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The Senate Commission on Animal Protection and Experimentation

Animal Experimentation in Research


The Senate Commission on Animal Protection and Experimentation

Animal Experimentation in Research


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Contents

Foreword �������������������������������������������������������������������������������������������������������������������������� 4 Animal experimentation and protection of animals:


Introduction�����������������������������������������������������������������������������������������������������������������������6
Ethical considerations
Development of the concept of animal protection in Germany�������������������39
Experiments with animals: Definition and figures Ethical aspects of animal experimentation and the principle of solidarity �� 40
What is animal experimentation? �������������������������������������������������������������������������9 Transferability from an ethical-legal viewpoint �����������������������������������������������45
How many animals are used in research? �����������������������������������������������������������9 The Three Rs principle ���������������������������������������������������������������������������������������������47
What are animals used for in research? �������������������������������������������������������������11 Alternatives to animal experimentation�������������������������������������������������������������51
What animal species are used?�����������������������������������������������������������������������������11 Limitations to alternative methods �������������������������������������������������������������������55
Developments across Europe �������������������������������������������������������������������������������13 The Basel Declaration�����������������������������������������������������������������������������������������������56

Animal experimentation in practice: Areas of use Animal experimentation in Germany:


Basic research �����������������������������������������������������������������������������������������������������������17 From proposal to implementation
Medical research������������������������������������������������������������������������������������������������������ 18 European regulations on animal experimentation �����������������������������������������59
Nobel Prize worthy: Outstanding scientific findings�������������������������������������� 20 Animal experiments subject to authorisation���������������������������������������������������59
Diagnostics�����������������������������������������������������������������������������������������������������������������21 Legal basis ���������������������������������������������������������������������������������������������������������������� 60
Transplantation medicine ��������������������������������������������������������������������������������������25 Approval procedures �����������������������������������������������������������������������������������������������63
Cell and tissue replacement in humans���������������������������������������������������������������25 Conducting animal experiments�������������������������������������������������������������������������� 64
Stem cell research�����������������������������������������������������������������������������������������������������27 Qualified monitoring���������������������������������������������������������������������������������������������� 68
Genome research ���������������������������������������������������������������������������������������������������� 28 Stress during animal experiments ���������������������������������������������������������������������� 68
Neuroscience �������������������������������������������������������������������������������������������������������������31 Animal welfare group lawsuit �����������������������������������������������������������������������������71
Veterinary research�������������������������������������������������������������������������������������������������� 32
Animal experiments in education, training and professional development���� 35 Appendix
The basic assumption of transferability �������������������������������������������������������������35
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Foreword

Animal experiments are essential to basic biological and medical research – cre- The brochure is the result of cooperation between members of the DFG Senate
ating a classic dilemma as the acquisition of knowledge for the good of man- Commission on Animal Protection and Experimentation and the DFG Head
kind places a burden on animals. The protection of animals is high on the Office in Bonn. At this point, I wish to thank everyone who has contributed
agenda of most European countries and sets limits on research. In 2010, fol- to the completion of the project by submitting texts and engaging in critical
lowing long and controversial discussions, the European Parliament adopted discussions.
a EU directive on the protection of animals used for scientific purposes. This
directive provides new and more stringent regulations in many aspects, while I hope that you will find it an illuminating read!
also setting uniformly high standards across Europe for the approval of animal
experiments and the accommodation and care of animals used for research
purposes.

The first edition of Animal Experiments in Research was first published in 2004 by
the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation).
Both the German-language and the English version are no longer available.
The amendment to the German Animal Welfare Act in 2013 to bring it in line Gerhard Heldmaier
with the EU directive resulted in a number of changes to the approval process, Chairperson of the Senate Commission on Animal Protection and
placing a greater administrative burden on applicants than before. With this Experimentation of the DFG
revised edition, we aim to present an overview of the current legal require-
ments, including practical information regarding the organisational processes
for the application and the performance of tests on animals, as well as explain
the legal and ethical principles of research using animal experimentation. In
addition to the brochure, the DFG website offers further information – scien-
tific papers, legal texts, application forms, etc. – which can be accessed under
www.dfg.de/tierschutz (available only in German).

In our society, discussions around animal experiments are controversial and


often very emotional, not least because of the absence of factual information
about the purpose of the experiments, the burden they place on the animals,
or the results and potential benefits. Within the framework of the Basel Dec-
laration, scientists have committed to engage in more communication with
the public and to provide people with more information. This brochure there-
fore also intends to inform the interested public about the scope and need for
animal testing. On the basis of specific examples and explanations of scientific
methods, we endeavour to explain the principles of experimental animal re-
search and thereby provide a contribution to a more objective debate on the
topic.
NOBEL PRIZES Emil von Behring Ronald Ross Ivan Pavlov
6 1901 The function of serum therapy,
1902 Scientific research
1904 The physiology of digestion
 7
particularly in cases of diphtheria on malaria

Introduction
The genetic material of animals contains similar characteristics to the genetic material of humans. This
makes e.g. the fruit fly a suitable candidate for research into human life processes and diseases.

The analysis of the hereditary informa- searchers of viewing human beings as


tion (DNA) of complex animals – such superior to animals. Another critique
as the fruit fly Drosophila melanogaster, states that results from animal experi-
the mouse, rat, pig, cow or the human ments are not transferable to human
being – is one of the most important beings and that animals are made to
scientific achievements of recent years. suffer solely to satisfy scientific curi-
Great progress also has been made in osity. From today’s perspective, some
other areas of the life sciences, includ- animal experiments conducted in the
ing new insights into the structure of ri- early days of animal research do in
bosomes (the protein factories of body fact seem cruel, although the same is
cells) and into the astonishing plastic- true of surgical procedures performed
ity of stem cells. These findings provide on humans. This is mainly due to
new insights into the complexity of insufficient surgical techniques and
vital processes, improve medical care anaesthetic options at the time. The
and nutrition for human beings and discovery of anaesthesia in the 19th
animals in the long run, and thereby century was a godsend for humans
contribute to an increase in the quality and animals alike, and today, its use
of life and life expectancy. in animal testing is obligatory as well
as routine.
Considerable progress is however not
conceivable without the use of ani- The criticism of animal testing has
mals in research. Only with the help led to the formulation of rules gov- specialist researchers as well as repre- mals used for scientific purposes. The
of animal experiments has it been erning the use of animals in scientific sentatives from animal protection or- directive stresses three principles that
possible to understand human and experiments as early as the 19th cen- ganisations, advises the authority. The must be met to ensure animal welfare
animal life processes. This includes tury. These have been continuously decision on the proposal is informed in scientific research. This is referred
the function of sensory organs and of expanded ever since. The German first and foremost by an evaluation of to as the Three Rs principle: Reduc-
the nervous, hormonal and immune Animal Welfare Act is one of the most the indispensability of the experiment. tion and Refinement of experimental
systems, as well as that of individual stringent acts worldwide. It ensures This means that the proposal must methods as well as the development
genes, which can only be decoded that animal tests are conducted only contain plausible arguments provid- of Replacement and complementary
within the context of the total organ- within the confines of socially accept- ing evidence that the scientific goal methods of animal testing. In addition,
ism. For research of such complex able norms and are subject to govern- cannot be attained without the use of the EU directive contains a number of
processes in the intact living organism, ment control. Every animal experi- animal tests or alternative methods. new regulations on the approval and
animal testing will also be necessary ment for biomedical research purposes performance of animal tests. In July
in future. requires a written application to the In order to safeguard a high bioethical 2013, the German Animal Welfare Act
competent authority of the relevant standard within animal experimental was revised and adapted to the Euro-
There have always been opponents state and must contain a detailed jus- research across Europe, the European pean directive. Old regulations were
to animal testing. Now as well as in tification for the experiment. An ani- Parliament in 2010 adopted Directive retained and supplemented with new
the past, opponents have accused re- mal welfare committee, consisting of 2010/63/EU on the protection of ani- specifications.
Robert Koch
1905 Transmission and treatment
9
of tuberculosis

Experiments with animals:


Definition and figures

What is animal experimen- The killing of animals for the sole pur-
tation? pose of organ extraction or the produc-
tion of cells does not constitute animal
The German Animal Welfare Act de- experimentation. Cells or organs are
fines animal experimentation as inter- either examined directly or used to
ventions and manipulations in animals create cell and tissue cultures. Such in
if this is associated with suffering, pain vitro cultures can supplement or par-
and injury to the animals. This applies tially replace experiments on live ani-
to all procedures subjecting animals to mals and make it possible to develop
stress “equivalent to, or higher than, alternatives to animal testing. About
that caused by the introduction of a one-third of all animals used for re-
needle in accordance with good veteri- search purposes is utilised for these in-
nary practice” (Article 3, 2010/63/EU). vitro methods.
In reality this means that each proce-
dure carried out on animals for scien-
tific purposes must be recorded as an How many animals are
animal experiment and approved by used in research?
an authority. Approval is required for
all vertebrates, cephalopods (e.g. octo- The German Ministry of Food and Ag-
puses) and decapods (e.g. lobsters). riculture and the Federal Statistical
Office annually record the total num-
As part of the approval process by the ber of all animals used in Germany.
competent authority, the reason for In 2014, 2.798 million animals were
the use of animals as well as their liv- used for research purposes. Included
ing and care conditions are examined. in this are 2.008 million animals used
Approval for an animal test is granted in animal testing and 789,926 used
only for the purposes expressly speci- for organ extraction. The number of
fied in the German Animal Welfare animals needed for research purposes
Act. This includes basic research, ap- corresponds to 0.35% of all 795 mil-
plied research for the prevention, lion animals used in Germany – this
detection and treatment of diseases, small percentage is essential for gain-
quality and efficacy testing of drugs, ing knowledge about the natural ba-
forensic investigations, environmen- sis of life and for medical progress. At
tal protection, promoting animal well- 788 million, the largest proportion of
being, improvement of animal hous- animals were cattle, pigs, poultry and
ing conditions, conservation of species, sheep; these were slaughtered to pro-
as well as education, training and pro- vide food for human consumption.
fessional development. Another 4 million animals were killed
Camillio Golgi, Santiago Ramón y Cajal Alphonse Laveran Ilya Mechnikow, Paul Ehrlich
10 1906 The structure of the
1907 The causative role of
1908 Immunity in
 11
nervous system protozoa in diseases infectious diseases

by hunting. Fishing and pest control in scientific research. Fish larvae can in 2013 by approx. 3% (2.997 mil- Numerous animal tests are conducted
also involve the killing of animals, but be very small, so that direct counting lion) compared to the previous year, within the framework of consumer
these are not counted. is not possible and the number of lar- and in 2014 by another 6.6% (2.798 protection and are required by law
vae can only be estimated. This initial million). (so-called “regulatory purposes”).
Since 2014, animals used for scien- figure is not included in the figures About 23.7% of all test animals in
tific purposes are registered accord- published by the German Ministry of Germany are used for such safety
ing to a new Europe-wide reporting Food and Agriculture. What are animals used for checks, quality controls or toxico-
procedure. Newly introduced was the in research? logical tests in accordance with the
registration of independently feeding There has been a slight decrease in legislation on chemicals, medicines
larval forms. The first count showed the overall number of animals used The majority of animals in science and food hygiene. These tests are re-
that 563,000 animal larvae were used for scientific research in recent years: are used in basic research (31.1%) quired for the approval of drugs and
and in “translational and applied re- other substances with which humans
search” (11.9%). The latter are pro- come into contact.
Chart 1:
jects that test basic research findings
Percentage of animals used for specific research purposes
for medical applications. Basic re-
search and translational and applied What animal species are
research are closely interconnect- used?
ed, and their combined percentages
Basic research: 31.1% make up the expenditure for medical Animals used in research are mainly
Translational and applied research: 11.9% research (43%). Animal experimen- small mammals such as mice, rats,
28.2% tation in medical research is conduct- guinea pigs and rabbits; fish and birds
31.1% Conservation breeding programmes of genetically ed to clarify previously unknown life are used for specific investigations.
modified, burdened animal colonies: 2.8%
processes and fundamental biological Mice (1.901 million in 2014, 68%)
Quality control, toxicology and relationships. In turn, these findings and rats (13%) are still the most
other safety evaluations: 23.7% are used to improve diagnostics and commonly used animals and are also
Environmental protection for the benefit treatment of human illnesses and most often killed for organ extraction.
1.8% of humans and animals: 0.2% diseases. The decoding of the mouse genome
a few years ago, and the relatively
0.3% Conservation of species: 0.3%
0.2%
About 28.2% of animals used in re- simple manipulation of this genome
Education, training and search are not exposed to experimen- from a technical point of view, makes
11.9% professional development: 1.8% tal treatments while alive but are put the mouse by far the most important
23.7%
2.8% Animals killed for scientific purposes down to gain cells or tissues. These research species as it offers insights
(not animal tests): 28.2% samples are used to examine basic into the genetic foundations of life
biochemical processes on a cellular processes and diseases. The slight
level and test new pharmacological drop in animal experiment num-
Source: Statistics of the German Ministry of Food and Agriculture, 2014 treatment methods. Ultimately, this bers over the last two years is mainly
percentage must also be allocated to due to a reduction in the number of
the cost of medical research. mice and rats. The use of fish has in-
Albrecht Kossel Alexis Carrel
12 1910 Cell chemistry and
1912 The development of techniques
 13
cell nucleus substance for suturing blood vessels

