problem with animal models

The problem with animal models

Here is what I find one of the most powerful, effective arguments for

replacing animal experiments with other methods of investigation.

It is an essay in logic of science and is written in a formal way, so

for those who are not inclined to read it all I'll try to summarize it

in non-formal style here.

The authors of the essay, entitled Two Models of Models in Biomedical

Research, Hugh LaFollette and Niall Shanks, make the crucial

distinction between two uses of animals as models. These two models

are normally confused in the general discourse, leading to the current

difficulties in clarifying the question of usefulness of animal

experiments (we are here letting aside the ethical question).

The two models are:

1) animals as models that are similar to the objects to be modelled,

ie humans, functionally (HAMs). To understand what it means, think of

the planetary model of the atom in physics. 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.

Or think of a spiral staircase as a model of DNA molecules.

In this way, though, the only use of a model is to inspire hypotheses,

but, crucially, not to test them.

There are indeed demonstrable functional similarities between humans

and our close biological relatives.

But there is a big difference between an animal model's being a good

source of hypotheses and its being a good means to test hypotheses.

2) animals as models that are similar to humans causally (CAMs). Here

is where the problem lies, because most biological phenomena do not

follow a simple linear cause-effect pattern (deterministic), but are

probabilistic: only in a certain percentage of cases the same effect

will follow the same cause.

In fact, biomedical experiments on animals are doubly probabilistic:

they involve not only the probabilistic causality within the

(non-human) laboratory population, but also the probabilistic

causality within the human population outside the laboratory.

In addition, there is an uncertainty about whether the results

observed in the non-human animal population will be (statistically)

relevant to the human biomedical phenomena of interest.

For this uncertainty to be small, there must be no causally relevant

disanalogies between the test subjects and humans (the model and the

thing modelled)..

The fact is: these important causal disanalogies exist.

Researchers who think non-human animals are good causal models (CAMs)

of human biomedical phenomena believe human and non-human animal

systems are causally similar because they are functionally similar.

But this is not so.

The same function in biological systems can be caused by entirely

different mechanisms. Both birds' and mammals' lungs oxygenate blood

(same function); but peribronchial lungs of birds, ventilated in a

unidirectional fashion using a series of air sacs, and the alveolar

lungs of mammals, ventilated in a tidal fashion using a diaphragm,

differ considerably in structure and mechanism.

Functional similarity does not guarantee underlying causal similarity,

nor does it make such similarity "probable".

This is predictable from Darwin's evolution theory. Different

organisms have evolved similar functions due to their phylogenetic

proximity, but "descent with modification" means, in part,

"modification of anatomical and physiological sub-systems, and the

relations between them."

Resultant species differences are biologically significant. "The

species is one of the basic foundations of almost all biological

disciplines. Each species has different biological characteristics"

(Mayr p. 331). Species differences, even when small, often result in

radically divergent responses to qualitatively identical stimuli.

This is why, for example, even when species are phylogenetically

close, as are the rat and the mouse, we cannot assume that the two

species will react similarly to similar stimuli. Tests for chemically

induced cancers in rats and mice yield the same results for only 70%

of the substances tested. The figure drops to 51% for site-specific

cancers.

Human mechanisms for metabolizing phenol are closer to the mechanisms

in rats than to the mechanisms in pigs, despite the fact that humans

are phylogenetically closer to pigs than to rats. And the carcinogenic

effect of aflatoxin B is more similar in rats and monkeys than in rats

and mice.

So, to reason that phylogenetic continuity implies underlying causal

similarity is a fallacy.

As if all this were not enough, an additional complication is given by

the fact that the various sub-systems of a biological organism

interact with each other, thus multiplicating the number of variations

of possible effects.

Biological objects are complex in the extreme: this is why the simple

modelling method to test hypotheses that animal experimenters have

imported from physics does not work in biomedical research.

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 and teratological (effect on the fetus) investigations.

As one widely-used pharmacology text sums it up: "The lack of

correlation between toxicity data in animals and adverse effects in

humans is well known".

In short: different animal species are similar functionally but not

causally, and that includes the human species. We tend to think they

are similar because we only consider what is visible, ie the

functions, not the underlying causal mechanisms.

Finally, the argument often used by animal experiments' advocates, "It

just works", is subjected to such a potent critical analysis that it

leaves it almost as naked as a tree in winter.

Partly, the authors here use an argument which is similar to the one

explaining the post hoc, propter hoc fallacy used by Pietro Croce in

his classical book Vivisection Or Science: A Choice To Make.

In a nutshell, simplified, it goes like this: how do we know that

animal experimentation works?

Because, wait for this, after experimenting on animals, we then test

the results of those animal experiments on humans!

posted by Of Human and Non-Human Animals at 2:29 PM

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