https://cosmosmagazine.com/biology/don-t-believe-the-mice
When you read that a lab animal with a human disease has been cured with a new drug candidate, do not get your hopes up. The stats for converting these successes into human patients are appalling. Results in animals are often the opposite of those seen in humans. For example: corticosteroids were shown to treat head injuries in animals, but then increase deaths in new-born babies in trials.
This is a big deal. A staggering 95% of drugs tested in patients fail to reach the market, despite all the promising animal studies that precede their use in humans.
“There are lots of reasons why, but in essence we are not 70 kilogram rats and we are not inbred strains,” says
Thomas Hartung, a toxicologist at Johns Hopkins University in the US.
Two industry studies showed that many key findings that triggered drug development could not be repeated.
Mice are the most popular lab animals, but their brains and biology are quite different from our own. Surprisingly, rats and mice predict each other for complex measures with only 60%. Different animals, different effects.
Newspapers headlines heralding cures for Alzheimer’s to autism, on the back of rodent studies, can be taken with a pinch of salt. Neurodegenerative disorders such as Alzheimer’s were one of the first areas to turn against the animal models, says Hartung.
“It was shown that the animal tests were misleading with respect to what is a cure and what is not,” he says.
After hundreds of human trials for promising treatments for Alzheimer’s, almost none helped patients.
This is a colossal waste of money. Industry has noticed.
“The pharma industry is now using about one-sixth the number of animals that they used in the past for drug studies,” says Hartung. “They go very late into these models.”
In a look at animal experiments, Hartung and colleagues found that pharma continues to reduce animal testing in Europe, despite rising R&D spend. From a stable 12 million used in Europe, the industry’s share dropped from 31% in 2005 to 23% in 2008, and then to 19% in 2011.
Disease researcher John Ioannidis at Stanford University in California
has written that the safety and effectiveness of interventions in humans can only “be speculated from animal studies”.
Speaking at the EuroScience Open Forum (
ESOF) in Toulouse, France, earlier this year, he said that “industry doesn’t want to waste money taking academic papers that promise that they have found a drug target and spend billions of dollars to develop it, and then come up with nothing”.
He pointed to just six of 53 landmark studies in cancer being repeatable and lamented that too many basic scientific discoveries are wrong.
One problem is that scientists often take a simple approach to mimicking a disease in mice, by just finding a gene that when knocked out stamps the mice with hallmarks of the human disease.
This is how the first
Alzheimer’s disease mouse was created, but the animal did not reflect the true Alzheimer’s condition of most patients.
“Single gene mouse models are different from the illness that we experience in humans,” says neuroscientist Malcolm MacLeod at the University of Edinburgh, UK, who describes mouse models for stroke, high blood pressure, Parkinson’s and more as failing to reflect the complexity of the human disease.
“This has been a failed strategy,” he warns, in terms of finding therapies.
Hartung too has
warned about the hype about these genetically modified animals.
Sometimes scientists discover therapies to cure mice, but not people. The record for inflammatory disease is especially striking. More than 150 trials have tested agents to block inflammation in critically ill patients. The candidates worked in animals, but all failed in patients.
With this in mind, Ronald Davis, at Stanford Genome Technology Centre in California, decided to compare how all genes in mice and all genes in people react when they encounter trauma, burns or bacterial toxins. There was
almost no connection whatsoever. Mice genes did one thing; human genes did another.
