Does animal research inform us about improving human health?
The Quick Answer: sometimes, maybe, it depends.
How many animals are used in research laboratories?
- Here in Canada: “In its 2021 report the CCAC (Canadian Council on Animal Care) reported: “In 2021, there were 3,692,479 animals used in research, teaching, and testing reported to the CCAC (see Figure 1 and Table 1). The three animal types most often used in 2021 were mice (34.1%; 1,259,196), fish (33.9%; 1,251,563), and birds (12.0%; 444,596)” . https://ccac.ca/Documents/AUD/CCAC_Animal_Data_Report_2021.pdf “
- It is obvious that in the US no one knows how many animals are being used in research: “guesstimates” vary from 15 million to >100 million. https://www.science.org/content/article/how-many-mice-and-rats-are-used-us-labs-controversial-study-says-more-100-million ; lots of uncertainly stems from the fact that animals for research do not fall under the US federal Animal Welfare Act.
Brief background and motivation
This essay was motivated by my personal concern for animal welfare and a work history that includes 18 years of participating in bioethical decisions regarding animal use and welfare. Changes are coming but rather than fully advocating against animal research, I accept the fact that until we become sufficiently knowledgeable and sophisticated to discover more surrogates for animals, we must perform well designed experiments with respect, gratitude and humanity: we must be the first line of defence for the humane use of animals and follow the 3Rs code of conduct and science methods. That said, there are valid reasons to believe that not all of the results from animal research are meaningful to humans. The “acid test” is this: Are the results verifiable and transferable to the human biosphere?
Animal research is a multibillion-dollar industry. Imagine the science, the reputations and infrastructure in-place today. A quick survey of the literature might lead us to this conclusion — — When you have a hammer most everything looks like a nail, i.e. only live animals can provide the answers to the questions science may ask. Or, can they?
This quote sums up a lot as to why research in mice (Mus musculus) is very often used to predict outcomes in humans: “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.).
Since legislation was passed in the US in 1938 animals have been increasingly used as experimental organisms as models for predicting the outcomes in humans. Meanwhile increasing numbers of scientists and animal welfare organizations arguing that animal testing often lacks sufficient strength of “transferability”. Quoting: “In recent years, the practice of using animals for biomedical research has come under severe criticism by animal protection and animal rights groups. Laws have been passed in several countries to make the practice more ‘humane’.” Studies on mice have contributed immeasurably to better understanding of human biology. However, mice may often respond to experimental interventions in ways that differ markedly from humans.
Molecular biology, genetics and physiological chemistry
Why use such small animals like mice and rats? A mouse might weigh in at 30 g and human 70 kg. How can we make such a leap in predictions of outcomes, from mouse to human? Humans have 23 chromosome pairs and mice 20. Humans possess about 3 billion base pairs (bp) of DNA. Mice, approx. 2.5 billion bp. When we check the number of proteins encoded, they are quite similar: 30k mouse and 20–25k for humans. Only about 2% of the mouse DNA is actually translated into protein. Most importantly is that in humans over 200 cell types interpret the information differently. Mice and humans share approximately 97.5% of their DNA.
There are only two genomes that have been manually annotated, accounting for every base pair in the DNA sequence in which it resides, including its function. These are the human and the mouse . Recent research has uncovered formerly unknown genes that differ among 16 mouse strains.
Pros
· Mice are invaluable for studying biological processes that have been conserved during the evolution of the rodent and primate lineages and for investigating the developmental mechanisms by which the conserved mammalian genome gives rise to a variety of different species.
· Animal experiments remain essential to understand the fundamental mechanisms underlying the onset of malignancies and to discover improved methods to prevent, diagnose and treat diseases.
· primary tumor xenografts are believed to offer relevant predictive insights into clinical outcomes when evaluating the efficacy of novel cancer therapies.
· See T. Vandamme for additional literature: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3895289/#:~:text=Mice%20have%20many%20advantages%20over,it%20a%20cost%2Defficient%20model
Cons
· Mice often respond to experimental interventions in ways that differ strikingly from humans. A better understanding of the mechanisms of gene regulation may provide needed insight to improve the predictability of animal models.
· Animals may evolve differently from humans in response to diseases. Although mice and humans are genetically similar it cannot be assumed that they will respond similarly when challenged with a disease.
Behavioural, neurological and psychiatric experiments.
