Mice are not humans: Re-evaluating animal models in clinical research

20170421120000, Zayani Bhatt
Some scientists are now rethinking animal studies to make them more effective for drug development.
Many potential drugs fail when they reach the stage of clinical trials, causing tremendous disappointment for both patients and clinical researchers.

One of the main reasons for these failures is that the scientists testing these drugs on animals such as mice and rats before testing on humans, view the animals as physiologically and biologically the same as humans.

Today, more than 115 million animals are used globally in scientific experiments or in the biomedical industry annually.

Using animals in research first began a hundred years ago, but animals were not regarded as human stand-ins then. Instead, scientists studied rats to understand them.

However, Todd Preuss, an anthropologist at the Yerkes National Primate Research Center at Emory University explains, "As this process went on, people stopped seeing them as specialised animals and started seeing them more and more as prototypical mammals.”

An industry for research rodents


The use of lab rats had started because the sellers “really believed that you could do almost anything” with these animals, according to Preuss. They had assumed that scientists could “learn about almost any feature of human organisation”, and thus, find therapeutic solutions for any disease.

This is now known to be untrue as humans and rodents had different evolutionary paths, and therefore drugs that work on rats do not work on humans. Despite this, entire scientific communities are built up around rats, mice and other lab animals.

“Once these communities exist, then you have an infrastructure of knowledge: how to raise the animals, how to keep them healthy,” Preuss says.

“You have companies that spring up to provide you with specialised equipment to study these animals.”

Additionally, scientists in different institutions studying the workings of the same disease tend to use the same strain of animal, and this is now expected by journals and funding agencies. In fact, there are hundreds of facilities dedicated solely to the care and feeding of mice.

Reproducibility in mice research a major issue


In mice research, scientists endeavor to make all parameters uniform so that identical experiments conducted in different facilities can achieve the same result. However, a study showed that reproducibility is exceedingly difficult because factors such as different bedding, diet, a mouse’s relationship with its human handlers, and lighting, all have a tremendous effect.

The laboratory environment of cold windowless rooms in confined spaces with artificial lighting and human noises are unnatural conditions that affect the study outcomes because these can cause stress and abnormal behaviours in the mice.

Joseph Garner, a behavioural scientist at the Stanford University Medical Center explains by saying, “Imagine you were doing a human drug trial and you said to the FDA, 'OK, I'm going to do this trial in 43-year-old white males in one small town in California where everyone lives in identical ranch homes, with the same monotonous diets and the same thermostat set to the same temperature.”

“And oh, they all have the same grandfather! The FDA would laugh that off as an insane setup. But that's exactly what we do in animals. We try to control everything we can possibly think of, and as a result we learn absolutely nothing,” he adds.

Out with the old, in with the new


Proponents of Garner’s ideas believe that variation is the crux of the issue. “Maybe we need to stop thinking of animals as these little furry test tubes that can be or even should be controlled,” he says.

Gregory Petsko, who studies Alzheimer’s disease at the Weil Cornell Medical School, believes the key is to treat animals as patients.

“The worst outcome though, is falling into the trap of thinking not that well-being doesn’t matter, but that animals can’t feel pain, or can’t be fearful, or can’t be depressed,” he says.

Petsko believes that scientists might learn more from studying human cells rather than whole animals, such as for neurological diseases.

Discontinuing animal research is not the solution, however. By comparing humans and other animals, scientists can learn a lot about disease biology without assuming what is true in rats is also true in humans. Animal models will also remain useful in clinical research for determining the safety of potential treatments.

“Scientists need to break out of a culture that is hampering progress,” Preuss says. MIMS

Read more:
How powerful is the evidence generated by different clinical trials?
Study claims many scientific publications from recent years are “unnecessary, misleading and conflicted”
3 reasons why translational research has seen little success

Sources:
http://www.npr.org/sections/health-shots/2017/04/10/522775456/drugs-that-work-in-mice-often-fail-when-tried-in-people
http://www.mnn.com/earth-matters/animals/stories/if-animal-lab-testing-doesnt-translate-humans-should-we-keep-doing-it-same-way