Chart 2: creased over the last few years (cur- Research on wild animals, however,
Animal consumption and animal species used for research purposes rently 9.8%) as the zebrafish genome is possible, but severely restricted
was decoded and enabled insights and subject to special requirements.
into the origins of the life processes To safeguard the protection of spe-
in vertebrates. Other species are used cies as required by law, additional
only to a minor extent. Their number approval by the relevant nature
may fluctuate slightly, but this has no conservation authorities is required.
influence on the overall figures. Wildlife research mainly investigates
Food: 99.15% the behaviour of animals and their
Since 1991, experiments on great interaction with their natural habi-
apes are no longer performed in Ger- tats. The findings of such studies are
many, and other primates are used primarily used to protect species. In
only in small numbers. In 2014, the most cases, the animals are merely
figure was 2,842, which corresponds being observed and only exposed to
to about 0.1% of all research animals. low levels of stress so as not to inter-
The most commonly used monkey fere with their natural behaviour.
Animals for research purposes (0.35%) species was the long-tail macaque
(2,100). In most cases (2,335 ani-
Hunting (0.50%) mals), primates were used for legally Developments across Europe
required scientific research, for ex-
ample in drug testing. Cats played The European Commission also re-
Mice: 68.0%
an even smaller role in research (997 cords the number of test animals in
Rats: 13.0% animals in 2014), and they too were order to track the development with-
used mainly for legally required pur- in Europe. For 2011 – more recent
Birds: 2.0% poses (519). figures were not available at press
Fish: 9.8%
time – 11.5 million test animals were
The use of stray and feral dogs and listed overall. Germany’s share in
Rats: 13% Rabbits: 3.8% cats is prohibited in experimental this figure is 2 million animals, be-
research with animals. They are not cause European statistics – in con-
Dogs: 0.1%
suitable for scientific research as their trast to national records – only count
Mice: 68% origin, state of health and genetic the actual animal experiments and
Primates: 0.1%
background, as well as their previ- not the killing of animals for organ
Livestock: 0.8% ous behaviour is unknown. Reliable extraction.
and reproducible research results can
Other animals: 2.4%
only be achieved under defined and Compared with the last count, there
standardised conditions. This applies has been a slight increase in the num-
Source: Statistics of the German Ministry of Food and Agriculture, 2014
to the status of test animals as well ber of test animals in some countries.
as all other experimental parameters. In most European countries, how-
Charles Richet
14 1913 Discovery of hypersensitivity
 15
to antigens

The number of animal tests with amphibians – including the European tree frog – has more than
halved across Europe.

ever, the number of test animals has


remained fairly constant or has fall-
en slightly, as in France and the UK.
Across Europe, mice are also the most
commonly used species for animal
testing. Their share is 61%, followed
by rats, guinea pigs, other rodents,
and rabbits. The share of monkeys
was 0.05%. Great apes have not
been used since 1999. Since 2008,
there has been a drop in the num-
ber of amphibians (– 52%), monkeys
(– 48%), birds (– 26.5%) and rodents
(excluding mice) (– 19.9%), whereas
the recorded numbers of fish (+ 29%),
rabbits (+ 7.5%) and other mammals
(+ 38%) have increased.

At the European level, more than


60% of animals were used for basic
research and for the research and de-
velopment of medical products and
devices for human medicine, dentist-
ry, and veterinary medicine. About
19% of all animals were used for tests
and checks of medical products and
devices. The number of animals used
in toxicological evaluations and other
safety tests has remained relatively
constant over the last few years, at
about 9% – despite the introduction
in 2006 of the EU’s REACH Directive
(Registration, Evaluation, Authorisa-
tion and Restriction of Chemicals),
which stipulates that all chemicals
used in larger quantities within the
EU require safety information often
based on animal studies.
Jules Bordet
1919 Fundamental discoveries
17
on immunity

Animal experimentation in practice:


Areas of use

Basic research tacks or neurological conditions such


as Parkinson’s disease.
The aim of basic research is to gain
knowledge and insights. Basic re- Many results in basic research are ob-
search has no immediate application tained using cell cultures, because cul-
but provides the scientific basis for tured cells develop relatively quickly
further research and applications. Be- and homogeneously and can be direct-
cause of the similarity between hu- ly stimulated with hormones or other
mans and animals in terms of their chemicals. Cell cultures are always ar-
metabolic processes and function of tificial systems and provide only limit-
organs, knowledge gained in ani- ed insight into life processes. Yet they
mal experiments can provide a better are the only way to directly manipu-
understanding of life processes and late and measure biochemical pro-
their disturbances in both humans cesses in the cell. In cancer research,
and animals. Although the transfer- for example, isolated tumour cells are
ability of results from basic research used to identify the characteristics and
to its application cannot be planned causes of cell degeneration. The true
and its direct short-term benefit can- nature of cancer, however, becomes
not be predicted, scientific and medi- apparent only when its development
cal breakthroughs are not conceivable is viewed in connection with other
without the knowledge gained from cells and tissues in the body. In order
basic research. to trace the development of a tumour
in the organism and test therapeutic
Animal testing is a necessity and of approaches, animal experiments are
particular importance where complex necessary in which tumour cells are
relationships between physiological transferred into mice.
processes and diseases can only be
studied on the living organism. This The close relationship between cellu-
applies in particular to studies on the lar basic research and animal testing
functioning of the nervous, cardiovas- also plays a central role in research on
cular and immune systems, as well as infectious diseases. It is the only path
the action of hormones. Very dynamic to understanding how bacteria and vi-
developments are currently taking ruses infiltrate and attack the animal
place in the field of genome and stem organism. Insights into the interaction
cell research. It is hoped that new between viruses and their host cells
therapeutic approaches can emerge enable the targeted treatment of virus
from stem cell research, using cell and infections such as influenza, herpes
tissue replacement to treat heart at- or smallpox, and the development of
August Krogh Archibald Hill, Otto Meyerhof Frederick Banting, John Macleod
18 1920 1922 1923  19
Discovery of the capillary Metabolism and heat generation Discovery of insulin
motor regulating mechanism of muscles

Marmots reduce their body functions to a minimum during hibernation. A better understanding of this
process could be conducive to saving the lives of seriously injured people.

preventive measures. A visible result injuries or in curbing the effects of a


of this type of research is the progress heart attack or stroke. Some clinics are
made in the area of vaccinations. Only already trying to trigger this process
a few years ago was it discovered that by subjecting patients to low tempera-
papilloma viruses are involved in tures. Transplantation medicine too
the development of cervical cancer. (see page 25f.) can benefit by increas-
Without animal experiments on mice, ing the shelf life of organs.
sheep, horses and goats, this discovery
would not have been possible. A vac-
cine against the viruses was success- Medical research
fully developed. The German virolo-
gist Harald zur Hausen was awarded Medical progress is inextricably linked
the Nobel Prize in Medicine for this with basic research. An example of
work in 2008. this is the development of treatment
methods for diabetes mellitus. In the
Basic research projects initially aimed 1920s, insulin was identified as a hor-
at gaining information about life pro- mone that regulates blood sugar levels.
cesses in animals may translate into Experiments on rabbits, dogs, pigs and
medical benefits at a later stage. A case cows helped to understand the effect of
in point is the study on the hibernation insulin on blood sugar levels and thus
of marmots and other small mammals. contributed to the development of new
Initially it was assumed that hiberna- therapies. In 1923, the Canadian scien-
tion is triggered by cold temperatures tists Frederick Banting and John J. R.
and lack of food, leading to a failure Macleod were awarded the Nobel Prize
of the temperature-regulating mech- for their discovery of insulin. Rabbits,
anism. The latest studies of ground dogs and other mammals have been
squirrels, dormice and marmots how- largely replaced by rats and mice in
ever show that these animals actively physiological research. The rapid re-
stifle their metabolism and regulate production of these species permitted
their body temperature to be near specific breeding for individual clinical
freezing, and that breathing and heart presentations. This includes, for exam-
rate come to a near standstill. A new ple, the “diabetes mouse” with raised
way of regulating metabolism was blood sugar levels and the “Zucker rat”
thus discovered that enables mammals that develops obesity. therapeutic applications in humans. medicine include the development of
to switch from “normal operation” Among other topics, immunology ex- the antiserum to diphtheria (in which
to “low flame”. To understand how Immunology provides numerous ex- amines resistance to pathogens and experiments with guinea pigs were
this switching process works could be amples of the utilization of findings the rejection of transplants after im- instrumental), vaccines against yellow
lifesaving in the treatment of severe from animal experimentation for plantation. Pioneering advances in fever and polio (mouse and monkey),
Willem Einthoven Johannes Fibiger
20 1924 Electrocardiogram
1926 Discovery of the nematode
 21
Spiroptera carcinoma (cancer research)

Emil von Behring was the first person to be awarded the Nobel Prize in Medicine in 1901. His serum
therapy, which was tested on animals, is the basis for vaccinations today.

studies on the pathogenesis of tu- have been awarded the Nobel Prize.
berculosis (sheep and cattle), typhus The first Nobel Prize went to the phys-
(mouse, rat and monkey), malaria iologist Emil von Behring in 1901 for
(dove), as well as antiretroviral agents his work on the treatment of diph-
to combat AIDS (monkey). theria. At the end of the 19th century,
nearly every second child died from
The discovery of the effects of vita- the disease. In 1890, von Behring and
min C was studied in the guinea pig his Japanese colleague Kitasato found
and led to the insight that the effect of that injecting low doses of the diph-
vitamins is the same in animals as in theria toxin triggered the formation
humans. Hormones such as calcitonin of antibodies in rats, mice and rabbits.
from salmon are used in the medi- The animals were then protected for
cal treatment of osteoporosis. Animal life. Injecting the serum of immunised
experiments have led to the develop- animals also prevented the outbreak
ment of new surgical techniques and of the disease in other animals. Von
to the refinement of operating meth- Behring thus discovered one of the
ods. The first experiments on tissue basic principles of immunology – im-
transplantation were performed in the munity – and paved the way for the
mouse as early as the start of the 20th development of vaccinations.
century. These days, animal models
(mainly pigs, but also dogs and sheep) The immense importance of animal
are used for kidney transplantation, experiments in biomedical research
bone marrow transfer and heart sur- and the resulting knowledge gain for
gery, to develop new methods for the medicine is revealed by the fact that
cure or alleviation of organ diseases in the Nobel Prize in Medicine and Physi-
humans. Artificial replacement organs, ology (with one exception, i.e. Barbara
having first been subjected to stand- McClintock for her studies in the area
ardised technical checks, are tested for of plant genetics) in the last 40 years of receptor proteins in the cell envelope medical research, and enable micro-
their biological compatibility in large has always been awarded to scien- of vertebrates, which plays an impor- scopical analysis of cellular processes
animals such as pigs. tists whose studies included the use tant function in various physiological that underlie the physiological func-
of animals (see timeline at the top of processes. In 2008, Osamu Shimomura, tions of the organism and its diseases.
the page). Outstanding scientific find- Martin Chalfie and Roger Y. Tsien were
Nobel Prize worthy: Out- ings that have been awarded the Nobel awarded the prize for the discovery of
standing scientific findings Prize in Physics or Chemistry have also the green fluorescent protein (GFP) in Diagnostics
made substantial contributions to pro- the bioluminescent jellyfish Aequorea
Since the beginning of the 20th cen- gress. Two chemists, Robert Lefkowitz victoria. This protein and several differ- In countries of the Western world,
tury, extraordinary achievements in and Brian Kobilk, received the award ent variants are now used as universal better hygiene conditions and medi-
the area of physiology and medicine for their research on an important class molecular markers in biological and cal care have led to a decrease in neo-
Charles Nicolle
22 1928 Research on typhoid
 23

Chart 3: new diagnostic options. In 1979, the In veterinary medicine, these highly
The most common causes of death worldwide in percent American Allan M. Cormack and the sensitive diagnostic procedures are of
Englishman Godfrey N. Hounsfield particular benefit to cats and dogs. Ex-
were awarded the Nobel Prize for perience in human medicine with ul-
Cardiovascular diseases developing computer tomography. trasound diagnostics, X-rays and other
They mainly used pig models in their imaging methods is also leveraged in
Infectious diseases
studies. modern veterinary medicine.
Cancer

Respiratory diseases
Computer tomography (CT) provides sectional images of the body. The pig was used as the model
Accidents organism in the development of this procedure, which was awarded the Nobel Prize.

