Why Rodent Models Are Critical in Infectious Disease R&D
In vivo infection models typically use rodent models because they are cheap, easy to house and work with, require fewer regulations to use, and for ease of euthanasia. TransPharm Preclinical Solutions uses only mice and rats for these reasons. Another good reason to use mice and rats for infectious disease research specifically, is their similarity to humans biologically, particularly their immune system.
Cost and ease of use
In general, mice are one of the cheapest laboratory animals to work with. An ICR strain of mouse costs around 10$ individually, with most other strains costing more, up to a couple hundred dollars per mouse on the high end. The most expensive mice are primarily ones that have been specially bred for a particular reason or model, such as germ-free mice and knockout mice. For most in vivo studies, however, mice are by far the most economical option compared to other species.
Mice are also rather cheap to house and maintain on site. Their food consumption is minimal compared to other species and they don’t require much in terms of enrichment. Group housing and corncob bedding alone can provide mice with sufficient enrichment, but cotton squares called Nestlets can also be provided for them. For rats, group housing and providing toys such as chewable Nyla bones or plastic structures for housing are good options.
Fewer regulatory requirements
Mice and rats are not USDA regulated like every other lab animal species, which means they require much less paperwork and compliance to work with. This makes it much easier for smaller labs such as TransPharm Preclinical Solutions to work with them.
Ease of euthanasia
The approved method of euthanasia for laboratory mice and rats is both humane and economical. CO2 overexposure is a cheap and effective way to euthanize either species and prepare them for necropsy to take samples or to simply end a study when it’s time.
Biological similarity
When mice and rats are infected and get sick, they have an immune response just like we do that they utilize in trying to fight back against the infectious agent. By infecting them with the same pathogens that make us sick and observing their clinical signs, we can get a very accurate look at what effects that pathogen has on the host it’s infecting and how easily or difficult it is to fight off the infection with no assistance from treatments.
This would typically be labelled as the negative control group in one of these models, which means the group that receives no treatment of any kind, or a placebo treatment, which should have no effect whatsoever in fighting the infection. When a novel treatment is introduced to one of the infected groups, then we can observe and compare that group with the negative control group in terms of clinical signs and survivability. Is there any difference between them? Are the treated mice doing better than the untreated mice or worse? How much better or worse? Are the results statistically significant or negligible? Can we say that the novel treatment used is effective against the pathogen based on this data?
That is the goal for every one of these studies, to find at least one novel treatment that has a significantly beneficial effect on the mice that received it in combatting their illness compared to the untreated mice. If a study turns out that way, then great! That’s essentially one data point of this drug being both safe and effective for its purpose in a biological organism.
But one study with good results is not enough, unfortunately. As good science is usually done, many studies need to be performed to confirm and reinforce previous results, which is why it can take upwards of 12-16 years for a typical drug to progress through the development pipeline to reach the market. All the safety and efficacy testing must be replicated repeatedly and reliably with the same results for the drug to make its case that it is in fact safe and effective for humans to use.
It is an unfortunate reality, but a reality nonetheless, that rodent models still are the best method for drug development research in infectious diseases. In vitro testing can only explain so much, as do computer models and other methods. Until somebody comes up with a better method, there is simply no replacement for in vivo models in this field. Nothing can replicate the human immune response better than the immune response of another mammal like the mouse. Currently, it is standard practice to test novel antimicrobial compounds against an infection in rodent models prior to testing in humans or even in larger animal species.