Table Of ContentTHE IMPORTANCE OF ANIMAL EXPERIMENTATION
FOR SAFETY AND BIOMEDICAL RESEARCH
The Importance of Animal
Experimentation for Safety
and Biomedical Research
edited by
S. Garattini
Pharmacological Research Institute 'Mario Negri'
Milan
Italy
and
D.W. van Bekkum
Radiobiological Institute 'TNO'
Rijswijk
The Netherlands
Kluwer Academic Publishers
Dordrecht / Boston / London
Library of Congress Cataloging-in-PubIication Data
The Importance of animal experimentation for safety and biomedical
research I edited by S. Garattini and D.W. van Bekkum.
p. CII.
Presents the proceedings of an international symposium organized
in Stasbourg, Oct. 24-25, 1988.
ISBN·13:978·94·010·7349·3 e·ISBN·13:978·94·009·1904·4
001: 10.1007/978·94·009·1904·4
1. Animal experimentation--Congresses. 2. Medicine--Research
-Methodology--Congresses. I. Garattini. Silvio. II. Bekkum, D. W.
van (Dirk Wi 119m), 1925- .
[DNLM: 1. Animal Welfare--congresses. 2. Animals, Laboratory
-congresses. 3. Research--congresses. OY 50 134 19881
R853.A53I46 1990
619--dc20
DNLM/DLC
for Library of Congress 89-24434
CIP
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Table of Contents
Foreword Vll
The necessity of animal experimentation
S. Garattini
ETHICAL AND LEGAL ASPECTS 5
Animal experimentation defended
C. Cohen 7
The ethics of animal use in biomedicine
T.L.S. Sprigge 17
Legal and political problems of animal experimentation, the 'Swiss
battle'
F. Bridel 29
Experimentation and the law
1.M. Varaut 35
Experimentation on animals: animals as machines and animals as
fetishes
1. Chanteur 39
RECENT PROGRESS OF MEDICINE REQUIRING
THE USE OF ANIMALS 47
The role of animal experiments in pharmacological brain research
A. Carlsson 49
Regeneration of the nervous system
A. Gorio & F. Cattabeni 57
Endocrine glands, neuroendocrinology and animal experimentation
P. Preziosi 71
Laboratory animals and cardiovascular pathology: means for better
use
1. Sassard 81
The importance of animal models for hypertension research
D. Ganten, K. Lindpaintner, Th. Unger & 1. Mullins 89
Vi
Animal experiments and recent progress in thrombosis research
G. de Gaetano, e. Cerletti, A. Poggi & M.B. Donati 97
Models of human renal disease
e. Zoja, N. Perico & G. Remuzzi III
The necessity of animal experimentation in tumor immunology
G. Forni, P. Caretto, P. Ferraiorni, M.e. Bosco & M. Giovarelli 125
The use of animals in cancer chemotherapy
T.A. Connors 133
The use of experimental animals in transplantation research
D.W. van Bekkum 141
Animal models for AIDS research
P. Bentvelzen 153
The need for animal experimentation in drug and vaccine
development against tropical diseases
A. Moncayo 163
USE OF ANIMALS FOR SAFETY REASONS 173
Toxicology: role of in vivo studies in establishing mechanisms of
toxicity
J.w. Bridges 175
Necessity of animal experiments for the safety evaluation and
necessary consequences for public health
J.R. Claude & H. Dutertre-Catella 185
The necessity of animal testing for safety evaluation and medical
progress in reproductive biology and toxicology
D. Neubert 191
The need for animal experimentation in studying the carcinogenic
risk of substances
I. Chouroulinkov 199
THE FUTURE OF ANIMAL RESEARCH 211
Transgenic animals for human diseases and gene therapy
M. Rossini, E. Di Martino & G. Bensi 213
Recent progress toward reducing the use of animal experimentation
in biomedical research
M. Balls 223
Animal use in drug research
M. Kramer 237
Vll
Foreword
Scientists are coming under increasing pressure from activist groups to stop
animal experimentation, branded as cruel and unnecessary for improving
human health. This attitude, however, stems from an unrealistic evaluation
of the situation and distorted information about present scientific knowledge.
