Animal Experimentation in Research - Tierversuche …...5 4 Foreword cre-man-animals. e research. l-d purposes. s e l h purposes. of Research y Foundation). available e , before. s

Page 1

The Senate Commission on Animal Protection and Experimentation

Animal Experimentation in Research

Page 2

The Senate Comm

ission on Anim

al Protection and Experimentation

Anim

al Experimentation in Research

Page 3

32

Contents

Foreword

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .4

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

Experiments w

ith animals: D

efinition and fi

gures

What is anim

al experimentation? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

How

many anim

als are used in research? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

What are anim

als used for in research? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

What anim

al species are used? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

Developm

ents across Europe . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13

Anim

al experimentation in practice: A

reas of use

Basic research . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17

Medical research

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .18

Nobel Prize w

orthy: Outstanding scientifi

c findings . . . . . . . . . . . . . . . . . . .20

Diagnostics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21

Transplantation medicine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25

Cell and tissue replacement in hum

ans . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25

Stem cell research

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27

Genom

e research . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .28

Neuroscience . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31

Veterinary research . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .32

Anim

al experiments in education, training and professional developm

ent . .35

The basic assumption of transferability . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35

Anim

al experimentation and protection of anim

als: Ethical considerations

Developm

ent of the concept of animal protection in G

ermany

. . . . . . . . . 39

Ethical aspects of animal experim

entation and the principle of solidarity. .40

Transferability from an ethical-legal view

point . . . . . . . . . . . . . . . . . . . . . . . 45

The Three Rs principle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47

Alternatives to anim

al experimentation

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51

Limitations to alternative m

ethods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55

The Basel Declaration

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56

Anim

al experimentation in G

ermany:

From proposal to im

plementation

European regulations on animal experim

entation . . . . . . . . . . . . . . . . . . . . 59

Anim

al experiments subject to authorisation

. . . . . . . . . . . . . . . . . . . . . . . . . 59

Legal basis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .60

Approval procedures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63

Conducting animal experim

ents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .64

Qualifi

ed monitoring

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .68

Stress during animal experim

ents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .68

Anim

al welfare group law

suit . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71

Appendix

Page 4

54

Foreword

An

imal ex

perim

ents are essen

tial to basic bio

logical an

d m

edical research

– cre-atin

g a classic dilem

ma as th

e acqu

isition

of k

no

wled

ge for th

e goo

d o

f man

-k

ind

places a bu

rden

on

anim

als. Th

e pro

tection

of an

imals is h

igh o

n th

e agen

da o

f mo

st Eu

rop

ean co

un

tries and

sets limits o

n research

. In 2

01

0, fo

l-lo

win

g lon

g and

con

troversial d

iscussio

ns, th

e Eu

rop

ean P

arliamen

t ado

pted

a EU

directive o

n th

e pro

tection

of an

imals u

sed fo

r scientifi

c pu

rpo

ses. Th

is d

irective pro

vides n

ew an

d m

ore strin

gent regu

lation

s in m

any asp

ects, wh

ile also

setting u

nifo

rmly h

igh stan

dard

s across E

uro

pe fo

r the ap

pro

val of an

imal

exp

erimen

ts and

the acco

mm

od

ation

and

care of an

imals u

sed fo

r research

pu

rpo

ses.

Th

e first ed

ition

of A

nim

al Experim

ents in

Research

was fi

rst pu

blished

in 2

00

4 by

the D

eutsch

e Fo

rschu

ngsgem

einsch

aft (DF

G, G

erman

Research

Fo

un

datio

n).

Bo

th th

e Germ

an-lan

guage an

d th

e En

glish versio

n are n

o lo

nger available.

Th

e amen

dm

ent to

the G

erman

An

imal W

elfare Act in

20

13

to brin

g it in lin

e w

ith th

e EU

directive resu

lted in

a nu

mber o

f chan

ges to th

e app

roval p

rocess,

placin

g a greater adm

inistrative bu

rden

on

app

licants th

an befo

re. With

this

revised ed

ition

, we aim

to p

resent an

overview

of th

e curren

t legal requ

ire-m

ents, in

clud

ing p

ractical info

rmatio

n regard

ing th

e organ

isation

al pro

cesses fo

r the ap

plicatio

n an

d th

e perfo

rman

ce of tests o

n an

imals, as w

ell as exp

lain

the legal an

d eth

ical prin

ciples o

f research u

sing an

imal ex

perim

entatio

n. In

ad

ditio

n to

the bro

chu

re, the D

FG

website o

ffers furth

er info

rmatio

n – scien

-tifi

c pap

ers, legal texts, ap

plicatio

n fo

rms, etc. – w

hich

can be accessed

un

der

ww

w.d

fg.de/tiersch

utz (available o

nly in

Germ

an).

In o

ur so

ciety, discu

ssion

s arou

nd

anim

al exp

erimen

ts are con

troversial an

d o

ften very em

otio

nal, n

ot least becau

se of th

e absence o

f factual in

form

ation

abo

ut th

e pu

rpo

se of th

e exp

erimen

ts, the bu

rden

they p

lace on

the an

imals,

or th

e results an

d p

oten

tial benefi

ts. With

in th

e framew

ork

of th

e Basel D

ec-laratio

n, scien

tists have co

mm

itted to

engage in

mo

re com

mu

nicatio

n w

ith

the p

ublic an

d to

pro

vide p

eop

le with

mo

re info

rmatio

n. T

his bro

chu

re there-

fore also

inten

ds to

info

rm th

e interested

pu

blic abou

t the sco

pe an

d n

eed fo

r an

imal testin

g. On

the basis o

f specifi

c exam

ples an

d ex

plan

ation

s of scien

tific

meth

od

s, we en

deavo

ur to

exp

lain th

e prin

ciples o

f exp

erimen

tal anim

al re-search

and

thereby p

rovid

e a con

tributio

n to

a mo

re objective d

ebate on

the

top

ic.

Th

e broch

ure is th

e result o

f coo

peratio

n betw

een m

embers o

f the D

FG

Sen

ate C

om

missio

n o

n A

nim

al Pro

tection

and

Ex

perim

entatio

n an

d th

e DF

G H

ead O

ffice in

Bo

nn

. At th

is po

int, I w

ish to

than

k everyo

ne w

ho

has co

ntribu

ted to

the co

mp

letion

of th

e pro

ject by subm

itting tex

ts and

engagin

g in critical

discu

ssion

s.

I ho

pe th

at you

will fi

nd

it an illu

min

ating read

!

Gerh

ard H

eldm

aierC

hairp

erson

of th

e Sen

ate Co

mm

ission

on

An

imal P

rotectio

n an

d E

xp

erimen

tation

of th

e DF

G

Page 5

76

Introduction

The an

alysis of the h

ereditary inform

a-tion

(DN

A) of com

plex anim

als – such

as th

e fruit fl

y Drosophila m

elanogaster, th

e mou

se, rat, pig, cow or th

e hu

man

bein

g – is one of th

e most im

portant

scientifi

c achievem

ents of recen

t years. G

reat progress also has been

made in

oth

er areas of the life scien

ces, inclu

d-in

g new

insigh

ts into th

e structu

re of ri-bosom

es (the protein

factories of body cells) an

d into th

e astonish

ing plastic-

ity of stem cells. Th

ese fin

dings provide

new

in

sights

into

the

complexity

of vital processes, im

prove medical care

and n

utrition

for hu

man

beings an

d an

imals in

the lon

g run

, and th

ereby con

tribute to an

increase in

the qu

ality of life an

d life expectancy.

Con

siderable progress is how

ever not

conceivable

with

out

the

use

of an

i-m

als in research

. On

ly with

the h

elp of

anim

al experim

ents

has

it been

possible

to u

nderstan

d h

um

an

and

anim

al life

processes. Th

is in

cludes

the fu

nction

of sensory organ

s and of

the n

ervous, h

ormon

al and im

mu

ne

systems, as w

ell as that of in

dividual

genes,

wh

ich

can

only

be decoded

with

in th

e context of th

e total organ-

ism.

For research

of

such

com

plex processes in

the in

tact living organ

ism,

anim

al testing w

ill also be necessary

in fu

ture.

There

have

always

been

opponen

ts to an

imal testin

g. Now

as well as in

th

e past, opponen

ts have accu

sed re-

searchers of view

ing h

um

an bein

gs as su

perior to anim

als. An

other critiqu

e states th

at results from

anim

al experi-m

ents are n

ot transferable to h

um

an

beings an

d that an

imals are m

ade to su

ffer solely to satisfy scientifi

c curi-

osity. From today’s perspective, som

e an

imal experim

ents con

ducted in

the

early days of anim

al research do in

fact seem

cruel, alth

ough

the sam

e is tru

e of surgical procedu

res performed

on

hu

man

s. Th

is is

main

ly du

e to

insu

fficien

t su

rgical tech

niqu

es an

d an

aesthetic option

s at the tim

e. The

discovery of anaesth

esia in th

e 19th

centu

ry was a godsen

d for hu

man

s an

d anim

als alike, and today, its u

se in

anim

al testing is obligatory as w

ell as rou

tine.

The

criticism

of an

imal

testing

has

led to the form

ulation

of rules gov-

ernin

g the u

se of anim

als in scien

tific

experimen

ts as early as the 19th

cen-

tury. Th

ese have been

contin

uou

sly expan

ded ever

since.

The

Germ

an

An

imal W

elfare Act is on

e of the m

ost strin

gent acts w

orldwide. It en

sures

that an

imal tests are con

ducted on

ly w

ithin

the con

fin

es of socially accept-able n

orms an

d are subject to govern

-m

ent

control.

Every

anim

al experi-

men

t for biomedical research

purposes

requires a w

ritten application

to the

competen

t auth

ority of the relevan

t state an

d mu

st contain

a detailed jus-

tification

for the experim

ent. A

n an

i-m

al welfare com

mittee, con

sisting of

specialist researchers as w

ell as repre-sen

tatives from an

imal protection

or-gan

isations, advises th

e auth

ority. The

decision on

the proposal is in

formed

first an

d foremost by an

evaluation

of th

e indispen

sability of the experim

ent.

This

mean

s th

at th

e proposal

mu

st con

tain

plausible

argum

ents

provid-in

g evidence th

at the scien

tific goal

cann

ot be attained w

ithou

t the u

se of an

imal tests or altern

ative meth

ods.

In order to safegu

ard a high

bioethical

standard w

ithin

anim

al experimen

tal research

across Eu

rope, the E

uropean

Parliam

ent in

2010 adopted Directive

2010/63/EU

on th

e protection of an

i-

mals u

sed for scientifi

c purposes. Th

e directive stresses th

ree principles th

at m

ust be m

et to ensu

re anim

al welfare

in scien

tific research

. This is referred

to as the Th

ree Rs prin

ciple: Redu

c-tion

and R

efin

emen

t of experimen

tal m

ethods as w

ell as the developm

ent

of Replacem

ent an

d complem

entary

meth

ods of anim

al testing. In

addition,

the E

U directive con

tains a n

um

ber of n

ew regu

lations on

the approval an

d perform

ance of an

imal tests. In

July

2013, the G

erman

An

imal W

elfare Act

was revised an

d adapted to the E

uro-

pean directive. O

ld regulation

s were

retained an

d supplem

ented w

ith n

ew

specification

s.

The genetic material of anim

als contains similar characteristics to the genetic m

aterial of humans. This

makes e.g. the fruit fl

y a suitable candidate for research into human life processes and diseases.

19011904

1902Em

il von BehringNOBEL PRIZES

Ivan PavlovRonald Ross

The function of serum therapy,

particularly in cases of diphtheriaThe physiology of digestion

Scientific research on m

alaria

Page 6

9

Experiments w

ith animals:

Defi

nition and figures

What is anim

al experimen-

tation?

