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Good Science With Less Animal Experimentation: Refine Reduce Replace
Good Science With Less Animal Experimentation: Refine Reduce Replace
Good Science With Less Animal Experimentation: Refine Reduce Replace
animal experimentation
Replace Reduce Refine
For the sake of both science
and laboratory animals
Non-animal tests cannot yet replace animal tests completely.
Despite great efforts made in the past, some animal testing is still
essential. Scientific questions exist that can only be answered
by performing animal experiments. And some animal-based tests
are required by law, for example for the toxicological testing of
chemicals.
The balance sheet is impressive: Over the last twenty years the
Foundation has awarded funds for over 100 research projects,
totalling a sum of 14 million Swiss Francs. Up until now this re-
search has led to numerous publications that reveal the creativity
of scientists in advancing the 3Rs in animal testing. Thanks to
the Internet, the publications are accessible worldwide.
2
Introduction Pain relief
4 The challenging way forward 18 Less pain, more reliable test results
International network
30 Globalisation also regarding the 3Rs
3R dialogue platform
34 Voices from authority, animal protection, industry,
and research
This brochure marks the 20th anniversary of the Pictures courtesy of: Publisher:
3R Research Foundation. © RDS/Wellcome Trust Photographic Library, iStock Stiftung Forschung 3R
International, Corbis Corporation, Christoph Gmuender Postfach 1372
Editors: Pictures on pages 9–11, 20: Courtesy of 3R Research CH-3110 Münsingen
Ernst Diener, Franz Paul Gruber, Adrian Heuss, Foundation Tel. ++41 31 722 08 30
Peter Maier, Ursula Moser, Heinz K. Müller Fax ++41 31 721 70 80
The excerpts (in unofficial English translation) from the E-mail secretary.3r@bluewin.ch
Layout: Continue AG, Basel Swiss Federal Animal Protection Act refer to the Law of www.forschung3r.ch
Concept: advocacy AG 2005 (Tierschutzgesetz vom 16. Dezember 2005: TSchG;
BBl 2006 327, SR 455), which was not yet in
force at the time this brochure was published. For legal
purposes please refer to the original versions (in German,
French, and Italian).
Introduction
The subject of animal testing in research to be satisfied with this achievement: “The vision of a world with no animal test-
confronts most people with a dilemma. Since 2001, there has been a slight in- ing or at least the vision of experiments
On the one hand, many people support crease in the number of laboratory animals causing no distress to the animals has
the performance of basic research, the used both in Switzerland and in Europe. therefore become more difficult to achieve
development of effective medications and This increase is most likely to result from than before,” explains Hugo Wick, chair-
warranty of the safety of chemicals. On the increase in biomedical research work man of the 3R Research Foundation.
the other hand, however, no one wants performed at universities and in pharma- “However, this makes it even more import-
this to imply that animals must suffer fear, ceutical industry, but also from more strin- ant to firmly anchor the 3Rs principle in
distress, and pain. This situation therefore gent safety regulations for medications basic research.”
leads to a number of questions: Does and chemicals.
research really require as many animals?
Animal experimentation:
Can animal testing be conducted in a way A vision difficult to achieve What does the Animal Protection Act say?
that the animals do not feel distress or Experts believe that a further decrease in
pain? Can testing be done without ani- the number of research animals used and Animal experiments are defined as any pro-
mals? These are exactly the three ques- especially a further minimisation of pain cedure involving the use of animals performed
with the goal (1) to verify scientific hypotheses,
tions that lead to the 3Rs principle. This and distress still remain possible, but will
(2) to observe the effects of a particular pro-
brochure explains the 3Rs and provides be more difficult to achieve than in the
cedure on the animal, (3) to test a substance
examples for how they are applied. past. The reason for this is that the more (with exceptions), (4) to obtain or test cells,
obvious 3R solutions have already been organs, or body fluids, (5) to meet the purpo-
From 1983 to 2000, the number of re- put into practice. For example, in the ses of teaching and continuing education
search animals in Switzerland decreased area of toxicity testing – the testing of the (Article 3 [c] of the Swiss Animal Protec-
tion Act). Persons who want to perform an
from approximately two million to half a hazardousness of substances – in the
experiment require its authorisation by the
million. A decrease by almost 80 per cent. last couple of years a number of ways to
responsible cantonal authority (Article 18 [1]
The 3Rs made a significant contribution replace animal testing have been de- of the Swiss Animal Protection Act).
to this success. But there are no grounds veloped and put into practice in Europe.
4
The two pioneers of the
3Rs principle: William
Russell and Rex Burch
5
Ethics
A person’s attitude towards animal testing this reason, no animal testing is con- Ethical considerations such as these are
can be categorical or pragmatic. Radical ducted in Switzerland for the testing of, not binding in all countries. The reason
animal welfare activists reject animal test- for instance, cosmetics. Lipstick and the for this is that people’s attitudes towards
ing categorically, because they consider like are considered to be luxury goods, animals are influenced by culture, religion,
animals to have equal rights to humans. and using cosmetic products does not and education. Other cultures come to
The pragmatic view, however, places represent an essential need to humans. different conclusions on the same issues
human welfare above the suffering of ani- It is more difficult to judge basic research, regarding animal experimentation.
mals, which makes the use of animals in since researchers can not make any pro-
research justifiable. This second approach mises about the information that will be
is laid down in current legislation. How- gained. However – despite great progress Ethical guidelines
ever, scientists using animals in research in the area of research on alternatives to
A number of organisations, universities, and
are required to weigh the distress imposed animal testing – medical progress often-
pharmaceutical companies require their mem-
on the animals against the expected gain times continues to be achieved only at the
bers and employees to adhere to ethical guide-
in knowledge. If this assessment leads to cost of animal experimentation. Therefore lines when conducting animal experiments.
the conclusion that the benefit of the ex- one must set the goal to ensure that each Ethical guidelines have been developed,
periment outweighs the cost to the animal, individual laboratory animal suffers as little amongst others, jointly by the Swiss Academy
the researcher can justify the experiment. as possible and that the numbers of ani- of Sciences and the Swiss Academy of Medi-
mals required for testing are reduced as cal Sciences. Those guidelines explicitly refer
to the 3Rs principle. In addition, a number of
No animal testing for cosmetics far as possible. The right taken by humans
different committees deal with this topic, such
The greater the distress inflicted upon the to use animals in research is coupled with as the Swiss Ethics Committee on Non-Hu-
laboratory animals used and the greater the obligation to conduct animal testing man Gene Technology (ECNH/EKAH) and the
the number of animals required for a re- only on a justified case-by-case basis after Federal Committee on Animal Testing (EKTV).