Infection of the respiratory tract

Infant mortality

Diseases of the gastrointestinal tract

HIV/AIDS

Deliberately induced injuries

Tuberculosis

Neuropsychiatric diseases

0 5 10 15 20 25 30 35

Source: Berlin Institute for Population and Development (Berlin-Institut für Bevölkerung und Entwicklung): S. Kröhnert, M. Karsch;
Lebensspanne und Todesursachen früher und heute (Past and present life-spans and causes of death) (current as of 2013 on the
basis of WHO data, 2008)

natal mortality and increased life ex- Refinement and improvement of di-
pectancy. Despite this progress, many agnostic processes is therefore one
diseases can only be treated sympto- of the focal points in research. Non-
matically as their development has invasive examination techniques
not yet been adequately researched. such as computer tomography (CT),
Accordingly, society continues to have positron emission tomography (PET),
high expectations of future medical magnetic resonance tomography
advances and medical care. (MRT) and functional MRT (fMRT),
as well as the development of con-
The successful treatment of many trast agents and biomarkers (indica-
diseases depends on early diagnosis. tors of abnormal processes) open up
Christiaan Eijkman, Frederick Hopkins Charles Sherrington, Edgar Adrian
24 1929 The importance of vitamins
1932 Research on the electrical
 25
activity in neurons

In xenotransplantation, cells or organs are transplanted from one animal species to another.
At present, cancer cells in particular are inoculated into nude mice for research purposes.

Transplantation medicine not been possible until now, trans-


plantations of organ parts and tissues
In 2014, 3,169 organ transplanta- have produced some very good results,
tions were performed in Germany. At e.g. heart valve transplants of porcine
the same time, 11,000 gravely ill pa- origin.
tients were waiting for a life-saving
donor organ. The surgical techniques The possibilities of xenotransplanta-
and all procedures to avoid rejection tion are currently controversial, pri-
reactions were mostly developed in marily because of ethical considera-
animal experiments after years of re- tions and the potential risk of immune
search. Of great importance for organ rejections. For the future it is hoped
transplantation are new findings on that genetically modified animals can
immunosuppression, i.e. methods for be bred whose immune system is even
suppressing immune reactions against more similar to the human one, there-
donated organs to minimise complica- by reducing the potential for rejection
tions in organ recipients. of the transplanted organ. Current re-
search in this area is at a very early
New ways of replacing organs are stage. An obvious way this technique
being studied because the num- could be used is already on the hori-
ber of donor organs is not sufficient. zon: in clinical emergencies where no
Xenotransplantation (from the Greek suitable human donor organ is imme-
xenos = foreign), i.e. the transplanta- diately available.
tion of organs from one animal spe-
cies to another, or from an animal to
a human, occupies a special position Cell and tissue replacement
in transplantation research. It could in humans
alleviate the shortage of donor organs.
The research aims to identify species Many of the diseases known today are
whose organs are suitable for trans- due to the loss of cells or tissue, or loss
plantation due to shared biomedical of their function. Neuro-degenerative
or physiological properties. For ana- diseases, such as Parkinson’s or Alz-
tomical and physiological reasons, the heimer’s disease, as well as arthrosis
domestic pig is currently regarded as and myocardial infarction, entail the
the most promising organ donor for loss of cells and tissue, with major
humans. Animal experimentation is consequences for the patient’s quality
therefore an important interface to of life. Drug treatment, surgical cor-
livestock research. While the trans- rection and implantation of skin or
plantation of whole animal organs has nerve cells, or of heart valves, artificial
Thomas Morgan George Whipple, George Minot, William Murphy Hans Spemann Henry Dale, Otto Loewi
26 1933 The role of chromosomes
1934 Discovery of liver therapy
1935 The “organiser effect”
1936 Discovery of neurotransmitters
 27
in heredity and pernicious anaemia in embryonic development

hearts, heart pacemakers or artificial Stem cells have already been success- Stem cell research rounders and have the ability to de-
joints, are all procedures that were de- fully used in bone marrow transplan- velop into any type of cell. They are
veloped with the help of animal ex- tations. This approach offers the possi- The aim of stem cell research is to de- referred to as “pluripotent”, meaning
perimentation. Artificial cultivation of bility of allowing some types of tissue cipher the principles of cell differen- that any organ or tissue of a mam-
replacement tissue from the patient’s to regrow. Moreover, in the so-called tiation and to discover the possibilities mal can be developed from this type
own body, known as “tissue engineer- “biohybrid implants”, the body’s own of how to control it. Stem cells are of cell. In adult organs such as bone
ing”, might be used in the future to cell structures and functions are com- cells which are still largely capable of marrow, skin, or central nervous sys-
replace damaged cells or organs with bined with electronic or mechanical dividing and developing and have the tem, adult stem cells can repair the
“material” from the patient’s own body. implants. ability to develop into specialised cells, damage in the organism. These are
tissues and organs. referred to as “multipotent” as they
only produce cells from an individual
Stem cells have great potential in medicine as they provide fresh cell material that can be used to There are different types of stem cells. organ or tissue. Foetal stem cells are
remedy diseases that have been difficult or impossible to treat up to now. Embryonic stem cells are cellular all- a mixture of embryonic and adult
Corneille Heymans Gerhard Domagk
28 1938 Regulation of breathing
1939 Discovery of the antibacterial
 29
effect of prontosil

stem cells that are no longer fully for transplantation. Progress in this eases, as the mouse genome and the fied animals are produced, there
adaptable, but grow faster and better area would greatly decrease the risk of human genome exhibit major similar- must be an ethical evaluation and
instead. In 2012, the stem cell stud- intolerance and rejection reactions. ities. Both the human and the mouse consideration of the stress for the
ies performed by the Japanese Shinya genome have now been fully decoded. parent animals and subsequent
Yamanaka and British John Gurdon Today, a variety of genetically modi- generations. This is irrespective of
were awarded the Nobel Prize. They Genome research fied mouse strains exist that can be whether the animals are produced
discovered how mature, differentiated used as model systems for studying by technical manipulation or solely
cells can be reprogrammed into stem Genome research investigates the ge- human diseases. by breeding a new line. Operations,
cells, which in turn can produce vari- netic make-up of living organisms. such as the transfer of egg cells to
ous types of tissue. Their insights into This involves not only the genetic code The German Animal Welfare Act de- surrogate mothers or cutting the
induced pluripotent stem cells (iPS – the sequence of nucleic-acid building mands that, before genetically modi- spermatic ducts in male animals, are
cells) were based on experiments with blocks in DNA – but, more important-
mice. ly, the function of the genes, as these The Californian lumpfish (Aplysia californica) is an important test model in the field of neurology
hold the key to the arrangement and due to its exceptionally large neurons and manageable nervous system. The Nobel Prize winner Eric
Animal experiments in stem cell re- structure of the body and to the inter- Kandel used its synapses to study learning at cellular level, among other things.
search pave the way for new therapeu- actions between different organs. To
tic approaches to currently incurable be able to analyse these interactions
diseases such as Parkinson’s, Alzhei- in a complex organism, it is neces-
mer’s and diabetes. In cancer therapy, sary to induce specific changes in the
insights into the differentiation pro- genetic material, i.e. the genome, by
cesses in cells have contributed to the means of animal experiments. Effects
understanding of the mechanisms on the “phenotype” of an animal – its
involved in the creation and division appearance, behaviour, organ func-
of cancerous cells. The medical appli- tion or blood count – enable conclu-
cation of cell and tissue replacement sions about the genetic basis for these
by stem cells has already been tested changes.
on animals. Adult stem cells from
the pancreas, liver and bone marrow Genome research uses both geneti-
could be successfully reprogrammed cally modified animals (transgenic
into insulin-producing cells and were animals) as well as animals exhibit-
able to alleviate type 1 diabetes symp- ing spontaneous changes to the ge-
toms in mice. The transplantation of nome (mutations) that are the result
muscle stem cells in mice not only of natural changes or produced by
led to the repair of damaged tissue in breeding. Genetic modification of flies,
mice but also stimulated new muscle round worms, zebrafish, mice, rats
growth. One long-term objective is to and even large animals such as pigs is
use human stem cells to culture com- now possible. The mouse is especially
plex cell structures or complete organs important in research on human dis-
Henrik Dam, Edward Doisy
30 1943  31
Discovery of vitamin K

performed under anaesthesia with from slight to severe. Embryonic different – if at all – from that of the son were awarded the Nobel Prize in
subsequent pain management and development can be so severely dis- wild type. Evidently the functional Medicine for their discoveries regard-
are associated with medium levels turbed that the embryos or foetuses impairment of a gene is compensat- ing signal transduction in the nervous
of stress in the individual animals. die before birth. However, experi- ed by other genetic, biochemical or system of mice, rats, rabbits, guinea
The degree of stress in the offspring ence has shown that the appearance physiological processes, so that devi­ pigs and marine gastropods. In 2013,
is often not predictable and can vary of transgenic animals is often hardly ations can only be detected upon James E. Rothman, Randy W. Schek-
more detailed analysis. man and Thomas C. Südhof were
Complex scientific questions such as brain processes can only be studied on the intact and living
awarded the Nobel Prize for their
organism. Recently, genome research with pigs discoveries of the transport processes
is also gaining in importance. It is within a nerve cell and their signifi-
now possible to specifically modify cance for the transmission of signals
the genome of an individual oocyte between nerve cells. They employed
and consequently breed animals that rats, hamsters and genetically modi-
can be used for studies on the genetic fied mice in their research. In 2014,
principles of diseases, for example in John O’Keefe and the married cou-
research on degenerative muscular ple Moser were awarded the Nobel
disorders. Another objective is to al- Prize in Medicine and Physiology for
ter the immune system of pigs so that their research on spatial orientation
they can produce replacement organs in mammals. They were able to iden-
for human use. tify specialised brain cells, the so-
called place and grid cells, responsi-
ble for spatial orientation, and could
Neuroscience verify their interaction. The network
of grid cells and their spatial organi-
Neuroscience investigates the struc- sation is similar to a 3D coordinate
ture and function of the peripheral system, and enables orientation and
and central nervous system. Their navigation in time and space. These
principal focus is the question how studies were performed using rats.
nerve cells communicate with each Further studies confirm that compa-
other and how they are connected, in rable structures of the biological ori-
order to gain a better understanding entation system exist in other species,
of the highly complex processing of such as mice, bats and primates, and
sensory information, the control and also in humans.
coordination of behaviour, and the
processes of thinking and feeling. Currently, studies on the function-
ing of the nervous system and the
In 2000, the researchers Eric Kan- brain are being intensively pursued.
del, Paul Greengard and Arvid Carls- The US is investing in large-scale re-
Joseph Erlanger, Herbert Gasser Alexander Fleming, Ernst Chain, Howard Florey Hermann Muller Gerty Cori, Carl Cori, Bernardo Houssay
32 1944 Research on the differential functions
1945 Discovery of penicillin
1946 Discovery of the mutagenic
1947 Research on carbohydrate
 33
of individual nerve fibres effects of X-rays metabolism

Hygiene is of utmost importance when dealing with animals. Animal keepers and scientists must
wear protective clothing when entering animal spaces to prevent the potential risk of infection to
the animals.

