Of Mice, Men and Medical Concern (article)

[Guest guest]

I think this will be of interest to almost everyone here.

Best, Pat

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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

Financial Times (London, England)

March 4, 2005 Friday

 

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 laboratory animals.

 

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 product safety?

 

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 blockbuster drug.

 

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 statistical significance.

 

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

 

(Found of course on SoFlaVegans this am, thanks to Fidyl)