search project, the greater the expected a careful ethical balancing of the costs and
benefit of the experiment has to be. For benefits of the experiment. www.samw.ch
6
Animal protection
Many animal protection organisations the animal than the testing itself. Incorrect propriate for the health and the well-being
recognise that the situation of research care and housing of animals can result in of the respective species as well as a lot
animals in Switzerland has improved over behavioural disorders and also in changes of empathy on the part of the responsible
the past 20 years. But they are equally in the animals’ immune systems. personnel. Regarding social species, it is
convinced that sufficient progress has not essential to provide a social environment
yet been made. Further improvements Adapted to the needs of the animals and to continuously monitor the compati-
are possible and necessary in many areas, For this reason Swiss animal welfare bility of the animals in the group. For larger-
for example in the care and housing of groups demand that the housing and sized animals exercise and space to move
laboratory animals. In the majority of ani- care of laboratory animals is adapted as about are important. Care must always
mal-based research projects, the housing far as possible to the animals’ natural be taken to provide the appropriate phys-
conditions of the animals cause greater needs. This requires a precise knowledge ical environment regarding illumination,
restrictions and thus greater distress for of the housing requirements that are ap- temperature, humidity, and noise level.
something wrong at the Foundation? Or would the number of Franz Gruber, University of Constance, Germany, Secretary and Editor in
Chief of ALTEX
animals used in research have increased far more pronouncedly
without the projects funded by the 3R Research Foundation?
We can only suppose that this is so. Should we target the
research areas responsible for the increase in the number of
research animals as the focus of our funding programme?
Or should the Foundation simply promote more thinking? For
example, reflections about the fact that no matter how many
genetically modified mice are developed and used, valid disease
models for humans can not be generated, because the genes
7
3R review
Highlights of 20 years of
funding research
Since the 3R Research Foundation was volved the efforts of numerous scientists, Detailed information on these and
established in 1987, it has funded over some of which are pictured below. other projects funded by the Foundation
100 research projects. The goal of these On the following pages, nine successful is available at www.forschung3R.ch
projects was to develop methods that use projects are presented that were sup- (Funded Projects).
fewer or no research animals and that ported by the 3R Research Foundation.
improve the housing and care of labora- The projects range from the search for
tory animals. Many of the projects were pain genes to ticks that feed on artificial
crowned with success. The projects in- membranes rather than on host animals.
L to r: R. Geoff Richards,
AO Foundation Davos;
Marianne Geiser Kamber,
University of Bern; Nicolau
Beckmann, University of
Basel/Novartis Pharma AG;
Thomas Kröber, University
of Neuchâtel
8
Better boxes. When
the cage contains more
than nesting material,
the animals show more
meaningful activity and
develop fewer stereotypic
behaviours.
1 3
Recognising pain. In
some animals it is difficult
to determine if they are
suffering. Rabbits, for
example, sometimes mask
signs of pain deliberately
(left). In cats, a scruffy
coat can indicate that the
animal is experiencing
pain (top).
2 3
Tracking down pain genes. Using DNA microarrays, the
researchers examined 130 genes that are associated with
pain and fear (photo shows microarray).
www.forschung3r.ch www.forschung3r.ch
Project number: 58-97 Project numbers: 88-03, 71-00
9
Use of intestinal cells. Epizootic agents are investigated in
cells instead of in the actual intermediate hosts, cats and dogs
(parasites shown in red) (4).
4 5
6
Unburden sheep. Testing implants not in living sheep but by using bones of animals from the slaughterhouse.
4 Cells replace dogs and cats 5 Molecular biology replaces 6 Testing implants using ex vivo
rodents bone core culture systems
The two parasites Neospora caninum When researchers work with rodents, Implants that are used in the treatment
(intermediate host: dog) and Toxoplasma it is important that the rodents are patho- of, for instance, bone fractures are mostly
gondii (intermediate host: cat) cause dis- gen free. The traditional test to screen ro- tested in sheep. However, an alternative
eases in humans and animals. Research dent strains for viruses used numerous exists: By using cultures of live bone
on these parasites is required in order animals. Researchers in Zurich and cores, it is possible to obtain osteal tissue
to find effective medications or vaccines. New York have developed a replacement that largely retains the same functions
Both parasites undergo a life cycle com- for the traditional mouse antibody pro- as bones in the intact organism. This is
posed of three distinct stages. Thanks duction (MAP) test. Today the test can achieved by periodically exerting a force
to the research projects, these stages of be conducted using molecular biological on the cultured bone material. Processes
the parasites can now be cultured to methods (PCR assay) – which require in the bone can be studied more effi-
some extent in vitro in intestinal cells. This no animals. The PCR technique not only ciently in this osteal tissue with the result
means that the studies can be performed reduces the use of animals but is also that part of the testing of implants no
without the use of dogs or cats as inter- cheaper, faster, and more reliable. longer needs to be performed in sheep.
mediate hosts. Additionally, the scientists Some bone cores are taken from dead
can also screen medications against the www.forschung3r.ch animals from the slaughterhouse; another
Project number: 74-00
respective diseases in the cell cultures. source is human bone that is no longer
required after hip operations.
www.forschung3r.ch
Project numbers: 85-03, 72-00 www.forschung3r.ch
Project numbers: 86-03, 78-01
10
Reduced blood flow.
With the use of brain cell
cultures, researchers
can investigate the mecha-
nisms and the progress
of ischemia.
7 9
Scantily studied particles. The effect of particles on the lungs A tick penetrates into a membrane using its proboscis
can be studied in a cell culture system. (left). Less thirsty ticks replete with blood (right).
7 Study particles in cell cultures, 8 Using brain cell cultures to 9 An artificial feeding system
not in lungs study brain damage for ticks
It has long been recognised that most Inadequate blood flow, or ischemia, leads Animal experiments are required to develop
respiratory diseases are caused by the to nerve cell damage in the brain within repellents against ticks. Host animals are
inhalation of particles. However, little is a short period of time. A large part of cur- necessary to allow the ticks to feed on their
known as yet about the health effects of rent brain ischemia research is conducted blood. Scientists have developed artificial
nanoparticles, in particular. Testing the using animals, and it can cause the ani- feeding membranes that simulate the
harmful effects of particles in a living sys- mals a lot of distress. Scientists have de- skin of host animals. The feeding medium
tem is very stressful for research animals, veloped a three-dimensional brain cell (blood) is located beneath the membrane,
time-consuming, and costly. In this project culture system that resembles brain tissue and test products can be added to it.
the researchers developed a three-dimen- in many of its characteristics. This means Female ticks feed until replete with blood
sional primary cell culture system in order that various aspects of ischemia research and then produce eggs, from which larvae
to study particle-lung interaction. In a spe- can now be investigated in the test tube hatch. The in vitro system can be auto-
cial chamber system, specific cells that instead of in animals. Due to its signifi- mated and can be used to test new anti-
react directly to inhaled particles (such as cance, this in vitro method is also being tick products. The system has many advan-
epithelial cells) are exposed to particles, evaluated by the EU ACuteTox Project as tages as compared to traditional testing
and the effect of the particles on the cells a model for identifying neurotoxic chem- methods, and a large number of host ani-
is measured. The use of this method can icals without laboratory animals. mals can be saved.
reduce animal experiments where inhal-
ation is required to identify possible lung www.forschung3r.ch www.forschung3r.ch
Project number: 64-97 Project number: 79-01
damage by certain substances.
www.forschung3r.ch
Project number: 89-03
11
Replace Cell culture in a Petri
dish. Sometimes it is
possible to refrain from
performing an animal
experiment by reverting
to cultured cells.
