Wednesday, May 24, 2006

The strange case of smoking animals, tobacco companies and research - Part II

Why animal experiments are unreliable

At this point people might say that yes, this was a case in which animal research retarded science and misled medicine, but it is an isolated case, the odd exception. But it is not an exception: it is indeed the rule, for obvious and necessary reasons, which will become apparent.

Animal experimentation is by its own very nature unreliable for application to humans. One of the reasons is that minuscule differences in biochemistry and miscroscopic composition of organisms produce enormous effects, hence the huge differences existing between not only species, but also individuals.

It’s easy to see that it is so. Think of how an incredibly tiny alteration at the microscopic level in the DNA can give rise to so many dramatic changes between individuals. In fact, it can give rise to a new species if the DNA change is a mutation.

Moreover, the differences between species will be greater and more difficult to compensate for exactly in those areas which interest animal researchers. This is the case, for example, of metabolic differences between species, which are centrally important in toxicological (effects of drugs and chemicals) and teratological (effect on the fetus) investigations.

Researchers refer to animals as models. But models which are useful to inspire hypotheses are not necessarily good to test them, in fact they often are terribly and disastrously bad at that.

For instance, to see what this means in practice, think of the planetary model of the atom in physics, according to which in atoms the electrons orbit the nucleus the way planets orbit the sun. In the early stages of the atomic theory, when knowledge was limited, the solar system has indeed served as a useful tool, something known to help understand the unknown.

But no one would dream of testing on the solar system a hypothesis about electrons’ behaviour, for example, even if it were physically possible.

If you are inclined towards logic and formal arguments, read Two Models of Models in Biomedical Research. Otherwise, what was just said would suffice.

The fundamental mistake of animal research is to transfer an experimental technique (replication of phenomena) from physics to biology. The problem is that biological entities like animals, including humans, are extremely more complex than physical objects. This technique which is valid in physics is not valid in biology, where such regularities as “effect B always follows cause A” do not apply.

Biological beings behave in a probabilistic way, not in a deterministic one. This is a major factor of great uncertainty in predictions. Even when animal research results were later confirmed, we only know that they were valid because they were confirmed by their application to humans. So, the latter was, in the end, the final test of the former, not the other way around.

It’s a classical case of post hoc propter hoc fallacy (mistaking time sequence with causation), as Prof. Pietro Croce, MD, an eminent pathologist, puts it in his brilliant book Vivisection or Science - A Choice to Make, which anyone who would like to develop a serious position on the subject, fruit of thought rather than pre-conception, should read. You can also find a short version of it published online.

Here’s an analogy that helps picture the problem of unreliability. Suppose I like mushrooms but I cannot recognize the good ones from the poisonous ones. I go and pick them in the wild. Then I call a mushroom expert, and he says they’re okay. It does not mean that I did the right thing by choosing them myself, I could just as easily have picked up the poisonous mushrooms. And it was only after, not before, the mycologist gave his opinion that I knew if the mushrooms were edible or not.

So it is with animal research: it’s only after, not before, its results are applied to humans that we know whether they are valid (for us humans) or not. And believe you me, when they are not, some of us are going to pay for it with our health. That’s why so many drugs are quietly and surreptitiously withdrawn from the market after they have caused some disaster. Remember that a new drug being introduced will make headlines, but a drug being withdrawn will likely be ignored by the media.

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