ETHICS IN USING ANIMALS FOR RESEARCH

FB6244/FK8124 RESEARCH METHODOLOGY

ANISAH NORDIN
DEPT PARASITOLOGY & MEDICAL ENTOMOLOGY
UKM ANIMAL ETHIC COMMITTEE (UKMAEC)
[email protected]
 LEARNING OUTCOMES

• Define ethical framework and principles of using

animals in research.
• Discuss the importance of the 3Rs as a guiding
principle in the use of animals in research.
• Explain the 5 Freedoms and how these apply to
laboratory species.
• Understand the role of UKMAEC in overseeing
scientific activities involving animals.

2
 ANIMALS IN RESEARCH
Develop new medicines & to test the safety of products
- Many caused pain/reduce quality of life
- Morally wrong to cause animals to suffer
Researcher:
- Aware of the ethical issues & acknowledge that
experiments should be made as humane as possible
- Wrong to use animals if alternative testing methods would produce
equally valid results

ACCEPTABLE if (and only if)

Suffering is minimized
Human benefits could not be obtained by using other methods
3
 ANIMALS IN RESEARCH
Advancing scientific knowledge
basic research
- to advance scientific knowledge about the way animals behave,
or develop and function biologically
- the study of basic physiological processes and genetic
mechanisms
Models to study disease mechanisms & develop
interventions
- disease processes, develop effective preventative & therapeutic
measures eg vaccines/medicines
- may also be used for, animals.
Models in toxicity testing
to test the safety of compounds that are potentially hazardous for animals, humans or the environment

4
 ANIMALS IN RESEARCH
Estimate (worldwide): 90-100 million animals used
2015: 79.9 million animals (58.3 million in 2005)

Comprehensive global data: 192.1 million animals (115.3 million in 2005)

- animal killed for tissues
- normal & GM animals used to maintain the strains
- animal bred for laboratory used but not used

MALAYSIA: 74,705 animals (21,443 in 2005)

- Taylor & Alvarez, 2019
95-97%: rats, mice, fish and birds
Majority 85%: rodents (mice and rats)

6
 HISTORY
150 AD Early Greek physician dissected animals (vivisection) for anatomical studies & to satisfy
scientist (Galen) anatomical curiosity
12th century Ibn Zuhr an experimental method for testing surgical procedures before applying
them to human patients
17th century (Age of enlightenment) physiological experiments on animals were carried for the purpose of
scientific progress
René Descartes animals were machine-like (interpreted as a belief that animal could not
feel pain)
Baruch Spinoza (1632-1677): did not deny animals’ ability to feel (sentient) but considered human
should nevertheless use them as we please and treat them in a way
which best suits
End of 17th Albrecht Von Haller acknowledge cruelty and animal suffering but justified as for the sake of
century to (1708-1777) humankind
18th century Immanuael Kant acknowledge the sentient of other species
(1724-1804)
8
 HISTORY
19th century whether vivisection was justifiable based on the benefit for humans.

Opposition to vivisection (England) but not in France and Germany

Francois Magendie dissected a dog’s facial nerve while the animal was nailed down by each
(1783-1855) paw and was left overnight for further dissection the following day
1874: Queen Victoria expressed her concern over the treatment of animals
1875 Victoria Street Society for the Protection of Animals Liable to Vivisection
(National Anti-Vivisection Society) was founded (1st society for animal
protection)
1876 Enactment of Cruelty to Animals Act (The Act)
• Prohibit painful experiments on animals
• Animal must be anaesthetized during procedures, and if the pain
continues after the procedure, animal must be killed before it
recovers from anesthesia
9
ANIMAL RIGHTS VS ETHICS ANIMAL SUFFERING

10
“A physiological demonstration with
vivisection of a dog,” by Émile-
Édouard Mouchy (1832).

11
ETHICAL FRAMEWORK

Weighing the harms and benefits of the projects

(HARM/BENEFIT ASSESSMENT)
• Produce great benefits for humanity that it is
morally acceptable to harm A FEW ANIMALS

Applying the 3Rs to minimized the harm,

maximize the benefits

Promote good ANIMAL WELFARE practices

• The 5 Freedoms

15
 HARM/BENEFIT ASSESSMENT
COST-BENEFIT ANALYSIS
to determine whether the obtained benefits of the
research will outweigh the cost to the animal(s).