Replacement means the use of methods skin that can be used for the evaluation Replace: What does the Animal
other than conducting experiments on of the effect of possibly harmful sub- Protection Act say?
animals. This is not a simple task, because stances. This is of interest to the cosmet-
a single 3Rs method rarely serves to ics industry, for example. Nevertheless, Based on the obligation to “limit to the indis-
directly replace a specific animal experi- research using cells, tissues, and isolated pensable extent”, an experiment with animals
must not be authorised if the goal of the ex-
ment. However, by combining one or organs also has its limitations, since
periment can be achieved by using methods
more 3Rs methods, one can perhaps al- complex phenomena of the intact body without animal testing that are suitable ac-
ready yield sufficient information to make can not be investigated. Or, stated more cording to the current state of knowledge. An
the animal experiment unnecessary. plainly: Cells neither experience fears animal experiment is particularly inadmissible
nor have diarrhoea. if it causes the animals a disproportionate
Cells have proved very useful. For in- degree of pain, suffering, injury, or excessive
fear in comparison to the expected gain in
stance, it has become possible to use
knowledge.
layers of cells to build a kind of artificial
Art. 17 and Art. 19 (4) of the Swiss Animal
Protection Act
12
No animal testing for cosmetic products in Switzerland invested 500 million Euro in alternative research. So far, the European
Until today, many Swiss are convinced that cosmetic products are tested Centre for the Validation of Alternative Methods (ECVAM) has validated
on animals before they are put on the market. However in Switzerland, nine alternative methods.
this has no longer been the case for several years. In the meantime, the
European Union (EU) has also responded to this issue. As of September The next milestone will be the date of the 11th of March, 2009, when
2004, it banned all animal testing of finished cosmetic products in the the EU will ban all animal testing of cosmetic ingredients within the
EU. In Germany, Austria, the United Kingdom, and the Netherlands ani- EU, irrespective of the availability of non-animal tests. In addition, apart
mal testing for cosmetics has been banned by national legislation since from a few exceptions, there will be a ban on the marketing of cosmetic
the late 1990s. Nowadays, most of the testing is conducted using cell products tested on animals from that day on. This new cosmetics EU
cultures instead of animals. In the past years, the cosmetics industry has Directive will affect 2,000 companies across Europe.
Blood cells save 500,000 Complete replacement of the 10,000 rats spared
rabbits every year Draize test foreseeable
The 21st of March, 2006, was an import- The Draize test for eye irritation, which Since the mid-1980s, Novartis has been
ant day for many laboratory rabbits, was developed in the 1940s, uses rabbits producing the active ingredient calcitonin.
since that was the day that members of to test whether chemicals, cosmetics, This substance provides patients with
the ECVAM Scientific Advisory Committee or pharmaceutical products irritate the bone diseases, such as osteoporosis,
(ESAC) issued a statement to the Euro- eye. The substance is applied to the eye with stronger bones, and in many cases
pean Commission recommending five of the animal and irritation is measured. it also reduces pain. However, before a
tests for the replacement of the rabbit Today, substances are started out at new batch of the medication can be put
pyrogen test. The pyrogen test is a safety being evaluated in non-animal in vitro on the market, tests have to be conducted
test for the detection of contaminants in methods. Severely irritant and corrosive to assure that the calcitonin in the chosen
medical products. The new assays use substances are not further tested on the preparation is safe and effective. Until
cell cultures instead of live rabbits. Ex- eyes of rabbits. Only chemicals that have recently these tests were performed using
perts estimate that these new methods revealed no effects in non-animal tests rats.
will save the lives of 200,000 rabbits in are applied, in strongly diluted form, to
the EU and of half a million rabbits world- the eyes of animals. Since the late 1990s, the Novartis Work-
wide every year. ing Group on Biological Analysis has been
Nevertheless, this does not suffice. The searching for a method that uses cells
Pyrogens are substances that can induce search for a replacement test continues. instead of live laboratory animals for this
fever in humans and even life-threatening In this context, a very promising approach evaluation. Finally, such a method was
shocks. Before medical products are being assessed is the artificial generation developed in cooperation with the Univer-
put on the market, they therefore have to of the human cornea making use of the sity of Heidelberg and optimised by the
be tested for these undesired substances. respective cell types. Such cultured cor- Novartis scientists. For this method, cells
For more than fifty years, pyrogen detec- nea epithels are already available on the are cultivated in vitro and then brought
tion relied on the use of rabbits: In the market. The reason the scientists are fo- into contact with calcitonin. The hormone
rabbit in vivo test, a sample of the medical cusing on the cornea is that it is the first calcitonin binds to the cell membrane and
product was injected into the animals, layer to come into contact with chemicals triggers a response in the cells. Depend-
and their body temperature measured and when they enter the eye. ing on the amount of calcitonin, the cells
recorded. An increase in body tempera- release a biochemical messenger (cAMP),
ture indicated pyrogen contamination. Another method to replace such sub- which can be detected unequivocally
stance evaluations on the eyes of living and therefore serves as an indicator for
The five assays endorsed by ESAC in animals makes use of the eyes of dead the activity of calcitonin.
2006 can fully replace the rabbit pyrogen cattle and chickens from the abattoir.
test. They offer a number of advantages: It is also in this area that progress has Using this method, which was validated
they take less time, are less costly, and been made in recent years. Thus, it is by Novartis and approved by the U.S.
show better sensitivity. All of the new to be hoped that these tests will be able Food and Drug Administration, 10,000
tests are conducted using human blood to fully replace the Draize test in Europe rats can be saved from calcitonin testing
cells in vitro. in the foreseeable future, thereby finally at Novartis alone.
completing the step from “reduce” to
www.forschung3r.ch “replace”.
Project number: 52-96
13
Researchers place an
Reduce anesthetised mouse
into an MRI scanner.
The MRI approach can
reduce the number of
animals used in a study
by up to 90 per cent.
