The National Research Council (NRC) recently produced a report titled Toxicity Testing in the Twenty-first Century: A Vision and a Strategy. In it, they outline a plan for utilising new technology to streamline toxicity testing. The plan’s aim is to increase efficiency whilst decreasing costs, time, and numbers of animals used.
The report notes that one of the ‘challenges’ of developing an in vitro test system to evaluate toxicity is "The current inability of cell assays to mirror metabolism in the integrated whole animal." (p5)
They go on to note that targeted testing in the future may be in vitro or vivo:
They could use transgenic species, isogenic strains, new animal models, or other novel test systems…
Whatever system is used, testing protocols would maximize the amount of information gained from whole-animal toxicity testing.
Contrary to what antivivs such as Europeans for Medical Progress have claimed in the wake of the report, animal models will not be fully replaced in the foreseeable future and are in fact likely to be improved to overcome their current shortcomings.
Throughout the report, brief summary, and press release the NRC acknowledges:
(i) that it is the advent of new technology that makes this possible
toxicological evaluation of chemicals is poised to take advantage of the on-going revolution in biology and biotechnology. This revolution is making it increasingly possible to study the effects of chemicals [using non-animal methods]
- NRC: Report in brief, July 2007, p1
(ii) the techniques will take time to develop and validate
The report concludes that substantial benefits will result from achieving the vision but that it will require coordinated efforts and resources over the next several decades
- NRC: Report in brief, July 2007, p4
(iii) that although animal numbers will be reduced, they will not be completely eliminated for the foreseeable future
Over time, the need for traditional animal testing could be greatly reduced, and possibly even eliminated someday, says the report. For the foreseeable future, however, targeted tests in animals would need to be used to complement the in vitro tests, because current methods cannot yet adequately mirror the metabolism of a whole animal.
- NRC press release, 12th June 2007
Unfortunately the magazine Chemistry World seems to have fallen for antiviv spin that all these techniques are already available and properly validated, and can fully replace animal use. The opening sentence of their article attributes an opinion to the NRC that is not apparent from actually reading the report:
Tests on mice, rats, rabbits and guinea pigs to stop harmful chemicals reaching humans were once a necessary evil. But such checks now seem embarrassingly old-fashioned, according to a report on toxicity testing from the US National Research Council
- Chemistry World, ‘A viable alternative’, August 2007
Let’s hope that serious organisations like the Royal Society of Chemistry, which publishes Chemistry World, accurately reflect the subject under consideration in their future publications.
The Chemistry World article is curious, though I find myself agreeing with its overall conclusions it does contain several odd statements.
The statement that really jumped out at me was that ‘A bioassay to find cancer-causing agents, for example, takes 400 rats, five years, and 800,000 Euro to conduct; but around half of the chemicals it finds guilty actually have no proven carcinogenicity in humans. That’s largely because humans aren’t rats or mice.’. The claim that species differences are responsible for this apparent difference in carcinogenicity forgets one key rule of science, namely that absence of evidence is not evidence of absence. For many compounds that are known to be carcinogenic in animal tests there is no conclusive evidence for their toxicity in humans simply because humans have not been exposed to sufficient concentrations or exposed in sufficient numbers for carcinogenicity in humans to be proven (eg Goodman G, Wilson R (1991) Regul Toxicol Pharmacol PubMed: 1792349). This should be no surprise given that the main reason that the animal tests are done is to estimate “safe” levels of exposure in humans. That the carcinogenic effects are not being seen in humans is arguably an indication that the animal tests and safety regulations are doing their job!
The other point that struck me was the implication that in vitro mutagenicity/genotoxicity tests are not recognised by regulators, when they have been for many years. The problem is that mutagenicity is only one of several causes of cancer and birth defects, other tests are required to test for other causes. For embryotoxicity ECVAM has recently recognised three in vitro methods, all of which use rodent cells or tissues, and while these are useful for pre-screening compounds before animal testing and as a complement to whole animal methods ECVAM states that they are not complete replacements for current methods.
Overall it was a potentially good article undermined by some sloppy writing, though it is possible that it was intended to provoke a response.
The NRC report’s strategy envisages that in the future, toxicity testing will based on the molecular biology of toxicity pathways, complemented by what it terms ‘targeted testing’, which will include whole animal testing. The report draws a distinction between this form of whole animal testing (which includes GM species and new animal models) and traditional methods; the latter ‘should be greatly reduced and possibly even eliminated’.
Thus non-traditional whole animal testing methods are an integral part of the vision. The report is not suggesting that animal testing, in and of itself, is old-fashioned; the implication is only that older (’tick-box’) methods will be rendered obsolete.
The NRC report’s vision consists of a red-blooded enactment of the principle of the 3Rs. In this respect, it is a severe embarrassment for Europeans for Medical Progress who repudiate reduction, refinement and replacement of the use of animals in medical research and toxicity testing. What they are pleased to call their ‘case for reform of drug safety testing’ involves nothing more and nothing less than the immediate total abolition of all animal use since, they say, it is inherently useless and/or dangerous.