COST: the expected harm, pain and distress that is likely

to be experienced by the animals during the conduct of
the research project.

BENEFIT: the potential benefits that might be realized for

humans, other animal species, or the environment.

“The use of animals in a research project is only acceptable when its expected benefits will
outweigh the physiological and psychological harm that will be caused to the animals. When
preparing a research protocol, special concern should be given to the minimization of pain, distress
and discomfort, and the maximization of possible benefits”
16
 THE 3Rs
Principles of good science to improve animal
welfare and scientific accuracy.
AIM: to reduce the impact of research on animals

Introduced by Russell & Burch (1957) in The Principles of Humane

Experimental Technique (commissioned by the Universities Federation for
Animal Welfare).
Adherence to the 3Rs: requirement of most if not all legislated and
self-regulated national systems of surveillance.

17
 REPLACEMENT
REPLACED WITH NON-ANIMAL MODELS
• Mannequin for dissection (teaching the structure of the
animal or the human body)
• mechanical models/computer simulations
• audiovisual aids
• in vitro modeling /established cell lines/cell cultures etc

REPLACING 'HIGHER' ANIMALS WITH 'LOWER‘ ANIMALS.

• Microorganisms, plants, egg/fetus, reptiles, amphibians, fish
invertebrates (Drosophila, nematode worm) may be used to
replace warm-blooded animals.

18
 REDUCTION
MINIMUM NUMBER OF ANIMALS REQUIRED TO OBTAIN SCIENTIFICALLY VALID
RESULTS.
HOW?
• improve experimental techniques & data analysis
• consult statistician for the minimum numbers of animals required to achieve significance.
• minimize variables that may affect outcome: disease, stress, diet, genetics, etc.
• conduct literature searches to ensure no duplication of experiments.
• share information/data (if possible) with other researchers/colleague
• use appropriate animal species for specific study.
• replace animals whenever possible.

19
 REFINEMENT
modification of procedures or husbandry & care practices so that pain,
suffering and distress is minimised and animal wellbeing is enhanced

Identify pain & distress (due to experimental protocol etc), how to

prevent/relieve
• Adequate training prior to performing a procedure.
• Proper handling techniques
• Modify the experiment/animal care to reduce suffering:
• less invasive techniques
• better medical care
• better living conditions (toys/enrichment)

Animals chosen must be of an appropriate species; and the scientific projects must take into account their specific
biological properties eg genetic constitution, behavior, and microbiological, nutritional and general health status

21
THE 3Rs CONCEPT - SUMMARY

• FRAMEWORK for the assessment of the humaneness of animal

use in research and teaching.

• Investigators are REQUIRED BY LAW to make sure that they minimise any pain or
other harm they cause to the animals they use for research, teaching, and testing.

• ensuring that animals are only used when necessary (REPLACEMENT), that no more
animals are used than are required to achieve the objectives of the work
(REDUCTION), and that if any noxiousness is caused during the work, it is kept as low
as possible (REFINEMENT).

22
 Adopted from a UK Government report on livestock husbandry in
THE 5 FREEDOMS 1965 by Prof. Roger Brambell.
FREEDOM FROM HUNGER OR THIRST
ready access to fresh water and diet to maintain full health and
vigour.

FREEDOM FROM DISCOMFORT

appropriate environment: shelter, comfortable resting area

FREEDOM FROM PAIN, INJURY OR DISEASE

prevention or rapid diagnosis & treatment.

FREEDOM TO EXPRESS (MOST) NORMAL BEHAVIOUR

sufficient space, proper facilities & company of the animal's own
kind.

