Here’s a good article on animal models in drug discovery, and their many limitations.
We have moved away from studying human disease in humans,” (Elias) Zerhouni lamented to the NIH’s Scientific Review Management Board meeting. “We all drank the Kool-Aid on that one, me included.”
“The problem is that it hasn’t worked, and it’s time we stopped dancing around the problem,” he continued, suggesting researchers have become too reliant on questionable animal data. “We need to refocus and adapt new methodologies for use in humans to understand disease biology in humans.”
The article notes the controversy over mouse inflammation models, among others. I’d add pain as an area where something is clearly off kilter with the traditional animal models, and no one has ever been happy with xenograft models in cancer. (An entire post on “worst animal models” is here).
Well, just use human cell cultures you say, or at least you say if you’ve never tried it. The problem, of course, is that primary human cell cultures are often hard to keep going, and the things you have to do to keep them going often skew them away from being the sorts of cells you were hoping to study. There’s nothing like a real in vivo system, unfortunately. Stem cells hold out a lot of promise for generating human cells of many types, but (as this article explains), the problem is that those cells are fresh, newly minted ones. And those don’t always recapitulate the sorts of changes that you see in (for example) aging neurons.
It looks like we’re moving towards re-creating real human organ-like tissue in vitro, as much as we can. That’s not the least bit easy – there are so many factors that influence cellular physiology, from the obvious ones (constantly changing signals from blood chemistry) to the nonobvious (mechanical forces from nearby muscle contractions). The other way to do it (not discussed in the linked article) is to humanize the animal models as much as possible. One could imagine a rather unnerving “mouse” consisting of mostly (or completely) human tissues out in the periphery, for example.
I’ve defended animal models many times on this site, but my strongest arguments for them are (and remain) that there have to be some intermediate steps on the way to human trials, and that we don’t have anything better that mice et al.. If something better comes along – and we do need something better – then out they go. The lack of really predictive models before human trials is the reason that 90% of all trials fail, and having 90% of all our trials fail is gradually squeezing drug research into a very tight corner indeed. Breaking out of it would be a real accomplishment.