Quiet as mice
August 29th 2017, 19:13
I'm not a mouse; nor, I suspect, are you (unless you're a highly intelligent one who reads our magazine when you're not eating cheese or whizzing around on one of those running wheels—fun, aren't they?)
If you don't have a very serious identity crisis, this is not earth-shattering news, although it could be if you're a drug company. Mice are usually on the front line when drug companies begin testing the safety and effectiveness of a new drug. If the mice give it the paw's up, the drug will be given to healthy young medical students who aren't anything like the frail and elderly people who'll actually be the targets of the drug.
But researchers from King's College London and Lund University in Sweden have just pointed out something obvious: mice aren't people. Drugs that do well in animal tests may not fare quite so successfully when they're given to humans.
They've discovered that two types of laboratory mice that have been used for more than a century in medical trials aren't very much like us after all. This astonishing insight came to them when they looked for receptors in mouse and human cells that produce insulin.1
Humans don't have anywhere near as many insulin-producing receptors as the mice do, and so drugs that are designed to stimulate or repress insulin production could have different effects in mice and humans. A diabetes drug that seems to be successful in tests on mice could have no effect—or even a harmful effect—in people.
This would explain the problems drug researchers have always experienced when they've tried to replicate results from animal studies in tests on human cell lines. "This is well known, and a source of great frustration for researchers and the pharmaceutical industry," says Albert Salehi from Lund University. "Is it then right to continue to develop drugs based on research conducted on mice, when these drugs cannot be used on humans?"
Good question, and he's not the first to raise it. Researchers at the London School of Hygiene took a look at six animal trials and discovered that none of the 'successes' could be replicated in tests on humans. One trial of a corticosteroid drug for head injuries helped the problem, at least according to the animal study, but was of no benefit at all when humans tried it, while a heart drug that was extremely effective in animal studies actually made things worse in humans.2
Human drug trials can sometimes go very wrong after a new drug has passed safety tests on animals. In 2016, six men suffered severe brain injuries, and one subsequently died, after they took a painkiller that was 'safe.' It had been tested on mice, rats, dogs and monkeys, and in doses that were 400 times greater than those given to the human volunteers.
Ten years earlier, a drug trial was stopped abruptly when six men were treated in intensive care with heart, liver and kidney failure after they had been given a drug to treat rheumatoid arthritis, which had proven safe in monkeys at doses that were
500 times higher.
Drug companies say these reactions are very rare, but then they would. In fact, they're under no obligation to reveal the results of early-stage trials, but one study discovered 11 serious adverse drug reactions in 394 trials.3 A Freedom of Information request discovered that, between 2010 and 2014 in the UK, 7,187 people suffered serious reactions and 761 died while participating in a drug trial.
In the US, a drug trial was stopped suddenly when five of the 15 participants suddenly died, and even a late-stage trial was abandoned in 2016 when several participants died while taking a drug for blood cancer, although the actual number of fatalities has never been revealed.
None of this is new. Back in 1984, three professors opined: "The methods of assessing toxicity in animals are largely empirical and unvalidated... it is necessary to know whether the tests as in fact conducted have sufficient predictive value to be justifiable, or whether they are a colossal waste of resources to no good purpose."4
The good professors miss the most important point of all: animal tests are cruel and cause unnecessary suffering, because mice and people really are different.
Sci Rep, 2017; 7: 46600
BMJ, 2007; 334: 197-200
BMJ, 2015; 350: h3271
Laurence DR et al. Safety Testing of New Drugs: Laboratory Predictions and Clinical Performance. London, Academic Press, 1984