The G

erman

An

imal W

elfare Act de-

fin

es anim

al experimen

tation as in

ter-ven

tions an

d man

ipulation

s in an

imals

if this is associated w

ith su

ffering, pain

an

d inju

ry to the an

imals. Th

is applies to all procedu

res subjectin

g anim

als to stress “equ

ivalent to, or h

igher th

an,

that cau

sed by the in

troduction

of a n

eedle in accordan

ce with

good veteri-n

ary practice” (Article 3, 2010/63/E

U).

In reality th

is mean

s that each

proce-du

re carried out on

anim

als for scien-

tific pu

rposes mu

st be recorded as an

anim

al experimen

t and approved by

an au

thority. A

pproval is required for

all vertebrates, cephalopods (e.g. octo-

puses) an

d decapods (e.g. lobsters).

As part of th

e approval process by the

competen

t auth

ority, the reason

for th

e use of an

imals as w

ell as their liv-

ing an

d care condition

s are examin

ed. A

pproval for an an

imal test is gran

ted on

ly for the pu

rposes expressly speci-fi

ed in th

e Germ

an A

nim

al Welfare

Act. Th

is inclu

des basic research, ap-

plied research

for

the

prevention

, detection

an

d treatm

ent

of diseases,

quality an

d efficacy testin

g of drugs,

forensic

investigation

s, en

vironm

en-

tal protection, prom

oting an

imal w

ell-bein

g, improvem

ent of an

imal h

ous-

ing con

ditions, con

servation of species,

as well as edu

cation, train

ing an

d pro-fession

al developmen

t.

The killin

g of anim

als for the sole pu

r-pose of organ

extraction or th

e produc-

tion of cells does n

ot constitu

te anim

al experim

entation

. Cells or organ

s are eith

er exam

ined

directly or

used

to create cell an

d tissue cu

ltures. Su

ch in

vitro cu

ltures can

supplem

ent or par-

tially replace experimen

ts on live an

i-m

als and m

ake it possible to develop altern

atives to anim

al testing. A

bout

one-th

ird of all anim

als used for re-

search pu

rposes is utilised for th

ese in-

vitro meth

ods.

How

many anim

als are used in research?

The G

erman

Min

istry of Food and A

g-ricu

lture

and

the

Federal Statistical

Offi

ce ann

ually record th

e total nu

m-

ber of all anim

als used in

Germ

any.

In 2014, 2.798 m

illion an

imals w

ere u

sed for research pu

rposes. Inclu

ded in

this are 2.008 m

illion an

imals u

sed in

anim

al testing an

d 789,926 used

for organ extraction

. The n

um

ber of an

imals n

eeded for research pu

rposes correspon

ds to 0.35% of all 795 m

il-lion

anim

als used in

Germ

any – th

is sm

all percentage is essen

tial for gain-

ing kn

owledge abou

t the n

atural ba-

sis of life and for m

edical progress. At

788 million

, the largest proportion

of an

imals w

ere cattle, pigs, poultry an

d sh

eep; these w

ere slaugh

tered to pro-vide

food for

hu

man

con

sum

ption.

An

other 4 m

illion an

imals w

ere killed

1905Robert Koch

Transmission and treatm

ent of tuberculosis

Page 7

1110

by hu

ntin

g. Fishin

g and pest con

trol also in

volve the killin

g of anim

als, but

these are n

ot coun

ted.

Since

2014, an

imals

used

for scien

-tifi

c pu

rposes are

registered accord-

ing to a n

ew E

urope-w

ide reporting

procedure. N

ewly in

troduced w

as the

registration of in

dependen

tly feeding

larval forms. Th

e first cou

nt sh

owed

that 563,000 an

imal larvae w

ere used

in scien

tific research

. Fish larvae can

be very sm

all, so that direct cou

ntin

g is n

ot possible and th

e nu

mber of lar-

vae can on

ly be estimated. Th

is initial

figu

re is not in

cluded in

the fi

gures

publish

ed by the G

erman

Min

istry of Food an

d Agricu

lture.

Th

ere has been

a slight d

ecrease in

the o

verall nu

mber o

f anim

als used

for scien

tific research

in recen

t years:

in 2

01

3 by ap

pro

x. 3

% (2

.99

7 m

il-lio

n) co

mp

ared to

the p

reviou

s year, an

d in

20

14

by ano

ther 6

.6%

(2.7

98

millio

n).

What are anim

als used for in research?

Th

e majo

rity of an

imals in

science

are used

in basic research

(31

.1%

) an

d in

“translatio

nal an

d ap

plied

re-search

” (11

.9%

). Th

e latter are pro

-jects th

at test basic research fin

din

gs fo

r m

edical

app

lication

s. B

asic re-

search an

d tran

slation

al and

app

lied research

are

closely

interco

nn

ect-ed

, and

their co

mbin

ed p

ercentages

mak

e up

the ex

pen

ditu

re for m

edical

research (4

3%

). An

imal ex

perim

en-

tation

in m

edical research

is con

du

ct-ed

to clarify p

reviou

sly un

kn

ow

n life

pro

cesses and

fun

dam

ental bio

logical

relation

ship

s. In tu

rn, th

ese find

ings

are used

to im

pro

ve diagn

ostics an

d treatm

ent

of

hu

man

illn

esses an

d d

iseases.

Abo

ut 2

8.2

% o

f anim

als used

in re-

search are n

ot ex

po

sed to

exp

erimen

-tal treatm

ents w

hile alive bu

t are pu

t d

ow

n to

gain cells o

r tissues. T

hese

samp

les are used

to ex

amin

e basic bio

chem

ical pro

cesses on

a cellular

level and

test new

ph

armaco

logical

treatmen

t meth

od

s. Ultim

ately, this

percen

tage mu

st also be allo

cated to

the co

st of m

edical research

.

Nu

mero

us an

imal tests are co

nd

ucted

with

in th

e framew

ork

of co

nsu

mer

pro

tection

and

are requ

ired by law

(so

-called

“regulato

ry p

urp

oses”).

Abo

ut 2

3.7

% o

f all test anim

als in

Germ

any

are u

sed

for

such

safety

check

s, q

uality

con

trols

or

tox

ico-

logical tests in

accord

ance w

ith th

e legislatio

n

on

ch

emicals,

med

icines

and

foo

d h

ygiene. T

hese tests are re-

qu

ired fo

r the ap

pro

val of d

rugs an

d o

ther su

bstances w

ith w

hich

hu

man

s co

me in

to co

ntact.

What anim

al species are used?

An

imals u

sed in

research are m

ainly

small

mam

mals

such

as

mice,

rats, gu

inea p

igs and

rabbits; fish

and

birds

are u

sed

for

specifi

c in

vestigation

s. M

ice (1.9

01

millio

n in

20

14

, 68

%)

and

rats

(13

%)

are still

the

mo

st co

mm

on

ly used

anim

als and

are also m

ost o

ften k

illed fo

r organ

extractio

n.

Th

e deco

din

g of th

e mo

use gen

om

e a few

years ago, an

d th

e relatively sim

ple m

anip

ulatio

n o

f this gen

om

e fro

m a tech

nical p

oin

t of view

, mak

es th

e mo

use by far th

e mo

st imp

ortan

t research

species as it o

ffers insigh

ts in

to th

e genetic fo

un

datio

ns o

f life p

rocesses

and

d

iseases. T

he

slight

dro

p

in

anim

al ex

perim

ent

nu

m-

bers over th

e last two

years is main

ly d

ue to

a redu

ction

in th

e nu

mber o

f m

ice and

rats. Th

e use o

f fish

has in

-

23.7%

0.3%

0.2%

1.8%

28.2%

31.1%

11.9%

2.8%

Basic research: 31.1%

Translational and applied research: 11.9%

Conservation breeding programm

es of genetically m

odified, burdened animal colonies: 2.8%

Quality control, toxicology and other safety evaluations: 23.7%

Environmental protection for the benefit

of humans and anim

als: 0.2%

Conservation of species: 0.3%

Education, training and professional developm

ent: 1.8%

Animals killed for scientific purposes

(not animal tests): 28.2%

Chart 1: Percentage of anim

als used for specific research purposes

Source: Statistics of the German M

inistry of Food and Agriculture, 2014

19071908

Alphonse LaveranIlya M

echnikow, Paul Ehrlich

The causative role of protozoa in diseases

Imm

unity in infectious diseases

1906Cam

illio Golgi, Santiago Ramón y Cajal

The structure of the nervous system

Page 8

1312

creased o

ver the last few

years (cur-

rently 9

.8%

) as the zebrafi

sh gen

om

e w

as d

ecod

ed

and

en

abled

insigh

ts in

to th

e origin

s of th

e life pro

cesses in

vertebrates. Oth

er species are u

sed o

nly to

a min

or ex

tent. T

heir n

um

ber m

ay flu

ctuate sligh

tly, but th

is has n

o in

flu

ence o

n th

e overall fi

gures.

Sin

ce 1

99

1,

exp

erimen

ts o

n

great ap

es are no

lon

ger perfo

rmed

in G

er-m

any, an

d o

ther p

rimates are u

sed o

nly in

small n

um

bers. In 2

01

4, th

e fi

gure w

as 2,8

42

, wh

ich co

rrespo

nd

s to

abou

t 0.1

% o

f all research an

imals.

Th

e m

ost

com

mo

nly

used

m

on

key

species

was

the

lon

g-tail m

acaqu

e (2

,10

0).

In

mo

st cases

(2,3

35

an

i-m

als), prim

ates were u

sed fo

r legally req

uired

scien

tific

research,

for

ex-

amp

le in

d

rug

testing.

Cats

played

an even

smaller ro

le in research

(99

7 an

imals in

20

14

), and

they to

o w

ere u

sed m

ainly fo

r legally requ

ired p

ur-

po

ses (51

9).

Th

e use o

f stray and

feral do

gs and

cats is

pro

hibited

in

ex

perim

ental

research w

ith an

imals. T

hey are n

ot

suitable fo

r scientifi

c research as th

eir o

rigin,

state o

f h

ealth

and

gen

etic back

grou

nd

, as

well

as th

eir p

revi-o

us beh

aviou

r is un

kn

ow

n. R

eliable an

d rep

rod

ucible research

results can

o

nly be ach

ieved u

nd

er defi

ned

and

stand

ardised

con

ditio

ns. T

his ap

plies

to th

e status o

f test anim

als as well

as all oth

er exp

erimen

tal param

eters.

Research

on

wild

anim

als, ho

wever,

is p

ossible,

but

severely restricted

and

subject to

special req

uirem

ents.

To safegu

ard th

e pro

tection

of sp

e-cies

as req

uired

by

law,

add

ition

al ap

pro

val by

the

relevant

natu

re co

nservatio

n au

tho

rities is requ

ired.

Wild

life research m

ainly in

vestigates th

e behavio

ur o

f anim

als and

their

interactio

n w

ith th

eir natu

ral habi-

tats. Th

e find

ings o

f such

stud

ies are p

rimarily u

sed to

pro

tect species. In

m

ost cases, th

e anim

als are merely

being o

bserved an

d o

nly ex

po

sed to

low

levels of stress so

as no

t to in

ter-fere w

ith th

eir natu

ral behavio

ur.

Developm

ents across Europe

Th

e E

uro

pean

C

om

missio

n

also

re-co

rds th

e nu

mber o

f test anim

als in

ord

er to track

the d

evelop

men

t with

-in

Eu

rop

e. Fo

r 20

11

– mo

re recent

figures w

ere no

t available at press

time – 1

1.5

millio

n test an

imals w

ere listed

o

verall. G

erman

y’s sh

are in

th

is figure is 2

millio

n an

imals, be-

cause

Eu

rop

ean

statistics –

in

con

-trast to

natio

nal reco

rds – o

nly co

un

t th

e actual an

imal ex

perim

ents an

d n

ot th

e killin

g of an

imals fo

r organ

ex

traction

.