FREEDOM FROM FEAR AND DISTRESS

Ensuring conditions & treatment which avoid mental
suffering/stress.
23
 ANIMAL RESEARCH – PLANNING A PROJECT

3 QUESTIONS TO ADDRESSED:
Question 1: “Do I need to use higher order animals?” (REPLACEMENT)
If “Yes” then Reduction and Refinement must be applied.
Question 2: “What is the minimum number of animals needed for this
work?” (REDUCTION)
Statistically significant: statistician? power of study?, animal species? pilot
study?
Question 3: “How will these procedures impact on the animals?”
(REFINEMENT)
Animal need, pain management, handling/restraining

24
 RESPONSIBILITY OF RESEARCHER
MUST have knowledge and trained in handling the particular animal
species in the study
PAIN AND DISCOMFORT should be minimized
• Anesthesia/analgesia (as required), repeated surgical
procedures on the same animal should be avoided
ONLY SKILLED PERSONNEL should perform surgical procedures,
anaesthesia, euthanasia (AVMA 2020) of animals
ASEPTIC technique should be used whenever possible
HUMANE treatment of the animals should be incorporated into the
study protocols

Start from the planning, receiving the animals until the end of the
study (euthanasia)

28
 REFINING ENDPOINTS
Majority are killed at the end of the experiment
• their tissues are required as part of the experiment
• the scientific objectives have been achieved and the animal can no longer be
used.
If the experiment leads to an increasing amount of suffering during its course, it
would be best to killed them as early as possible - HUMANE ENDPOINTS

PRINCIPLE: SETTING THE EARLIEST POSSIBLE ENDPOINT FOR THE EXPERIMENT.

If the necessary information can be gathered before the animal experiences any ill effects from the
experiment, this should be defined as the endpoint.

32
 FEDERAL REGULATIONS - MALAYSIA
Principal legislation governing the care and use of laboratory animals in Malaysia
1. ANIMAL WELFRE ACT (ACT 772) 2015: AWA 2015
2. Animal (Amendment) Act 2013: Veterinary authority: Animals Act 1953 (Act 647)
ANIMAL: Any living creature other than a human being and includes any beasts, bird, aquatic
animals, reptile or insect but does not include wildlife under the Wildlife Conservation Act 2010
(Act 716)
Animal welfare: include the animal needs as specified in section 24 (1)(a)
its need for a suitable environment
Its need for a suitable diet
The need for it to be able to exhibit its normal behavior patterns
The need for it to be housed with or apart from other animals
The need for it to be protected from pain, suffering, injury and disease

OWNER: any person who owns any animal and includes any person for the time being in charge of any animal
or any person occupying any premises.
34
 FEDERAL REGULATIONS - MALAYSIA
KEY CONTENT (MyCODE):
1. General principles for the care and use of animals in scientific
research
 Justifications for animal use
 Applications of 3R principles (Reduce, Refine, Replace)
2. Responsibilities of IACUC
 Establishment & TOR of IACUC
 Composition of the IACUC (Categories A, B, C & D membership)
3. Responsibilities of the investigator(s)
 Project planning, suitability of models, procedures, termination and disposal
of animals
4. Acquisition and care of animals in breeding and holding facilities
 Transportation, quarantine, husbandry & veterinary care
 Special sub-section on non-human primate care
5. Veterinary care
 Role and responsibilities of the attending veterinarian
35
 KEY EXCERPT IN AWA 2015 – THE USE OF ANIMALS IN RT&T

Section 16(1) – (4) License application made to AWB, and AWB grants the license to an individual
- IACUC: bridging body for review, records, monitoring, & will assist should in the event of an
investigation or legal query

Section 24 Duties of owner or licensee

- Based on the 5 Freedoms

Section 26(1) Requirement for license for RT&T

Section 29(1) Description of cruelty offences

- any procedures that are nor declared under IACUC can be persecuted under this section, eg:
inappropriate restraints, diet alteration etc WITHOUT APPROVAL

Section 29(2) Exemptions from 29(1) by the Board-approved authorities eg. IACUC

36
Section 30 Killing of animals (Section 30(1)), circumstances where animals can be euthanised by a competent
vet authority and/or IACUC (Section 30(2)), REFERENCE TO IACUC (Section 30(3), Section 30(4)
Penalty.
**Researchers have to abide

