Few students go into medical research dreaming of one day giving a mouse a tumour or heart disease to a rabbit. But animal experimentation of this kind has become fundamental to modern medicine. For regulatory bodies around the world, treatments that might save human lives must be proven safe and effective in animals with similar conditions before they can be put on the market.
So how is this ethical bargain holding up? Not well enough, suggests a paper in PLOS Biology by Benjamin Ineichen of the University of Zurich and his colleagues. Out of 367 biomedical therapies tested on animals over thousands of studies, a surprisingly low proportion—only 5%—eventually obtained the approval of the Food and Drug Administration, America’s regulatory agency for drugs, to be used in humans.
To arrive at this figure, Dr Ineichen and his team analysed 122 research reviews which evaluated how well results from animal studies translated to humans. These reviews spanned more than 50 diseases ranging from diabetes mellitus to lung cancer, and covered therapies from anticoagulants through to non-pharmaceutical interventions such as exercise and green tea.
In all, the researchers found that half the therapies tested in animals had results encouraging enough to warrant subsequent tests in humans, but only one in 20 eventually made its way to the market. Some rate of failure is inevitable, says Dr Ineichen. For one thing, laboratory animals are, after all, not exact models for humans. What’s more, factors other than clinical success, including lack of commercial interest, can also influence a therapy’s fate. “Even if every drug that worked in animals also worked in humans, we’d only see a 25% success rate,” says Joseph Garner of Stanford University, who was not involved in this study. Once you bear that in mind, he says, “the 5% number is nowhere near as shocking.”
Nonetheless, there are ways of making the process more efficient. Most obviously, says Dr Ineichen, animal studies are not all conducted with the same rigour. Many mouse trials are conducted on young, male animals with untested immune systems, whereas the prospective human patients may be both male and female, of all ages, with multiple concurrent diseases. Some animal studies are not randomised, and yet others are not blinded—procedures deemed essential for generating accurate results. Dr Ineichen’s analysis also found that of the trials whose results were most frequently reproduced (an indicator for how well conducted a study is) 86% led to similar results in humans.
To further strengthen the evidence base, he recommends designing animal experiments to more closely resemble the human trials that may one day follow. This means, among other things, ensuring more diversity between individuals—and not giving genetically similar individuals identical diets, while housing them in identical cages at identical temperatures. After all, patients in clinical trials will rarely be so accommodating. There are already indications that such an approach will work. A 2017 study found that wild mice with natural microbiomes were more accurate models for humans than were laboratory animals with artificially controlled microbiomes. Similar successes have been obtained since.
More sophisticated animal replacements may also help reduce waste. So-called “organs-on-a-chip”, which are battery-sized devices lined with human cells, or organoids, which are replica organs built from lab-grown tissue, can imitate a body’s response to a therapy. Computer simulations have helped confirm the viability of therapies before they are tested on animals, and an artificial-intelligence model trained on existing studies has been shown to predict how a chemical will affect humans, without having to involve a lab rat. Such methods are promising, but have yet to reliably demonstrate whole-body effects in the way that animal models do. For now, at least, animal experimentation is here to stay.
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