There is no question that most medical progress - perhaps all, in fact -
has been attained through knowledge derived initially from experiments in
various animal species. There is practically no way of replacing animals in
these investigations and so-called 'alternative methods' are in reality merely
complementary. Tissue cultures, cell, microorganisms, enzymes, membranes,
mathematical models - all are useful for preliminary screening tests and for
testing hypotheses, but the complexity of a living organism is such that in
vivo studies are essential before any test can responsibly be made in man.
This book presents the proceedings of an international symposium organized
in Strasbourg (October 24-25, 1988), with the aim of assessing present-day
requirements as regards animal experimentation in research related to major
medical and toxicological problems still awaiting solutions.
Analysis of these chapters will convince any unbiased reader that animals
are still needed in the laboratory. However on the positive side scientists are
finding ways of using ever-fewer animals as advances are made in technology
and non-invasive investigational methods become accessible on a wide scale.
1. The necessity of animal experimentation
SILVIO GARATTINI
Research Institutefor Pharmacology 'Mario Negri', Milan, Italy
This volume presents a panorama of biomedical areas in which there is still
an urgent need for experimental research. Diseases which affect large numbers
of people such as cancer, malaria, leprosy, filariasis, atherosclerosis, dementia,
AIDS, as well as rare diseases such as muscular dystrophy, hereditary disorders,
inborn metabolic errors and immunodeficiency are all awaiting effective
remedies. These calamities call for action. Today the answer is an intensification
of biomedical research. It is obvious from the various contributions that
progress can only be attained using suitable models of human diseases and
these models are based on the use of animals. In no instance is there a single
suggestion about using the so-called 'alternative techniques' in place of animals.
In this sense it would perhaps be more appropriate to speak of 'complementary'
methods because at best they can cut down the number of animals or enable
us to obtain more and better information with the same number.
Even in the area of carcinogenesis of chemicals, where the Ames test, with
its various modifications, has raised great hopes, there are still no alternative
methods to in vivo studies. What's more, reports summarizing a large amount
of data indicate that the predictive reliability of in vitro tests for carcinogenicity
is too low since they can still give too many false positive or false negative
results.
Historically, models of human diseases reproduced in animals have long
been a requisite for discovering new therapies. It is in fact difficult to imagine
how to set up in vitro techniques for diseases which are expressed under the
influence of complex systems such as blood circulation, nervous system
regulation, neuroendocrine secretion, immune defences. The animals may not
be necessarily the usual ones, as shown by the key role of armadillos in the
development of leprosy vaccine and by ferrets in the discovery of antivomiting
agents.
Animal research should actually gain fresh impetus from the new technologIes
available in the area of genetic engineering. The development of transgenic
animals is a powerful tool for reproducing human diseases with more accuracy,
allowing the expression or the suppression of enzymes, proteins and hormones
characteristic of certain human diseases.
S. Garallini (ed.), The Importance 0/ Animal Experimentation/or Safety and Biomedical Research, 1-3.
© 1990 KluI<'er Academic Publishers, Dordrecht - Printed in the Netherlands.
2
The emphasis on the need for animals is not intended to reduce the
importance of in vitro techniques; these are particularly useful when a problem
has to be studied in simplified well-controlled conditions. There is certainly
no need to stress how widely these methods are employed in research
laboratories, partly, of course, because they were developed by scientists and
not by the opponents of animal experimentation.
Nevertheless, in line with the availability of in vitro techniques, the de
velopment of better and more sensitive analytical techniques and to the use
of appropriate statistical methods, the utilization of animals is decreasing in
proportion to the number of scientists. For instance, at the Mario Negri Institute
in the last decade the use of laboratory animals has been cut by 40% while
in the same period the number of scientists has doubled.
