Our board has been asked to comment on the scientific aspect of the proposed
CPCBN. The comment is based on the short release from the University of Cambridge, entitled "Details of the proposed science" to take place at the CPCBN.
According to this release, basic and clinical research at the projected
facility should contribute to:

*   the understanding of the link between behaviour and the neuronal structure
     of the brain,

*   the understanding of the link between this structure and neuronal pathologies,

*   the development of clinical diagnosis and therapeutic strategies, the testing of       
     drug treatment,

*   the understanding of how existing therapies work.

Although not explicitly stated in the release, we suppose that the primates
are considered here as models of human behaviour and pathologies. This is a
frequent assumption, which is, however, false. The very idea that one
species can serve as a model for a different species, demonstrates a
complete lack of understanding of fundamental principles of modern biology.
Any individual species is defined by its reproductive isolation, which
implies that its chromosomes (genome) cannot match, complement or recombine
with those of any other species.

Hence each species has a uniquely designed genome, i.e. the gene structure,
the control and regulation of gene expression etc. are all strictly
species-specific. Since the genes determine all biological activities, it
follows that the species' physiology, its behaviour, its response to
internal disorders (pathologies) or to some external stimuli (e.g. toxins),
are strictly species-specific also. No species can therefore function as a
biological model for another species, no matter how closely related they are
in evolution.

This statement is especially valid in neurological matters. Our central
nervous system distinguishes us most dramatically from that of any other
known living species, including the great apes. Therefore, using monkeys to
predict the human biological responses, in any of the five fields considered
by the CPCBN, is pointless. No result obtained from primate studies can be
seriously considered valid in humans as long as the observation has not been
made in man also. Hence the preliminary primate experiment was useless. It
can even be counterproductive or dangerous, as it could pave the way to
false conclusions (remember the French blood scandal, a consequence of the
absence of reaction of chimpanzees to the AIDS agent HIV, which led
"experts" to OK the circulation of HIV-contaminated blood samples). Many
drugs, found efficient and free of side-effects in primates, subsequently
proved to be lethal in man (the anticholesterol cerivastatin (Bayer) is a
recent example to point). Conversely, how many drugs, perhaps very promising
for human treatment, have been discarded because they did not pass the
monkey model?

Let us then briefly review the relevance of the five scientific priorities
assigned to the CPCBN.

The brains of thousands of animals, especially monkeys, have been explored
since the 19th century to try to understand how their behaviour is embedded
in this organ. Libraries are full of voluminous books detailing the very
many studies. Electrodes were placed in the brain to monitor its electric
activities, whilst keeping the animal awake for days, or when removing the
young from her mother just after birth, etc. While the relevance to humans
was already questionable - and questioned - when these experiments were
performed, those results became almost overnight museum archives, when
non-invasive methods (PET-, NMR-scan...) enabled the investigation of the
human brain at work. Would the monkey show which part of its brain is
working when doing such basic human activities as speaking, reading,
writing, counting, singing? Not to speak of evolved behavioural traits like
reasoning or sophisticated social attitudes. Today, no serious scientist
would go back to monkey models for such investigations.

Human neuropathologies are at present of great concern in industrialized
countries. The very fact that they most frequently occur in the last quarter
of the human lifespan proves that these conditions are age-related and occur
in humans at an age which exceeds by far the life expectancy of even the
great apes. So even if the latter were good models for these pathologies -
which remains to be proven, since in the wild so far no monkey was found
suffering from these conditions - monkeys would not allow the study of these
pathologies, unless they were artificially provoked. In a human individual
these conditions almost invariably have multiple causes, most of which will
be missed in the artificial pathology: again the animal model would be
useless. Chemical methods used to induce parkinsonism in chimps for
instance, were found almost 30 years ago, yet no understanding of how the
pathology develops in humans and how to treat it permanently has emerged
from the chimp model since.

Clinical diagnosis and therapeutic strategies in monkeys which have
artificially acquired a given neuropathology, are of no relevance to human
patients, for the reason just given.

The use of animal models to test the toxicity or effects of drugs in human
patients is highly problematic. In France, the Health Ministry ascribes 20
000 fatalities a year due to adverse drug reactions, in addition to 1.3
million hospitalizations, despite the fact that the law requires that drugs
be extensively tested on animal models. Among the many reasons for this, is
the metabolism of the drug and drug-drug interactions, both of which are
strictly species-specific (because the nuclear receptors of the drugs and
the metabolizing enzymes they control are species-specific).

The project to try to understand how existing human therapies work in
animals which never develop the condition is somewhat surprising. Wouldn't
the money be spent better on more worthwhile projects?


This critique was written by DLRM vice president Dr Claude Reiss PhD.  Dr Reiss
is also President of the French organization PRO ANIMA.

* PRO ANIMA (16, rue Vezelay, Paris F75008, Tel. +33 1 45 63 10 89, Fax +33
1 45 63 47 94, email pro.anima@wanadoo.fr, web site proanima.asso.fr) is a
scientific committee (not an animal welfare institute). Board members are
research scientists from government laboratories, academics and the medical
field. PRO ANIMA is free of any political, philosophical or religious ties.
The aim of the committee is to apply progress in science, and in biology in
particular, to the benefit of human health and welfare. The committee
restricts itself exclusively to scientific and logical considerations.

Doctors and Lawyers for Responsible Medicine, November 2001.
dlrm@gn.apr.org

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