by. Why?
Because BigPharma is motivated to look successful, not to advertise their failures. So I've only seen reference to the failure rate in odd bits and drabs of talking with Pharma scientists like Derek Lowe. It would be nice if some of these Pharma companies started to understand that they could help communicate the necessity and value of animal experiments if they were a bit more open about the failure numbers.
[h/t: Abel Pharmboy]
*admittedly this overlooks the miss rate- the proportion of drugs found toxic or ineffective in animal models that would have been perfectly good drugs in humans. I don't know how we could possibly estimate this number.