search projects such as the Brain Ac- disease and its concomitant move-
tivity Map Project (BRAIN initiative) ment disorders.
while Europe is spending billions on
brain research with the Human Brain Knowledge gained from animal ex-
Project. Only greater insight into the periments is also used in the devel-
basic functions of nerve cells will en- opment of prosthetic devices and the
able researchers to understand what treatment of paralysis. For example,
causes diseases of the nervous sys- using electrical stimulation of the
tem and to develop treatment meth- spinal nerves, non-human primates
ods for stroke, Alzheimer’s and Par- suffering from paralysis of their limbs
kinson’s disease, multiple sclerosis, due to spinal cord injury were able
epilepsy, depression, schizophrenia, again to move their hand and grasp
anxiety dis­orders and paraplegia. objects. Nerve conduction could be
partially restored in paraplegic rats
A substantial number of therapeutic by transplanting embryonic stem
approaches are based on knowledge cells into their spinal cord. However,
gained from animal experiments. the molecular and cellular processes
For example, stem cell transplanta- involved are not yet understood well
tions into the brain of mice, which enough to be applied to humans. In
were previously genetically modified the same vein, there are promising
or subjected to chemical substances initial approaches to using stem cell
producing pathologies similar to hu- therapy for the transplantation of
man diseases such as Parkinson’s specific stem cells into affected areas
disease, multiple sclerosis or stroke, of the brain.
led to improvements in the general
condition and the disappearance of
typical symptoms. Chip-based retina Veterinary research
implants providing basal vision to
the blind, or cochlear implants for The findings from animal experiments
the deaf, are based on scientific ex- are of use not only in human medi-
periments with chickens, rabbits, cats, cine, but also in the development of of cancer, diabetes, ulcers and blood Tumour therapy in small animals is
pigs and non-human primates. Deep new diagnostic and therapeutic proce- disorders. Dogs with a naturally oc- another example.
brain stimulation combines neu- dures in veterinary medicine. Certain curring blood clotting disorder, lead-
rosurgical and electrophysiological diseases occur both in animals as well ing to profuse and life-threatening A transfer of treatment methods is
approaches, which were mainly de- as humans. Among these are arterio- internal bleeding, can be treated for generally possible without difficulties,
veloped on the basis of non-human sclerosis and congenital deformities of haemophilia A on the basis of a gene as the methods practised in human
primate models. It is now used suc- the spine in rabbits, diseases of the vis- therapy developed for humans, which medicine were developed in animal
cessfully in patients with Parkinson’s ual system in cats, and specific forms stops their bleeding in the long term. experiments. However, veterinary
Paul Müller Walter Hess, Antonio Moniz Edward Kendall, Tadeus Reichstein, Philip Hench Max Theiler
34 1948 Discovery of the
1949 Research on the functional organisation
1950 Structure and function of adrenal hormones
1951 Vaccine against yellow fever
 35
insecticide DDT of the brain in the surgical treatment of psychosis

medicine likewise cannot dispense studies are usually designed such that Vaccination strategies for fatal dis- which are difficult to teach in the
with the use of experimental animals the target species, i.e. the potential eases such as leukosis, distemper and context of clinical routine, enable
in basic research and in the develop- patient, is the subject of the investi- bovine tuberculosis were successfully physicians to expand their skills for
ment of new treatment methods. The gation. developed on this basis. Vaccines and surgical procedures on humans and
veterinary medicines help to reduce to learn new techniques. The Ger-
Veterinary medicine was able to develop vaccination strategies against fatal diseases such as dis- livestock losses as a result of diseas- man Animal Welfare Act treats the
temper and leukosis by using test animals. es. Additionally, these medicines are handling of experimental animals
used in nature preservation projects as part of a training programme in
for the protection of endangered spe- the same way as animal experimen-
cies and especially to prevent the tation, i.e. as subject to application
spread of diseases. and approval.

Animal experiments in edu- The basic assumption of


cation, training and profes- transferability
sional development
The components of body cells and
Proper handling of experimental the biochemical mechanisms neces-
animals by researchers and animal sary for the processes of life are very
keepers needs to be learned. This similar across different animal spe-
includes the routine tasks of animal cies. Molecular genetics can dem-
keeping as well as blood sampling, onstrate that all organisms living
injections and surgical procedures. today have the same origin. They
Careful and comprehensive train- share genes which are responsible
ing of personnel should ensure that for body structure and which are
any suffering in animals is reduced modified during the course of evo-
to a minimum. This is also necessary lution, thus providing the material
from a scientific point of view. In or- basis for the sequence of living crea-
der to obtain reliable and reproduci- tures throughout the geological eras.
ble results, stress and pain symptoms These similarities even allow com-
must be minimised as much as pos- parisons of human genes and meta-
sible. bolic processes with those of bacteria,
fungi and yeasts.
In human medicine, especially in
the fields of surgery and anaesthesia, However, body functions are much
practical training with large animals more complex in higher animals and
is an important element of educa- man than in the lower organisms,
tion. Such practical training units, as body functions in higher animals
Selman Waksman Hans Krebs, Fritz Lipmann John Enders, Thomas Weller, Frederick Robbins Axel Theorell
36 1952 Discovery of streptomycin
1953 The citric acid cycle
1954 Discovery of growing the poliovirus in cell cultures
1955 The effect of
 37
oxidant enzymes

Examples of animals used in research.

are based on a multitude of special- are not used in subsequent clinical


ised cell types and organs. For exam- tests on humans due to undesirable
ple, an active substance may have side effects and safety risks, and are
the desired effect in the liver, but be Mouse, rat excluded from the development pro-
chemically modified by the liver cells Cancer research
cess. Animal experimentation thus
in such a way that the resulting com- Rabbits prevents the administration of po-
Metabolic disorders Development of vaccines
pound is toxic to the central nervous tentially harmful or life-threatening
system. This shows that the transfer Efficacy testing of drugs Efficacy testing of drugs substances to humans.
of reaction patterns from cell struc- Genome research
tures to the total organism can be ex- However, there is no such thing as
tremely difficult. For this reason, not absolute safety. The Thalidomide ca-
only studies at the cellular level are tastrophe in the 1960s made this
needed (using alternative methods, tragically clear. Prior to this event, the
see page 51ff.), but also always stud- potential of a drug to cause develop-
ies of the complete organism to check Dog
mental malformations was not inves-
both the efficacy and side effects of a tigated. It was only after the scandal,
Transplantation surgery
substance. Cattle, horse, pig
in 1978, that the German Drug Law
Osteosynthesis was tightened and the effect on em-
Emergency surgery Vaccine development
Animal experiments make it pos- bryonic development was added to
and isolation
sible to predict the desired as well Diabetes research the testing catalogue for drug safety
Veterinary research
as about 70% of the adverse effects Cardiovascular diseases and efficacy.
on humans. One example is acetyl- Osteoporosis research
salicylic acid (the active substance in The basic assumption of transferabil-
Veterinary research
the analgesic Aspirin®). It alleviates ity is also an important aspect in the
pain in both rats and humans, but evaluation of pain and sensitivity in
can increase bleeding in both spe- animals. The anatomical structure of
cies. Other examples are the effects the brain as well as the conduction
of building materials and of solvents, of pain stimuli and their perception
which have damaging effects on both Cat in the central nervous system are
rats and humans. Asbestos causes Heart surgery
similar in higher animals. This per-
lung cancer in rats and humans, and Non-human primates
mits analogies to be drawn regarding
Neurophysiological studies
plastic solvents cause liver cancer in pain sensitivity and possibly even the
Basic and applied research Development of hearing aids
both. From these experiences it can capacity for suffering. The transfer-
in neurobiology
be concluded that safety and efficacy Research on feline leukaemia ability of results from animal to hu-
Vaccine development
tests on animals can significantly re- Veterinary research mans thus also applies in the oppo-
duce the risk of new treatment meth- SIV/HIV research site direction. Drugs that have been
ods for humans. 36% of substances successfully used to treat humans can
tested in preclinical animal studies also be used for domestic animals.
André Cournand, Werner Forssmann, Dickinson Richards
1956 Development of cardiac catheterisation
39

Animal experimentation and protection


of animals: Ethical considerations

Development of the concept cruelty to animals and “vivisection”


(operations on living animals). As ex-
of animal protection in perimental research and consequently
Germany the number of animal experiments
increased within the same period, this
The idea that humans have a special re- inevitably led to conflict between sci-
sponsibility for animals in their care is ence and animal welfare. Even back
the result of the historical development then, people’s reasons for rejecting ani-
of the relationship between animals mal experimentation varied depending
and humans. Cultural, philosophical, on their scientific, religious or societal
social and official standards define the background.
framework for our attitudes towards
animals and their needs. The animal The first German Animal Welfare Act
welfare laws and regulations that are was passed in the 1930s and remained
in place today are an expression of this in force until after the Second World
development, which began in the 17th War. For the first time, it laid down
century. Since then, an anthropocen- regulations for working with labora-
tric view of animal protection has been tory animals. In the 1960s and 1970s,
advocated – with man at the centre. public discussion of the safety of farm
and laboratory animals was revived;
In the 18th and 19th centuries, influ- this encouraged the creation of new
ential members of a socially and politi- laws on animal protection. The Animal
cally active stratum of the population Welfare Act adopted in the Federal Re-
became active. They loathed all forms public of Germany in 1972 was based
of cruelty to animals and regarded this on ethical concepts of animal protec-
attitude as a sign of their level of edu- tion, and exploited scientific findings
cation. The focus of interest was not on species-specific and behaviourally
the animal, but concerns about the correct standards and the needs of the
brutalisation of individuals and of soci- animals as criteria for evaluation.
ety. In Germany, a variety of laws were
passed at first, and the Law on the Pre- Subsequent changes in the law in the
vention of Cruelty to Animals was only 1980s and 1990s were influenced by
first included in the German Criminal economic, scientific and political con-
Code in 1871. This legal harmonisation siderations. These changes increased
promoted animal protection as a social the emphasis on animals as fellow
goal and led to the formation of nu- creatures and strengthened regulation
merous societies for animal protection, of animal experiments. To enhance
with the main objective of preventing the protection of animals as living
Daniel Bovet Frank Burnet, Peter Medawar Georg von Békésy
40 1957 Development of substances which
1960 Discovery of acquired
1961 Discovery of the mechanical
 41
inhibit the action of biological amines immunological tolerance function of the inner ear

creatures in the legal system, ani- dealings with animals is that humans vant position here is the “biocentric” theology – Thomas Aquinas. The es-
mal protection was enshrined in the are vested with the basic moral right view, which assigns ethical value to sential tenet of Kant’s position is that
constitution of the Federal Republic to use animals for their own ends. all living organisms, including lower man alone has moral capacity, which
of Germany. In July 2002, the con- This right, however, is subject to animals and plants. Whilst the ex- results both in prerogatives and obli-
stitution was amended with Article limits where animals are significant- treme versions of these three posi- gations. Animal protection is thus ul-
20a, which reads: “Mindful also of its ly harmed by human actions or are tions are incompatible with one an- timately rooted in the self-respect of
responsibility toward future genera- killed without sufficient reason. In other, their more moderate forms are humans, which forbids acting cruelly.
tions, the state shall protect the natu- the established system of normative generally regarded as reconcilable.
ral foundations of life and animals by positions on animal ethics, this po-
legislation and, in accordance with sition is classified as “pathocentric”. According to the strong variant of an-
law and justice, by executive and ju- This means that a living organism’s thropocentrism, our treatment of an- Immanuel Kant (left) was a follower of anthro-
pocentrism – the belief that humans are the
dicial action, all within the framework ability to suffer entails an obligation imals should be assessed solely based
measure of all things but that they have a re-
of the constitutional order.” Ethical to protect it. On the other hand, a on human interests, sentiments and sponsibility to treat animals humanely. Accord-
treatment of animals has thus been position is defined as “anthropocen- feelings. This position has dominated ing to Arthur Schopenhauer (centre), animals
given an unusually high legal status. tric” if it categorically makes humans our culture’s philosophical outlook exhibit the same characteristics as humans.
This means they are capable of suffering and
“the measure of all things”, including for centuries. Its most prominent ad-
feeling. Albert Schweitzer (right) represented
Furthermore, the Third Amendment when it comes to the treatment and vocates were Immanuel Kant and – radical biocentrism, which extends an inherent
to the Animal Welfare Act was in- protection of animals. A third rele- representing leading Christian moral value to all living things.
troduced in July 2013, which trans-
poses into national law the Directive
2010/63/EU of the European Parlia-
ment and Council of 22 September
2010 on the protection of animals
used for scientific purposes. It ensures
a higher level of animal protection and
raises the minimum standards, taking
into consideration the latest scientific
findings and developments in keeping
with the Three Rs principle (Reduce,
Refine, Replace – see pp. 47ff.).

