The article discusses drugs and products that made it onto the market only
because animal tests failed to predict their danger to humans. Conversely, it
tells us, "the evidence suggests animal tests may be unduly sensitive, wrongly
predicting toxicity in compounds that are in fact harmless to humans. If so, it
would be an ironic twist to the widely held belief that tests of animal are
crucial to the advancement of medicine, as they may in fact be blocking the
development of many safe and effective new treatments."
It ends with: "What is clear is that, given the paucity of systematic evidence,
it is not necessary to be a placard-waving protestor to harbour doubts about the
validity of animal testing."
Since our human animal nature seems to encourage the greatest interest in the
welfare of our own kind, it is great to see this issue tackled from the
standpoint of efficacy. However, the article opens the door to letters that
point to the immense animal suffering endured in the questionable testing. The
Financial Times takes letters at:
Friday, March 4,
Financial Times (London)
"Of mice, men and medical concern: Recent health alerts suggest you don't have
to be an anti-vivisectionist to doubt the validity of animal testing."
By ROBERT MATTHEWS
Two huge industries affecting the lives of millions of
people are currently subject to big health alerts. Concern over serious
side-effects has cast a long shadow over promising new painkillers, known as
cox-2 inhibitors, developed by the pharmaceutical industry. Evidence linking the
drugs to an increased risk of heart attacks led the US giant Merck to withdraw
its version, known as Vioxx, from the market last September, and an
investigation by the -US Food and Drug Administration is currently under way.
More recently, it was the turn of the UK food industry, with the discovery of
traces of a banned dye known as Sudan I in a sauce made by Premier Foods, a
leading UK supplier. In the ensuing health scare, the UK Food Standards Agency
found that hundreds of products had been inadvertently contaminated by the dye,
which has been linked to cancer.
As the initial furore starts to fade, both these health alerts are being seen
primarily as wake-up calls to business and regulators alike about the monitoring
of product safety.
In the case of cox-2 inhibitors, the FDA looks set to allow their continued use
- albeit with much sterner safety warnings to protect those most at risk from
side-effects. Meanwhile, as shops and supermarkets in the UK hunt down produce
contaminated with Sudan I, the FSA has continued to stress that the risks
involved are "very small".
As well it might, for it is now clear that the scientific case against Sudan I
is far from compelling. Laboratory safety tests involved feeding rodents with
levels of Sudan I equivalent to human consumption of the sauce that triggered
the scare at a rate of three tonnes a day for two years.
Even after such gargantuan exposure, the animals failed to produce consistent
evidence of a cancer risk. Other tests hinted at links with bladder and liver
tumours - but only after the dye was injected directly into the organs of
While the scientific basis for both the Sudan I and cox-2 inhibitor health
scares may be contentious, they have highlighted the need for close surveillance
and prompt action if problems emerge. At the same time, however, an even more
fundamental question has gone begging: just how reliable are animal tests of
In the case of food safety, the relevance to humans of animal tests involving
colossal intakes or direct injection into organs is clearly questionable. The
use of animals in drug safety testing raises altogether more complex issues,
however - as the cox-2 painkillers controversy shows.
In line with standard practice, Vioxx and the other drugs were tested in at
least two different types of animal before entering clinical trials with humans.
One of the main aims of such "pre-clinical" testing is to detect signs of
serious side-effects. In the case of the cox-2 drugs, the animal testing failed
to warn of the cardiovascular effects that have prompted the current furore.
Indeed, several animal studies suggested the drugs would actually reduce the
risk of such side-effects.
So what went wrong? Anti-vivisectionists have been quick to voice their standard
objection: animals are not humans.
For all its familiarity, it is an argument that does have relevance to the cox-2
inhibitors. In 2000, barely a year after the launch of Vioxx, a study of more
than 8,000 patients suggested that those taking the drug faced a significantly
increased risk of heart attack. Yet subsequent animal-based research continued
to suggest such drugs could reduce the risk - prompting even Merck's experts to
concede in The American Heart Journal that: "The relevance of these animal
models in predicting effects in humans is uncertain."
It is becoming clear that such uncertainty extends far beyond one class of
Leading journal Nature Reviews Drug Discovery last year published a review of
the evidence that animals are reliable predictors of toxic effects in humans.
The authors found that the evidence was "fragmentary", with the few published
studies pointing to "significant over- and under-prediction of adverse effects
from animal studies that varies with the particular organ or system".
The review also highlighted the lack of basic data needed for a scientific
assessment of animal testing, such as measures of predictive power and their
As it stands, the evidence suggests animal tests may be unduly sensitive,
wrongly predicting toxicity in compounds that are in fact harmless to humans. If
so, it would be an ironic twist to the widely held belief that tests of animal
are crucial to the advancement of medicine, as they may in fact be blocking the
development of many safe and effective new treatments.
Yet in the absence of large-scale studies comparing drug responses in animals
and humans, it is impossible to know. Supporters and critics of animal testing
continue to trade anecdotes of individual successes and failures, most published
studies being so small they lack statistical credibility.
In another irony, the drive to minimise the use of animals has compelled
researchers to draw conclusions from meagre evidence. For example, the studies
designed to investigate the effect of cox-2 inhibitors on cardiovascular risk
typically involved fewer than 20 mice.
The authors of last year's review called on regulatory bodies and drugs
companies to publish data currently languishing in their files. Whether the
outcome will confirm or confound the view that animals usefully predict human
reactions remains to be seen.
What is clear is that, given the paucity of systematic evidence, it is not
necessary to be a placard-waving protestor to harbour doubts about the validity
of animal testing.
The writer is visiting reader in science at Aston University, Birmingham