Ground breaking Grewall

Systematic animal testing began in the 17th century and one of the first animals to be used extensively for anatomical dissection and study were pigs. Rabbits were introduced in the 18th century, particularly for infectious diseases. Louis Pasteur used rabbits to develop the anthrax vaccine in 1878. In the 19th century, Ivan Pavlov used dogs to study physiology of digestion and behaviour [1]. Did you know, in 2021, 4,277 regulated experiments were carried out on dogs in Britain, out of which 4,016 have been beagles [2]. 

As a young research enthusiast, I decided to unravel the reasons why certain species are used for experimentation. During this journey, I have also come across some interesting facts and shared them here.

Rodents

The earliest recorded use of rodents (Mus musculus) in biomedical research dates back to the early 1900s to study inheritance patterns. This low cost model with a short generation time and genetic similarity to humans has been used to study complex diseases such as atherosclerosis, diabetes, hypertension and cancer [12]. They’re definitely better than using Drosophila or Caenorhabiditis models. 

Experimentation with knockout mice or immunodeficient mice have aided research but one such model, a rat named #42, decided to try his luck with Harvard scientists studying the impacts of obesity on brain function. The scientists observed the eating habits of rats but #42 showed unusual behaviour. He over-ate and showed erratic behaviour like running into the walls of the cage but would be “normal and sane” at night, significantly impacting data collection. Apparently, #42 has ruined previous experiments such as one studying the effects of cat scent on rats, where he not only pushed the button but also “winked and held his paws out for his treat” [13].

Elephant seals can sleep underwater (and even as they dive!)

It was believed that African elephants could get by with only 2 hours of sleep whereas some others, like the koalas need 20 hours. Northern elephant seals (Mirounga angustirostris) can take short naps of around 20 minutes while diving 377m deep into the sea [3]. 

Dr. Kendall-Bar explains that once they dive and begin to glide deep underwater, their brain activity slows down and transitions into rapid-eye-movement (REM) sleep, wherein they flip upside-down and spin in a circular path. The seals are oblivious to their slow descent but they suddenly wake up after 10 minutes and find their way to the surface. 

These dives in total provide them about 2 hours of sleep per day at sea, contradictory to the 10 hours on land. 

Beagles are the most common dog breed in animal testing

Beagles are small, docile, easily manageable dogs. They are genetically homogeneous which makes them useful while studying genetic and inherited diseases. They have a well-documented history of being bred specifically for laboratory use with a low incidence of health problems [5]. Some have even called them the “most forgiving” breeds. Dogs share 350 genetic disorders with humans, including cancers, neurological disorders, immune-mediated diseases and retinal degeneration which is similar to human retinitis pigmentosa. Their size, life-span and ability to exhibit the same clinical signs and symptoms make them a “valuable model” for studying age-related diseases [6].

Koalas get high on eucalyptus leaves- false

A recent rumour suggested that koalas (Phascolarctos cinereus) get intoxicated by eating eucalyptus tree leaves. While it is true that they can sleep up to 20 hours a day and occasionally fall off the trees, they do not get intoxicated or have hallucinations. It is simply that eucalyptus leaves are low in nutrients and thus, these marsupials need more sleep to conserve energy. During heatwaves, the leaves they feed on lose their moisture content and they can suffer from dehydration and heat stress, due to which they can fall off tree branches- not because they lose balance due to intoxication [4].

Rabbits and horses are good models for vaccine development

Louis Pasteur first used rabbits to create the live attenuated rabies vaccine. Much later, in the 19th century, did pharmaceutical companies breed cows and horses for making medical products [7]. Infections like HIV1 produce similar pathological changes in rabbits as in humans. The New Zealand white rabbits (Oryctolagus cuniculus) are especially used to study cardiovascular diseases due to their phylogenetic proximity and intermediate size [8].

If rabbits are used due to similar pathogenesis and disease susceptibility, horses have been bred for producing antitoxins and large amounts of high-quality antibodies. They are also models for research related to musculoskeletal diseases like osteoarthritis and tendon injuries, because they have the most similar host-pathogen interaction and development and maintenance of the musculoskeletal system and to humans. Their immune system is also very sensitive and highly susceptible to infections [9].