Ethical aspects of animal


experimentation and the
principle of solidarity
A predominant view within the cur-
rent ethical discussion on human
John Eccles, Alan Hodgkin, Andrew Huxley Konrad Bloch, Feodor Lynen
42 1963 1964  43
The initiation of the action potential in neurons Fatty acid metabolism and
the regulation of cholesterol

However, anthropocentrism was sub- Biocentrismin in turn extends this in- An ethical system – such as a patho- Even though patho-inclusive ethics
ject to a far-reaching and now general- trinsic ethical value to all living beings, centric one – that is premised on the ascribe particular rights to animals,
ly accepted critique from a pathocen- including lower animals and plants. position that sentient animals have a this system is not premised on the as-
tric perspective by Jeremy Bentham The most prominent example of this moral status alongside humans, occu- sumption that animals possess these
and Arthur Schopenhauer. According view is Albert Schweitzer’s The Ethics pies a compromise position between rights inherently and independently
to Bentham, the point is not whether of Reverence for Life. Many supporters the two extremes mentioned above. of their bestowal by man. Rather, the
animals think or speak like humans, of this view even go so far as to ascribe This compromise ascribes to sentient undisputed position amongst animal
but rather whether they can suffer an equally strong right to life and de- animals an intermediate moral status ethicists of epistemic anthropocen-
like humans. All sentient beings must velopment to all non-human living that is lower than that of humans, but trism – not to be confused with the
be ascribed with intrinsic value. beings. much higher than that of non-sen- normative anthropocentrism referred
tient animals and plants. to above – rightly acknowledges that
only humans are capable of estab-
Edward Hicks: The Peaceable Kingdom (1846/47). lishing, understanding and following
Patho-inclusive rather than patho- moral obligations. Even if animals
centric: What’s the difference? are the subject of human obligation,
they depend on the benevolence and
A pathocentric animal ethics postu- the efforts of people to interpret their
lates moral obligations towards ani- needs. The obligation not to inflict
mals and places the avoidance of suf- suffering on humans and to actively
fering at its core. However, it would relieve it is recognised in all ethical
be incorrect to assert that the avoid- systems. The principal argument for
ance of suffering in its entirety, and expanding these obligations beyond
therefore also of human suffering, the sphere of humans is that it is not
is to be regarded as the most impor- evident why corresponding obliga-
tant of all standards. Overall, this ap- tions should not in principle also ap-
proach might more appropriately be ply to sentient animals.
classified as a “patho-inclusive” eth-
ics: It is not only reconcilable with The patho-inclusive position is also
valuing human interests over those the basis for the German Animal Wel-
of sentient animals, but also with the fare Act. In contrast with older ver-
position that other human interests, sions, which only afforded animals the
such as life and health, knowledge amount of protection called for to pre-
gain, and pleasure, may justify caus- vent public nuisances or the potential
ing distress to animals. Moreover, brutalisation of human beings, the cur-
this view does not preclude the kill- rent version protects animals for their
ing of animals, but does demand that own sake. The infliction of suffering is
the killing should not cause fear or only acceptable where the associated
suffering, if possible. action (such as an animal experiment)
Peyton Rous, Charles Huggins Haldan Hartline, George Wald, Ragnar Granit Robert Holley, Marshall Nirenberg, Gobind Khorana
44 1966 Discoveries on the cause
1967 Physiology of vision
1968 Interpreting the genetic code
 45
and treatment of tumours and its function in protein synthesis

After mice, rats are the most commonly used laboratory animals.

has the potential to protect, secure or scientific, therapeutic or other signifi-


realise potential higher values for hu- cance of the experimental objective in
mans and animals, whilst also being accordance with the Three Rs princi-
indispensable to that end. This view ple (see page 47 ff.). The criterion of
requires two forms of complex assess- suffering capacity thus imposes limits
ment and balancing to justify animal on the experiments that may be per-
experimentation: a weighing of moral formed on sentient animals, although
goods, and the determination of indis- it does not imply any categorical rejec-
pensability. Both assessments are diffi- tion of stressful animal experiments.
cult, but not arbitrary.
Moreover, it may be presumed that
Human values such as life and health only some of the animal experiments
generally carry a stronger weight than carried out are stressful. Keeping cog-
the avoidance of suffering for animals. nitively low-developed animals in
Moreover, there is also less certainty in laboratories, for example, need not be
relation to animal suffering than there classified as causing suffering in gen-
is for human suffering. Since animals eral. In fact, laboratory animals often
cannot help us to interpret their feel- live longer and are healthier com-
ings and therefore depend on human pared to those living in the wild. Fur-
empathy, experience and knowledge thermore, many laboratory animals
to determine their welfare, there is a are kept in control groups without
considerable likelihood of error asso- being subject to procedures, and some
ciated with assessing whether an ani- are killed for their organs, without Transferability from an tion of animals used for scientific pur-
mal suffers and how much. Moreover, having been previously involved in an poses has three aims:
individual capacity for suffering will experiment. In addition, there is also
ethical-legal viewpoint
probably differ significantly between the category of “final animal experi- In the public discussion on the ethical ► to significantly improve the welfare
animals – as it does between humans. ments”. Here, the animals are drugged evaluation of animal experiments, the of animals used in scientific experi-
Where there is great uncertainty re- prior to the start of the experiment direct transferability of findings to hu- ments,
garding animal suffering, the “proven” and then killed under anaesthesia at mans is often claimed to be a measure
claims of humans take priority from the end of the experiment in order to of legitimacy. However, this claim un- ►
to ensure fair competition within
the standpoint of various moral and spare them painful experiences. derestimates the complexity of trans- the EU and
ethical approaches. ferability. During animal experiments,
Patho-inclusive ethics has no funda- animal life processes are investigated ►
to strengthen research within the
The “indispensability” of inflicting suf- mental objection against such experi- that can only be indirectly extrapolat- EU.
fering means that no alternative meth- ments, provided they are associated ed to humans. This is also expressed in
ods are available, that animal experi- with advances in biological or medical legislation. Directive 2010/63/EU of The transferability of the results from
ments are optimised and the suffering knowledge that are expected to ben- the European Parliament and Council animal experiments to humans is not
of animals is minimised relative to the efit humans. of 22 September 2010 on the protec- stipulated in the directive. Instead, it
Bernard Katz, Ulf von Euler, Julius Axelrod Earl Sutherland Rodney Porter, Gerald Edelman
46 1970 Synaptic storage, release and inactivation
1971 Discoveries concerning the
1972 Chemical structure of antibodies
 47
of neurotransmitters mechanisms of the action of hormones

contains intentions and measures to ple are alike and each person is their obligations will remain the theme of sary minimum. The Three Rs principle,
improve animal welfare and to hon- own ideal model. Human-oriented ethical discussions. From the stand- devised by W. Russell and R. Burch in
our the Three Rs principle. The di- research is therefore desirable, but it point posited here, there will never 1959, can be taken as the guideline
rective specifies the purposes of the is insufficient. be a general answer to the question for animal experiments. The Three Rs
procedures for which animals can whether an animal experiment is jus- stand for
be used. These purposes are not re- tified – each individual case requires
stricted to procedures on live animals The conflict between the solidarity its own answer. ► refinement,
with results that are transferable to principle and animal welfare
humans. The directive does require ► reduction and
an ethical evaluation that weighs the Complete prohibition of experimen- The Three Rs principle
expected harm caused to the animals tal animal research would also con- ► replacement.
against the expected benefits. But flict with another valid fundamental Although animal experimentation
it leaves open how these benefits moral standard, the solidarity princi- cannot be completely avoided in re- The aim of the principle is to avoid
are ultimately defined or how soon ple. This is the principle of providing search, there is a general consensus animal experiments where possible,
they should materialise: “... to pro- the best possible support to the needy, that it must be restricted to the neces- to reduce their number and to limit
tect human and animal health and the weak and the sick. The solidarity
the environment.” This unspecific principle is not only one of the many
formulation takes into account the preconditions for life in human com- Three Rs Principle for Alternative Methods
experience that it often takes years munities; it is a hallmark of human www.bf3r.de/en/home © German Centre for the Protection of Test Animals (Bf3R), 2015
before discoveries from animal ex- beings to be morally responsible and
periments translate into benefits for capable of solidarity.
human and animal health. Requir- R eplace
(by
Testing
without animals:
Cells

ing immediate benefits for humans People who perform animal experi- alternative
methods)
Impact of chemical
substances under
is a moral-ethical demand that can ments always experience conflict be- the influence of
light on skin health
hardly ever be fulfilled. Just like hu- tween two obligations. The first of

For example by using cells and/or skin models


Test substance

Alternative methods
mans, animals are extremely com- these is positive: the obligation to use ± UV light

Experiments
plex organisms, but they do differ one’s knowledge and abilities to re-
from humans, despite a few funda- duce human and animal suffering. In
mental similarities. These differences contrast, the negative obligation is not R educe
(the number
of test animals) Damage of
are the result of various evolutionary to inflict avoidable suffering on other cells: yes/no?

mechanisms which in the past have creatures. It is human nature to find


had an effect on highly complex sys- it difficult to reach a decision if this Non-animal test
Reconstructed
human skin models Test substance
Skin irritation:
yes/no?
tems such as animals and humans, means violating one of these obliga- for skin irritation

and continue to have an effect today tions in order to meet another. As


via multifactorial mechanisms such long as it is scientifically impossible R efine
(minimise
pain and suffering
as genetic preposition, whilst also to unravel complex causal activity re- of the test
animals)
being subject to epigenetic and en- lationships in living animals without
vironmental influences. No two peo- animal research, this conflict between
Konrad Lorenz, Nikolaas Tinbergen, Karl von Frisch Albert Claude, George Palade, Christian de Duve Renato Dulbecco, Howard Temin, David Baltimore Carleton Gajdusek, Baruch Blumberg
48 1973 Organisation of social behavioural patterns
1974 Structural and functional
1975 Discoveries in the area of interrelationships between
1976 Discoveries concerning new mechanisms
 49
organisation of cells tumour viruses and the genetic material of a cell for the origin and dissemination of infectious diseases

the harm caused to animals during Researchers are challenged time and Refinement fering based on their respective level
the experiments to the necessary min- again to optimise their methods and of neuronal development. Particular-
imum. The consistent and responsible use objective parameters – such as the The refinement of animal experi- ly important to the gradation of ethi-
implementation of the Three Rs prin- animals’ behaviour – to estimate the ments has the objective of minimis- cally grounded animal protection is
ciple accommodates ethical concerns degree of harm caused. This requires ing the adverse effects of research the animal’s capacity for self-percep-
against the use of animals, and also both personal sensitivity and good procedures on animals. An animal’s tion. The strongest protection should
improves the quality of the test results. training. capacity for suffering is central to this therefore be given to animals pre-
assessment. The human obligation sumed to have the greatest capacity
to minimise stressful animal experi- for experience due to their advanced
Non-human primates, such as rhesus monkeys, behave similarly to humans. For this reason, the ments must be guided by the extent stage of development, such as pri-
investigation of complex cognitive functions is only possible in these species. to which animals are capable of suf- mates. However, it must also be con-
sidered that less developed animals
occasionally react to an experimental
setup with greater stress than those
able to adapt to the stress through
training.

By carefully selecting the animal


models, alleviating pain using anal-
gesia and anaesthesia, improving the
technology used in measurement pro-
cedures and developing non-invasive
research methods, it has been possi-
ble to make great progress in the re-
finement of animal experiments. Im-
proved animal husbandry conditions,
for example thanks to species-specific
enrichment of the environment, also
help to improve laboratory animals’
welfare and give them a greater qual-
ity of life. As an example, rodents are
provided with nesting materials that
help support their thermoregulation,
or paper rolls that give them the op-
tion to retreat. These improvements
are also in the interest of research as
they improve the reproducibility of
experimental results.
Roger Guillemin, Andrew Schally, Rosalyn Yalow Godfrey Hounsfield, Allan Cormack Baruj Benacerraf, Jean Dausset, George Snell
50 1977 Hypothalamic hormones
1979 Development of computer tomography
1980 Discovery of specific cellular surface structures
 51
controlling immunological reactions

Alternatives to animal testing are encouraged in Germany.