Reducing the number of animals used in 3Rs not always in unison individual animal is more important than
research is a must, both ethically and Almost always, the 3Rs principle is de- reducing the number of research animals.
economically. However, scientists have to scribed as a unit, but in practice there
ensure that the number of animals used can be conflicts between the Rs, as the
is not reduced to a point where the data following example shows. In one experi-
can no longer support a meaningful statis- mental set-up, ten rats have to suffer pain Reduce: What does the Animal
tical analysis. Otherwise, the results lack and distress. A second possible research Protection Act say?
validity, and the tests have to be repeated. design requires 20 rats, but here the rats
will suffer only little or no pain and dis- Experiments with animals, which cause the
The main task in Reduction is to determine tress. Which design should the scientist animal pain, suffering, injury, fear, or signifi-
cantly disturb their general condition or which
the optimum number of animals per group choose? This is a decision that has to
can disregard its dignity in any other way, must
in a given animal test. Additionally, parallel be made on a case-by-case basis. Never- be limited to the indispensable extent.
investigations using non-animal test meth- theless, in principle, experts agree that
ods can generate information that can re- the second variant is the better choice. Art. 17 of the Swiss Animal Protection Act
duce the amount of animal testing needed. Reducing the pain and distress of the
14
More information using The LD50 test Experiments with animals only
fewer animals no longer exists after extensive test batteries
Non-invasive methods exist for investiga- In November 2000, the OECD reached Today, computer methods also contribute
ting research animals. Some examples agreement to delete OECD Test Guideline towards reducing animal experiments.
are magnetic resonance imaging (MRI), 401, the LD50 Acute Toxicity Test. This In drug discovery and development, for
positron emission tomography (PET), and test evaluated, which dose of a test sub- example, potential points of therapeutic
computerised tomography (CT). The rapid stance would kill 50 per cent of the ani- intervention in the organism, the so-called
progress that has been made in regard to mals used within two weeks, the lethal drug targets, are identified in a first step.
these image-producing techniques in re- dose for 50 per cent of the animals. Ac- Once sufficient information is available –
cent years can now also benefit research cordingly, the test served to determine for instance regarding drug binding sites –
animals. For instance, scientists in the acute toxicity, a measure of the immedi- compounds can be designed on the
pharmaceutical industry follow the effects ate toxicity of a substance. The test was computer that fit into these binding sites.
of drugs in an animal’s body by continu- mainly used for determining the toxicity This process is called computer model-
ously observing a single animal with the of chemical substances. ling. With the help of computers (the so-
help of MRI, rather than killing different called in silico methods) and in automated
animals at different time points for their Even though the new alternative methods tests (the so-called high-throughput
investigations (ref. interview on page 25). adopted by the OECD could not fully screening), out of tens of thousands of
replace the acute toxicity test, instead of substances, those compounds are iden-
In 2006, Nicolau Beckmann of the No- the 150 animals required in the 1970s, tified that show the desired results in vitro
vartis Institutes for BioMedical Research now only an average of 8.5 animals is (mostly in cell cultures). Only these few
(NIBR) evaluated the applicability of MRI to necessary. This is achieved through a substances are then further investigated
evaluate pulmonary inflammations in small stepwise dosing of the animals, applying in studies using animals.
rodents. “Using MRI, a significant reduc- higher doses until symptoms appear.
tion in the number of animals used for ex- Once that is the case, the animals are However, drugs do not only have to be
perimentation was achieved. Depending killed. effective, but they should also be safe.
on the application, the number of animals An initial prediction, whether a compound
was 80 to 90 per cent lower than with In a next step, it is aimed to replace also may possibly trigger side effects in the or-
conventional methods,” explains Beck- these alternative methods currently ap- ganism, can be made with the so-called
mann. Further advantages of MRI are min- proved by the OECD, with the final aim QSAR methods (quantitative structure-
imal distress to the animals and the poten- to test for acute toxicity without the use activity relationship). The basic assump-
tial to standardise the test method. There of animals. This is important in the face tion in a QSAR model is that similar mol-
are limitations, however: Currently, only a of the EU REACH regulation, the pro- ecules will show similar harmful effects.
few MRI scanners exist that are adequate gramme for the Registration, Evaluation, Another method aiming in a related direc-
for the scanning of small rodents. and Authorisation of Chemicals. Starting tion is presented on page 24 below.
in 2008, 30,000 chemicals will be tested
www.forschung3r.ch in the EU (see page 30). It is estimated For many years it has been thought
Project number: 82-02
that despite the non-animal test methods that one day it would be possible to fully
available today, several million additional replace the testing of compounds by in
laboratory animals will still be needed to silico methods – that is, by modelling the
conduct the large-scale testing and evalu- effects of compounds in the computer.
ation programme. However, this will not be possible in the
foreseeable future, due to the complexity
www.acutetox.org of the human body.
15
In company. Dogs should
not be kept as single ani-
Refine mals. Nowadays, systems
for the housing of dog
exist that make it possible
to keep dogs in groups
without influencing the
results of the experiments.
Refinement encompasses all measures on animal welfare grounds, but also for sci- this reason, animals that were bred for
that make a contribution to reducing the entific reasons, since distress of the animals research purposes are used almost ex-
distress, pain and suffering of the animals can distort the results of the experiment. clusively today. Distress is also caused
before, during, and after the experiment. by uncaring handling of the animals,
However, Refinement is important not only Refinement involves the application of ster- cages without enrichments, and social
ile surgical procedures, the proper use of isolation. Nowadays, these discomforts
analgesics, and provisions to handle the can be prevented.
Refine: What does the Animal
animals with the least possible stress dur-
Protection Act say?
ing experimentation – but not only then. In Switzerland, Refinement methods are
Pain, suffering, injury, or fear may only be For it is not only the experiment as such promoted by the Swiss Laboratory Ani-
inflicted on an animal to the extent that is un- that causes distress to the animals, but mal Science Association, in particular.
avoidable for the purpose of the experiment. also the way in which the animals are kept Many of the members of the association
and housed. Animals experience particu- are veterinarians.
Art. 20 (1) of the Swiss Animal Protection Act
larly high levels of distress if they are taken
from wild habitats for use in research. For www.sgv.unizh.ch
16
Enrichment: When the cage Social behaviour: Rodents Humane endpoints: Prevent
contains more than just straw live in groups avoidable suffering
Laboratory mice and rats spend their lives With the exception of hamsters, rodents – A humane endpoint is the earliest possible
in a cage. Different studies demonstrate the animals used most frequently in ani- point in time, at which an experiment can
that rodents housed in stimulus-poor mal experiments – live in groups. There- be ended before the animal used has to
cages had impaired brain development, fore it is important that mice and rats are experience too much distress or pain. It is
and expressed stereotypies and anxious housed in groups and that group housing defined as the point in time when the test
behavioural profiles. Through environ- is only refrained from in exceptional cases. can be stopped because its objectives
mental enrichment by means of shelters, Rats, especially, are very social animals have been met, but the animals have not
shredded paper, pieces of wood, and that groom each other and communicate yet suffered severe distress. Already prior
climbing opportunities, these develop- in the group with scents and sounds. to the testing, it is important to define,
mental impairments can be reduced. under which circumstances and by which
Mice and rats want to explore their en- Within a group, rats and mice have a means pain and distress in the individual
vironment, build nests, and seek refuge stable ranking order, which, however, can animal will be avoided or terminated.
when in danger. “A number of studies only be established if the group is not too These criteria are then assessed and re-
have shown that rodents make use of large. Studies have revealed that the opti- corded using so-called score sheets
these structures, with the result that they mum group size for mice is four to eight (such as rapid loss in body weight, diffi-
become less anxious and develop fewer animals and for rats three to four animals. cult respiration, reduced grooming, or
behavioural disorders,” explains Hanno If the groups are larger, there is increased paralyses).