Co

mp

ared w

ith th

e last cou

nt, th

ere h

as been a sligh

t increase in

the n

um

-ber o

f test anim

als in so

me co

un

tries. In

m

ost

Eu

rop

ean

cou

ntries,

ho

w-

Mice: 68%

Food: 99.15%

Animals for research purposes (0.35%

)

Hunting (0.50%)

Rats: 13%

Mice: 68.0%

Rats: 13.0%

Birds: 2.0%

Fish: 9.8%

Rabbits: 3.8%

Dogs: 0.1%

Primates: 0.1%

Livestock: 0.8%

Other animals: 2.4%

Chart 2: Anim

al consumption and anim

al species used for research purposes

Source: Statistics of the German M

inistry of Food and Agriculture, 2014

1912Alexis Carrel

The development of techniques

for suturing blood vessels

1910Albrecht Kossel

Cell chemistry and

cell nucleus substance

Page 9

1514

ever, the n

um

ber of test an

imals h

as rem

ained

fairly con

stant o

r has fall-

en sligh

tly, as in F

rance an

d th

e UK

. A

cross E

uro

pe, m

ice are also th

e mo

st co

mm

on

ly u

sed

species

for

anim

al testin

g. Th

eir share is 6

1%

, follo

wed

by rats,

guin

ea p

igs, o

ther

rod

ents,

and

rabbits. Th

e share o

f mo

nk

eys w

as 0

.05

%.

Great

apes

have

no

t been

u

sed

since

19

99

. S

ince

20

08

, th

ere has been

a dro

p in

the n

um

-ber o

f amp

hibian

s (– 52

%), m

on

keys

(– 48

%), bird

s (– 26

.5%

) and

rod

ents

(exclu

din

g mice) (– 1

9.9

%), w

hereas

the reco

rded

nu

mbers o

f fish

(+ 2

9%

), rabbits (+

7.5

%) an

d o

ther m

amm

als (+

38

%) h

ave increased

.

At

the

Eu

rop

ean

level, m

ore

than

6

0%

of an

imals w

ere used

for basic

research an

d fo

r the research

and

de-

velop

men

t of m

edical p

rod

ucts an

d d

evices for h

um

an m

edicin

e, den

tist-ry, an

d veterin

ary med

icine. A

bou

t 1

9%

of all an

imals w

ere used

for tests

and

check

s of m

edical p

rod

ucts an

d d

evices. Th

e nu

mber o

f anim

als used

in to

xico

logical evalu

ation

s and

oth

er safety tests h

as remain

ed relatively

con

stant o

ver the last few

years, at abo

ut 9

% – d

espite th

e intro

du

ction

in

20

06

of th

e EU

’s RE

AC

H D

irective (R

egistration

, Evalu

ation

, Au

tho

risa-tio

n

and

R

estriction

o

f C

hem

icals), w

hich

stip

ulates

that

all ch

emicals

used

in larger q

uan

tities with

in th

e E

U req

uire safety in

form

ation

often

based

on

anim

al stud

ies.

The n

um

ber o

f anim

al tests with

amp

hib

ians – in

clud

ing

the Eu

rop

ean tree fro

g – h

as mo

re than

halved

across Eu

rop

e.

1913Charles Richet

Discovery of hypersensitivity to antigens

Page 10

17

Anim

al experimentation in practice:

Areas of use

Basic research

The aim

of basic research is to gain

kn

owledge

and

insigh

ts. B

asic re-

search h

as no im

mediate application

bu

t provides

the

scientifi

c basis

for fu

rther research

and application

s. Be-

cause

of th

e sim

ilarity betw

een

hu

-m

ans an

d anim

als in term

s of their

metabolic processes an

d fun

ction of

organs,

know

ledge gain

ed in

an

i-m

al experimen

ts can provide a better

un

derstandin

g of

life processes

and

their

disturban

ces in

both

h

um

ans

and

anim

als. A

lthou

gh

the

transfer-

ability of results from

basic research

to its application can

not be plan

ned

and its direct sh

ort-term ben

efit can

-n

ot be predicted, scientifi

c and m

edi-cal breakth

rough

s are not con

ceivable w

ithou

t the kn

owledge gain

ed from

basic research.

An

imal testin

g is a necessity an

d of particu

lar importan

ce wh

ere complex

relationsh

ips betw

een

physiological

processes an

d diseases

can

only

be stu

died on th

e living organ

ism. Th

is applies in

particular to stu

dies on th

e fu

nction

ing of th

e nervou

s, cardiovas-cu

lar and im

mu

ne system

s, as well as

the action

of horm

ones. V

ery dynam

ic developm

ents

are cu

rrently

taking

place in th

e field of gen

ome an

d stem

cell research

. It

is h

oped th

at n

ew

therapeu

tic approach

es can

em

erge from

stem cell research

, usin

g cell and

tissue replacem

ent to treat h

eart at-

tacks or neu

rological condition

s such

as Parkin

son’s disease.

Man

y results in

basic research are ob-

tained u

sing cell cu

ltures, becau

se cul-

tured cells develop relatively qu

ickly an

d hom

ogeneou

sly and can

be direct-ly stim

ulated w

ith h

ormon

es or other

chem

icals. Cell cu

ltures are alw

ays ar-tifi

cial systems an

d provide only lim

it-ed in

sight in

to life processes. Yet they

are the on

ly way to directly m

anipu

-late

and

measu

re bioch

emical

pro-cesses in

the cell. In

cancer research

, for exam

ple, isolated tum

our cells are

used to iden

tify the ch

aracteristics and

causes of cell degen

eration. Th

e true

natu

re of cancer, h

owever, becom

es apparen

t only w

hen

its developmen

t is

viewed

in

conn

ection

with

oth

er cells an

d tissues in

the body. In

order to trace th

e developmen

t of a tum

our

in th

e organism

and test th

erapeutic

approaches, an

imal experim

ents are

necessary in

wh

ich tu

mou

r cells are tran

sferred into m

ice.

The close relation

ship betw

een cellu

-lar basic research

and an

imal testin

g also plays a cen

tral role in research

on

infectiou

s diseases. It is the on

ly path

to un

derstandin

g how

bacteria and vi-

ruses in

filtrate an

d attack the an

imal

organism

. Insigh

ts into th

e interaction

betw

een viru

ses and th

eir host cells

enable th

e targeted treatmen

t of virus

infection

s such

as infl

uen

za, herpes

or smallpox, an

d the developm

ent of

1919Jules Bordet

Fundamental discoveries

on imm

unity

Page 11

1918

preventive m

easures. A

visible result

of this type of research

is the progress

made in

the area of vaccin

ations. O

nly

a few years ago w

as it discovered that

papilloma

viruses

are in

volved in

th

e developm

ent

of cervical

cancer.

With

out an

imal experim

ents on

mice,

sheep, h

orses and goats, th

is discovery w

ould n

ot have been

possible. A vac-

cine again

st the viru

ses was su

ccess-fu

lly developed. The G

erman

virolo-gist H

arald zur H

ausen

was aw

arded th

e Nobel Prize in

Medicin

e for this

work in

2008.

Basic research

projects initially aim

ed at gain

ing in

formation

about life pro-

cesses in an

imals m

ay translate in

to m

edical benefi

ts at a later stage. A case

in poin

t is the stu

dy on th

e hibern

ation

of marm

ots and oth

er small m

amm

als. In

itially it was assu

med th

at hibern

a-tion

is triggered by cold temperatu

res an

d lack of food, leading to a failu

re of

the

temperatu

re-regulatin

g m

ech-

anism

. Th

e latest

studies

of grou

nd

squirrels, dorm

ice and m

armots h

ow-

ever show

that th

ese anim

als actively stifl

e th

eir m

etabolism

and

regulate

their

body tem

perature

to be

near

freezing, an

d that breath

ing an

d heart

rate come to a n

ear standstill. A

new

w

ay of

regulatin

g m

etabolism

was

thu

s discovered that en

ables mam

mals

to sw

itch

from

“norm

al operation

” to “low

flam

e”. To un

derstand h

ow

this sw

itchin

g process works cou

ld be lifesavin

g in th

e treatmen

t of severe

inju

ries or in cu

rbing th

e effects of a h

eart attack or stroke. Some clin

ics are already tryin

g to trigger this process

by subjectin

g patients to low

tempera-

tures.

Transplan

tation

medicin

e too

(see page 25f.) can ben

efit by in

creas-in

g the sh

elf life of organs.

Medical research

Medical progress is in

extricably linked

with

basic

research.

An

exam

ple of

this is th

e developmen

t of treatmen

t m

ethods for diabetes m

ellitus. In

the

1920s, insu

lin w

as identifi

ed as a hor-

mon

e that regu

lates blood sugar levels.

Experim

ents on

rabbits, dogs, pigs and

cows h

elped to un

derstand th

e effect of in

sulin

on blood su

gar levels and th

us

contribu

ted to the developm

ent of n

ew

therapies. In

1923, the C

anadian

scien-

tists Frederick Ban

ting an

d John

J. R.

Macleod w

ere awarded th

e Nobel Prize

for their discovery of in

sulin

. Rabbits,

dogs and oth

er mam

mals h

ave been

largely replaced by rats and m

ice in

physiological

research.

The

rapid re-

production

of these species perm

itted specifi

c breeding for in

dividual clin

ical presen

tations. Th

is inclu

des, for exam-

ple, the “diabetes m

ouse” w

ith raised

blood sugar levels an

d the “Zu

cker rat” th

at develops obesity.

Imm

un

ology provides nu

merou

s ex-am

ples of the u

tilization of fi

ndin

gs from

an

imal

experimen

tation

for

therapeu

tic application

s in

h

um

ans.

Am

ong oth

er topics, imm

un

ology ex-am

ines

resistance

to path

ogens

and

the rejection

of transplan

ts after im-

plantation

. Pion

eering

advances

in

medicin

e inclu

de the developm

ent of

the an

tiserum

to diphth

eria (in w

hich

experim

ents

with

gu

inea

pigs w

ere in

strum

ental), vaccin

es against yellow

fever an

d polio (mou

se and m

onkey),

Marm

ots reduce their body functions to a minim

um during hibernation. A

better understanding of this process could be conducive to saving the lives of seriously injured people.

19221920

Archibald Hill, Otto Meyerhof

August Krogh

Metabolism

and heat generation of m

usclesDiscovery of the capillary m

otor regulating mechanism

1923Frederick Banting, John M

acleod

Discovery of insulin

Page 12

2120

studies

on

the

pathogen

esis of

tu-

berculosis (sh

eep and cattle), typh

us

(mou

se, rat

and

mon

key), m

alaria (dove), as w

ell as antiretroviral agen

ts to com

bat AID

S (mon

key).

The discovery of th

e effects of vita-m

in C

was stu

died in th

e guin

ea pig an

d led to the in

sight th

at the effect of

vitamin

s is the sam

e in an

imals as in

h

um

ans. H

ormon

es such

as calcitonin

from

salm

on

are u

sed in

th

e m

edi-cal treatm

ent of osteoporosis. A

nim

al experim

ents h

ave led to the develop-

men

t of new

surgical tech

niqu

es and

to the refi

nem

ent of operatin

g meth

-ods. Th

e first experim

ents on

tissue

transplan

tation w

ere performed in

the

mou

se as early as the start of th

e 20th

centu

ry. These days, an

imal m

odels (m

ainly pigs, bu

t also dogs and sh

eep) are

used

for kidn

ey tran

splantation

, bon

e marrow

transfer an

d heart su

r-gery, to develop n

ew m

ethods for th

e cu

re or alleviation of organ

diseases in

hu

man

s. Artifi

cial replacemen

t organs,

havin

g first been

subjected to stan

d-ardised tech

nical ch

ecks, are tested for th

eir biological compatibility in

large an

imals su

ch as pigs.