Reduction portance and are widely used, par-


ticularly to elucidate cellular process-
Statistical and methodological im- es or the effect of medications on cell
provements help to reduce the num- metabolism. Significant methodolog-
ber of laboratory animals. In addition ical progress has been made in recent
to carefully selecting suitable animal decades in working with in vitro sys-
models and determining the absolute- tems. Especially in drug testing and
ly necessary number of test animals, the development of pharmacological
this entails the consistent application substances, they have helped to re-
of statistical methods. Even centrally duce the use of laboratory animals.
registering and recording results from However, they cannot completely re-
animal experiments can reduce the place animal experiments as the com-
need for them. plexity of the entire organism – i.e.
the interaction between organs and
tissues – cannot be fully reproduced
Replacement in these isolated, artificial systems.
Furthermore, producing and growing
Replacement seeks to substitute ani- organ and cell cultures requires the
mal experiments with alternative killing of animals.
methods as much as possible, or to
avoid them completely. If the research Another method for avoiding experi-
question permits, simple organisms ments on live animals comes from
such as bacteria or invertebrates, cell regenerative medicine and is known
and tissue cultures, computer models, as “body on a chip”. This method was
or other alternative methods will be developed from tissue engineering
used. or bioprinting, whereby replacement
organs for humans are grown from
human tissue and created using a 3D
Alternatives to animal printer. These mini-organs are placed
experimentation on a microchip and supported by an
artificial maintenance system. Sen-
Cell lines that have been harvested sors on the microchip measure certain
from animal or human tissue are of- parameters, such as organ tempera-
ten used and then bred further in a ture and oxygen content, and record
laboratory culture. These experimen- changes in the system. The “body on
tal methods outside the organism – a chip” method is used for testing the
known as “in vitro methods” (in vitro toxicity or pharmacological properties
= in the test tube) – are of major im- of biological and chemical substances.
Roger Sperry, David Hubel, Torsten Wiesel Bengt Samuelsson, John Vane, Sune Bergstrom Niels Jerne, Georges Köhler, César Milstein
52 1981 Visual information processing
1982 Discovery of prostaglandins
1984 Theories concerning the specific development
 53
of the brain and control of the immune system

The declared aim of research is to reduce the number of laboratory animals and their suffering.

“In silico methods” (in silico = on a where possible, legitimise alternatives


computer) are also becoming increas- to animal experimentation. It is an in-
ingly important as alternatives to ani- formation centre for alternative meth-
mal experimentation. These comput- ods, and also researches and validates
er-controlled analysis and simulation methods not involving animal experi-
techniques are used for assessing risk mentation in order to promote them.
when researching tolerance to sub- The validation is necessary to obtain
stances or theoretically modelling life inclusion in the international testing
processes, among other purposes. As a guidelines for safety toxicology.
result, experimental data in neurobi-
ology is increasingly being entered in At the European level, this work is
computer models to portray and pre- the responsibility of the European
dict the functions of the central nerv- Centre for the Validation of Alter-
ous system. Computer simulation is native Methods (EURL ECVAM) in
also used in higher education to visu- Rome. The EURL ECVAM Search Guide:
alise complex biological relationships. Good Search Practice on Animal Alterna-
Instructional videos on animal ex- tives also contains numerous informa-
perimentation serve as teaching aids tion sources on alternative methods
to prepare learners for the work with and is designed for employees of ap-
living animals and promote a respon- proval authorities, animal welfare of-
sible approach. ficers and researchers working in ani-
mal experimentation. Furthermore,
The German Centre for the Protection the annex to the European Directive
of Laboratory Animals (Bf3R) is part EC 761/2009 and the guidelines is- ► skin burns EU directive on the protection of ani-
of the Federal Institute for Risk Assess- sued by the Organisation for Eco- mals used for scientific purposes with
ment in Berlin and coordinates efforts nomic Cooperation and Development ► skin irritations recommendations for work with ex-
to implement and promote the Three (OECD) list all officially recognised perimental animals. In the paper, the
Rs principle across the country. To this alternative methods. Within Europe, ► skin absorption ESF calls for recognition of the Three
end, the Bf3R is divided into several the following areas no longer require Rs principle and for targeted efforts
areas of competence that not only as- animal testing: ► mutagenic properties to reduce and improve animal ex-
sume advisory roles but also conduct periments. The Basel Declaration So-
research on refinement in animal ex- ► acute toxicity ► properties with hormonal effects. ciety (Basel Declaration, see below),
perimentation and the development founded in 2011, and its members, as
of alternative methods. One of these ► eye irritations The Three Rs principle is already well as the Forum on Animal Experi-
areas is the Centre for Documentation widely supported by scientific policy ments in Research, have undertaken
and Evaluation of Alternative Meth- ► genotoxicity in mammalian cells initiatives. As a result, the European to implement the Three Rs principle
ods to Animal Experiments (ZEBET). Science Foundation (ESF) issued a and other ethical principles wher-
Its mission is to record, evaluate and, ► acute phototoxicity position paper in 2011 regarding the ever animals are used for research
Michael Brown, Joseph Goldstein Rita Levi-Montalcini, Stanley Cohen Susumu Tonegawa James Black, Gertrude Elion, George Hitchings
54 1985 Discoveries on the regulation
1986 Isolation and characterisation of the nerve
1987 Discovery of the genetic mechanism
1988 Discoveries of important biochemical
 55
of cholesterol metabolism growth factor and epidermal growth factor that produces antibody diversity principles of pharmaceutical therapy

purposes. The forum’s statements on with the aim of reducing the number national and state level. Outstanding body possesses more than 200 dif-
refinement and on stress assessment of laboratory animals and replacing progress is rewarded with research ferent cell types whose interactions
are publicly available. mammals with less developed spe- prizes, such as the DFG’s Ursula M. are coordinated in organs and tissue
cies. This includes in vitro tests for Händel Animal Welfare Prize. structures. To study this complexity
The Association of Research-Based skin irritation or tests for mutagenic is an important part of biological re-
Pharmaceutical Companies (VfA) in properties of active ingredients using search, and this can only be done on
Germany and its member companies fish embryos, which otherwise would Limitations to alternative an intact organism. Even if a drug ap-
also implement the Three Rs principle have been performed on rats and methods pears to be useful during its develop-
rabbits. The methodological devel- ment in cell culture, it may turn out
Active ingredients can be tested on zebrafish
opment for implementing the Three In spite of favourable aspects, these to be inactive or even toxic in other
embryos, thereby reducing the number of labo- Rs principle in research is also sup- alternative methods have a severe cell types, or lead to the formation
ratory animals. ported by funding programmes at the disadvantage. The human or animal of breakdown products in the body,
causing damage in other organs.
Conversely, a substance may be inac-
tive in cell culture but effective in an
intact organism. For example, with-
out using animals, the synthetic an-
tibiotic Prontosil® would never have
been discovered in the 1930s. While
Prontosil® showed no effect in the
cell culture, it was proven that it has
very strong antibacterial properties in
a living organism. Gerhard Domagk
was awarded the Nobel Prize for this
discovery in 1939.

In case of the chronic infectious dis-


ease leprosy, it has so far not been
possible to cultivate the disease-trig-
gering bacterium Mycobacterium lep-
ra in a laboratory. It is assumed that
the high ambient temperature in cell
cultures limits growth. This means
that it is not possible to research this
disease in cell cultures. However, the
lower body temperature of immuno-
deficient mice and armadillos favours
bacteria growth. For this reason, re-
Michael Bishop, Harold Varmus Joseph Murray, Donnall Thomas Erwin Neher, Bert Sakmann Edmond Fischer, Edwin Krebs
56 1989 Discovery of the cellular origin of
1990 Organ transplant techniques
1991 Development of the patch clamp technique
1992 Discovery of mechanism controlling
 57
potentially carcinogenic retroviruses in humans for the measurement of individual ion channels metabolic processes in organisms

On the basis of the Basel Declaration, research is committed to greater transparency and communica-
tion when it comes to animal experimentation.

search into leprosy and possible ther- standards when handling laboratory
apeutic approaches is solely carried animals. Across philosophical views,
out on living animals. the signatories hold that animals
deserve respect for their own sake
Both in basic research and in appli- and should be kept in a species-ap-
cation-oriented research, alternative propriate fashion. Not only do they
methods and animal experiments explicitly recognise the Three Rs
are used in a complimentary manner. principle, but they also call for its
While individual molecular and cel- on-going further development, and
lular aspects of life processes are re- for quick and effective implementa-
searched in vitro or in silico as much tion of such enhancements. To this
as possible, scientific work on ani- end, the basic impetus behind the
mals is irreplaceable in order to fur- declaration is regularly substantiated
ther our understanding of complex and updated on the Basel Declara-
relationships within the entire or- tion Society’s website (www.basel-
ganism. By carefully considering and declaration.org).
selecting the most suitable methods,
we have the chance to significantly To ensure that the commitments of
reduce the number of test animals the declaration do not remain empty
and the stress caused to them. promises, the signatories have agreed
to greater transparency and commu-
nication on the purpose and execu- to open their laboratories to interest- gress – with a view to reducing ani-
The Basel Declaration tion of their animal experiments, and ed journalists. mal experiments and protecting the
thereby hope to build trust among animals used.
The Basel Declaration, adopted in the public and decision-makers. In The signatories of the Basel Decla-
2010, follows the patho-inclusive this spirit, they express their willing- ration criticise the fact that many The limits of dialogue are reached
approach described above (see pp. ness to discuss the sense and purpose human- and veterinary-medicine where violence against researchers or
40ff.), which does not prohibit ex- of animal experimentation with the benefits from experimental animal research facilities is being perpetrat-
perimental animal research in princi- public – including critics of experi- research are leveraged tacitly, while ed or encouraged. Regardless of such
ple, but seeks to reduce it and make mental animal research. The goals this research is at the same time excesses, however, the signatories
it as gentle as possible on the animals. specified on the Basel Declaration constantly being discredited. In this continue see a solid basis for justify-
In line with the Helsinki Declaration Society’s website make it clear that regard, they call on the self-critical ing experimental animal research in
on Ethical Principles for Medical Re- this dialogue must not be a one-way public to be more honest and coher- a factual and communicative manner
search Involving Human Subjects street, but rather a mutual exchange. ent in its attitude and arguments in according to the patho-inclusive ap-
(1964), over 2,500 researchers, re- The researchers and their institutions order to foster mutual dialogue. At proach. This task is based on the ethos
search institutes and organisations are therefore called upon to be pro- the same time, they also signal their of science, which sees itself as part of
have signed the Basel Declaration so active and willing to engage in these willingness to question themselves society and is therefore prepared to
far, and are committed to upholding discussions, and always be prepared critically and to make effective pro- be accountable for its actions.
Richard Roberts, Phillip Sharp
1993 Identification of the discontinuous structure
59
of some genetic material in cell organisms

Animal experimentation in Germany:


From proposal to implementation

§
European regulations on The treaty law for the European Un-
animal experimentation ion (EU) also contains Community
competence for animal welfare, un-
As part of the European Union (EU), der the aspect of environmental pro-
Germany is bound by EU legislation. tection (Article 191 TFEU). As part of
This includes the legal framework for the Treaty of Amsterdam of 2 October
carrying out procedures on animals. 1997, the Protocol on Animal Welfare
Regulations on animal experimen- was adopted, which is a binding part
tation were harmonised in 2010 by of the Community’s primary legisla-
the adoption of a directive for all EU tion. It expresses the wish to ensure
members (2010/63/EU). The EU’s ani- that animal protection is improved
mal welfare standards are some of the and that the welfare of animals, as
strictest in the world. sentient creatures, is considered.

Article 1(a) of the Statues of the Coun- The EU also ties the allocation of re-
cil of Europe, dated 5 May 1949, states: search funds to qualitatively high
“The aim of the Council of Europe is standards for animal experiments. The
to achieve a greater unity between its same is expected of Member States
members for the purpose of safeguard- when they award research funding.
ing and realising the ideals and princi- Accordingly, the approach to animal
ples which are their common heritage experimentation is a result of the EU’s
and facilitating their economic and so- authority to standardise legislation.
cial progress.” The protection of the en- This is the basis on which Directive
vironment, including the protection of 2010/63/EU of the European Parlia-
animals, is part of the Council’s mission. ment and of the Council of 22 Septem-
Against this background, the European ber 2010 on the protection of animals
Convention for the Protection of Ver- used for scientific purposes was passed.
tebrate Animals Used for Experimen- Germany implemented this directive
tal and Other Scientific Purposes was on 4 July 2013 with an amendment to
passed on 18 March 1986. As a multi- the Animal Welfare Act.
lateral international treaty, the Conven-
tion requires ratification. With the act
of assent of 11 December 1990 (BGBl. Animal experiments subject
1991 II, p. 740), this agreement became to authorisation
binding for Germany. The German Ani-
mal Welfare Act corresponds with these Animal experiments may only be car-
Council of Europe guidelines in the area ried out if they have been approved
of animal experimentation. by the competent authorities. This is
Alfred Gilman, Martin Rodbell Edward Lewis, Christiane Nüsslein-Volhard, Eric Wieschaus Peter Doherty, Rolf Zinkernagel Stanley Prusiner
60 1994 Discovery of cell communication and the
1995 Research on the genetic control
1996 Discovery concerning how the immune
1997 Discovery and characterisation of prions
 61
discovery of G-proteins in particular of early embryonic development system identifies virus-infected cells

