WHAT ARE THE MOST COMMON ANIMAL MODELS IN DRUG DISCOVERY?

“Animal research and testing has played a part in almost every medical breakthrough of the last century. It has saved hundreds of millions of lives worldwide...” – Former UK Home Office minister Joan Ryan.

Albert Sabin, who developed the Polio vaccine said, "Without animal research, polio would still be claiming thousands of lives each year.”

Why animal models?

·         If you are going to study a human disease you can’t directly perform the initial work in humans; you have to develop a model. Some models may be in vitro – literally, in glass tubes – but as you learn more and more, you must eventually test ideas in vivo.  That means you have to have a way of producing the disease that allows you to study it.  As mentioned earlier, humans cannot be used for this purpose for ethical reasons, therefore – living animals are used as models.

·         New medicines require testing because researchers must measure both the beneficial and the harmful effects of a compound on a whole organism. A medicine is initially tested in vitro using tissues and isolated organs, but legally and ethically it must also be tested in a suitable animal model before clinical trials in humans can take place.  Therefore, a new drug or a surgical technique is tested in animals to make sure that it is safe and effective.

·         Chimpanzees share more that 99% of DNA with humans and mice share more than 98% DNA with humans.  There is a 67% similarity between the DNA of humans and earthworms.

[Please understand the difference between ‘Shared genes’ and ‘Working DNA’ – You end-up seeing different % similarity values, but do read it carefully if the discussion is done based on ‘Shared genes’ or ‘Working DNA’]

Are animals as model is proper in research? 

Ø  Although humans and animals may look different, at a physiological and anatomical level they are remarkably similar. Animals, from mice to monkeys, have the same organs (heart, lungs, brain etc.) and organ systems (respiratory, cardiovascular, nervous systems etc.) which perform the same functions in pretty much the same way.

Ø  Many basic cell processes are the same in all animals, and the bodies of animals are like humans in the way that they perform many vital functions such as breathing, digestion, movement, sight, hearing and reproduction.

Ø  In particular, mammals are essential to researchers because they are the closest to us in evolutionary terms. For example, many diseases that affect human beings also affect other mammals, but they do not occur in insects, plants, or bacteria.

Ø  Humans and animals share hundreds of illnesses, and consequently animals can act as models for the study of human illness.

o   For example, rabbits suffer from atherosclerosis (hardening of the arteries), as well as diseases such as emphysema, and birth defects such as spina bifida.

o   Dogs suffer from cancer, diabetes, cataracts, ulcers and bleeding disorders such as haemophilia, which make them natural candidates for research into these disorders.

o   Cats suffer from some of the same visual impairments as humans.

From such models we learn how disease affects the body, how the immune system responds, who will be affected, and more.

What are the advantages of animal models?

v  Animals also offer experimental models that would be impossible to replicate using human subjects.

v  Animals have a shorter life cycle than humans and as a result, they can be studied throughout their whole life span or across several generations. 

v  In addition, scientists can easily control the environment around animals (diet, temperature, lighting), which would be difficult to do with humans.

v  Animals can be fed identical and closely monitored diets. As with inbred mice, members of some animal species are genetically identical, enabling researchers to compare different procedures on identical animals.

v  Animals such as rats, mice, birds, rabbits, guinea pigs, sheep, fish, frogs, pigs, birds, dogs, cats, primates, among others are used in biomedical research.

v  Approximately 95% of these animals used in biomedical research are rats and mice specifically bred for research and 4.25% of these animals include rabbits, guinea pigs, sheep, fish, frogs, insects, and other species.  Most importantly, only 0.75% of the animals in research are cats, dogs, and primates.

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RAT

Lifespan: Brown rat: 2 years, Black rat: 12 months

Gestation period: Brown rat: 21 – 24 days, Polynesian rat: 21 – 24 days

Mass: Brown rat: 230 g, Black rat: 110 – 340 g

MOUSE

Lifespan: African pygmy mouse: 2 years

Gestation period: House mouse: 20 days, African pygmy mouse: 20 days

Mass: House mouse: 19 g, African pygmy mouse: 3 – 12 g

                                                                                                   

GUINEA PIG

Lifespan: 4 – 8 years

Gestation period: 59 – 72 days (Adult)

Mass: 0.7 – 1.2 kg (Adult)

Length: 20 – 25 cm (Adult)

                                                               

FERRET

Lifespan: 6 – 10 years

Gestation period: 42 days; Mass: 0.7 – 2 kg; Length: 38 cm (Without Tail)

Gestation period: The period from fertilization of the egg (ovum) to the birth of the child.

ü  For example, 28 days study of a drug on an animal model has to be conducted – which animal model should we choose if we are given a choice between a mouse and a rat?           Mice / mouse (~20 g wt of each mouse) and (rat - ~120 g wt of each rat).                                   Each day blood sample from mouse might not be a good idea.  But each day blood sample from rat should not be a problem.  Therefore, choice would be rat.

ü  Though (for initial studies) mouse data is collected (as less amount of compound needed for this study) later rat data is needed

ü  Few studies cannot be done on rat – then they are switched to other animals according to disease of study – like dog, ferret, guinea pigs, rabbit.  

Compiled from several sources.