Nobel Prize w

orthy: Out-

standing scientific fi

ndings

Since th

e beginn

ing of th

e 20th cen

-tu

ry, extraordin

ary ach

ievemen

ts in

th

e area of physiology an

d medicin

e

have been

awarded th

e Nobel Prize.

The fi

rst Nobel Prize w

ent to th

e phys-

iologist Em

il von B

ehrin

g in 1901 for

his w

ork on th

e treatmen

t of diph-

theria. A

t the en

d of the 19th

centu

ry, n

early every second ch

ild died from

the disease. In

1890, von B

ehrin

g and

his Japan

ese colleague K

itasato foun

d th

at injectin

g low doses of th

e diph-

theria toxin

triggered the form

ation

of antibodies in

rats, mice an

d rabbits. Th

e anim

als were th

en protected for

life. Injectin

g the seru

m of im

mu

nised

anim

als also prevented th

e outbreak

of the disease in

other an

imals. V

on

Beh

ring th

us discovered on

e of the

basic principles of im

mu

nology – im

-m

un

ity – and paved th

e way for th

e developm

ent of vaccin

ations.

The

imm

ense

importan

ce of

anim

al experim

ents

in

biomedical

research

and th

e resultin

g know

ledge gain for

medicin

e is revealed by the fact th

at th

e Nobel Prize in

Medicin

e and Ph

ysi-ology (w

ith on

e exception, i.e. B

arbara M

cClin

tock for her stu

dies in th

e area of plan

t genetics) in

the last 40 years

has

always

been

awarded

to scien

-tists w

hose stu

dies inclu

ded the u

se of an

imals (see tim

eline at th

e top of th

e page). Ou

tstandin

g scientifi

c fin

d-in

gs that h

ave been aw

arded the N

obel Prize in

Physics or C

hem

istry have also

made su

bstantial con

tribution

s to pro-gress. Tw

o chem

ists, Robert Lefkow

itz an

d Brian

Kobilk, received th

e award

for their research

on an

importan

t class

of receptor proteins in

the cell en

velope of vertebrates, w

hich

plays an im

por-tan

t fun

ction in

various ph

ysiological processes. In

2008, Osam

u Sh

imom

ura,

Martin

Ch

alfie an

d Roger Y. Tsien

were

awarded th

e prize for the discovery of

the green

flu

orescent protein

(GFP) in

th

e biolum

inescen

t jellyfish

Aequ

orea victoria. Th

is protein an

d several differ-en

t variants are n

ow u

sed as un

iversal m

olecular

markers

in

biological an

d

medical

research,

and

enable

micro-

scopical analysis of cellu

lar processes th

at u

nderlie

the

physiological

fun

c-tion

s of the organ

ism an

d its diseases.

Diagnostics

In

coun

tries of

the

Western

w

orld, better h

ygiene con

ditions an

d medi-

cal care have led to a decrease in

neo-

Emil von

Behring

was th

e first p

erson

to b

e award

ed th

e No

bel Prize in M

edicin

e in 1901. H

is serum

th

erapy, w

hich was tested

on

anim

als, is the b

asis for vaccin

ation

s tod

ay.

1926Johannes Fibiger

Discovery of the nematode

Spiroptera carcinoma (cancer research)

1924W

illem Einthoven

Electrocardiogram

Page 13

2322

natal m

ortality and in

creased life ex-pectan

cy. Despite th

is progress, man

y diseases can

only be treated sym

pto-m

atically as

their

developmen

t h

as n

ot yet been adequ

ately researched.

Accordin

gly, society contin

ues to h

ave h

igh

expectations

of fu

ture

medical

advances an

d medical care.

Th

e su

ccessful

treatmen

t o

f m

any

diseases d

epen

ds o

n early d

iagno

sis.

Refin

emen

t and

imp

rovem

ent o

f di-

agno

stic p

rocesses

is th

erefore

on

e o

f the fo

cal po

ints in

research. N

on

-in

vasive ex

amin

ation

tech

niq

ues

such

as com

pu

ter tom

ograp

hy (C

T),

po

sitron

emissio

n to

mo

graph

y (PE

T),

magn

etic reso

nan

ce to

mo

graph

y (M

RT

) and

fun

ction

al MR

T (fM

RT

), as w

ell as the d

evelop

men

t of co

n-

trast agents an

d bio

mark

ers (ind

ica-to

rs of abn

orm

al pro

cesses) op

en u

p

new

diagn

ostic o

ptio

ns. In

19

79

, the

Am

erican A

llan M

. Co

rmack

and

the

En

glishm

an

Go

dfrey

N.

Ho

un

sfield w

ere aw

arded

th

e N

obel

Prize

for

develo

pin

g co

mp

uter

tom

ograp

hy.

Th

ey main

ly used

pig m

od

els in th

eir stu

dies.

In veterin

ary medicin

e, these h

ighly

sensitive diagn

ostic procedures are of

particular ben

efit to cats an

d dogs. Ex-

perience in

hu

man

medicin

e with

ul-

trasoun

d diagnostics, X

-rays and oth

er im

aging m

ethods is also leveraged in

m

odern veterin

ary medicin

e.

05

1015

2025

3035

Cardiovascular diseases

Infectious diseases

Cancer

Respiratory diseases

Accidents

Infection of the respiratory tract

Infant mortality

Diseases of the gastrointestinal tract

HIV/AIDS

Deliberately induced injuries

Tuberculosis

Neuropsychiatric diseases

Chart 3: The m

ost comm

on causes of death worldw

ide in percent

Source: Berlin Institute for Population and Development (Berlin-Institut für Bevölkerung und Entw

icklung): 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 W

HO data, 2008)

Co

mp

uter to

mo

grap

hy (C

T) pro

vides sectio

nal im

ages o

f the b

od

y. The p

ig w

as used

as the m

od

el o

rgan

ism in

the d

evelop

men

t of th

is pro

cedu

re, wh

ich w

as award

ed th

e No

bel Prize.

1928Charles Nicolle

Research on typhoid

Page 14

2524

Transplantation medicine

In

2014, 3,169

organ

transplan

ta-tion

s were perform

ed in G

erman

y. At

the sam

e time, 11,000 gravely ill pa-

tients w

ere waitin

g for a life-saving

donor organ

. The su

rgical techn

iques

and all procedu

res to avoid rejection

reactions

were

mostly

developed in

an

imal experim

ents after years of re-

search. O

f great importan

ce for organ

transplan

tation are n

ew fi

ndin

gs on

imm

un

osuppression

, i.e. meth

ods for su

ppressing im

mu

ne reaction

s against

donated organ

s to min

imise com

plica-tion

s in organ

recipients.

New

w

ays of

replacing

organs

are bein

g stu

died becau

se th

e n

um

-ber of don

or organs is n

ot suffi

cient.

Xen

otransplan

tation (from

the G

reek xen

os = foreign

), i.e. the tran

splanta-

tion of organ

s from on

e anim

al spe-cies to an

other, or from

an an

imal to

a hu

man

, occupies a special position

in

transplan

tation research

. It could

alleviate the sh

ortage of donor organ

s. Th

e research aim

s to identify species

wh

ose organs are su

itable for trans-

plantation

due to sh

ared biomedical

or physiological properties. For an

a-tom

ical and ph

ysiological reasons, th

e dom

estic pig is curren

tly regarded as th

e most prom

ising organ

donor for

hu

man

s. An

imal experim

entation

is th

erefore an

im

portant

interface

to livestock

research.

Wh

ile th

e tran

s-plan

tation of w

hole an

imal organ

s has

not

been

possible u

ntil

now

, tran

s-plan

tations of organ

parts and tissu

es h

ave produced som

e very good results,

e.g. heart valve tran

splants of porcin

e origin

.

The

possibilities of

xenotran

splanta-

tion are cu

rrently con

troversial, pri-m

arily becau

se of

ethical

considera-

tions an

d the poten

tial risk of imm

un

e rejection

s. For the fu

ture it is h

oped th

at genetically m

odified an

imals can

be bred w

hose im

mu

ne system

is even

more sim

ilar to the h

um

an on

e, there-

by reducin

g the poten

tial for rejection

of the tran

splanted organ

. Cu

rrent re-

search in

this area is at a very early

stage. An

obvious w

ay this tech

niqu

e cou

ld be used is already on

the h

ori-zon

: in clin

ical emergen

cies wh

ere no

suitable h

um

an don

or organ is im

me-

diately available.

Cell and tissue replacement

in humans

Man

y of the diseases kn

own

today are du

e to the loss of cells or tissu

e, or loss of th

eir fun

ction. N

euro-degen

erative diseases, su

ch as Parkin

son’s or A

lz-h

eimer’s disease, as w

ell as arthrosis

and m

yocardial infarction

, entail th

e loss

of cells

and

tissue,

with

m

ajor con

sequen

ces for the patien

t’s quality

of life. Dru

g treatmen

t, surgical cor-

rection an

d implan

tation of skin

or n

erve cells, or of heart valves, artifi

cial

In xen

otran

splan

tation

, cells or o

rgan

s are transp

lanted

from

on

e anim

al species to

ano

ther.

At p

resent, can

cer cells in p

articular are in

ocu

lated in

to n

ud

e mice fo

r research p

urp

oses.

1932Charles Sherrington, Edgar Adrian

Research on the electrical activity in neurons

1929Christiaan Eijkm

an, Frederick Hopkins

The importance of vitam

ins

Page 15

2726

hearts, h

eart pacemakers or artifi

cial join

ts, are all procedures th

at were de-

veloped with

the h

elp of anim

al ex-perim

entation

. Artifi

cial cultivation

of replacem

ent tissu

e from th

e patient’s

own

body, know

n as “tissu

e engin

eer-in

g”, migh

t be used in

the fu

ture to

replace damaged cells or organ

s with

“m

aterial” from th

e patient’s ow

n body.

Stem cells h

ave already been su

ccess-fu

lly used in

bone m

arrow tran

splan-

tations. Th

is approach offers th

e possi-bility of allow

ing som

e types of tissue

to regrow. M

oreover, in th

e so-called “bioh

ybrid implan

ts”, the body’s ow

n

cell structu

res and fu

nction

s are com-

bined w

ith electron

ic or mech

anical

implan

ts.

Stem cell research

The aim

of stem cell research

is to de-ciph

er the prin

ciples of cell differen-

tiation an

d to discover the possibilities

of how

to control it. Stem

cells are cells w

hich

are still largely capable of dividin

g and developin

g and h

ave the

ability to develop into specialised cells,

tissues an

d organs.

There are differen

t types of stem cells.

Em

bryonic stem

cells are cellular all-

roun

ders and h

ave the ability to de-

velop into an

y type of cell. They are

referred to as “pluripoten

t”, mean

ing

that an

y organ or tissu

e of a mam

-m

al can be developed from

this type

of cell. In adu

lt organs su

ch as bon

e m

arrow, skin

, or central n

ervous sys-

tem, adu

lt stem cells can

repair the

damage in

the organ

ism. Th

ese are referred to as “m

ultipoten

t” as they

only produ

ce cells from an

individu

al organ

or tissue. Foetal stem

cells are a

mixtu

re of

embryon

ic an

d adu

lt Stem

cells have g

reat po

tential in

med

icine as th

ey pro

vide fresh

cell material th

at can b

e used

to rem

edy d

iseases that h

ave been

diffi

cult o

r imp

ossib

le to treat u

p to

no

w.