Hippos produce red sunscreen

A group of Japanese scientists tested the secretions of hippopotamuses (Hippopotamus amphibius) and found two highly unstable, acidic compounds. They named the red one as hipposudoric acid and the orange one as norhipposudoric acid. These compounds combine in the presence of mucus and form a dry layer on the skin that can remain for hours at a time as a protection against sun rays. Hipposudoric acid also contains antibiotic properties, controlling the growth of pathogenic bacteria. The group has hypothesised this to explain why hippos remain largely free of infection [10, 11].

REFERENCES:

1. Franco, N. H. (2013). Animal experiments in biomedical research: a historical perspective. Animals, 3(1), 238-273. https://doi.org/10.3390/ani3010238
2. Naturewatch Foundation. (n.d.). Beagle testing. Retrieved April 21, 2023, from https://naturewatch.org/campaigns/animal-experiments/beagle-testing/ 
3. Kendall-Bar, J. M., Williams, T. M., Mukherji, R., Lozano, D. A., Pitman, J. K., Holser, R. R., … & Costa, D. P. (2023). Brain activity of diving seals reveals short sleep cycles at depth. Science, 380(6642), 260-265. https://doi.org/10.1126/science.adf0566
4. World Wildlife Fund. (2022, March 10). 10 interesting facts about koalas. Retrieved April 21, 2023, from  https://www.wwf.org.au/news/blogs/10-interesting-facts-about-koalas.
5. The Beagle Freedom Project. (n.d.). Beagle breed information. Retrieved April 21, 2023, from https://bfpuk.org/ 
6. Hasiwa, N., Bailey, J., Clausing, P., Daneshian, M., Eileraas, M., Farkas, S., Gyertyán, I., Hubrecht, R., Kobel, W., Krummenacher, G., Leist, M., Lohi, H., Miklósi, A., Ohl, F., Olejniczak, K., Schmitt, G., Sinnett-Smith, P., Smith, D., Wagner, K., Yager, J. D., … Hartung, T. (2011). Critical evaluation of the use of dogs in biomedical research and testing in Europe. ALTEX, 28(4), 326–340. https://doi.org/10.14573/altex.2011.4.326 
7. Science History Institute. (2021, March 16). Animals and the making of human vaccines. Google Arts & Culture. Retrieved April 21, 2023, from https://artsandculture.google.com/story/animals-and-the-making-of-human-vaccines-science-history-institute/ugUBP0D2x-JygA?hl=en.
8. Peng, X., Knouse, J. A., & Hernon, K. M. (2015). Rabbit models for studying human infectious diseases. Comparative medicine, 65(6), 499-507.
9. Ribitsch, I., Baptista, P. M., Lange-Consiglio, A., Melotti, L., Patruno, M., Jenner, F., … & Penning, L. C. (2020). Large animal models in regenerative medicine and tissue engineering: to do or not to do. Frontiers in Bioengineering and Biotechnology, 8, 972.
10. Saikawa, Y., Hashimoto, K., Nakata, M., Yoshihara, M., Nagai, K., Ida, M., & Komiya, T. (2004). The red sweat of the hippopotamus. Nature, 429(6990), 363-363. https://doi.org/10.1038/429363a 
11. Thompson, A. (2016). Hippos Produce Their Own Sunscreen. Fisher Scientific. Retrieved April 21, 2023, from https://www.fishersci.com/us/en/education-products/publications/headline-discoveries/2016/issue-3/hippos-produce-their-own-sunscreen.html
12. Bryda, E. C. (2013). The Mighty Mouse: the impact of rodents on advances in biomedical research. Missouri medicine, 110(3), 207. 
13. Srivastava, A. (2015). Meet The World’s Most Badass Rat Messing With Scientific Studies At Harvard. IndiaTimes. Retrieved April 21, 2023, from https://www.indiatimes.com/news/world/meet-the-world-s-most-badass-rat-messing-with-scientific-studies-at-harvard-250413.html