THOUSANDS of laboratory rodents are being needlessly sacrificed each year
in toxicity tests that are scientifically flawed, a leading toxicologist
claims.
Michael Festing of the Medical Research Council鈥檚 toxicology unit at the
University of Leicester blames the problem on the reluctance of pharmaceuticals
companies to phase out the use of 鈥渙utbred鈥� rats and mice in favour of inbred,
genetically defined strains.
An outbred stock comprises a group of animals that are often closely related,
but not genetically identical. Given that reactions to chemicals can vary with
an individual鈥檚 genetic constitution, drugs companies have always assumed that
testing for toxicity in a genetically varied stock of animals is the best
option.
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But Festing argues otherwise. 鈥淭he reasoning is illogical,鈥� he says. 鈥淥utbred
stocks have serious disadvantages when used in controlled experiments.鈥� The
problem, he says, is that each colony of mice or rats bred from the same
original stock will be genetically different due to mutations, selection by
animal breeders and the genetic drift that occurs down the generations. In some
cases, there may be significant genetic differences between mice assigned to the
experimental and control groups in the same test.
鈥淭his resulting `noise鈥� can obscure biologically important treatment effects
or even produce false positive results for toxic chemicals,鈥� claims Festing. 鈥淚t
also makes it impossible to adequately compare new results with the historical
data of tests from that stock.鈥�
He argues that toxicologists should move to using inbred strains, produced by
mating brothers and sisters for many generations until the entire stock is
genetically identical. In this week鈥檚 Nature (vol 388, p 321), Festing
says that comparisons between experiments can then be made with much more
confidence.
John Ishmael, who works at the drugs company Zeneca鈥檚 Central Toxicology
Laboratory at Macclesfield in Cheshire, argues that it is possible to get round
the problems raised by Festing. 鈥淲e can accurately compare new results with
previous data if the tests are performed on the same breeding stock within a
tightly defined period of five years or less,鈥� he claims.
But Festing argues that drugs companies are ducking the issue鈥攁nd in
doing so are hampering efforts to reduce the number of rodents used in toxicity
testing. 鈥淭he genetic variability of outbred stocks means we have to test larger
numbers of animals to confirm results, which is costly and unethical,鈥� he
says.
Festing says he understands the resistance of drugs firms to change, given
the preference of drug licensing agencies for standardised tests: 鈥淏y changing
their testing methods, they risk slowing down the process of drug
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