1936Henry Dale, Otto Loew

i

Discovery of neurotransmitters

19341935

1933George W

hipple, George Minot, W

illiam M

urphyHans Spem

annThom

as Morgan

Discovery of liver therapy and pernicious anaem

iaThe “organiser effect” in em

bryonic development

The role of chromosom

es in heredity

Page 16

2928

stem

cells th

at are

no

longer

fully

adaptable, but grow

faster and better

instead. In

2012, the stem

cell stud-

ies performed by th

e Japanese Sh

inya

Yaman

aka and B

ritish Joh

n G

urdon

w

ere awarded th

e Nobel Prize. Th

ey discovered h

ow m

ature, differen

tiated cells can

be reprogramm

ed into stem

cells, w

hich

in tu

rn can

produce vari-

ous types of tissu

e. Their in

sights in

to in

duced

pluripoten

t stem

cells

(iPS cells) w

ere based on experim

ents w

ith

mice.

An

imal experim

ents in

stem cell re-

search pave th

e way for n

ew th

erapeu-

tic approaches to cu

rrently in

curable

diseases such

as Parkinson

’s, Alzh

ei-m

er’s and diabetes. In

cancer th

erapy, in

sights

into

the

differentiation

pro-

cesses in cells h

ave contribu

ted to the

un

derstandin

g of

the

mech

anism

s in

volved in th

e creation an

d division

of cancerou

s cells. The m

edical appli-cation

of cell and tissu

e replacemen

t by stem

cells has already been

tested on

an

imals.

Adu

lt stem

cells

from

the pan

creas, liver and bon

e marrow

cou

ld be successfu

lly reprogramm

ed in

to insu

lin-produ

cing cells an

d were

able to alleviate type 1 diabetes symp-

toms in

mice. Th

e transplan

tation of

mu

scle stem cells in

mice n

ot only

led to the repair of dam

aged tissue in

m

ice but also stim

ulated n

ew m

uscle

growth

. On

e long-term

objective is to u

se hu

man

stem cells to cu

lture com

-plex cell stru

ctures or com

plete organs

for tran

splantation

. Progress

in

this

area wou

ld greatly decrease the risk of

intoleran

ce and rejection

reactions.

Genom

e research

Gen

ome research

investigates th

e ge-n

etic m

ake-up

of livin

g organ

isms.

This in

volves not on

ly the gen

etic code – th

e sequen

ce of nu

cleic-acid buildin

g blocks in

DN

A – bu

t, more im

portant-

ly, the fu

nction

of the gen

es, as these

hold th

e key to the arran

gemen

t and

structu

re of the body an

d to the in

ter-action

s between

different organ

s. To be able to an

alyse these in

teractions

in

a com

plex organ

ism,

it is

neces-

sary to indu

ce specific ch

anges in

the

genetic m

aterial, i.e. the gen

ome, by

mean

s of anim

al experimen

ts. Effects

on th

e “phen

otype” of an an

imal – its

appearance,

behaviou

r, organ

fu

nc-

tion or blood cou

nt – en

able conclu

-sion

s about th

e genetic basis for th

ese ch

anges.

Gen

ome

research

uses

both

geneti-

cally m

odified

anim

als (tran

sgenic

anim

als) as well as an

imals exh

ibit-in

g spon

taneou

s ch

anges

to th

e ge-

nom

e (mu

tations) th

at are the resu

lt of

natu

ral ch

anges

or produ

ced by

breeding. G

enetic m

odification

of flies,

roun

d w

orms,

zebrafish

, m

ice, rats

and even

large anim

als such

as pigs is n

ow possible. Th

e mou

se is especially im

portant in

research on

hu

man

dis-

eases, as the m

ouse gen

ome an

d the

hu

man

genom

e exhibit m

ajor similar-

ities. Both

the h

um

an an

d the m

ouse

genom

e have n

ow been

fully decoded.

Today, a variety of genetically m

odi-fi

ed mou

se strains exist th

at can be

used as m

odel systems for stu

dying

hu

man

diseases.

Th

e Germ

an A

nim

al Welfare A

ct de-

man

ds th

at, before gen

etically mo

di-

fied

anim

als are

pro

du

ced,

there

mu

st be an eth

ical evaluatio

n an

d co

nsid

eration

o

f th

e stress

for

the

paren

t an

imals

and

su

bsequ

ent

generatio

ns.

Th

is is

irrespective

of

wh

ether th

e anim

als are pro

du

ced by tech

nical m

anip

ulatio

n o

r solely

by breedin

g a new

line. O

peratio

ns,

such

as the tran

sfer of egg cells to

surro

gate m

oth

ers o

r cu

tting

the

sperm

atic du

cts in m

ale anim

als, are

The C

aliforn

ian lu

mp

fish

(Ap

lysia californ

ica) is an im

po

rtant test m

od

el in th

e field

of n

euro

log

y d

ue to its excep

tion

ally large n

euro

ns an

d m

anag

eable nervo

us system

. The N

ob

el Prize winn

er Eric K

and

el used

its synap

ses to stu

dy learn

ing

at cellular level, am

on

g o

ther th

ing

s.

19381939

Corneille Heymans

Gerhard Domagk

Regulation of breathingDiscovery of the antibacterial effect of prontosil

Page 17

3130

perfo

rmed

u

nd

er an

aesthesia

with

su

bsequ

ent

pain

m

anagem

ent

and

are asso

ciated

with

m

ediu

m

levels o

f stress in th

e ind

ividu

al anim

als. T

he d

egree of stress in

the o

ffsprin

g is o

ften n

ot p

redictable an

d can

vary

from

sligh

t to

severe.

Em

bryon

ic d

evelop

men

t can be so

severely dis-

turbed

that th

e embryo

s or fo

etuses

die

before

birth.

Ho

wever,

exp

eri-en

ce has sh

ow

n th

at the ap

pearan

ce o

f transgen

ic anim

als is often

hard

ly

differen

t – if at all – from

that o

f the

wild

type. E

viden

tly the fu

nctio

nal

imp

airmen

t of a gen

e is com

pen

sat-ed

by oth

er genetic, bio

chem

ical or

ph

ysiolo

gical pro

cesses, so th

at devi-

ation

s can

o

nly

be d

etected

up

on

m

ore d

etailed an

alysis.

Recen

tly, genom

e research w

ith pigs

is also

gainin

g in

im

portance.

It is

now

possible

to specifi

cally m

odify th

e genom

e of an in

dividual oocyte

and con

sequen

tly breed anim

als that

can be u

sed for studies on

the gen

etic prin

ciples of diseases, for example in

research

on

degen

erative m

uscu

lar disorders. A

noth

er objective is to al-ter th

e imm

un

e system of pigs so th

at th

ey can produ

ce replacemen

t organs

for hu

man

use.

Neuroscience

Neu

roscience

investigates

the

struc-

ture an

d fun

ction of th

e peripheral

and

central

nervou

s system

. Th

eir prin

cipal focus is th

e question

how

n

erve cells

comm

un

icate w

ith

each

other an

d how

they are con

nected, in

order to gain

a better un

derstandin

g of th

e high

ly complex processin

g of sen

sory inform

ation, th

e control an

d coordin

ation

of beh

aviour,

and

the

processes of thin

king an

d feeling.

In

20

00

, th

e research

ers E

ric K

an-

del, P

aul G

reengard

and

Arvid

Carls-

son

were aw

arded

the N

obel P

rize in

Med

icine fo

r their d

iscoveries regard

-in

g signal tran

sdu

ction

in th

e nervo

us

system o

f mice, rats, rabbits, gu

inea

pigs an

d m

arine gastro

po

ds. In

20

13

, Jam

es E. R

oth

man

, Ran

dy W

. Sch

ek-

man

an

d

Th

om

as C

. S

üd

ho

f w

ere aw

arded

th

e N

obel

Prize

for

their

disco

veries of th

e transp

ort p

rocesses

with

in a n

erve cell and

their sign

ifi-

cance fo

r the tran

smissio

n o

f signals

between

nerve cells. T

hey em

plo

yed rats, h

amsters an

d gen

etically mo

di-

fied

mice in

their research

. In 2

01

4,

Joh

n O

’Keefe an

d th

e married

cou

-p

le Mo

ser were aw

arded

the N

obel

Prize in

Med

icine an

d P

hysio

logy fo

r th

eir research o

n sp

atial orien

tation

in

mam

mals. T

hey w

ere able to id

en-

tify sp

ecialised

brain

cells, th

e so

-called

place an

d grid

cells, respo

nsi-

ble for sp

atial orien

tation

, and

cou

ld verify th

eir interactio

n. T

he n

etwo

rk o

f grid cells an

d th

eir spatial o

rgani-

sation

is similar to

a 3D

coo

rdin

ate system

, and

enables o

rientatio

n an

d n

avigation

in tim

e and

space. T

hese

stud

ies w

ere p

erform

ed

usin

g rats.

Fu

rther stu

dies co

nfi

rm th

at com

pa-

rable structu

res of th

e biolo

gical ori-

entatio

n system

exist in

oth

er species,

such

as mice, bats an

d p

rimates, an

d also

in h

um

ans.

Cu

rrently,

stud

ies o

n

the

fun

ction

-in

g of th

e nervo

us system

and

the

brain are bein

g inten

sively pu

rsued

. T

he U

S is in

vesting in

large-scale re-

Co

mp

lex scientific q

uestio

ns su

ch as b

rain p

rocesses can

on

ly be stu

died

on

the in

tact and

living

org

anism

.

1943Henrik Dam

, Edward Doisy

Discovery of vitamin K

Page 18

3332

search p

rojects su

ch as th

e Brain

Ac-

tivity Map

Pro

ject (BR

AIN

initiative)

wh

ile Eu

rop

e is spen

din

g billion

s on

brain

research w

ith th

e Hu

man

Brain

P

roject. O

nly greater in

sight in

to th

e basic fu

nctio

ns o

f nerve cells w

ill en-

able researchers to

un

derstan

d w

hat

causes d

iseases of th

e nervo

us sys-

tem an

d to

develo

p treatm

ent m

eth-

od

s for stro

ke, A

lzheim

er’s and

Par-

kin

son

’s d

isease, m

ultip

le sclero

sis, ep

ilepsy,

dep

ression

, sch

izop

hren

ia, an

xiety d

is ord

ers and

parap

legia.

A su

bstantial n

um

ber of th

erapeu

tic ap

pro

aches are based

on

kn

ow

ledge

gained

fro

m

anim

al ex

perim

ents.

Fo

r ex

amp

le, stem

cell

transp

lanta-

tion

s into

the brain

of m

ice, wh

ich

were p

reviou

sly genetically m

od

ified

or su

bjected to

chem

ical substan

ces p

rod

ucin

g path

olo

gies similar to

hu

-m

an

diseases

such

as

Park

inso

n’s

disease, m

ultip

le sclerosis o

r strok

e, led

to im

pro

vemen

ts in th

e general

con

ditio

n an

d th

e disap

pearan

ce of

typical sym

pto

ms. C

hip

-based retin

a im

plan

ts p

rovid

ing

basal visio

n

to th

e blin

d,

or

coch

lear im

plan

ts fo

r th

e deaf, are based

on

scientifi

c ex-

perim

ents w

ith ch

icken

s, rabbits, cats, p

igs and

no

n-h

um

an p

rimates. D

eep brain

stim

ulatio

n

com

bines

neu

-ro

surgical

and

electro

ph

ysiolo

gical ap

pro

aches, w

hich

were m

ainly d

e-velo

ped

on

the basis o

f no

n-h

um

an

prim

ate mo

dels. It is n

ow

used

suc-

cessfully in

patien

ts with

Park

inso

n’s

disease

and

its

con

com

itant

mo

ve-m

ent d

isord

ers.