Würbel, Professor at the University of fighting for rank order position. To prevent
Giessen. fighting among the animals, the group As a rule of thumb, animals have a similar
should be formed of young animals as capacity as humans to experience pain
There were fears that enriched housing early as possible and then left unchanged. and distress. But this insight alone does
conditions would adversely affect the not suffice. Trained personnel must be
robustness of the data from animal re- Dogs, too, should not be kept alone. Cer- able to assess the animal’s pain during
search. A study conducted in 2004 by tified systems for housing dogs in groups experimentation. If animals must be killed
Würbel disproved these reservations. exist, which still enable to track the ne- during or after the experiment, this must
“Our study showed that enrichment by cessary data (for example, food uptake) be done as painlessly as possible and
no means affects the significance of for each animal individually. according to accepted methods that con-
animal experiments,” says Würbel. firm with legal regulations (see page 18).
www.forschung3r.ch
Project numbers: 77-01, 66-99
17
Replace
3R Reduce
Refine | Pain relief
“It is a common misperception that you ing. If the animals experience less pain, Allowing the animals to become accus-
can clearly see when an animal is in pain,” test results are more reliable. tomed to the planned procedure through
says Peter Maier, scientific advisor to the training is another important prerequisite
3R Research Foundation. However, for in- For analgesics to be administered cor- to reduce the animals’ anxiety and pain. In
stance, pain in mice and rats can be rec- rectly, however, specialised knowledge is this context, the care staff and their hand-
ognised only by trained personnel. “If a required. The signs of pain differ not only ling of the animals play an important role.
mouse shows abnormal behaviour, has between animal species, but also de-
an unnatural body posture, or loses body pending on the type of surgical procedure A good planning of a research project
weight, then it has to be assumed that it or the organ causing pain. Researchers also includes the determination of criteria
is already experiencing very strong pain,” and care personnel must be able to rec- for discontinuation of the experiment.
says Maier. In contrast, dogs show obvi- ognise and assess how effective the pain These are criteria that must already be
ous signs of pain, and they can also alert relief measures are for the respective defined in the application for a license
people to their pain by the sounds that species. This requires knowledge regard- to conduct the experiment and that lay
they make. In sheep it is not yet known ing the way analgesics work, their dur- down when the procedure must be ter-
how they show pain or enduring distress. ation of effectiveness, which parts of the minated (humane endpoints).
organism they act upon, and the possible
Some years ago it became regular forms of administering the analgesic. The administration of analgesics admit-
practice to give laboratory animals pain tedly also has disadvantages, for merely
relievers, if it was likely that they would There are exceptions picking up an animal, even if it is done
suffer pain. Today, and especially for Today, analgesics are withheld only in properly, can cause it anxiety. Therefore,
post-operative pain, the administration exceptional cases, such as in research the degree of pain reduction has to be
of analgesics is standard practice and trials investigating rheumatism, cancer, weighed against the degree of additional
is mostly also required by law. The ad- or similar diseases, because analgesics stress. A stressed animal will experience
vantages of pain relievers are obvious: distort the results in those cases. In the greater distress during the procedure.
Pain can affect the entire organism in course of such investigations, the trial is
an unpredictable manner to such an ex- ended and the animal is killed as soon
tent that a test can yield worthless re- as the scientist recognises that the new
sults, and without the researcher notic- drug does not have the desired effect.
18
Knowledge required. It requires specialised knowledge to administer pain relievers in the correct dose at the right time,
since animals do not all show pain in the same way.
19
Genetically modified animals
20
Using genetically modified mice, signifi- power of research using genetically modi- ically modified strain of mice is available
cant advances were made in the investi- fied animals. Experts are of the opinion for use: Its development can take up to
gations on the most common inherited that the transferability of data from ani- several months or years. In addition, ani-
disease in Western Europe, cystic fibro- mals to humans varies greatly from case mal welfarists point to the suffering of the
sis (CF). About one in 2,000 children are to case. research animals that can be caused by
born with CF. These children produce a the genetic alterations.
thick mucus in their lungs that can not be Nevertheless, transgenic animals are
coughed up. A cure still does not exist, helpful and therefore sought-after models,
but thanks to transgenic mouse models particularly in basic research. This is one
of CF, much more is now known about reason why the number of animals used Genetically modified? Transgenic?
this disease. This is the prerequisite for in research is once again on the rise –
Genetically modified organisms are organ-
better therapies. especially since the mapping of the human
isms, whose genetic material has been altered
genome. Whereas researchers now
in a targeted manner with the help of genetic
Several genes are usually involved know all of the human genes, they still do engineering techniques. The narrower term
However, genetically engineered mice not know the functions of many of them. “transgenic” describes a similar condition:
also do not enable scientists to answer all Genetically altered animals can help find Transgenic animals are organisms, in which
open questions. Many human diseases the answer to this question, because an existing gene has been switched off or
are not caused by a change in one indi- many human genes are found in mice in in which foreign DNA has been inserted into
the cells. In the year 2005 in Switzerland,
vidual gene, but rather by the interaction a similar form.
94,000 genetically modified mice were used
of several errant genes. This makes the in experimental procedures. Twelve per cent
analysis of diseases considerably more In spite of this, it is disadvantageous that of these animals were subjected to moderate
difficult. For this reason, opponents to ani- it can take a very long time and require to severe distress.
mal testing point to the limited explanatory a large number of animals before a genet-
Disputed experiments
“The long-tail macaques are trained to cooperate in the experiments. This reduces stress, both
for the animals and the caretaker, and the results of the experiments are improved,” explains
Walter Stamm, animal caretaker at Roche. Still, experiments using primates remain disputed.
