Animal Experimentation in Research - The Senate Commission on Animal Protection and Experimentation - DFG
←
→
Page content transcription
If your browser does not render page correctly, please read the page content below
The Senate Commission on Animal Protection and Experimentation Animal Experimentation in Research
The Senate Commission on Animal Protection and Experimentation Animal Experimentation in Research
2 3
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
4 5
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 ofAugust 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 upChristiaan 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, artificialThomas 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 adultCorneille 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, veterinaryPaul 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 animalsSelman 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 livingYou can also read