comparable to a building permit or order.” The addition of “and animals” new knowledge is the legally required ► to promote the welfare and improve
a restaurant licence. Animal experi- makes it clear that the Animal Wel- good reason for conducting research the treatment of farm animals
ments are thus subject to a preventive fare Act can constitutionally restrict on animals.
prohibition. This means that they are freedom of research. ► for conservation purposes
prohibited in principle and permitted The EU directive goes beyond this
only in individual cases if the legal However, this does not change the interpretation and defines any pro- ► to protect the environment in the
requirements are met. Therefore, for factual or legal character of the cur- cedure in which animals are used interest of the health or welfare of
every animal experiment application rent regulations. As animal protec- in science as a project subject to people and animals
received, the approval authorities tion is a national goal in the context authorisation. This definition has
check whether the comprehensive le- of the constitutional order, it is an been adopted in the German Animal ► to test the quality, effectiveness and
gal requirements are met and whether exclusive duty of the legislature to Welfare Act. As a consequence, the safety of drugs, foodstuffs, pesti-
the necessity of the procedures is doc- reconcile freedom of research and number of approval applications for cides, chemicals or other hazardous
umented and justified. ethical animal protection. With the animal experiments in Germany rose substances
Animal Welfare Act and the regula- significantly.
The last stipulation in particular tions, the legislature has already done ► for forensic examinations
points to the unresolvable conflict this successfully. Seeking new findings may be the driv-
with a fundamental right that is re- ing force behind research, but is not ►
for education, training and profes-
stricted by the preventive prohibi- reason enough by itself to approve an sional development.
tion: the freedom of science guaran- Legal basis animal experiment. The Animal Wel-
teed in the constitution. Interferences fare Act distinguishes between Animal experiments are absolutely
with this right require special justifi- As animal experiments require ap- unlawful, i.e. always prohibited, if
cation according to the system of le- proval, it must be clear what an ani- ► lawful (essential) research purposes, they are related to the development
gal protection of fundamental rights. mal experiment is. The definition of and testing of weapons, munitions
For fundamental rights – such as the animal experimentation is based on ►
absolutely unlawful (prohibited) and related equipment.
freedom of science – which are not the purpose of the law as laid down in and
subject to legislation, intervention § 1 of the Animal Welfare Act: accord- Animal experiments are unlawful and
by law is only permitted for the sake ing to it, no one may inflict pain, suf- ► principally unlawful (prohibited in prohibited in principle (but with the
of constitutionally protected rights. fering or damage on an animal with- principle) purposes. possibility of specific exceptions) if
Since July 2002, this constitutional out good reason. they are related to the development
justification has been supplied by Ar- Animal experiments are lawful if they of tobacco products, detergents or cos-
ticle 20a of the constitution: “Mind- Any investigation or operation on an are essential for one of the following metics.
ful also of its responsibility toward animal that could result in pain, suf- purposes, for example:
future generations, the state shall fering or damage is deemed to be ani-
protect the natural foundations of life mal experimentation and therefore ► in basic research What is the legal definition of
and animals by legislation and, in ac- requires approval. In research, animal “essential”?
cordance with law and justice, by ex- tests are only justified if they are the ►
to prevent, recognise or treat ill-
ecutive and judicial action, all within only way in which new knowledge nesses and to recognise physiological Researchers are expected to be in-
the framework of the constitutional can be gained. As a result, seeking conditions in humans and animals formed about the state of research
Robert Furchgott, Louis Ignarro, Ferid Murad Günter Blobel
62 1998 Insights into nitrogen monoxide as a secondary messenger
1999 Discovery of signal peptides
 63
and its role in the cardiovascular system

when planning their experiment and Essentiality must not only be verified the experiment against the scientific cessfully complete the project are
to consider whether their planned to determine the lawfulness of the an- knowledge gain. This is a difficult in place. The procedure consists of a
project can lead to new knowledge. imal experiment (“whether”), but also decision in specific cases, since the review on three levels, which deter-
An experiment is only “essential” if for the specific procedure (“how”). benefit of findings in basic research, mines whether or not applicants will
there is no equally valid alternative, The Three Rs principle applies to both for example, cannot be known in be granted permission.
given the intended purpose. On the (see pp. 47ff.). advance, and the suffering caused
basis of available scientific knowledge, to laboratory animals is difficult to 1. P
roject-related: The project must
it must accordingly be considered quantify. be scientifically justified, and its es-
whether there is any other procedure What is the legal definition of sentiality and ethical defensibility
that eliminates the need for the ani- “ethically justifiable”? In certain areas, however, animal must be demonstrated. In addition,
mal experiment. All accepted results experiments are required by law. the desired experimental result
must be considered, including minor- The question of ethical justifiabil- This includes the Drug Law, the Or- must not be already available from
ity opinions, if they are of adequate ity is concerned with weighing the dinance on Hazardous Substances, other sources. The appropriate au-
scientific quality. stress inflicted on the animal during the Ordinance on Pesticides, and en- thorities (such as ministries or state
vironmental legislation. In these cas- government offices) are responsi-
es, the question whether an animal ble for evaluation and reviewing
Since 2013, cosmetic products that were developed using animal experiments can no longer be sold experiment is ethically defensible the plausibility of the application.
in the EU.
is not subject to an approval proce- In their decision, authorities may
dure. It has already been answered not substitute the applicants’ sci-
by the legislature on behalf of soci- entifically plausible description of
ety – to prevent health risks and to the value of the experiment with
protect people and the environment. their own views.
It goes without saying that the le-
gal requirement to minimise stress 2. P
 erson-related: Principal inves-
caused to the animals also applies in tigators and their deputies must
this area. possess the necessary professional
qualifications and be personally re-
liable. This implies that they must
Approval procedures not have violated the Animal Wel-
fare Act in the past.
Before an animal experiment can be
performed, it must be reported to 3. F
 acility-related: The structural and
the responsible authorities and ap- personnel requirements for the
proved by them. In the application, conduct of the animal experiment
the planned research project must be must be ensured. These include
justified scientifically and it must be qualified animal keepers, suitable
proven that the personnel and spa- spaces for keeping animals, and
cial/technical prerequisites to suc- the designation of an animal wel-
Eric Kandel, Paul Greengard, Arvid Carlsson Leland Hartwell, Timothy Hunt, Paul Nurse John Sulston, Robert Horvitz, Sydney Brenner Peter Mansfield, Paul Lauterbur
64 2000 2001 2002 2003  65
Discoveries concerning the transmission Discovery of important regulators Research in the area of genetic regulation Discoveries in connection with
of signals in the nervous system in the cell division process of organ development and programmed cell death magnetic resonance imaging

Wild animals, such as these field hamsters, are particularly protected – research using these animals
is subject to strict preconditions.

fare officer. When it comes to ani- tions of the planned experiments


mal husbandry, care must be taken should be chosen. Mice and rats
that laboratory animals are kept in are the preferred laboratory ani-
a manner that is suitable for their mals as they tolerate being kept in
species and needs, and that their cages and reproduce quickly.
medical care is ensured.
► Laboratory animals must be bred
If all conditions are met, the approval specifically for experimental pur-
must be granted. The approval is for poses to make comparability of re-
a limited time period and may be sub- sults possible. This limitation does
ject to conditions. In the event of ex- not apply to farm animals. If other
periments that cause severe stress or animals are required for a project,
experiments using primates, the au- this must be expressly justified –
thorities will demand a retrospective this particularly applies to wild
evaluation following the conclusion animals and protected species.
of the project. In case of violations,
financial penalties of up to 25,000 ►
Primates are under special protec-
euros or prison sentences may be im- tion. Their use is strictly limited,
posed in justified cases. Bans on ex- and keeping them is subject to par-
perimentation or on keeping animals ticularly high technical and person-
are also possible. nel requirements.

► Painful interventions, such as op-


Conducting animal erations, may only be performed
experiments under anaesthesia. If pain is an-
ticipated once the anaesthetic has
The guiding principle of essentiality worn off, additional pain-relieving
also affects the performance of the measures must be implemented.
experiments: The number of animals In general, it should be ensured
used and the pain, suffering and dam- that pain and suffering are kept to
age caused to these animals must be a minimum by implementing such
limited to what is strictly essential. measures, which must be taken ► The use of great apes, as well as car- authorities can only provisionally
The Three Rs principle applies here as into consideration when designing rying out experiments involving approve this kind of project. Fur-
well (see pp. 47ff.). The following ap- the experiment. long-lasting, severe pain that can- thermore, the responsible Federal
plies as a matter of principle: not be minimised, is fundamentally Ministry of Food and Agriculture
►
Highly stressful interventions may prohibited. If such experiment are (BMEL) must be informed and the
►
Where possible, the species that not be performed on vertebrates absolutely essential, they must be decision must be justified. The min-
will suffer least under the condi- more than once. approved by EU authorities. Local istry will present such cases to the
Richard Axel, Linda Buck Barry Marshall, Robin Warren Andrew Fire, Craig Mello Mario Capecchi, Martin Evans, Oliver Smithies
66 2004 Research on odour receptors and the
2005 Discovery of Helicobacter pylori bacteria and
2006 Discovery of RNA interference
2007 Research on the knockout mouse
 67
organisation of the olfactory system their role in stomach ulcers and stomach cancer

Beagles are robust, docile and well-balanced – this is why they are the most commonly used breed
of dog for research purposes. All persons who work with animals in research must be competent and
trained, and must participate in continuing education – this is prescribed by law.

the case of wild animals – be re- tween different universities. There


leased into the wild. A prerequisite are no established training plans that
for this is that they are transferred are legally binding across all federal
to a suitable type of shelter or habi- states. Students are generally pro-
tat. In doing so, it must be ensured vided with the necessary training
that the animals can become accus- during advanced practical courses
tomed to the new situation and that and lectures at the university or in
they do not pose any danger. courses presented by scientific soci-
eties. Training may follow the rec-
ommendations of the Council of Eu-
Who is allowed to perform animal rope for the education, training and
experiments? professional development of persons
who work with experimental ani-
The most important guarantee for the mals. These recommendations are
proper conduct of animal experiments based on suggestions from the in-
is that the researchers and keepers are ternational professional organisation
well trained, prudent, and sensitive to FELASA (Federation of European
the needs of the animals. Laboratory Animal Science Associa-
tions, London). Depending the scope
According to German law, animal of tasks, the training takes up to 80
experimentation may only be per- hours.
formed by persons with the requisite
knowledge and skills. These are in- The DFG recommends taking advan-
dividuals with a university degree in tage of such offers and can provide
medicine (veterinarians, physicians, financial support for the professional
dentists) or natural sciences, or with development of scientists. Numer-
a professional qualification, such as ous universities hold courses that are
specially trained biology technicians certified by the Society of Labora-
or laboratory animal keepers. Opera- tory Animal Science (GV-Solas). This
tions may only be carried out by the range of courses is supplemented by
first group of persons with the neces- the online platform LAS interactive
EU Commission immediately, who sional – will decide whether the sary knowledge and skills. (www.las-interactive.de). This plat-
can revoke the provisional approval animal can stay alive. If laboratory form is available to all universities
within 30 days. animals could only continue living and research institutions to aid with
in pain or with damages, they must How does the training take place? education, training and professional
► At the end of the experiment, the be killed humanely. If they are re- development regarding experimen-
veterinarian – or in the case of small turned to full health, they can be Available training in working with tal animals, and is supported by the
rodents, another qualified profes- given to private individuals or – in laboratory animals varies widely be- DFG.
Harald zur Hausen, Françoise Barré-Sinoussi, Luc Montagnier Elizabeth Blackburn, Carol Greider, Jack Szostak Robert Edwards Jules Hoffmann, Bruce Beutler, Ralph Steinman
68 2008 The role of HPV and HIV in the
2009 Discoveries in the area of telomers
2010 Development of
2011 Discoveries in the area of innate
 69
development of diseases and telomerase research in vitro fertilisation and acquired immunity

Knowledge protects animals: this is the motto of the LAS interactive information and training portal.
LAS stands for Laboratory Animal Science.

