Drug research has got so hooked on working with genetically modified animals that it has lost touch with human disease

Is what ails the animal also what ails us? sidsnapper/Getty

“WE HAVE moved away from studying human disease in humans,” said Elias Zerhouni, the former director of the US National Institutes of Health, in 2013. The ability to knock out or insert specific genes in lab animals – mice in particular – has led ever more researchers to shift focus away from people. “The problem is that it hasn’t worked, and it’s time we stopped dancing around the problem… We need to refocus and adapt new methodologies for use in humans to understand disease biology in humans.”

That was three years ago, but little has changed. The latest warning that medical research is barking up the wrong tree comes from Joseph Garner of Stanford University in California (see “Lab mice are sending us on a wild goose chase“). Garner is interested in why so few new drugs that get into clinical trials actually make it to market, and says that one important contributor is animal models that do not genuinely model human disease. For example, drug research on cognitive conditions relies heavily on animals that have been genetically manipulated into displaying characteristics that are Parkinson’s-like, OCD-like, anxiety-like, autism-like – you name it, there’s probably a mouse, or a primate, for it.

Find a way to treat such animals, the conventional thinking goes, and you might discover a treatment that works in humans too. But is what ails the animal also what ails us? Increasingly not, meaning that less and less animal research is benefiting humans. The investment needed to bring a drug to market roughly doubles every decade, partly because of animal models increasingly failing to model human disease.


Another problem is the ruthless standardisation of the animals. That is understandable; it is easier to control for confounding factors when there aren’t any. But it drags research animals even further away from representing human populations. Humans aren’t all the same, with identical environments and diets. Yet the supposed “models” of our diseases are.

“Animal research is only ethically justified when it produces clear benefits for humanity“

The dangers of excessive standardisation have been known for decades. In 1935, the great mathematical biologist Ronald Fisher pointed out the risks in his seminal book The Design of Experiments: “The exact standardisation of experimental conditions, which is often thoughtlessly advocated as a panacea, always carries with it the real disadvantage that a highly standardised experiment supplies direct information only in respect of the narrow range of conditions achieved by standardisation.”

One solution is to start performing animal experiments as if they were human trials, with levels of variety that are seen in human populations.

If anything, however, the problem is likely to worsen. The use of genetically altered animals in biomedical research is set to explode because creating them is getting ever easier and cheaper, courtesy of new gene-editing techniques.

If we’re not vigilant, ever more public money will be squandered on esoteric research into the unique quirks of genetically modified animals, with little relevance to humans.

That is not fair on taxpayers or the animals themselves. Animal research is only ethically justified when it produces clear benefits for humanity. It is also grossly unfair to those people the research is meant to benefit. As Garner puts it: “Once you start meeting patients, you realise the urgency of getting this right.”

This article appeared in print under the headline “Man or mouse?”