Experiments with primates are disputed Human Gene Technology (ECNH/EKAH). A few research projects using primates
mainly on ethical grounds, for these ani- However, a majority of the members of causing severe distress are also being
mals are our closest relatives. The great the Committee for Science of the Swiss conducted in Switzerland. For certain
apes especially – gorillas, orang-utans, National Council is of the opinion that a questions, this is indispensable – for ex-
and chimpanzees – should not be used rigorous harm-benefit analysis would ample, when it comes to the safety of
for experiments. Some EU countries serve people better than an explicit ban. pharmaceutical products. In Switzerland
(Austria, Sweden, and the Netherlands) in 2005, 148 primates were used in bio-
have already implemented this request. In the view of the EKTV and ECNH com- logical and medical basic research and
Animal welfarists demand that such a ban mittees, research using other, non-human 260 in the areas of discovery, develop-
should already apply even if the animals primates (such as rhesus monkeys and ment, and quality control in medical sci-
are submitted to only minor or no di- long-tail macaques) should only be ap- ences (transplantation medicine, asthma
stress. This opinion is also held by a ma- proved after a thorough consideration of research, brain research, neurobiology,
jority of the members of the Swiss Fed- the ethical issues, a comprehensive pharmacology). The research was con-
eral Committee on Animal Testing (EKTV) harm-benefit assessment, and only with ducted in industry and at universities.
and the Swiss Ethics Committee on Non- the “greatest restraint”.
22
Research using long-tail macaques: Trust and cooperation are vital
Walter Stamm is one of four animal care- Before we begin with the training pro- to be handled directly by humans by
takers at Roche that takes care of long-tail gramme, in a first phase it is essential to being petted and stroked every day. They
macaques. Each caretaker is responsible build mutual trust between the human have to learn to accept my reaching into
for approximately 15 animals. The maca- being and the animal. It is important for the cage. In the next phase, the primates
ques are used for pharmacokinetic stud- the animals to learn that I do not intend learn to voluntarily present an arm or a
ies, during which the distribution of sub- to do them harm. Trust can be built, for leg from the cage. This is important for
stances throughout the body is evaluated. example, during feeding: The animals be- the experiments to come, when blood
Since these tests cause the animals come accustomed to being fed by hand. samples must be taken from the animals
little distress, the same animals are kept By the way, primates do not all like to (see picture below left). In the tests using
for years and used again and again for eat bananas. For some, it is only a prefer- long-tail macaques, usually a substance
testing. ence acquired over time. When feeding is administered and then blood samples
the monkeys, it is my job as a caretaker are taken over the course of two to three
“All of the macaques that we use in re- to respect the rank order within the group. days. After that, the animals have a rest-
search come from controlled breeding First I feed the highest-ranking male, ing period that lasts a month. Thus, the
stations abroad that breed the animals followed by the second-ranking, or beta animals are trained in order to cooperate
exclusively for use as laboratory animals. male, and then the rest of the group. during the experiments. This reduces the
This largely ensures that the animals are distress for the animal and also for the
free of infectious diseases and parasites. No training without trust caretaker when collecting blood samples
Nevertheless, we examine the animals’ To build trust, it is also important to pro- and the research data are more reliable.
health status thoroughly when they first vide the animals with the time necessary For this reason, a lot of time is invested
arrive. to become accustomed to their new in training the animals, usually one to one
environment – to noises, the daily routine, and a half years.”
the food, and, of course, to us care staff.
Once trust has been established between
the caretaker and the animal, the training
programme can begin. The animals learn
23
Replace
Angelo Vedani
Reduce | Computational methods University of Basel
Refine
Angelo Vedani’s dream is evident: One Which other advantages exist? would bind to some other receptor that
day, computer mice shall be the only mice One advantage is that computational is not recorded in our database. It is
required to conduct toxicological testing. methods are reproducible – this means also possible that the structure of the
Such tests serve to determine harmful that scientists will obtain the same re- candidate substance will change in the
effects of substances. Vedani specialises sults on a test regardless of whether living organism and will therefore bind
in computer aided drug discovery (CADD). they are at work in London or Peking. to other structures. We are currently
CADD is now routinely being used in the That is not always the case when per- working on recognising such false nega-
pharmaceutical industry in order to design forming tests on live organisms. We can tive predictions beforehand.
optimal substances on the screen and test an active substance within a short
also to identify possible adverse effects period of time. And computer methods What remains to be done?
of the substances. Angelo Vedani explains are cost-saving in comparison to animal At present there is not yet one single in
his CADD project in an interview. tests, because all that is needed is a silico method (computer-based method)
powerful computer and the right soft- that has been accepted worldwide for
What are the advantages of CADD? ware. toxicological testing. Together with the
Angelo Vedani: In the course of the authorities we are currently working
development of new pharmacological How exactly does the method work? to establish the criteria that a software
substances the question might be At the present time, our system con- programme must fulfil in order to gain
which of 20 active substances to de- tains models of eight important human regulatory acceptance.
velop further. Our computer models can receptors (see box) – amongst others
predict which substances to withdraw the androgen receptor, estrogen recep- Which contribution can in silico methods
from further testing. Thus, we do not re- tor, and the enzyme cytochrome P450. make to REACH, the new EU testing
place animal testing, but we sometimes We can model how strongly a candi- programme for chemicals (see page 30)?
prevent very distressful animal tests. date substance will bind to one or more We can make an important contribution
of these receptors. If its binding affinity to this programme. Many environmental
is strong, the candidate substance will chemicals bind to exactly the same re-
be withdrawn from the evaluation pipe- ceptors that we already have in our sys-
line, because it is very likely to cause tem. We therefore have a good basis
Like a lock and key undesired side effects. for predicting, which substances will
cause harmful effects. However, the EU
Many active ingredients in drugs unfold their
What are the limitations of the model? has not yet decided, which methods it
effects by binding to receptors. A receptor is a
protein that, for example, is located on the sur-
Those substances that fail in our tests will accept and use for REACH.
face of a cell and transmits signals into the cell. are withdrawn. But this does not neces-
The better an active ingredient binds to the sarily mean that the other substances
www.forschung3r.ch
receptor in question, the better the medication will not cause side effects. It might very Project number: 75-00
will work. The better an active ingredient binds well be that a candidate substance
to a receptor that triggers an undesired effect,
the greater the probability that the active ingre-
dient will cause side effects.
24
Replace
Markus Rudin
Reduce | Non-invasive methods University of Zurich
Refine and ETH Zurich
The research area of non-invasive imaging over a long period of time, without hav- maceutical industry. And, by the way,
techniques encompasses a wide range of ing to kill the animal for a specific inves- the pharmaceutical industry has many
methods for observing organisms. Which tigation. One can recognise changes in years of experience with such methods.
are these methods? the animal that are not visible externally The industry is a pioneer in this area.
Markus Rudin: They include, for exam- and that might cause pain, which then
ple, methods such as the conventional points to the need to stop the test early. Are the methods being used at the
X-ray technique or its further develop- Fewer animals are therefore needed to universities?
ment, the computerised tomography perform an experiment, because each Presently, this type of research is also
(CT). Another important method is the animal serves as its own control. At increasingly being performed at the
so-called magnetic resonance imaging best, the savings can be 80 per cent universities, such as at the University of
(MRI), which allows detailed structural and higher. Zurich and at the ETH Zurich, where the
and functional investigation of the brain, Zurich Center for Imaging Science and
for example. Some other methods are What is the third advantage? Technology (CIMST) was opened in
positron emission tomography (PET) The third advantage is that we can 2005. On the one hand, this Center has
and fluorescence tomography. study an effect in a living organism. For the mission to promote the development
example, we can give a substance to of the methods and on the other hand
What are the advantages of these a mouse and then observe how the or- to promote biomedical research at the
methods? ganism as a whole reacts to it. University and the ETH Zurich.
