When I started my research career in 2004 I did not think much about laboratory mice. I remember talking with scientist specializing in human immunology about adopting and adapting on mouse cells the assay his lab developed. He asked me “do you think human and mouse immune system behave the same way?” I did not even pause a second, immediately replying “of course, they do”. Really?
Of course, I was always felt bad when harvesting lymphoid cells from experimental mouse that was a living breathing organism just few seconds earlier. Notwithstanding what laboratory animal husbandry suggests, sacrificing small animals through cervical dislocation, a method, believe it or not, considered to be the most humane way of euthanasia of laboratory mice, is still quite distressing. More frequently than not, I was able to accomplish a clean and swift cervical break, but in situations when I was not good, it felt terrible. Is it really worthy all of these experiments, especially on mouse?
National Institutes of Health (NIH) has many progressive guidelines on a paper. It actually mandates that before you conduct your first experiment on live animals, you need to justify that there are no other non-terminal, or non-invasive ways of accomplishing the experimental objectives. However, anyone can “easily” justify the necessity of in vivo experiments. Even if you just want to do purely in vitro cellular assays, how else can you harvest mouse cells except sacrificing the mouse first? Yes, you can harvest blood cells from tail vein but it will provide very few cells. So, what can be done?
First, people who approve protocols should ask themselves “is this model relevant for human disease”? Just because you can modify mice in such a way that it will develop asthma-like symptoms or can be infected with M. tuberculosis, it does not mean that the model has any relevance to humans. If mice works were so easily applicable for humans there would not be so many clinical failures in first place (TB, flu, dengue, ebola, all these pathogens do not replicate human diseases in mice, and still NIH is issuing grants for them).
I my view, NIH should make it obligatory that any new protocol requiring terminal or invasive procedures on laboratory mice to have strict human equivalency comparison. Moreover, NIH should mandate in silico modeling for any protocol. Advances in gene modification, like CRISPR-Cas9 technology, made it easier to convert normal human cells into any knockouts in vitro and this methods are accessible. It is much more relevant to conduct experiments on human cells rather than on mouse cells. Now you can study any molecular pathway in human cells you want. Why are we still clinging to mouse?
Some can say because FDA demands it. Not necessarily. FDA, like NIH, is a federal agency and maybe it is time to make some modification in its rules. Non-invasive, non-lethal experimentation in combination with in silico modeling is a better and more productive alternative to current state. It will force scientists to develop better computer modeling and better disease models.
posted by David Usharauli