However, pressure from societies for animal protection to orient biomedical
research predominantly to in vitro studies, and the tendency among biomedical
scientists to accept this pressure, may severely jeopardize the outcome of
research. It is common knowledge that cells cultured in vitro do not retain
all their properties and because they are freed from nervous and hormonal
influences they acquire some new properties. Therefore to limit research to
in vitro techniques may be a source of considerable errors and artifacts.
Excessive polarization in discussion of the relevance of in vitro techniques
is misleading because anyone familiar with biomedical research knows very
well that discoveries are just one stage in an unbroken path from clinical
observations to laboratory research, from in vivo to in vitro studies and vice
versa, and clinical control of whatever is developed experimentally. The essence
of biomedical research lies in this continuous effort and all available techniques
- in vivo and in vitro - must be exploited to reach the goal of improving
medical assistance.
The importance of animal research in medicine does not negate the need
for regulation to assure humane treatment for animals and to improve the
quality of experimental research. In general avoiding suffering, discomfort
and stress to animals is in good agreement with the value of results and therefore
scientists themselves should be interested in backing these regulations. In this
sense the animal protectionists' requests may be useful to the progress of
science in the long run if they do not become unrealistic and paralyzing.
A number of regulations can therefore be supported and accepted. They
include adequate space and environment for animals; competence of animal
caretakers, suitable technicians and scientists, authorizations to institutions,
use of anesthesia whenever is an indication. There are however some regulations
that scientists cannot accept. These concern essentially the authorization of
protocols for experimental research. When working at the frontiers of know
ledge it is impossible to decide whether an experiment will be meaningful;
history is full of experiments which revealed new information to a particular
scientist because he was 'ready' to interpret the results in an unconventional
way. Research is like any other human activity and scientists can make mistakes
just like other professionals; however, an essential characteristic of research
3
workers is creativity. Only creativity can open up new ideas and new solutions
to biomedical problems. But creativity can be judged only a posteriori, not
a priori. It would be absurd to call on a committee, usually including laymen
and opponents to the use of animals, to decide whether a given experiment
is likely to yield useful results. Advance checks on protocols from anything
but the 'legislative' viewpoint are an obstacle to scientific progress and amount
to discrimination against science. It has never been suggested that a writer
should submit an outline of a future book to be approved by a committee;
yet the consequences of a book for society may be more harmful than the
sacrifice of a few animals.
Though review of single protocols is unacceptable, checks on the aims of
institutions where animals are used for research seem more equitable. Single
protocols could be reviewed appropriately inside the institution by ad hoc
committees, not so much to check the scientific aspects as to verify that all
the rules for humane treatment of animals are respected.
Scientists are therefore urged not to agree to preliminary authorization of
scientific protocols. The excess of attention for 'animal rights' which seems
to be gaining ground in modern society should be viewed critically because
it distracts attention from man. If studies on toxicity of xenobiotics are
minimized to avoid the use of animals, man will pay because he will certainly
be less protected from the chemicals which are part of our life.
The suggestion that we should rely on in vitro tests - which are certainly
less predictive than extensive in vivo tests - undoubtedly has advantages from
the point of view of the time and expenses involved. Less time and less cost
may appear to be in the interests of industry, but it could amount to potential
danger for man. It is indeed impossible to call - as the public does - for
better drugs, safer chemicals and a less polluted environment and at the same
time to expect the abolition of animal experiments.
This symposium was very useful to verify the present status of research
in some fields of medicine and led to the conclusion that today and in the
foreseeable future progress in the cure of disease is still linked to the use
of animals in research. The proceedings of the symposium will certainly be
useful not only for scientists but also as a source of information for divulgation.
The symposium, however, has not and will not solve this problem. It is to
be expected that antiscientific movements will become more vocal and vigorous
in the near future. It is the task and the duty of scientists to explain why
we need to use animals and what would be the consequences of banning
their use for the progress of medicine. If we are persistent and clear, and
particularly if we can resist the temptation to compromise, there is no doubt
that rational thinking will prevail.
ETHICAL AND LEGAL ASPECTS
