Of mice and medicine – Hive Review Series
In a long article published late last year in Slate magazine , Daniel Engber posed some questions that the pharmaceutical industry should be paying attention to. His article, ‘The Mouse Trap’, begins with an observation made by the neuroscientist Mark Mattson in 2007, when he ‘“began to realize that the ‘control’ animals used for research throughout the world are couch potatoes.”’ Mattson went on to co-author an analysis of the problem for the Proceedings of the National Academy of Sciences, finding that lab mice are ‘insulin-resistant, hypertensive, and short-lived.’
This has happened because ad libitum feeding and zero exercise are standard conditions in the rodent-breeding factories that provide scientists with mice (a $1.1 billion dollar industry). But why does it matter? It matters because, as Engber writes, ‘the inbred, factory-farmed rodents in use today – raised by the millions in germ-free barrier rooms, overfed and understimulated and in some cases pumped through with antibiotics – may be placing unseen constraints on what we know and learn.’
The problem is, so invested are researchers in the mouse that no one wants to acknowledge the possibility that there’s a problem. But if there is a problem with mice, there’s a problem with drug development: scientists chew through 88 million mice a year in experiments and drug testing, and since 1965 the number of papers involving mice and rats has more than quadrupled. According to Engber ‘we’ve arrived at something like a monoculture in biomedicine,’ the main reasons being cheapness, docility, and the mouse’s amenability to ‘the most advanced tools of genetic engineering.’
In late 2010 Francis Collins, director of America’s National Institutes of Health, established a new agency to analyse what he called the ‘pipeline problem’ in biomedicine. The problem is that ‘innovation has slowed to a trickle. It takes more than a decade, and some $800 million, to produce a viable, new drug; among the compounds considered for testing, only 1 in 10,000 come to fruition.’ Could this perhaps be because ‘rats and mice were never so good at curing disease as they were at making data for its own sake’? Of the thousands of mouse studies for tuberculosis, ‘not one has been used to pick a new drug regimen that succeeded in clinical trials.’
The geneticist and statistician Michael Festing, one of the world’s experts on inbred lab mice, notes that ‘“the more research you do on something, the more valuable it becomes.”’ ‘A format war hides in the history of biomedicine,’ Engber writes, describing how not just one species but one particular strain, the Black-6, has become the most widely used organism in drug research. The problem is, since 1999 it’s been accepted that, for one, different mice have different responses to pain (prior to that the consensus was that every kind of mouse was essentially the same). And mice have different pain responses to other rodent species. And rodent species have different pain responses humans.
Experimental science does recognise certain fields where specific animals prove useful: for example armadillos in leprosy, prairie voles for autism, finches for language acquisition, but these models ‘live only at the margins of biomedicine…For most questions [the mouse is] a skeleton key that’s tried at every one of Nature’s doors.’ This despite the fact that, in the case of cancer, mice are prone to lymphomas and sarcomas as opposed to the carcinomas which are much more common in humans. Mouse tumours are much less varied than those seen in any hospital oncology department. They serve up ‘a bland and homogenized product, a fast-food version of the disease’. According to Robert Weinberg, the MIT biologist who discovered the first human oncogene and tumour suppressor gene, mice are ‘“the rate-limiting step in cancer research”’, and drug companies are ‘“wasting hundreds of millions of dollars on animal research that has little predictive value.’”
Engber’s article, which portrays both the problems with the mouse model and the ‘institutional inertia’ that prevent those problems from being formally acknowledged by the very people who would benefit most from their resolution, is essential reading.