The studies on animals  cannot be equal to work on human beings

Krishna: Animal research often provides the rationale for hypotheses studied by epidemiologists and clinical researchers. However, animal studies may not predict human reactions.

The concept that animal research, particularly that relating to pharmaceuticals and environmental agents, may be a poor predictor of human experience.

One reason why animal experiments often do not translate into replications in human trials(1,2) is that many animal experiments are poorly designed, conducted and analysed. Another possible contribution to failure to replicate the results of animal research in humans is that reviews and summaries of evidence from animal research are methodologically inadequate.

A paper by researchers (3)  has made an important methodological contribution to understanding why animal studies may not predict human reactions. The authors conducted systematic reviews of the animal research relevant to studies in humans in six areas of research where confident estimates of intervention effects (benefit or harm) have been demonstrated in systematic reviews of randomized trials. The interventions studied were: corticosteroids for head injury; antifibrinolytics to reduce bleeding; tissue plasminogen activator to reduce death and disability after stroke; tirilazad for ischaemic stroke; antenatal corticosteroids to reduce lung morbidity and death in preterm newborns; and bisphosphonates to increase bone mineral density. In three of the research areas the animal studies and human trials were substantially discordant; in three others the results were essentially similar. In all areas of research, however, major methodological limitations of the animal research and evidence of widespread publication bias were identified.

The few systematic reviews of the animal literature that have been done also pointed to the poor quality of other animal research, and the difficulty of extrapolating from it to humans,(4) a concern which is being increasingly made in other fields of drug development and evaluation. 

Researchers  recently challenged (5) those who have claimed that ‘virtually every medical achievement of the last century has depended directly or indirectly on research with animals’ to provide evidence justifying their assertion.

Some of the key problems have been summarized by researchers (6):

• Disparate animal species and strains, with a variety of metabolic pathways and drug metabolites, leading to variation in efficacy and toxicity;
• Different models for inducing illness or injury, with varying similarity to the human condition;
• Variations in drug dosing schedules and regimens of uncertain relevance to the human condition;
• Variability in animals for study, methods of randomization, choice of comparison therapy (none, placebo, vehicle);
• Small experimental groups with inadequate statistical power; simple statistical analyses that do not account for confounding; and failure to follow intention-to-treat principles;
• Nuances in laboratory technique that may influence results, for example, methods for blinding investigators, being neither recognized nor reported;
• Selection of outcome measures, which being surrogates or precursors of disease, are of uncertain relevance to the human clinical condition;
• Variable duration of follow-up, which may not correspond to disease latency in humans.

In personalised medicine, diagnostic testing is often employed for selecting appropriate and optimal therapies based on the patient's genetics or their other molecular or cellular characteristics. The use of genetic information has played a major role in certain aspects of personalized medicine.

Experimental rats

(Image source: iStock)

Then, why are experiments still conducted on rats? 

Humans and mice don't look alike, but both species are mammals and are biologically very similar.

Almost all of the genes in mice share functions with the genes in humans. That means we develop in the same way from egg and sperm, and have the same kinds of organs (heart, brain, lungs, kidneys, etc.) as well as similar circulatory, reproductive, digestive, hormonal and nervous systems. These similarities make it possible for scientists to study the physiology of mice to glean information about how human beings grow, develop diseases and age.

This genetic similarity also means that mice and humans inherit traits in the same way. This includes physical traits such as hair color (coat color in mice) and susceptibility to diseases such as heart disease or Alzheimer’s.

Because mice live short lives compared to humans — about two years in laboratory care, but much less in the wild — it’s possible to learn a great deal about how chronic diseases progress over a lifetime, and about the processes of aging. Mice are small and relatively economical to maintain, making them the ideal laboratory animal model.

However, work on rats or mice gives a preliminary idea. We cannot directly use human beings when we are entering an unknown arena. That is why researchers use rats. 

Now comes the Q of ethics. Rats are also living beings with nervous systems. They feel the pain.

So is it ethical to use them or any other animal for clinical studies where they face pain and agonizing death? NO!  

Developing a well-reasoned response to a moral problem in Scientific Research is extremely important as it will have a great impact on all living beings. Therefore, the impact on the public should always be considered when making ethical decisions.  Scientific discoveries, inventions and scientific activities can have impacts on things like our environment, our planet as a whole, the safety of living beings,  our health  and  treatments offered for various diseases,  and so forth. [7]

Research or experiments can be done through in-vitro methods instead of in-vivo methods which require use of an animal. India is the first country to issue  guidelines for such experiments and we should be proud of it. The guidelines are very progressive. We hope that similar rules are issued for toxicity testing of drugs on animals. Alternatives like cell culture, use of human cells, robotics and AI can be used. Then where is the need to use live animals on a large scale to conduct experiments? [7]

 

Yes, although  the studies on animals  cannot be equal to work on human beings, sometimes it becomes necessary to get a preliminary knowledge to form a theory based on animal models. This need not translate into human facts. 

Footnotes: 

1.  Roberts I, Kwan I, Evans P, Haig S. Does animal experimentation inform human healthcare? Observations from a systematic review of international animal experiments on fluid resuscitation. BMJ. 2002;324:474–6. [PMC free article] [PubMed] 

2.  Hackam DG, Redelmeier DA. Translation of research evidence from animals to humans. JAMA. 2006;296:1731–2. [PubMed]

3. Perel P, Roberts I, Sena E, et al. Comparison of treatment effects between animal experiments and clinical trials: systematic review. BMJ. 2007;334:197. [PMC free article] [PubMed]

4. Bebarta V, Luyten D, Heard K. Emergency medicine animal research: does use of randomization and blinding affect the results? Acad Emerg Med. 2003;10:684–7. [PubMed]

5. Matthews RAJ. Medical progress depends on animal models – doesn't it? J R Soc Med. 2008;101:95–8. [PMC free article] [PubMed] [Google Scholar]

6. Pound P, Ebrahim S, Sandercock P, Bracken MB, Roberts I. Where is the evidence that animal research benefits humans? BMJ. 2004;328:514–17. [PMC free article] [PubMed]

7. https://kkartlab.in/group/some-science/forum/topics/science-and-ethics

8. https://en.wikipedia.org/wiki/Personalized_medicine#:~:text=Persona....