Kn

ow

ledge

gained

fro

m

anim

al ex

-p

erimen

ts is also u

sed in

the d

evel-o

pm

ent o

f pro

sthetic d

evices and

the

treatmen

t of p

aralysis. Fo

r exam

ple,

usin

g electrical

stimu

lation

o

f th

e sp

inal n

erves, no

n-h

um

an p

rimates

sufferin

g from

paralysis o

f their lim

bs d

ue to

spin

al cord

inju

ry were able

again to

mo

ve their h

and

and

grasp o

bjects. Nerve co

nd

uctio

n co

uld

be p

artially resto

red

in

parap

legic rats

by tran

splan

ting

embryo

nic

stem

cells into

their sp

inal co

rd. H

ow

ever, th

e mo

lecular an

d cellu

lar pro

cesses in

volved

are no

t yet un

dersto

od

well

eno

ugh

to be ap

plied

to h

um

ans. In

th

e same vein

, there are p

rom

ising

initial ap

pro

aches to

usin

g stem cell

therap

y fo

r th

e tran

splan

tation

o

f sp

ecific stem

cells into

affected areas

of th

e brain.

Veterinary research

The fi

ndin

gs from an

imal experim

ents

are of use n

ot only in

hu

man

medi-

cine, bu

t also in th

e developmen

t of n

ew diagn

ostic and th

erapeutic proce-

dures in

veterinary m

edicine. C

ertain

diseases occur both

in an

imals as w

ell as h

um

ans. A

mon

g these are arterio-

sclerosis and con

genital deform

ities of th

e spine in

rabbits, diseases of the vis-

ual system

in cats, an

d specific form

s

of cancer, diabetes, u

lcers and blood

disorders. Dogs w

ith a n

aturally oc-

currin

g blood clotting disorder, lead-

ing

to profu

se an

d life-th

reatenin

g in

ternal bleedin

g, can be treated for

haem

ophilia A

on th

e basis of a gene

therapy developed for h

um

ans, w

hich

stops th

eir bleeding in

the lon

g term.

Tum

our th

erapy in sm

all anim

als is an

other exam

ple.

A

transfer

of

treatmen

t m

etho

ds

is gen

erally po

ssible with

ou

t diffi

culties,

as the m

etho

ds p

ractised in

hu

man

m

edicin

e were d

evelop

ed in

anim

al ex

perim

ents.

Ho

wever,

veterinary

Hyg

iene is o

f utm

ost im

po

rtance w

hen

dealin

g w

ith an

imals. A

nim

al keepers an

d scien

tists mu

st w

ear pro

tective cloth

ing

wh

en en

tering

anim

al spaces to

preven

t the p

oten

tial risk of in

fection

to th

e anim

als.

1947Gerty Cori, Carl Cori, Bernardo Houssay

Research on carbohydrate m

etabolism

19451946

1944Alexander Flem

ing, Ernst Chain, Howard Florey

Hermann M

ullerJoseph Erlanger, Herbert Gasser

Discovery of penicillinDiscovery of the m

utagenic effects of X-rays

Research on the differential functions of individual nerve fibres

Page 19

3534

med

icine

likew

ise can

no

t d

ispen

se w

ith th

e use o

f exp

erimen

tal anim

als in

basic research an

d in

the d

evelop

-m

ent o

f new

treatmen

t meth

od

s. Th

e

wh

ich are d

ifficult to

teach in

the

con

text

of

clinical

rou

tine,

enable

ph

ysicians to

exp

and

their sk

ills for

surgical p

roced

ures o

n h

um

ans an

d to

learn n

ew tech

niq

ues. T

he G

er-m

an A

nim

al Welfare A

ct treats the

han

dlin

g o

f ex

perim

ental

anim

als as p

art of a train

ing p

rogram

me in

th

e same w

ay as anim

al exp

erimen

-tatio

n, i.e. as su

bject to ap

plicatio

n

and

app

roval.

The basic assumption of

transferability

Th

e com

po

nen

ts of bo

dy cells an

d th

e bioch

emical m

echan

isms n

eces-sary fo

r the p

rocesses o

f life are very sim

ilar across d

ifferent an

imal sp

e-cies.

Mo

lecular

genetics

can

dem

-o

nstrate

that

all o

rganism

s livin

g to

day

have

the

same

origin

. T

hey

share

genes

wh

ich

are resp

on

sible fo

r bo

dy

structu

re an

d

wh

ich

are m

od

ified d

urin

g the co

urse o

f evo-

lutio

n, th

us p

rovid

ing th

e material

basis for th

e sequ

ence o

f living crea-

tures th

rou

gho

ut th

e geolo

gical eras. T

hese

similarities

even

allow

co

m-

pariso

ns o

f hu

man

genes an

d m

eta-bo

lic pro

cesses with

tho

se of bacteria,

fun

gi and

yeasts.

Ho

wever, bo

dy fu

nctio

ns are m

uch

m

ore co

mp

lex in

high

er anim

als and

man

th

an

in

the

low

er o

rganism

s, as bo

dy fu

nctio

ns in

high

er anim

als

stud

ies are usu

ally design

ed su

ch th

at th

e target species, i.e. th

e po

tential

patien

t, is the su

bject of th

e investi-

gation

.

Vaccin

ation

strategies

for

fatal d

is-eases su

ch as leu

ko

sis, distem

per an

d bo

vine tu

berculo

sis were su

ccessfully

develo

ped

on

this basis. V

accines an

d veterin

ary med

icines h

elp to

redu

ce livesto

ck lo

sses as a result o

f diseas-

es. Ad

ditio

nally, th

ese med

icines are

used

in n

ature p

reservation

pro

jects fo

r the p

rotectio

n o

f end

angered

spe-

cies an

d

especially

to

preven

t th

e sp

read o

f diseases.

Anim

al experiments in edu-

cation, training and profes-sional developm

ent

Pro

per

han

dlin

g o

f ex

perim

ental

anim

als by researchers an

d an

imal

keep

ers n

eeds

to

be learn

ed.

Th

is in

clud

es the ro

utin

e tasks o

f anim

al k

eepin

g as well as blo

od

samp

ling,

injectio

ns

and

su

rgical p

roced

ures.

Carefu

l an

d

com

preh

ensive

train-

ing o

f perso

nn

el sho

uld

ensu

re that

any su

ffering in

anim

als is redu

ced to

a min

imu

m. T

his is also

necessary

from

a scientific p

oin

t of view

. In o

r-d

er to o

btain reliable an

d rep

rod

uci-

ble results, stress an

d p

ain sym

pto

ms

mu

st be min

imised

as mu

ch as p

os-

sible.

In

hu

man

m

edicin

e, esp

ecially in

th

e fields o

f surgery an

d an

aesthesia,

practical train

ing w

ith large an

imals

is an

im

po

rtant

elemen

t o

f ed

uca-

tion

. S

uch

p

ractical train

ing

un

its,

Veterin

ary med

icine w

as able to

develo

p vaccin

ation

strategies ag

ainst fatal d

iseases such

as dis-

temp

er and

leuko

sis by u

sing

test anim

als.

1951M

ax Theiler

Vaccine against yellow fever

19491950

1948W

alter Hess, Antonio Moniz

Edward Kendall, Tadeus Reichstein, Philip Hench

Paul Müller

Research on the functional organisation of the brain in the surgical treatm

ent of psychosisStructure and function of adrenal horm

onesDiscovery of the insecticide DDT

Page 20

3736

are based o

n a m

ultitu

de o

f special-

ised cell typ

es and

organ

s. Fo

r exam

-p

le, an

active

substan

ce m

ay h

ave th

e desired

effect in th

e liver, but be

chem

ically mo

difi

ed by th

e liver cells in

such

a way th

at the resu

lting co

m-

po

un

d is to

xic to

the cen

tral nervo

us

system. T

his sh

ow

s that th

e transfer

of reactio

n p

atterns fro

m cell stru

c-tu

res to th

e total o

rganism

can be ex

-trem

ely diffi

cult. F

or th

is reason

, no

t o

nly stu

dies at th

e cellular level are

need

ed

(usin

g altern

ative m

etho

ds,

see page 5

1ff.), bu

t also alw

ays stud

-ies o

f the co

mp

lete organ

ism to

check

both

the effi

cacy and

side effects o

f a su

bstance.

An

imal

exp

erimen

ts m

ake

it p

os-

sible to p

redict th

e desired

as well

as abou

t 70

% o

f the ad

verse effects o

n h

um

ans. O

ne ex

amp

le is acetyl-salicylic acid

(the active su

bstance in

th

e analgesic A

spirin

®). It alleviates p

ain in

both

rats and

hu

man

s, but

can

increase

bleedin

g in

bo

th

spe-

cies. Oth

er exam

ples are th

e effects o

f build

ing m

aterials and

of so

lvents,

wh

ich h

ave dam

aging effects o

n bo

th

rats an

d

hu

man

s. A

sbestos

causes

lun

g cancer in

rats and

hu

man

s, and

plastic so

lvents cau

se liver cancer in

bo

th. F

rom

these ex

perien

ces it can

be con

clud

ed th

at safety and

efficacy tests o

n an

imals can

significan

tly re-d

uce th

e risk o

f new

treatmen

t meth

-o

ds fo

r hu

man

s. 36

% o

f substan

ces tested

in p

reclinical an

imal stu

dies

are no

t used

in su

bsequ

ent clin

ical tests o

n h

um

ans d

ue to

un

desirable

side effects an

d safety risk

s, and

are ex

clud

ed fro

m th

e develo

pm

ent p

ro-

cess. A

nim

al ex

perim

entatio

n

thu

s p

revents

the

adm

inistratio

n

of

po

-ten

tially harm

ful o

r life-threaten

ing

substan

ces to h

um

ans.

How

ever, there is n

o such

thin

g as absolu

te safety. The Th

alidomide ca-

tastrophe

in

the

1960s m

ade th

is tragically clear. Prior to th

is event, th

e poten

tial of a drug to cau

se develop-m

ental m

alformation

s was n

ot inves-

tigated. It was on

ly after the scan

dal, in

1978, that th

e Germ

an D

rug Law

w

as tighten

ed and th

e effect on em

-bryon

ic developm

ent

was

added to

the testin

g catalogue for dru

g safety an

d efficacy.

Th

e basic assum

ptio

n o

f transferabil-

ity is also an

imp

ortan

t aspect in

the

evaluatio

n o

f pain

and

sensitivity in

an

imals. T

he an

atom

ical structu

re of

the brain

as well as th

e con

du

ction

o

f pain

stimu

li and

their p

erceptio

n

in

the

central

nervo

us

system

are sim

ilar in h

igher an

imals. T

his p

er-m

its analo

gies to be d

rawn

regardin

g p

ain sen

sitivity and

po

ssibly even th

e cap

acity fo

r su

ffering.

Th

e tran

sfer-ability o

f results fro

m an

imal to

hu

-m

ans th

us also

app

lies in th

e op

po

-site d

irection

. Dru

gs that h

ave been

successfu

lly used

to treat h

um

ans can

also

be used

for d

om

estic anim

als.

Mouse, rat

Cancer researchM

etabolic disordersEffi

cacy testing of drugsG

enome research

RabbitsD

evelopment of vaccines

Efficacy testing of drugs

Cattle, horse, pigVaccine developm

ent and isolationV

eterinary research

CatH

eart surgeryN

europhysiological studiesD

evelopment of hearing aids

Research on feline leukaemia

Veterinary research

Dog

Transplantation surgeryO

steosynthesisEm

ergency surgeryD

iabetes researchCardiovascular diseases

Osteoporosis researchVeterinary research

Non-hum

an primates

Basic and applied research in neurobiology

Vaccine development

SIV/H

IV research

Examp

les of an

imals u

sed in

research.