Pros
· Behaviour is heritable. Selection in 70 generations of rats compared to the human genome database Ensembl …” in our genome-wide study, we uncovered natural selection against underexpression of human aggressiveness-related genes and proved it using F1 hybrid mice. “
· Human Brain organoids transplanted into rat brains: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(23)00004-8;
· We conclude that processing of collinear features is indeed different between rats and humans. We speculate that the observed difference between rat and human is caused by the combined impact of differences in the statistics in natural retinal images, the representational capacity of neurons in visual cortex, and attention
Reshaping Memories in the Brains of Mice https://www.the-scientist.com/scientist-to-watch/steve-ramirez-reshapes-memories-in-the-brains-of-mice-70633?utm_campaign=TS_DAILY_NEWSLETTER_2023&utm_medium=email&_hsmi=244951852&_hsenc=p2ANqtz--hWaZPqNoSSvjVY4wCk9aKg662tTjcn5onRySSAx5DAP6tcnnr6h6ieHUdX0fxC1uejK4n5PHcy4CKjUSDXt3fVb2jlACRRq1yptIx1DNXa0bg7i4&utm_content=244951852&utm_source=hs_email
Cons
Drug may promote neural growth but fail to improve mobility: https://www.the-scientist.com/news-opinion/drug-spurs-neuron-growth-in-mice-with-chronic-spinal-cord-injury-70550?utm_campaign=TS_DAILY_NEWSLETTER_2023&utm_medium=email&_hsmi=245128144&_hsenc=p2ANqtz-99WoVTMGRFUuZ6Y2d9c1JM6VRYJxVOuXYFPOfWcBbPUBdeg4EaOE-kcoM8wWRDZK4YMNpgK1xpudAcgROYoTVuY0_EwIvZu22buZ4kIPHyi0JIXhg&utm_content=245128144&utm_source=hs_email
Rats and humans differ in processing visual images: “We conclude that processing of collinear features is indeed different between rats and humans.”
The following is taken from an extensive review of the literature. While there are numerous cases where rodent-human diseases were declared concordant, the variability among animal studies and overall numbers of animals compared to human studies can make it difficult to predict what might happen in the human biosphere : “It is well known that animal models often do not capture key aspects of human cognition and disorders such as neurodevelopmental disorders (Zhao and Bhattacharyya, 2018); multiple sclerosis (Denic et al., 2011a); neurological and psychiatric disorders (Fernando and Robbins, 2011; Monteggia et al., 2018); psychoactive drug use and addiction (Müller, 2018; Venniro et al., 2020); and obesity and diabetes modeling (Kleinert et al., 2018) where rodents do not exhibit similar human behavior coinciding with the disease.
Final Remarks and Transfer Problems
We know that there is experimental evidence that suggests that rodent models (rats and mice) could be transferred to humans to mitigate a disease or some limitation. After an extensive review these authors wrote: “We conclude that there is sufficient evidence for selection of an age-appropriate rodent model that is predicated on biochemical and neuroanatomical changes during early postnatal development, as well as the emergence of age-specific behaviors. Ongoing research across the gamut of cerebral development in both humans and rodents in parallel will provide a greater understanding of how all these factors interact, and manifest as age-dependent behavioral changes.” My note: “age appropriate” was important.
Contrary to the above
“More than 30 clinical trials have been conducted in TBI (traumatic brain injury, _Zack Florence_) without a single success (Kabadi and Faden, 2014). The most recent phase III trial, which addressed progesterone therapy, failed after more than 300 positive animal studies (Stein, 2015). Clearly, the pathophysiology and treatment of TBI differ between humans and model animals. These differences must be understood so they can be accounted for when interpreting results. These differences exist on several levels: genomic, transcriptomic, proteomic, functional and biomechanical. The distribution of stress and strain across key tissues during head impact differs widely between the rat and the human. “ source: https://doi.org/10.1016%2Fj.clinbiomech.2018.01.015
Alternatives to animal-use
- monitoring animal behaviours and species conservation: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9265132/
- “The (Replacement, Reduction and Refinement) were developed over 50 years ago providing a framework for performing more humane animal research. Since then they have been embedded in national and international legislation and regulations on the use of animals in scientific procedures, as well as in the policies of organisations that fund or conduct animal research. Opinion polls of public attitudes consistently show that support for animal research is conditional on the 3Rs being put into practice. We divide replacement into two key categories, full and partial replacement.
- Full replacement refers to methods that avoid the use of animals for research and testing purposes. It includes the use of human volunteers, tissues and cells, mathematical and computer models, and established cell lines — often referred to collectively as non-animal technologies or NATs.
- Partial replacement includes the use of some animals that, based on current scientific thinking, are not considered capable of experiencing suffering. This includes invertebrates1 such as Drosophila, nematode worms and social amoebae, and immature forms of vertebrates2. Partial replacement also includes the use of primary cells (and tissues) taken from animals killed solely for this purpose (i.e. not having been used in a scientific procedure that causes suffering).”
Thank you for using your time to read my work: Zack Florence