Apart from the fact that one does not
have to intrude into the body with any To which extent are these methods being Which are the limitations of the methods?
instruments, there are three other im- used in laboratories nowadays? At the moment there are limitations as
portant advantages. In principle, the Imaging techniques are finding increas- to resolution and sensitivity, with these
method is identical for humans and ani- ing use in animal testing. In spite of this, two aspects being partly connected. For
mals. This results in a better compara- wide-spread use and acceptance of the example, it is not yet possible to image
bility of the results. Another advantage techniques is being held back, because individual cells or cell assemblies in a liv-
comes into effect when studying long- many of the newly developed methods ing organism with these techniques. For
lasting chronic diseases, in particular: are not yet, or not yet comprehensively, most of the techniques, however, such
Using non-invasive methods, the re- validated. Nevertheless, they show limitations are not of physical origin, but
searcher can observe the same animal great potential, especially for the phar- rather dictated by the current state of
the technology. Therefore I do believe
that we can expect to see a lot happen-
ing in the next couple of years.
Functional MR imaging
Neuroactive substances cause
changes both in blood flow and
blood volume in the respective
area of the brain. In this com-
puter image, areas with a high
blood supply appear in red. 25
The 3Rs concept in practice
Implementation is decisive
Whether the methods will indeed be used and benefit the animals is decided in the world of
practice. It can take years for a method to become officially accepted by the authorities, for it
has to be studied in lengthy tests first.
Many experts agree: While the 3Rs as a The Swiss Federal Animal Protection Act – that is, they were tested for their suitabil-
concept may be a matter of course now- regulates both of these areas. According ity. In Europe, ECVAM (European Centre
adays, implementing the 3Rs in routine to this legislation, an experiment shall not for the Validation of Alternative Methods)
laboratory practice takes constant effort. be approved if its scientific goal can be is responsible for such scientific valid-
When it comes to implementation, two met with a non-animal test method that is ation. By the spring of 2007, a total of 25
areas are to be distinguished (see figure valid according to the current state of alternative methods have been validated
below): knowledge. by ECVAM, and ten of them have been
– Legally required testing (such as accepted by regulatory authorities, such
toxicological tests for chemicals, drugs, Legally required testing as the OECD (all of these are methods for
and vaccines). As regards legally required testing, inter- the toxicological testing of chemicals or
– Basic research with, in principle, free national committees determine, which medications). At the same time, another
choice of research methods. Scientists 3Rs methods may be used. The proto- 40 methods were in the final phase of the
generally choose the experimental cols to perform tests with alternative time-consuming and costly validation
method that leads to the goal most methods have been laid down in detail. process and 190 in the initial phase.
reliably. At first, these protocols were prevalidated
Validation is the process by which the scientific significance and reprodu- taken. Next, the significance of the method in comparison to the respective
cibility of a method are established according to defined criteria. During animal test must be determined. A successful validation is the necessary
validation, the method undergoes practical testing in several, independent prerequisite for an official acceptance of the test method by the regulatory
laboratories and ideally on different continents. A large number of different authorities. The authorities stipulate which tests must be conducted, for in-
test substances are tested following a precisely defined procedure (stand- stance, for the registration of chemicals or the authorisation of medications.
ardised protocol). If the results obtained conform, the first hurdle has been
26
The long road to validation. In order for new 3Rs methods to become applicable for legally required testing, they first have to be
validated. Validation ensures that the method is indeed an alternative that yields safety levels that are comparable to the animal test.
The freedom of basic research In Switzerland, the implementation of pub- searcher to apply a specific method, the
All of the methods evaluated by ECVAM, lished methods takes place via the official license application as it stands will pro-
however, are of little importance for basic authorisation process. A scientist who bably not be approved.
research at universities or for applied re- submits an application for a license to
search in industry. The reason for this is conduct an animal experiment has to indi- http://ecvam.jrc.cec.eu.int
that in these areas neither validations nor cate whether other methods exist for the
choice of 3Rs methods are mandatory. purpose he is intending to pursue that
Instead, freedom of research is essential. do not use animals or that cause less di-
Methods are being disseminated by pub- stress to the animals. If the researcher
lishing them in scientific journals, so that overlooks an available method, the licens-
every researcher can try them, test them, ing authority will call the researcher’s at-
and improve them. Once a method is a tention to this and ask why the method
part of the scientific literature, it gains offi- was not taken into consideration. Where-
cial status and the authorities can refer to it. as the authority can not force the re-
27
Training and continuing education
http://3R-training.tierversuch.ch
28
“The 3Rs
are a concept, not
an ideology.”
Peter Maier, University of Zurich,
3R Research Foundation
In the past, discussions on the application cent safety. It is not possible to re-exam- verned by the Federal Ordinance, and
of the 3Rs principle were often ideologic- ine all data, which was originally gained they are coordinated and monitored by
al. Today this discussion has become in rodents, in humans. For instance, it is the cantonal veterinary offices. Each year,
somewhat calmer. Personnel, which is self-evident that acute toxic dose tests all persons supervising and performing
well educated and informed, can decide can not be performed in humans. In such animal experiments must fulfil a day of
whether animal tests are necessary for cases, the researchers can only perform continuing education in order to keep up
investigating a scientifically relevant ques- a rough estimation. Therefore there are al- with the state of knowledge. These per-
tion and, if so, which ones. Frequently, a ways incidences where substances that sons include veterinarians, biologists,
combination of animal testing and in vitro were previously tested and found to be physicians, biochemists, biology labora-
methods delivers the best results. “The safe in animals cause unforeseeable side tory technicians, and animal caretakers.
3Rs are a concept, not an ideology,” ex- effects in clinical trails with humans. One They work at universities, at universities
plains Maier. Ideally, it is possible to gain of the problems is that side effects in peo- of applied sciences, in the pharmaceuti-
sufficient information with in vitro methods ple, such as sweating, dizziness, nausea, cal industry, or at institutes that are con-
to make animal testing superfluous. or individual allergic reactions can hardly tracted to carry out animal testing.
be revealed in an animal experiment.
During their training, researchers carrying www.bvet.admin.ch/themen/tierschutz
The license application as a quality control ers to examine their plans: What exactly do I want to investigate, and how?