19531955

1954Hans Krebs, Fritz Lipm

annAxel Theorell

John Enders, Thomas W

eller, Frederick Robbins

The citric acid cycleThe effect of oxidant enzym

esDiscovery of grow

ing the poliovirus in cell cultures1952

Selman W

aksman

Discovery of streptomycin

Page 21

39

Anim

al experimentation and protection

of animals: Ethical considerations

Developm

ent of the concept o

f anim

al pro

tection

in G

ermany

The idea th

at hu

man

s have a special re-

sponsibility for an

imals in

their care is

the resu

lt of the h

istorical developmen

t of

the

relationsh

ip betw

een

anim

als an

d h

um

ans.

Cu

ltural,

philosoph

ical, social an

d official stan

dards defin

e the

framew

ork for our attitu

des towards

anim

als and th

eir needs. Th

e anim

al w

elfare laws an

d regulation

s that are

in place today are an

expression of th

is developm

ent, w

hich

began in

the 17th

cen

tury. Sin

ce then

, an an

thropocen

-tric view

of anim

al protection h

as been

advocated – with

man

at the cen

tre.

In th

e 18th an

d 19th cen

turies, in

flu

-en

tial mem

bers of a socially and politi-

cally active stratum

of the popu

lation

became active. Th

ey loathed all form

s of cru

elty to anim

als and regarded th

is attitu

de as a sign of th

eir level of edu-

cation. Th

e focus of in

terest was n

ot th

e an

imal,

but

concern

s abou

t th

e bru

talisation of in

dividuals an

d of soci-ety. In

Germ

any, a variety of law

s were

passed at first, an

d the Law

on th

e Pre-ven

tion of C

ruelty to A

nim

als was on

ly fi

rst inclu

ded in th

e Germ

an C

rimin

al C

ode in 1871. Th

is legal harm

onisation

prom

oted anim

al protection as a social

goal and led to th

e formation

of nu

-m

erous societies for an

imal protection

, w

ith th

e main

objective of preventin

g

cruelty

to an

imals

and

“vivisection”

(operations on

living an

imals). A

s ex-perim

ental research

and con

sequen

tly th

e n

um

ber of

anim

al experim

ents

increased w

ithin

the sam

e period, this

inevitably led to con

flict betw

een sci-

ence an

d anim

al welfare. E

ven back

then

, people’s reasons for rejectin

g ani-

mal experim

entation

varied dependin

g on

their scien

tific, religiou

s or societal backgrou

nd.

The fi

rst Germ

an A

nim

al Welfare A

ct w

as passed in th

e 1930s and rem

ained

in force u

ntil after th

e Second W

orld W

ar. For the fi

rst time, it laid dow

n

regulation

s for

workin

g w

ith

labora-tory an

imals. In

the 1960s an

d 1970s, pu

blic discussion

of the safety of farm

an

d laboratory

anim

als w

as revived;

this en

couraged th

e creation of n

ew

laws on

anim

al protection. Th

e An

imal

Welfare A

ct adopted in th

e Federal Re-

public of G

erman

y in 1972 w

as based on

ethical con

cepts of anim

al protec-tion

, and exploited scien

tific fi

ndin

gs on

species-specific an

d behaviou

rally correct stan

dards and th

e needs of th

e an

imals as criteria for evalu

ation.

Subsequ

ent ch

anges in

the law

in th

e 1980s an

d 1990s were in

flu

enced by

econom

ic, scientifi

c and political con

-sideration

s. These ch

anges in

creased th

e em

phasis

on

anim

als as

fellow

creatures an

d strength

ened regu

lation

of an

imal

experimen

ts. To

enh

ance

the

protection

of an

imals

as livin

g

1956André Cournand, W

erner Forssmann, Dickinson Richards

Development of cardiac catheterisation

Page 22

4140

creatures

in

the

legal system

, an

i-m

al protection w

as ensh

rined in

the

constitu

tion of th

e Federal Repu

blic of G

erman

y. In Ju

ly 2002, the con

-stitu

tion

was

amen

ded w

ith

Article

20a, wh

ich reads: “M

indfu

l also of its respon

sibility tow

ard fu

ture

genera-

tions, th

e state shall protect th

e natu

-ral fou

ndation

s of life and an

imals by

legislation

and,

in

accordance

with

law

and ju

stice, by executive an

d ju-

dicial action, all w

ithin

the fram

ework

of th

e con

stitution

al order.”

Eth

ical treatm

ent of an

imals h

as thu

s been

given an

un

usu

ally high

legal status.

Furth

ermore, th

e Third A

men

dmen

t to

the

An

imal

Welfare

Act

was

in-

troduced in

July 2013, w

hich

trans-

poses into n

ational law

the D

irective 2010/63/E

U

of th

e E

uropean

Parlia-

men

t and C

oun

cil of 22 September

2010 on

th

e protection

of

anim

als u

sed for scientifi

c purposes. It en

sures

a high

er level of anim

al protection an

d raises th

e min

imu

m stan

dards, taking

into con

sideration th

e latest scientifi

c fi

ndin

gs and developm

ents in

keeping

with

the Th

ree Rs prin

ciple (Redu

ce, R

efin

e, Replace – see pp. 47ff.).

Ethical aspects of animal

experimentation and the

principle of solidarity

A p

redo

min

ant view

with

in th

e cur-

rent

ethical

discu

ssion

o

n

hu

man

dealin

gs with

anim

als is that h

um

ans

are vested w

ith th

e basic mo

ral right

to u

se anim

als for th

eir ow

n en

ds.

Th

is righ

t, h

ow

ever, is

subject

to lim

its wh

ere anim

als are signifi

cant-

ly harm

ed by h

um

an actio

ns o

r are k

illed

with

ou

t su

fficien

t reaso

n.

In

the establish

ed system

of n

orm

ative p

ositio

ns o

n an

imal eth

ics, this p

o-

sition

is classified

as “path

ocen

tric”. T

his m

eans th

at a living o

rganism

’s ability to

suffer en

tails an o

bligation

to

pro

tect it. On

the o

ther h

and

, a p

ositio

n is d

efin

ed as “an

thro

po

cen-

tric” if it categorically m

akes h

um

ans

“the m

easure o

f all thin

gs”, inclu

din

g w

hen

it com

es to th

e treatmen

t and

pro

tection

of an

imals. A

third

rele-

vant p

ositio

n h

ere is the “bio

centric”

view, w

hich

assigns eth

ical value to

all living o

rganism

s, inclu

din

g low

er an

imals

and

p

lants.

Wh

ilst th

e ex

-trem

e versio

ns

of

these

three

po

si-tio

ns are in

com

patible w

ith o

ne an

-o

ther, th

eir mo

re mo

derate fo

rms are

generally regard

ed as reco

ncilable.

Acco

rdin

g to th

e stron

g variant o

f an-

thro

po

centrism

, ou

r treatmen

t of an

-im

als sho

uld

be assessed so

lely based o

n h

um

an in

terests, sentim

ents an

d feelin

gs. Th

is po

sition

has d

om

inated

ou

r cu

lture’s

ph

iloso

ph

ical o

utlo

ok

for cen

turies. Its m

ost p

rom

inen

t ad-

vocates w

ere Imm

anu

el Kan

t and

– rep

resentin

g leadin

g Ch

ristian m

oral

theo

logy – T

ho

mas A

qu

inas. T

he es-

sential ten

et of K

ant’s p

ositio

n is th

at m

an alo

ne h

as mo

ral capacity, w

hich

resu

lts both

in p

rerogatives an

d o

bli-gatio

ns. A

nim

al pro

tection

is thu

s ul-

timately ro

oted

in th

e self-respect o

f h

um

ans, w

hich

forbid

s acting cru

elly.

Imm

anuel Kant (left) w

as a follower of anthro

-p

ocen

trism – th

e belief th

at hum

ans are th

e m

easure of all things but that they have a re-sponsibility to treat anim

als humanely. A

ccord

-in

g to

Arth

ur Sch

op

enh

auer (cen

tre), anim

als exh

ibit th

e same ch

aracteristics as hu

man

s. Th

is mean

s they are cap

able o

f sufferin

g an

d feelin

g. A

lbert Sch

weitzer (rig

ht) rep

resented

radical b

iocen

trism, w

hich

extend

s an in

heren

t valu

e to all livin

g th

ing

s.

19571961

1960Daniel Bovet

Georg von BékésyFrank Burnet, Peter M

edawar

Development of substances w

hich inhibit the action of biological am

inesDiscovery of the m

echanical function of the inner ear

Discovery of acquired im

munological tolerance

Page 23

4342

How

ever, anth

ropocentrism

was su

b-ject to a far-reach

ing an

d now

general-

ly accepted critique from

a pathocen

-tric perspective by Jerem

y Ben

tham

an

d Arth

ur Sch

openh

auer. A

ccording

to Ben

tham

, the poin

t is not w

heth

er an

imals th

ink or speak like h

um

ans,

but

rather

wh

ether

they

can

suffer

like hu

man

s. All sen

tient bein

gs mu

st be ascribed w

ith in

trinsic valu

e.

Biocen

trismin

in tu

rn exten

ds this in

-trin

sic ethical valu

e to all living bein

gs, in

cludin

g low

er an

imals

and

plants.

The m

ost promin

ent exam

ple of this

view is A

lbert Schw

eitzer’s Th

e Eth

ics of R

everence for L

ife. Man

y supporters

of this view

even go so far as to ascribe

an equ

ally strong righ

t to life and de-

velopmen

t to

all n

on-h

um

an

living

beings.

An

ethical system

– such

as a patho-

centric on

e – that is prem

ised on th

e position

that sen

tient an

imals h

ave a m

oral status alon

gside hu

man

s, occu-

pies a comprom

ise position betw

een

the tw

o extremes m

ention

ed above. Th

is comprom

ise ascribes to sentien

t an

imals an

interm

ediate moral statu

s th

at is lower th

an th

at of hu

man

s, but

mu

ch

high

er th

an

that

of n

on-sen

-tien

t anim

als and plan

ts.

Patho-inclusive rather than patho-centric: W

hat’s the difference?

A

path

ocen

tric an

imal

ethics

po

stu-

lates mo

ral obligatio

ns to

ward

s ani-

mals an

d p

laces the avo

idan

ce of su

f-ferin

g at its core. H

ow

ever, it wo

uld

be inco

rrect to assert th

at the avo

id-

ance o

f sufferin

g in its en

tirety, and

therefo

re also o

f hu

man

sufferin

g, is to

be regarded

as the m

ost im

po

r-tan

t of all stan

dard

s. Overall, th

is ap-

pro

ach m

ight m

ore ap

pro

priately be

classified

as a “path

o-in

clusive” eth

-ics: It is n

ot o

nly reco

ncilable w

ith

valuin

g hu

man

interests o

ver tho

se o

f sentien

t anim

als, but also

with

the

po

sition

that o

ther h

um

an in

terests, su

ch as life an

d h

ealth, k

no

wled

ge gain

, and

pleasu

re, may ju

stify caus-

ing

distress

to

anim

als. M

oreo

ver, th

is view d

oes n

ot p

reclud

e the k

ill-in

g of an

imals, bu

t do

es dem

and

that

the k

illing sh

ou

ld n

ot cau

se fear or

sufferin

g, if po

ssible.

