The recent success of PETA’s protests against overseas shipping of primates for laboratory research in the US highlights the less talked about issues of using animal controls. Whereas primates were the focus of the protests at hand, the PETA has also been actively engaged in raising awareness about treatment of other lab animals including mice. Their investigations at the University of Chapel Hill labs show the need for increased awareness about such issues, especially when they are the most commonly used mammalian animal model, but lab mice are not protected under the Animal Welfare Act administered by USDA APHIS. However, the Public Health Service Act administered by the National Institutes of Health do provide a guideline for the care and use of such animals. This standard of care is maintained by the Association for Assessment and Accreditation of Laboratory Animal Care (AAALAC), but strangely enough, this accreditation is voluntary, although most academic research institutes do ask for it, and not a prerequisite for US federal funding. Regardless of the upcoming and proposed alternatives to animal testing (ref), the need for such use of animals remain somewhat indisputable as 93% of researchers (as of 2009) still supported it and the US federal law requires animal testing for all drugs and some chemicals (ref).

As mainstream researchers adhere more and more strictly to the “Three Rs” guideline (Replacement, Reduction, Refinement) for animal experimentation, the use of lab mice as animal controls have come in question. The lab mouse has come a long way from the cheese-loving corner-dwelling innocent-but-cute animal to being the animal model of choice to study complex diseases such as cancer (ref). The advent of Genetically Engineered Mice (GEM) and their subsequent commercial successors, the JAX mice, has allowed the biomedical research field to make great advances in not only the study of diseases and treatment options, but also in related public health issues such as obesity. Such success has even earned lab mouse the accolade of “Best supporting role in a medical drama“. But this success comes with its limitations – how far can the mouse model tell us about diseases and drugs?

In terms of cancer research, the focus has narrowed from the large scope of how population dynamics affect cancer incidence to the molecular mechanisms of the disease, thus leading to modelling of individual mutations. The GEM models used are inbred for such purposes and ironically, has come to represent a single individual in a population rather than the population as a whole (ref). Because of the process of generating such mice, their genetic history gets murkier and thus polymorphisms are introduced back into the genetic mix, which may not always show up in the phenotype (example here). The lack of control over the genetic background and testing for it may produce unreliable results as the introduced variability will not have been considered for a measure of control. The single variable inbred system may shed light on the workings of a particular mutation, but with such inherited variability involved, it becomes difficult to pinpoint the cause of cancer incidence even in such models.

It is not quite possible to able to strictly control all variables involved in the incidence of a multi-faceted disease such as cancer. The aim of the control group in any scientific experiment is to provide a means of comparison of the concept being tested. This may reduce the problem of untested variability in mice used as control subjects, but as the study by Martin et al (2010)  shows, a large majority of such animals are “metabolically morbid”. Lab mice are usually sedentary and overweight, mainly due to the large intake of food and lack of movement. The standard lab conditions result in such mice becoming overweight, insulin resistant, hypertensive and may experience premature death (ref). The same study also shows that cutting daily food intake by 20-40% of the usual standard, or providing food intermittently, results in significant decrease in the likelihood of incidences of cancer, type 2 diabetes, renal failure and can even extend the lifespan up to 40%.  These findings raise the concern that the pathologies associated with obesity and cancer may not have been properly controlled in the control group and thus, the cause of incidence may not be accurately pinpointed (ref).

The problems of using the lab mouse as animal model highlighted above are, of course, solvable. Suggestions have already been made in the studies mentioned above and a recent study shows that mice, which are allowed to build nests to keep themselves thermally stable (30-32 degree Celsius), provide a better model for studying humans compared to the mice housed under standard lab conditions (20-24 degree Celsius). While the colder temperature suppress aggression and allow female mice to lactate better, if kept towards the lower end, the mice show decreased immunity and growth retardation. The study also showed that the nest-building mice actually ate less compared to their inactive counterparts, since their metabolic demand to keep themselves warm had been reduced by higher temperature and nest building (ref). In addition to such research, the NIH has already proposed revised guidelines for animal care which includes increased housing space for a breeding female mouse, among others (ref, ref). Researchers have also been questioning the undisputed position of the mouse species as the lab animal of choice, since not all physiological processes in the mice are translatable to humans (ref). Other researchers, instead of inducing a disease in the rodents, try to use healthy rodents as models for how human health could be improved to fend off cancer and other deadly diseases. One such animal is the naked mole rat, which as Dr. Rochelle Buffenstein at the Barshop Institute, Texas, pointed out, do not develop cancer even when irradiated, chemically treated or even through xenograft transplantation (ref).  [On a side note, Daniel Engber has a fantastic series of articles in Slate where he explores the ubiquitous use of lab mice as test subjects]

The utilitarian and reductionist approach to science may not allow researchers to provide the best treatment to mice, but the guidelines in place ensure that the most humane approach is taken when working with such animals. Although cases as seen in the PETA’s investigations of the UNC labs do occur, it is a misunderstanding that such phenomena constitute the norm. But because it is only such news that gets out to the general public, the scientists themselves must come forward and dispel accusations of performing atrocious acts on animals. For let us not forget that such experimentation is undertaken to feed the constant consumption of humans, arising from endless craving for a materialistic life.