In DM’s thread on a Nature article concerning the bombing of a UCLA researcher whimple asks to hear from pain researchers:
Good idea, let’s throw out pain research based on animal models altogether.
Yes, this is a possibility that some people are willing to consider, the sarcastic tone of the statement notwithstanding. The best refutation would be evidence that pain research based on animal models has directly resulted in improvements in pain management in animals (including humans as animals).
How about it pain researchers? Can you compile a quickie list of such instances? Even stipulating that the ends can be used to justify the means, if causing pain to animals is “bad”, then this research is going to need to demonstrate that it is “worth it”. There’s a lot of arguing over how bad the badness is, but not a lot arguing over how good the goodness is. In the absence of a list of pain research successes, a cynic might suppose this is because there in fact isn’t any good that has resulted from this research.
To which I responded:
“Yo Whimple, pain researcher here to address your points:
1) Go to any pain research conference and you will quickly learn that most pain researchers don’t work with animals, most work with humans. These include physicians doing clinical work, electrophysiologists doing peripheral nerve recordings, fMRI people doing what fMRIers do, psychologists looking at comorbidity, nurses looking at outcomes, etc., and the list goes on and on.
2) Then there are us basic researchers who work with cells, animal tissues, human tissues and so on. Most of this work does not involve causing any pain at all. Genetic studies are done, patch clamp recordings are made, biochemical experiments on all sorts of channels and kinase are performed all with the aim of understanding the physiology of nociceptors and pain transmission neurons. These studies have led to an exponential increase in our understanding of the channels and kinase (and other proteins) that mediate nociception.
3) There are, obviously, preclinical pain models. Some of the first ones (back in 50s and 60s) were extreme and have been discarded on ethical grounds. Most models used now cause a mild pain stimulus (certainly no worse than the shock applied in fear conditioning). Others involve long-term inflammation and largely the same as preclinical models used to study inflammation or arthritis. In other words, these models are not exclusive to pain research as they are co-opted from other areas of research on important human diseases that also involve pain. Nerve injury models are slightly different and somewhat unique to the pain area but let’s remember that this is the hardest type of human pain to treat and it leads to a terrible quality of life…
4) So what are the treatments that have resulted from this work? A) massive improvement in opiate efficacy and safer formulations based on preclinical work. B) new generation neuropathic pain meds including gabapentin, pregabalin and the clinical rationale for the use of 5HT and NE reuptake blockers and improvements on their clinical use based on real basic science. C) anti TNFalpha, anti IL-6 and anti NGF treatments either now coming out or in late trials. Some of these originated in other areas and some originated in the pain area but the rationale for the clinical use is all based on preclinical basic science. That’s just a start to a long list.
5) If you doubt the importance of basic science pain research take a trip to your local university hospital and go talk to the patients in the pain clinic.”
Whimple then returns with:
Juniorprof, good list. Personally, I think if the studies can be done on humans, they should be done on humans. My concern is that animal research slows down human research because it’s so easy to work with mice (or whatever) so people spend a lot of resources on finding effective treatments for mice and doing “basic research” studies with mice, which don’t necessarily (usually?) translate into humans. My big whatif goes something like this:
Suppose researchers were not allowed to work with animal models, but could do human subjects research with all the current legal and ethical limits on human research currently in place still in effect (cell culture work on all species still allowed). Would that slow down the development of useful human clinical treatments, speed up the development of useful human clinical treatments, or would things progress at about the same pace? If we took all the animal model researchers and said, “If you’re going to use animals, they have to be human,” would that wind up being good or bad for science from the point of view of the taxpayer funding the work and waiting for treatments and cures?
Can pain researchers (for example) say, “without studies in animal X, currently useful product Y would have been impossible to develop.” Where “impossible” really means impossible, not just more difficult or costly or slower to get working?
Is it in the taxpayers’ best interest to make animal work easier to do, or would the taxpayers be better off long-term if animal work was more difficult to do? (leaving aside the above extreme example of animal work not being allowed at all) Usually I get jumped on for asking this kind of question, but I think it’s worth discussing since the answer to this question helps determine the “goodness” side of the “animal research bad” (less than / equal to / more than) “animal research good” equation.
To which I added:
First, I largely agree, I would prefer to do the work in humans too but in many cases it is simply not possible. On the other hand, we have recently developed a new treatment preclinically that we are now trying to take into a trial in humans. We never would have gotten anyone to believe us without the preclinical data but now that we have it a trial is feasible (its a synergistic drug combo wherein both drugs are approved for human use so we can proceed). From a basic science perspective the trial isn’t very interesting at all. From a treatment perspective its interesting and will certainly be exciting if it translates. From a personal perspective, its about the most exciting thing I can think of… taking treatments form the bench to the clinic is why I wanted to enter this field and I can’t wait to work with some humans!
On your other question, are there examples where the clinical never would have been possible without the preclinical the answer is also yes. My example is not a good one because I likely would have been able to instigate a trial but it would have been much more difficult without the preclinical. On the other hand, the anti-NGF treatments for chronic pain are an excellent example of where it would not have been possible. We have known for a long time that NGF is involved in preclinical pain models and in human pain. We have also known that genetic mutations in humans that block NGF signaling (mostly receptor mutations) cause a terrible disease wherein people with the mutation have profound mental retardation, total lack of pain and inability to sweat. While it was the view of most researchers that this was due to a developmental issue, it was not known if blocking NGF signaling later in life would lead to similar deficits and this made any trial on anti-NGF therapies impossible due to very serious safety issues. After decades of preclinical work it is now known that anti-NGF treatments later in life do not cause similar problems and this animal work has made the safety issue a much smaller issue. So, due to literally thousands of papers on NGF signaling in animal models we have a good idea that these treatments will not cause devastating side effects in humans and these therapies are now late in clinical development. If they gain FDA approval I expect that they will become important treatments for chronic pain disorders. That is but one of several examples wherein animal work was absolutely neccessary to develop new pain treatments.”
Perhaps we can continue the conversation here…