According to the Animal Usage Figures submitted to MAF by your committee for the year 2000, you reported that 183 mice were subjected to category X (very severe suffering) research. I would like a list of the titles and authors of all research protocols that reported category X suffering on mice in 2000.
Title: Investigation of the therapeutic activity of novel anticancer drug candidates.
1. threats to teh safety of experimenters/research staff undertaking this study; and
2. the need to ensure that the location of the experimental animals is not disclosed as there have been numerous examples overseas where attempts have then been made to "liberate" the animals concerned;
the university must withhold this information from the request. However, in order to provide the requester with more information about the trial and the fact that while 183 mice were listed as having suffered, in fact many of the mice were sacrificed before they experienced any significant suffering, the following information in offered.
The project investigates the utility of new classes of potential anticancer drugs by assessing their activity against tumours in mice. An important component of the research is to determine the maximum tolerated dose (MTD) of each drug. This is necessary prior to determining antitumour activity because most anticancer drugs have narrow therapeutic ranges, with significant activity only achievable at the MTD. (When used in humans, anticancer drugs are also usually administered at the MTD).
In most cases, toxicity is not evident at the MTD itself; it is only by exceeding the MTD that its value can be determined. Thus, in establishing the MTD for a new drug, some animals necessarily receive doses that are above the MTD. Our dose escalation strategy is designed to minimise this, but some animal suffering does occur as a result of drug overdose. In addition, in some cases drug dose levels that have been established to be safe in MTD experiments turn out to be less well tolerated in subsequent therapy studies in mice with tumours. There is thus a need to ensure that the trials are sufficiently extensive to reliably estimate the MTD in each situation.
Our policy has always been that, when signs of toxicity are detected, the animals are terminated promptly to minimise the duration of any suffering. The research team therefore points out to the inquirer that the animals classed as code X in this project were ones, either:
1. in which drug toxicity effects
were observed (and which were then terminated); or
2. which died following drug treatment without morbidity having been observed. The latter animals are assumed to have suffered, although depending on the mechanism of death this will not necessarily have been the case.
We consider the minimising of animal suffering to be of central importance in our work, and the honest (if overstated) recording of adverse effects to be part of our ethical responsibility in undertaking these studies.
The research team therefore stresses that the extent of the suffering of the animals is llikely to be significantly overstated on a literal reading of the MAF literature.
Animal Ethics Committee