Section 31(1) Administrations of poisons

-Requirement to obtain permission from AWB approved bodies (eg IACUC) to treat animals with
drugs and ‘poisons’
-**Importance of IACUC approval

Section 33(1) & (2) Failure to exercise reasonable care and supervision (to animals)
- Importance of animal care description in IACUC form.
Section 34 Powers in relation to animal in distress
- Authority of a registered veterinarian and AWO to order the destruction, relocation of distressed
animals

All RT&T activity related to animals in an institution is REQUIRED BY LAW to

be REGULATED AND APPROVED by AEC/IACUC
37
 UKM ANIMAL ETHICS COMMITTEE (UKMAEC)
All animal use in RESEARCH, TESTING & TEACHING at UKM IS
REGULATED BY LAW to be screened and approved under the
jurisdiction of the UKM Animal Ethics Committee (UKMAEC)

The general role of UKMAEC:

• Reviews and monitors animal use protocols
• investigate./assures animal welfare concerns

ANIMAL: Any member of the animal kingdom, and includes

i. any mammal (other than man), bird, reptile, amphibian, fish, arthropod, or other
All life deserves protection vertebrate or invertebrate, whether alive or dead from thereof; and
ii. any readily recognisable part of a derivative of an animal as defined in the
International Trade in Endangered Species Act 2010 (Act 716).
38
The functions of UKMAEC:
• to approve and monitor research involving the use
of laboratory animals from UKM, other
universities, other research institutions and private
entities, taking into consideration the scientific
merit or educational benefits.
• to ensure that the animal house facilities or
vivarium and its animals are properly maintained
and equipped with basic facilities for breeding or
research based on international standards.
• to ensure that the animals are cared for, the
experiments are humanely carried out, and the
number of animals used in a project are
appropriate.
• to ensure animal handlers including students and
researchers have received appropriate training.

39
 UKM ANIMAL ETHICS COMMITTEE

MUST APPRAISE AN APPLICATION WITH REGARD TO THE 3RS (as required by

the Code).
• evaluate the animal husbandry and housing, the experience of the scientific and technical
staff and students involved.
Any pain or distress that may result from any procedures must be CLEARLY
STATED in the proposal and the AEC must consider how this is to be MONITORED
AND ALLEVIATED if not prevented.
• application of humane end points, the appropriateness of the method of euthanasia (if
required) and the competence of the staff to perform it humanely.

40
 CONDUCTING EXPERIMENT WITHOUT APPROVAL?
Animal Welfare Act 2015

• Animal activities listed in the schedule need to be

LICENCED
 (SECTION 15)

• Any person who carry out activities WITHOUT

LICENSED COMMITS AN OFFENCE

Fine : not less than RM15,000 and not more than

RM75,000 or imprisonment for a term not more than 2
years or both

41
 MISCONDUCT/CRUELTY TO ANIMALS?
Section 29 (Cruelty to animals) & Section 30 (animal killing)

If both these sections are violated by any researcher, they are

committing an offence directly under the Act whereby this
offence is not entitled for compound or improvement notice.

Upon conviction
will be subject to PENALTY UNDER SECTION 29 (NOT LESS THAN
RM20,000 OR NOT MORE THAN RM100, 000) OR NOT MORE
THAN 3 YEARS IMPRISONMENT OR BOTH .

6/16/2021 AN UKMAEC MONITORING WSHOP 2019 43

Although animals cannot yet be completely replaced, it is important that
researchers maximize refinement and reduction
The benefits of animal research have been enormous and it would have
severe consequences for public health and medical research if it were
abandoned

44
AIMS Contributing to the humane use of animals in
biomedical research and the collection of
informative unbiased and reproducible data

Influence of external factors

Planning experiments &

Managing the human

Characteristic of the
Regulation & ethics

research design
animals

factors
MEANS

Anatomy, Environmental Quality control

Laws, Communication,
physiology, conditions, systems, SOP,
regulations, cooperation,
genetics, intervention, GLP, statistics,
guidelines, 3R, coordination and
biochemistry, ANAESTHESIA, experimental
ethics contracts
microbiology surgery, etc design 46