Qualified monitoring veterinary offices. These may inspect


documents and take samples without
Effective monitoring of an animal ex- prior notice. If violations are identi-
periment by the authorities is only fied, these authorities can also take
possible if the experiment is properly the necessary steps. These include
documented. For this reason, the de- instructions to cease animal experi-
tails of the experiment must be record- ments performed without the neces-
ed. This documentation must include sary approval or in contravention of
the number of animals, the species the Animal Welfare Act. Violations of
and procedures, as well as the names the regulations are regarded as admin-
of the persons who carried out the istrative offences, in extreme cases as
experiments. In the case of dogs, cats criminal offences.
and primates, their gender, any mark-
ings, and the procedures must also be
documented in such a way that the Stress during animal
animal’s life from birth to experiment, experiments
and beyond, can be traced.
According to current scientific knowl-
The internal monitoring is carried edge, the sensitivity of vertebrates to
out by animal welfare officers, who pain is similar to that of humans. Be-
are generally qualified veterinarians. havioural responses suggest that ani-
They monitor the experiments and mals not only perceive pain, but also
comment on submitted applications. suffer subjectively. Legislation recog-
In addition, they advise the research- nises this by demanding an evaluation
ers and are active within the institu- of the consequences for the animal
tion to help implement the Three Rs before granting approval of an animal
principle. When fulfilling their duties, experiment. As part of the evalua-
animal welfare officers act indepen- tion, the duration of the experiment,
dently and also provide veterinary the frequency of the procedures, the
care for the animals. In their work, intensity, duration and frequency of
they are also supported by the animal pain, and the influence on natural be-
welfare committee, which mainly has haviour must be considered.
an advisory role.
Many animal manipulations can be
In addition to this internal moni- minimised by implementing suitable
toring, institutions in which animal complementary measures. Therefore,
experiments are performed are sub- providing painkillers and ensuring the
ject to monitoring by the responsible best possible husbandry and care con-
John Gurdon, Shinya Yamanaka James Rothman, Randy Schekman, Thomas Südhof May-Britt und Edvard Moser, John O'Keefe William Campbell, Satoshi Omura, Youyou Tu
70 2012 Discovery that mature cells can be
2013 Discovery of the control system for the
2014 Spatial orientation
2015 Antiparasitic agents (active substances
 71
converted to stem cells transport and delivery of cellular loads to combat malaria and worm diseases)

ditions are crucial for the animal’s well- awakens are considered stress-free.
being and absence of pain and anxiety. These experiments are classified sepa- Article 20a Basic Law
rately under “non-recovery”.
Animal suffering is divided into four cat- “Mindful also of its responsibility toward future generations, the state
egories: “non-recovery”, “mild”, “mod- Procedures regarded as “mild” are shall protect the natural foundations of life and animals by legislation
erate” and “severe”. those that do not cause significant
and, in accordance with law and justice, by executive and judicial action,
harm to the animal’s welfare and
Experiments that are carried out en- general health, or are expected to all within the framework of the constitutional order.”
tirely under general anaesthesia and cause only low-level pain, suffering
from which the animal no longer or stress for short periods. Such pro-
cedures would also be performed on tion, and an animal’s emotional state organisations can take action if envi-
humans in medical practice without must be adequately taken into con- ronmental law is contravened. Several
Providing painkillers is crucial for the animal’s well-being. anaesthesia or protective measures. sideration. Significant stress or states federal states recently established a le-
This includes, for example, injections of anxiety for laboratory animals, as gal framework for class actions by ani-
and taking blood samples. well as social factors, can have a sig- mal welfare groups that question the
nificant impact on the results of the legitimacy of a project and the deci-
Procedures that humans would judge experiment. To obtain reliable results, sion by the competent authorities.
to be unpleasant are classed as “mod- it is essential that the laboratory ani-
erate”. Both the animal’s condition mals are in a normal physiological Furthermore, opinions differ on
and the pain it experiences are taken state and free of pain and fear, if pos- whether class action is even legally
into consideration here. This includes sible. Scientific interests and animal possible at the state level. Animal
operations under anaesthesia that welfare are therefore not in opposi- welfare falls within the federal gov-
lead to minor consequent stress, such tion but rather mutually dependent. ernment’s concurrent legislation. Fed-
as laying an in-dwelling catheter. eral states only have the authority to
legislate to the extent that the federal
Severe stress would include an organ Animal welfare group government makes no use of its juris-
transplant, during which it is expected lawsuit diction. However, in 1972, the federal
that the rejection of the organ could government already passed the Ani-
lead to serious adverse effects on the For a long time, animal welfare groups mal Welfare Act currently in effect. In
general well-being of the animal. Final have called for collective action to pro- June 2013, the federal legislature’s
efficacy tests for vaccines and acute tect and lend more weight to the rights Committee on Food, Agriculture and
toxicity tests also fall under this cat- of animals, who are unable to defend Consumer Protection decided by a
egory. their own rights, against the claims of majority to reject a proposal to intro-
human beings. They justify this with duce the right to class action for ani-
It is inherently difficult to estimate the constitutional amendment (Arti- mal welfare groups at the federal level.
stress, because fluctuations in stress cle 20a Basic Law). The model is the The committee justified this decision
levels within a particular experiment, right to class action in environmental by citing the comprehensive animal
species-specific differences in reac- protection: Environmental protection welfare laws already in force.
73

Appendix Questions and answers (FAQs)

Question (Q): Is any unnecessary and Q: Is animal testing still performed for
senseless animal testing done in Ger- cosmetic products?
many?
A: Animal testing for the evaluation of
Answer (A): The performance of un- cosmetic products has been banned in
necessary animal testing is illegal in Germany since 1998. From 2004, ani-
Germany due to strict laws. Any ani- mal testing for finished cosmetic prod-
mal experiment must be submitted ucts is no longer permissible within
to the competent authority and ap- the EU. Moreover, since July 2013,
proved before it can be carried out. animal experiments are no longer per-
During the approval process, animal missible for testing the ingredients in
welfare concerns, the necessity of the cosmetic products.
experiment as well as its ethical jus-
tification are examined by an Animal
Protection Committee, which also in- Q: Is any animal testing involving great
cludes representatives of animal wel- apes performed in Germany?
fare organisations.
A: There have been no experiments
with great apes in Germany since
Q: Can researchers make arbitrary use of 1991. The use of apes for animal test-
experimental animals? ing is strictly prohibited and may only
be approved in exceptional cases (e.g.
A: Each application for animal test- life-threatening diseases). The Euro-
ing is evaluated for distress caused pean Commission must be informed
to the animals and is controlled by in such a case.
permit from the competent author-
ity. Researchers working in the ani-
mal experiment field must be suitably Q: Are stray and feral dogs and cats cap-
qualified. The necessary skills and tured and used in animal experiments in
knowledge to protect the well-being Germany?
of the animals and to minimise their
pain and suffering is taught in the A: The use of stray and feral dogs and
relevant training programmes. In ad- cats is strictly prohibited. Animal ex-
dition to this, animal welfare officers periments can only be approved if the
working at the test sites monitor the origin and health status of the animals
experiments. is known. Feral populations may only
be used for research purposes in ex-
ceptional cases, i.e. to protect animal
74 75

stocks from epidemics. This only ap- not directly applicable to every hu- This brochure was prepared by the DFG’s Senate Commission on Animal Protection and Experimentation.
plies to Eastern European countries man being, as each human being is an The section “Ethical aspects of animal experimentation and the principle of solidarity” is based on chapter
of the EU, where large populations of individual with an anatomy, physiol- 3.1 of the ad-hoc statement “Animal Experimentation in Research: Statement on the Transposition of EU
feral animals of domestic species still ogy and genetic make-up all of their Directive 2010/63/EU into German Law” by the German National Academy of Sciences Leopoldina and the
exist and these pose a potential threat own. The interpretation of scientific Union of German Academies of Sciences and Humanities (2012). The Senate Commission would like to
to other animals. results from animal experiments is thank Prof. Dieter Birnbacher and Prof. Bettina Schöne-Seifert for their support on this section.
very demanding but makes a substan-
tial contribution to the clarification
Q: Are animals also used for the develop- of the root causes of disease-induced
ment of alternative methods to animal changes and disease mechanisms, and The Senate Commission on Animal Protection and Experimentation
testing? in turn to the improvement the safety
and efficacy of drugs. The Senate Commission on Animal Protection and Experimentation deals with current issues in
A: In 2014, 789,926 animals (the ma- relation to experimental research with animals and animal welfare in research. It has an advisory
jority of which were mice and rats) role to the statutory body of the DFG and authorities at EU, federal and state level. The commission
were killed to obtain organs and cells Q: Is it true that 25 years of AIDS research provides advice to researchers as well as universities and research institutions on practical ques-
for experiments. This constitutes ap- using primates has not led to any vaccina- tions and problematic cases. The commission fosters in-depth training of early career researchers
prox. 28% of all animals that were re- tion or drug for human beings?
in animal research by developing specific training programmes and drives public dialogue through
corded as test animals. Some of these
animals were also used for the re- A: A vaccine against HIV has in fact the creation of information materials and organisation of talks and discussions.
search and development of alternative not been developed to date. The re-
Scientific members during the 2014 – 2017 term:
methods to animal testing. search has however contributed to
Professor Dr. Gerhard Heldmaier (Chairperson) / University of Marburg
a marked reduction in the viral load
of patients and therefore produced a Professor Dr. Peter Dabrock / University of Erlangen-Nuremberg
Q: Is it true that results obtained from significant improvement in the qual- Professor Dr. Bernd Fleischmann / University of Bonn
animal experiments are not transferable ity of life and survival time of pa- Professor Dr. Nils Hoppe / University of Hanover
to humans? tients. This was only possible because
Professor Dr. Inga D. Neumann / University of Regensburg
the mechanism of action of the virus
A: For each experiment, the animal could largely be clarified, and highly Professor Dr. Heiner Niemann / Friedrich Loeffler Institute
model is specifically selected for its effective drugs and treatment meth- Professor Dr. Ingo Nolte / Foundation of the University of Veterinary Medicine in Hanover
suitability to answer the questions of ods could subsequently be developed Professor Dr. Heidrun Potschka / Ludwig-Maximilian University of Munich
the particular research. The results and applied.
Professor Dr. Ruth Esther von Stebut-Borschitz / University of Mainz
from the animal experiment must be
analysed carefully and interpreted Professor Dr. René H. Tolba / Aachen University Hospital
in relation to their relevance to hu- Professor Dr. Stefan Treue / German Primate Center
man beings. Direct transferability is
Coordinator:
generally not to be expected. How-
ever, the same also applies to results Dr. Cornelia Exner / University of Marburg
from human studies that are equally
76

List of image sources

Title images (from left to right): fotolia; Anton Säckl / German Primate Centre; LAS interactive; dpa / Hans
Wiedl; Melanie Bernhardt / University of Marburg ; LAS interactive; Geir Mogen / NTNU; Wikimedia Com-
mons / Lmbuga)
Photos used in the text: Wikimedia Commons / Botaurus (p. 7); iStock (p. 8); Wikimedia Commons /
Andrei Daniel Mihalca (p. 14 / 15); fotolia (p. 16); LAS interactive (p. 19); University of Marburg, Behring
Estate – digital (p. 21); LAS interactive (p. 23); www.signalsblog.ca / Sara M. Nolte (p. 24); Wikimedia
Commons / Oleg Tsupykov (p. 26); Wikimedia Commons / Genny Anderson (p. 29); fotolia (p. 30); iStock
(p. 33); fotolia (p. 34 and p. 36 / 37); Wikimedia Commons / Kleuske (p. 38); Wikimedia Commons / Esquilo
(p. 40) / Scewing (p. 41) / Nobel Foundation (p. 41); www.dma.org (p. 42); CC-BY-SA-NC, Novartis (p. 45);
Karin Tilch / German Primate Center (p. 48 / 49); iStock (p. 50); LAS interactive (p. 53); Wikimedia Com-
mons / Marrabbio2 (p. 54 / 55); fotolia (p. 58 and p. 62); Wikimedia Commons / katanski (p. 65); fotolia
(p. 66); www.understandinganimalresearch.org.uk (p. 70); www.riboworld.com (p. 72)
All photos on the timeline of Nobel Prize winners: fotolia

Published by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation),


Senate Commission on Animal Protection and Experimentation, Kennedyallee 40, 53175 Bonn,
Telephone: + 49 228 885-1, Fax: + 49 228 885-2777, postmaster@dfg.de, www.dfg.de/en

Concept & text: Senate Commission on Animal Protection and Experimentation, DFG
Scientific editors: Dr. Cornelia Exner, Dr. Christoph Limbach, DFG
Translation: oneword GmbH and Norbert G. Kramer
Editors: Diana Fehmer, Inken Kiupel, DFG
Basic layout: Tim Wübben, DFG / besscom, Berlin
Production layout: Olaf Herling, Warstein / Berlin

Print: Druckerei Hachenburg GmbH

Version dated: 10/15/2016


Further information:
www.dfg.de/tierschutz
ISBN: 978-3-527-34355-3 (available only in German)
Deutsche Forschungsgemeinschaft
German Research Foundation
Kennedyallee 40 · 53175 Bonn
Postal address: 53170 Bonn
Tel: + 49 228 885-1
Fax: + 49 228 885-2777
postmaster@dfg.de
www.dfg.de/en

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