Let’s do a little experiment. Read the following headlines from these recently published scientific articles and try to find the one thing that all of them have in common: “The Pancreas Provides a Potential Drug Candidate for Brain Disease,” “Chimera Viruses Can Help the Fight Against Lymphomas,” “What Was Once Considered Cell Waste Could Now Treat Pancreatic Cancer,” “Cellular Tango: Immune and Nerve Cells Work Together to Fight Gut Infections,” “Scientists Reveal Fire Ant Venom Could be Used as a Skin Treatment.” The answer? All of the listed studies are based on the results of experiments conducted on mice. And that is a huge problem.
Using lab mice to understand how the human body works is nothing new. This practice officially started in 1902 when French biologist Lucien Cuénot used mice to research the nature of genes. Inspired by the works of Gregor Mendel, the father of modern genetics, Cuénot wanted to see if Mendel’s laws of inheritance applied to more than just sweet peas. Beforehand, Mendelian genetics only applied to tested plants, so the Cuénot discovery that animals follow the laws of inheritance sent shockwaves across the scientific community.
Not long after, more scientists began to use mice to explore the field of genetics, establishing mating programs that created inbred strains of mice and leading efforts to fully map the mouse genome. As decades went by, lab mice skyrocketed in popularity and ended up contributing to numerous award-winning discoveries. Out of the 106 times the Nobel Prize for Physiology or Medicine has been awarded so far, 42 of them involved research on mice or rats in some major way. These studies include the discovery of penicillin, the yellow fever vaccine, the polio vaccine and the HIV-AIDS virus.
It is easy to see how the lab mice became such an iconic symbol of biomedical research. Xavier Montagutelli, the head of the animal facilities at Institut Pasteur in Paris, explains, “[Mice] are small and inexpensive, they reproduce quickly… and they age quickly too, making them ideal for studying age-related complaints. We know how to freeze their embryos, sperm, and ova. We now know how to manipulate their genes…They are remarkable tools.”
Unfortunately, the acceptance of mice as the ideal test subject has led to the rigid assumption that they are some kind of prototypical “blank slate” mammals rather than a species with its own unique features and body mechanisms. As a result, the field of biomedicine has built an entire infrastructure of knowledge around these rodents and has become dependent on their bodily responses to measure clinical success. But they simply don’t work as models of human disease, much less for human drug treatment.
For instance, scientists have used mice to find treatments for tuberculosis for decades. However, mice respond in a drastically different manner in comparison to humans. For one thing, mice don’t cough and aren’t contagious when they have the disease. In addition, the human body triggers an immune response when the bacteria responsible for the disease is detected. Mice don’t have this immune response—they get the disease and die. So it’s no surprise that scientists have found an antibiotic called Linezolid that works spectacularly well on human patients but not on mice.
The opposite can happen as well. In the late 1950s, German doctors prescribed Thaliomide under the drug name Contergan to pregnant women to alleviate morning sickness. Since the drug was successful in mice, they assumed that the same would happen in humans. Instead, Contergan led to countless birth defects and only 40 percent of the children survived. And this isn’t just a fluke, either. Dr. Jean-Marc Cavaillon, head of the cytokines and inflammation unit at Institut Pasteur, explained how researchers have discovered a monoclonal antibody that treats inflammatory conditions in mice but would send human patients to intensive care. “Mice are great for basic research, for understanding overall patterns and grasping mechanisms. But once you start modeling a human disease to find the right treatment, you run up against major differences between us and mice,” he said.
As a result, drug treatments that were successfully tested in mice have a high chance of failure when tested on humans. According to a 2014 study on animal models, researchers have found that, on average, less than eight percent of experimental cancer treatments have successfully transitioned from animal testing to clinical cancer trials. Similarly, researchers trying to find a cure for ALS have submitted about a dozen experimental treatments for clinical testing over the past decade after finding success in mice. But when tested on humans, all but one of them failed and the one that didn’t only showed marginal benefits.
It also doesn’t help that these clinical trials are ridiculously expensive—we’re talking about hundreds of millions of dollars and years’ worth of time. In October 2014, the New England Journal of Medicine published a report about how the clinical trials of three tuberculosis treatments ended in complete failure, despite promising results in lab mice. According to the head researcher, the clinical trials alone cost more than $200 million.
But that raises the question: Can we find a suitable replacement for the lab mouse? Unfortunately, no one can say for sure. It’s not like replacing mice with a different animal will solve everything, since animal testing as a whole is still rather dubious. So far, there are only two major possible alternatives, computer models and in vitro cell culture, neither of which offer much of a substitute since they don’t provide a lot of information regarding the complex interactions of living systems.
In addition, the push to stop the use of lab mice has been very controversial within the scientific community, especially for those who would rather turn a blind eye to the issue. Simply put, lab mice are incredibly cheap, convenient and easy to handle. The initiative would also place a large bulk of biomedical research into jeopardy and cast a shadow of doubt across countless pre-existing studies on disease treatment. Scientists today still continue to experiment on mice and spend millions of dollars on clinical trials, only to wonder why their product didn’t work. But what other choice do they have?
A survey of the National Library of Medicine’s database showed that experiments conducted on mice and rats make up almost half of the 20 million academic citations across the field of biomedicine. Despite all the problems they have caused, lab mice remain deeply entrenched in the field of medical research. Clearly, this isn’t a problem that can be solved in a single day.
But what’s even worse is that many news publications are making it seem as if these experimental treatments have worked on human patients and are bound to hit the shelves in the near future. Remember those headlines mentioned in the beginning of this article? All those articles were based on mouse studies and yet none of them mentioned the word “mice” in the headline. It’s sloppy journalism like this that helps fuel people’s doubt and confusion toward the sciences. In the end, one must always remain diligent when reading about the latest discoveries and findings. Science is already a difficult field to grasp, and diving into the literature blindly won’t make things any easier in the long run.
Originally published on September 21, 2017, in The Miscellany News: Experiments on mice should not be generalized to humans