GLUTTONOUS lab rats are ruining the results of screening programmes for drugs and food additives. The scale of the problem has prompted the US Food and Drug Administration to draw up new guidelines, which recommend that laboratories put their rodents on controlled diets instead of allowing them to eat as much as they like.
Rats on an eat-as-much-as-you-can plan grow fat and unhealthy, particularly now that germ-free housing and advanced animal care technology have eliminated most other worries from their lives, according to William Allaben, associate director of the FDA鈥檚 National Center for Toxicological Research in Jefferson, Arkansas.
Over the past 25 years, the average weight of some strains of lab rat has nearly doubled, leading to much higher rates of heart disease, kidney disease and tumours even among rats that have never been exposed to potentially toxic chemicals.
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This presents serious problems for toxicologists. In the FDA鈥檚 standard test to identify toxic or carcinogenic chemicals, scientists give high doses of a chemical to one or more groups of rats over a two-year period, and keep a control group of rats for comparison.
But when the control rats suffer serious health problems of their own, it becomes difficult to spot the effect of the experimental substance. At some point, says Ronald Hart, a toxicologist and former director of the FDA centre, 鈥測ou have to ask which is the correct predictive model. Is it an obese, sick animal, or is it a lean, healthy animal?鈥�
Indeed, today鈥檚 fat rats are often so unhealthy that fewer than 25 per cent of them survive to the end of the two-year test. The FDA鈥檚 guidelines recommend that at least 50 per cent of the control animals survive to the end of the test period, and the agency has sometimes refused to accept the results of tests where survival is too low, says Allaben.
The rats鈥� overeating can even confuse results to the point that a toxic drug looks like a beneficial one. The standard chemical assay is carried out with several different doses, with the maximum dose usually set so high that the animals lose weight slightly. Ironically, this chemically induced weight loss brings such big health benefits that they often compensate for the toxic effect of the drug, and researchers commonly note that animals on the highest doses outlive the control rats.
鈥淭he joke 鈥� though it wasn鈥檛 a funny joke 鈥� in our lab is that the most deadly thing we鈥檝e tested has been a perfectly healthy diet given in ad libitum amounts. We literally kill them with kindness,鈥� says Kevin Keenan, a veterinary pathologist at Merck Research Laboratories in West Point, Pennsylvania.
Faced with problems like these, researchers have begun to recognise a need for change. The FDA will soon propose that rats being used in toxicological tests should be fed a controlled diet at a rate that maintains the animals at a standard growth rate and adult body weight, says Allaben, who chairs the committee making the recommendations. For most labs this means reducing rats鈥� intake by between 5 and 25 per cent.
Labs will have to pay a higher price for healthier rats because staff will have to dole out measured amounts of food to each animal every day instead of simply filling a hopper once every few days, says Keenan.
Any change in assay procedures makes it more difficult to compare new results against earlier data. However, rats鈥� weights 鈥� and therefore their basic level of health 鈥� often vary considerably from one lab to another at present, making comparisons questionable anyway, says Keenan. Standardising the rats鈥� weights by controlled feeding will increase the reproducibility of assays in the future, he says.
The restricted diet improves the health of rats so much that some researchers practise the same regime themselves. 鈥淚 make an effort to reduce my intake by about a quarter compared to what I was eating 20 years ago,鈥� says Keenan.