During training, great importance is attached to ensuring that the researchers This ensures that the researcher weighs the procedures he is planning in
learn to correctly describe and give the reasons for an animal experiment. Be- every detail – including the question of how he will treat pain in the animals.
fore each animal experiment, an extensive application for a license to perform The Cantonal Commission on Animal Experiments reviews the applications
the animal experiment must be submitted that states the aim for conduct- and makes recommendations. If there is nothing to object to, the license to
ing the test and describes the methodology chosen. The researcher must perform the animal experiment is granted. This procedure assures and legit-
also perform a harm-benefit analysis (harm to the animal versus anticipated imates the quality and the indispensability of the animal experiment. Such a
knowledge gain for humans) and lay it open in the application form. Thus, procedure, which depends on external reviewers, is unique in basic research
the application for a license is a valuable instrument that requires research- and is not found in any other area of research.
29
International network
Nevertheless, smaller and larger differ- the severity of animal experiments. In the protection – work together towards the
ences can be found from country to United States, the Animal Welfare Act 3Rs. The European umbrella organisation
country in regard to the performance of does not apply to rodents – in Switzerland of these 3R organisations is called ecopa
animal experiments. These also encom- 90 per cent of all laboratory animals are (European Consensus Platform for
pass cultural differences. In most Europe- rodents. Some countries, like Switzerland, Alternatives), and it is based in Belgium.
an countries and in developed countries are known for a consistent monitoring of ecopa is a platform facilitating the mutual
on other continents, the expected degree the regulations as well as for inspections exchange of scientific information and
of severity for the animals, classified using of the laboratories in the area of animal expertise to promote the 3Rs. It was
numbers or letters, is stated on the appli- testing. Others, such as some developing founded in the fall of 2002 with the active
cation for a license to perform an animal countries, are more lax in applying their support of the 3R Research Foundation.
experiment. In Switzerland, at the end of standards or have none at all. The aim of ecopa is, amongst other
each year, scientists are even required to issues, to coordinate very large and com-
retrospectively report to the Federal Veter- A platform for exchanging ideas plex projects in the area of 3R research.
inary Office the severity of the distress ac- In many European countries, national ecopa has also established contact links
tually experienced by each individual ani- consensus platforms have been formed, to similar organisations in Japan and in
mal. The United Kingdom, however, does in which the four interest groups – indus- the United States.
not yet have an official system to classify try, government, academia, and animal
30
Spreading the 3Rs concept in Europe
Thomas Hartung,
University of Constance/ECVAM
31
3R Research Foundation celebrates its 20th anniversary
At the particular initiative of Susi Eppen- And so the idea of a “Financial Pool areas of biomedical research and drug
berger and Hugo Wick, members of the 3R” assumed shape. It was its goal to development. That is where the greatest
Swiss National Council, the Swiss Parlia- promote research in the area of the 3Rs number of animals are used, and for that
mentary Group on Animal Testing was methods with funds from the Federal reason, scientists are needed that, while
formed in the fall of 1985. This came Government and those pharmaceutical focusing on their research questions, are
about in response to many years of de- companies involved in research, as re- also willing to develop new 3Rs methods
bate on the petition for a referendum “to presented by Interpharma. in the course of their research projects.
ban vivisection”, which was turned down “This is precisely where the Foundation
by the voters during the vote of 1 Decem- Funds have been flowing for can support the scientists and can en-
ber 1985, and to the next attempt to 20 years courage new ideas,” explains Peter Maier,
petition “a ban on animal testing and vivi- On 13 February 1987 the step was accom- scientific advisor to the 3R Research Foun-
section”, which was not accomplished. plished: the 3R Research Foundation was dation. Frequently, grants are awarded
The Parliamentary Working Group looked launched by three members of Parliament, by the 3R Research Foundation as a com-
for a way to bring together the interested Interpharma, and the Fund for Animal-Free plement to other research grants, such as
parties – politicians, government, animal Research (FFVFF). The same year, the first the Swiss National Science Foundation.
protection, and industry – to find objective research grants were awarded.
solutions to the problems. “We wanted The Foundation attaches great import-
to do something for laboratory animals, The 3R Research Foundation supports a ance to the publication of research results
without driving the pharmaceutical indus- broad range of research projects, pro- upon completion of the projects. This is
try out of Switzerland,” says Hugo Wick, vided that they present promising new ap- the only way to ensure that the insights
former (CVP party) member of the Na- proaches to replacing, reducing, or refin- gained come to the attention of other rel-
tional Council and chairman of the 3R ing animal testing. Currently, it is especially evant researchers and will be taken into
Research Foundation from 1995 to 2007. important to apply the 3Rs principle in the consideration in the future.
Milestones
■ Since its founding in 1987, the 3R Research Foundation has ■ In 1995, in 29 different laboratories in Switzerland, the in vitro
approved 108 projects for funding and awarded a total of approxi- production of mouse monoclonal antibodies using bioreactors
mately 15 million Swiss Francs in grants (to date, mid-2007). A list instead of mice was validated, achieving a breakthrough for this
of all projects with English descriptions of the project goals, meth- in vitro (test-tube) method.
ods, and results is available on the Foundation’s website. Each
year, the Foundation approves on average five projects, which ■ Available since 2005, the Foundation offers an online training
then mostly receive funding for a period of two to three years. course for the personal and professional training and continuing
education of persons that carry out or supervise animal experi-
■ Since 1994, successful research projects have been high- ments. Using the texts, illustrations, links, and documents
lighted in a short, illustrated publication called the 3R Info Bulletin. provided, interested people can learn about 3R topics and the
To date in mid-2007, 36 issues of the Bulletin have been pub- legal regulations governing animal testing.
lished. The 3R Info Bulletin is sent to more than 1,000 interested
readers and is also available on the Foundation’s website.
32
Hugo Wick is a founding
member of the 3R Research
Foundation and served as
Chairman of the Foundation
for 12 years.
33
3R dialogue platform
34
Thomas Cueni Max Gassmann
Interpharma University of Zurich
Industry Research
35
The 3R Research Foundation
The 3Rs stand for Replacement, Reduction, and Refinement. The Administrative Board of the Foundation has appointed an
This implies the concept to replace animal testing, to reduce Evaluation Committee, which has been assigned with the task
the number of animals used in testing, or to refine methods to to review the proposed research projects and applications for
minimise the distress for research animals. The 3R Research grants. The members of the Evaluation Committee are re-
Foundation provides funding to research projects in the area nowned scientists from academia and industry as well as rep-
of the 3Rs. It is a joint undertaking by the Parliamentary Group resentatives of the Government and of animal protection.
for Animal Experimentation Issues (Government), Interpharma
(Swiss Association of Pharmaceutical Companies that perform The projects that were funded by the 3R Research Foundation
research), and the Fund for Animal-Free Research (formerly have made a contribution to developing new and better meth-
FFVFF). Financially, the 3R Research Foundation is supported ods and thereby to reducing the number of animals used
equally by the pharmaceutical industry association (Inter- in experimentation in Switzerland. Since it was established in
pharma) and the Swiss Federal Veterinary Office. 1987, the Foundation has funded over 100 research projects.
www.forschung3r.ch