Even

th

ough

path

o-inclu

sive eth

ics ascribe

particular

rights

to an

imals,

this system

is not prem

ised on th

e as-su

mption

that an

imals possess th

ese righ

ts inh

erently an

d indepen

dently

of their bestow

al by man

. Rath

er, the

un

disputed position

amon

gst anim

al eth

icists of

epistemic

anth

ropocen-

trism – n

ot to be confu

sed with

the

norm

ative anth

ropocentrism

referred to above – righ

tly acknow

ledges that

only

hu

man

s are

capable of

estab-lish

ing, u

nderstan

ding an

d followin

g m

oral obligation

s. E

ven

if an

imals

are the su

bject of hu

man

obligation,

they depen

d on th

e benevolen

ce and

the efforts of people to in

terpret their

needs.

The

obligation

not

to in

flict

sufferin

g on h

um

ans an

d to actively relieve it is recogn

ised in all eth

ical system

s. The prin

cipal argum

ent for

expandin

g th

ese obligation

s beyon

d th

e sphere of h

um

ans is th

at it is not

evident

wh

y correspon

ding

obliga-tion

s shou

ld not in

principle also ap-

ply to sentien

t anim

als.

The

patho-in

clusive

position

is also

the basis for th

e Germ

an A

nim

al Wel-

fare Act. In

contrast w

ith older ver-

sions, w

hich

only afforded an

imals th

e am

oun

t of protection called for to pre-

vent pu

blic nu

isances or th

e potential

brutalisation

of hu

man

beings, th

e cur-

rent version

protects anim

als for their

own

sake. The in

fliction

of sufferin

g is on

ly acceptable wh

ere the associated

action (su

ch as an

anim

al experimen

t)

Edw

ard H

icks: The Peaceab

le Kin

gd

om

(1846/47).

19631964

John Eccles, Alan Hodgkin, Andrew Huxley

Konrad Bloch, Feodor Lynen

The initiation of the action potential in neuronsFatty acid m

etabolism and

the regulation of cholesterol

Page 24

4544

has th

e potential to protect, secu

re or realise poten

tial high

er values for h

u-

man

s and an

imals, w

hilst also bein

g in

dispensable to th

at end. Th

is view

requires tw

o forms of com

plex assess-m

ent an

d balancin

g to justify an

imal

experimen

tation: a w

eighin

g of moral

goods, and th

e determin

ation of in

dis-pen

sability. Both

assessmen

ts are diffi-

cult, bu

t not arbitrary.

Hu

man

values su

ch as life an

d health

gen

erally carry a stronger w

eight th

an

the avoidan

ce of sufferin

g for anim

als. M

oreover, there is also less certain

ty in

relation to an

imal su

ffering th

an th

ere is for h

um

an su

ffering. Sin

ce anim

als can

not h

elp us to in

terpret their feel-

ings an

d therefore depen

d on h

um

an

empath

y, experience an

d know

ledge to determ

ine th

eir welfare, th

ere is a con

siderable likelihood of error asso-

ciated with

assessing w

heth

er an an

i-m

al suffers an

d how

mu

ch. M

oreover, in

dividual capacity for su

ffering w

ill probably differ sign

ifican

tly between

an

imals – as it does betw

een h

um

ans.

Wh

ere there is great u

ncertain

ty re-gardin

g anim

al sufferin

g, the “proven

” claim

s of hu

man

s take priority from

the stan

dpoint of variou

s moral an

d eth

ical approaches.

The “in

dispensability” of in

flictin

g suf-

fering m

eans th

at no altern

ative meth

-ods are available, th

at anim

al experi-m

ents are optim

ised and th

e sufferin

g of an

imals is m

inim

ised relative to the

scientifi

c, therapeu

tic or other sign

ifi-

cance of th

e experimen

tal objective in

accordance w

ith th

e Three R

s princi-

ple (see page 47 ff.). The criterion

of su

ffering capacity th

us im

poses limits

on th

e experimen

ts that m

ay be per-form

ed on sen

tient an

imals, alth

ough

it does n

ot imply an

y categorical rejec-tion

of stressful an

imal experim

ents.

Moreover, it m

ay be presum

ed that

only som

e of the an

imal experim

ents

carried out are stressfu

l. Keepin

g cog-n

itively low

-developed an

imals

in

laboratories, for example, n

eed not be

classified as cau

sing su

ffering in

gen-

eral. In fact, laboratory an

imals often

live

longer

and

are h

ealthier

com-

pared to those livin

g in th

e wild. Fu

r-th

ermore,

man

y laboratory

anim

als are

kept in

con

trol grou

ps w

ithou

t bein

g subject to procedu

res, and som

e are

killed for

their

organs,

with

out

havin

g been previou

sly involved in

an

experimen

t. In addition

, there is also

the category of “fi

nal an

imal experi-

men

ts”. Here, th

e anim

als are drugged

prior to the start of th

e experimen

t an

d then

killed un

der anaesth

esia at th

e end of th

e experimen

t in order to

spare them

painfu

l experiences.

Patho-in

clusive eth

ics has n

o fun

da-m

ental objection

against su

ch experi-

men

ts, provided they are associated

with

advances in

biological or medical

know

ledge that are expected to ben

-efi

t hu

man

s.

Transferability from an

ethical-legal viewpoint

In th

e public discu

ssion on

the eth

ical evalu

ation of an

imal experim

ents, th

e direct tran

sferability of fin

dings to h

u-

man

s is often claim

ed to be a measu

re of legitim

acy. How

ever, this claim

un

-derestim

ates the com

plexity of trans-

ferability. Du

ring an

imal experim

ents,

anim

al life processes are investigated

that can

only be in

directly extrapolat-ed to h

um

ans. Th

is is also expressed in

legislation.

Directive

2010/63/EU

of

the E

uropean

Parliamen

t and C

oun

cil of 22 Septem

ber 2010 on th

e protec-

tion of an

imals u

sed for scientifi

c pur-

poses has th

ree aims:

► to sign

ifican

tly improve th

e welfare

of anim

als used in

scientifi

c experi-m

ents,

► to en

sure fair com

petition w

ithin

th

e EU

and

► to stren

gthen

research w

ithin

the

EU

.

Th

e transferability o

f the resu

lts from

an

imal ex

perim

ents to

hu

man

s is no

t stip

ulated

in th

e directive. In

stead, it

After m

ice, rats are the m

ost co

mm

on

ly used

labo

ratory an

imals.

19671968

Haldan Hartline, George Wald, Ragnar Granit

Robert Holley, Marshall Nirenberg, Gobind Khorana

Physiology of visionInterpreting the genetic code and its function in protein synthesis

1966Peyton Rous, Charles Huggins

Discoveries on the cause and treatm

ent of tumours

Page 25

4746

con

tains in

tentio

ns an

d m

easures to

imp

rove an

imal w

elfare and

to h

on

-o

ur th

e Th

ree Rs p

rincip

le. Th

e di-

rective specifies th

e pu

rpo

ses of th

e p

roced

ures

for

wh

ich

anim

als can

be u

sed. T

hese p

urp

oses are n

ot re-

stricted to

pro

cedu

res on

live anim

als w

ith resu

lts that are tran

sferable to h

um

ans. T

he d

irective do

es requ

ire an

ethical evalu

ation

that w

eighs th

e ex

pected

harm

caused

to th

e anim

als again

st th

e ex

pected

ben

efits. B

ut

it leaves

op

en

ho

w

these

benefits

are ultim

ately defin

ed o

r ho

w so

on

th

ey sho

uld

materialise: “... to

pro

-tect h

um

an an

d an

imal h

ealth an

d th

e en

viron

men

t.” T

his

un

specific

form

ulatio

n tak

es into

accou

nt th

e ex

perien

ce that it o

ften tak

es years befo

re d

iscoveries

from

an

imal

ex-

perim

ents tran

slate into

benefits fo

r h

um

an

and

an

imal

health

. R

equ

ir-in

g imm

ediate ben

efits for h

um

ans

is a mo

ral-ethical d

eman

d th

at can

hard

ly ever be fulfilled

. Just lik

e hu

-m

ans,

anim

als are

extrem

ely co

m-

plex

o

rganism

s, bu

t th

ey d

o

differ

from

hu

man

s, desp

ite a few fu

nd

a-m

ental sim

ilarities. Th

ese differen

ces are th

e result o

f variou

s evolu

tion

ary m

echan

isms w

hich

in th

e past h

ave h

ad an

effect on

high

ly com

plex

sys-tem

s such

as anim

als and

hu

man

s, an

d co

ntin

ue to

have an

effect tod

ay via m

ultifacto

rial mech

anism

s such

as

genetic

prep

ositio

n,

wh

ilst also

being su

bject to ep

igenetic an

d en

-viro

nm

ental in

fluen

ces. No

two

peo

-

ple are alik

e and

each p

erson

is their

ow

n

ideal

mo

del.

Hu

man

-orien

ted research

is therefo

re desirable, bu

t it is in

sufficien

t.

The conflict betw

een the solidarity principle and anim

al welfare

Com

plete proh

ibition

of experim

en-

tal anim

al research w

ould also con

-fl

ict with

anoth

er valid fun

damen

tal m

oral standard, th

e solidarity princi-

ple. This is th

e principle of providin

g th

e best possible support to th

e needy,

the w

eak and th

e sick. The solidarity

principle is n

ot only on

e of the m

any

precondition

s for life in h

um

an com

-m

un

ities; it is a hallm

ark of hu

man

bein

gs to be morally respon

sible and

capable of solidarity.

People w

ho

perform

anim

al experi-

men

ts always experien

ce confl

ict be-tw

een

two

obligations.

The

first

of th

ese is positive: the obligation

to use

one’s kn

owledge an

d abilities to re-du

ce hu

man

and an

imal su

ffering. In

con

trast, the n

egative obligation is n

ot to in

flict avoidable su

ffering on

other

creatures. It is h

um

an n

ature to fi

nd

it difficu

lt to reach a decision

if this

mean

s violating on

e of these obliga-

tions

in

order to

meet

anoth

er. A

s lon

g as it is scientifi

cally impossible

to un

ravel complex cau

sal activity re-lation

ships in

living an

imals w

ithou

t an

imal research

, this con

flict betw

een

obligations w

ill remain

the th

eme of

ethical

discussion

s. From

th

e stan

d-poin

t posited here, th

ere will n

ever be a gen

eral answ

er to the qu

estion

wh

ether an

anim

al experimen

t is jus-

tified – each

individu

al case requires

its own

answ

er.

The Three Rs principle

Alth

ough

an

imal

experimen

tation

cann

ot be completely avoided in

re-search

, there is a gen

eral consen

sus

that it m

ust be restricted to th

e neces-

sary min

imu

m. Th

e Three R

s principle,

devised by W. R

ussell an

d R. B

urch

in

1959, can be taken

as the gu

ideline

for anim

al experimen

ts. The Th

ree Rs

stand for

► refi

nem

ent,

► redu

ction an

d

► replacem

ent.

The aim

of the prin

ciple is to avoid an

imal

experimen

ts w

here

possible, to redu

ce their n

um

ber and to lim

it

Experiments

Alternative methodsFor example by using cells and/or skin models

Testing w

ithout animals:

Impact of chem

ical substances under the influence of

light on skin health

Non-anim

al testfor skin irritation

Cells

Reconstructed

human skin m

odels Test substance

Skin irritation: yes/no?

Test substance± U

V light

Dam

age of

cells: yes/no?

R eplace

(by

alternative

methods)

R efine (m

inimise

pain and suffering of the test anim

als)

R educe (the num

ber of test anim

als)

Three Rs Principle for Alternative Methods

w

ww

.bf3r.de/en/home ©

Germ

an Centre for the Protection of Test Animals (Bf3R), 2015

19701972

1971Bernard Katz, Ulf von Euler, Julius Axelrod

Rodney Porter, Gerald Edelman

Earl Sutherland

Synaptic storage, release and inactivation of neurotransm

ittersChem

ical structure of antibodiesDiscoveries concerning the m

echanisms of the action of horm

ones