Animals in Labs Article from All-Creatures.org

Flawed Science

From CAARE Citizens for Alternatives to Animal Research
August 2024

Evidence continues to mount that animal research is the wrong way to strive for progress in human medicine, but unfortunately, millions of animals continue to be used as the default method for research. The status quo method of using animals has been questioned, but not nearly enough. Until research moves to a fully human system, the flaws and inhumanity of animal research will persist.

Perhaps the best argument against animal research – one that does not rely on any individual ethics, politics, or beliefs – is that it often fails to provide relevant information for human health. Animal research is an unsuccessful method for researching the cause and treatment of human diseases, for three main reasons:

1. We cannot extrapolate from animals to humans due to profound genetic differences that arose from years of evolutionary divergence.
2. Animal tests do not predict human outcomes.
3. Artificially induced disease states in animals, even those created with genetic modification, do not yield accurate results for human medicine.

Animals and humans are complex biological systems. We have evolved over millions of years to have very specific characteristics. In addition, living organisms are adaptive systems - not static. They constantly respond to nuances in the environment, and within their own bodies.

Each complex system of a single animal is comprised of hundreds of thousands or even millions of biological interactions. The likelihood of two species modeling one another – reliably and predictably – is nil.

1. Extrapolation

The belief that different species react the same to stimuli underlies all animal research. But animal researchers themselves have shown that you cannot extrapolate accurately from one species to another.

Over the course of evolution, each species has established well-defined physiological, biochemical, anatomical and genetic differences. These differences are profound, particularly on the cellular or sub-cellular levels, where most diseases have their impact.

Our animal companions don’t catch colds, flu, measles, chicken pox, or mumps. And we don’t get distemper, parvo virus, or the same upper respiratory infections as dogs and cats, though we do suffer from cold viruses specific to humans. This is not insignificant. It has to do with crucial differences that underlie the physical integrity of each species, built right into the genetic code.

Rats are commonly used in the laboratory for a vast range of studies of human disease. But rat physiology differs significantly from human in ways that invalidate much of the research. For example, rats can eliminate cholesterol from the body faster than we can, so rats are very resistant to diet-induced plaque in the arteries. This greatly impacts studies of heart disease and cholesterol.

And stroke due to vascular occlusion is very rare in rats, while it is the third leading cause of human death in the U.S. Rats have a very different cardiovascular anatomy and their normal heart rate is 300-500 beats per minute. (Human is about 70 – 80). Rats don’t vomit. Rats synthesize their own vitamin C, a capacity that is not shared by humans. Spontaneous colon tumors are rare in rats, and even when induced they take a different form than in humans. Yet rats are frequently used to study this human disease which is the second leading cause of cancer death in Americans.

2. Predictability

Animal research is poor science because it lacks predictability. Any scientific method needs to predict the outcome, with great reliability, given known factors.

Consider the following examples:

Of over 1,200 chemicals found to cause birth defects in animals, only 30 cause them in humans. [1] Thirty out of 1,200 is only 2.5 percent effectiveness. How valuable a prediction is 2.5 percent effectiveness?

Because rodent toxicity testing is understood to be only about 50 percent predictive of human toxicology – the same as tossing a coin – the pharmaceutical industry has begun to reduce its reliance on animal data, as well as regulatory agencies that evaluate drugs and toxins for human safety, such as the Environmental Protection Agency and the Food and Drug Administration. [2]

A 2013 publication revealed the widespread failure of mouse “models” to develop drug treatments for sepsis, a severe form of infection. Mice are highly resilient to infection and can withstand exposure to bacterial toxins at doses nearly a million times higher than humans. [3]

Why are we using animal models when we have the capability to study the human body – ethically and non-invasively – through clinical studies, autopsies, diagnostic imaging, the human genome, and human tissue and human stem cells available through the use of cell cultures?

Why use the mouse genome when we can use the human genome to accurately predict human outcomes? Mice and humans are separated by approximately 75 million years of evolution.

Animal models do not extrapolate well to human diseases, and are not predictive of human conditions. They do not give accurate results for use in human medicine and, worse yet, they provide results that are misleading.

These two critical flaws give rise to fraudulent science, in which “results” are obtained by working backwards. Researchers using animals begin with an observation derived from human studies, and then try to reproduce it through animal studies. Because it is generated in the laboratory, it appears scientific, but it is not true science because we knew the outcome first. Reproducing results is not the same as the ability to predict.

As stated in the Handbook of Laboratory Animal Medicine: “It is impossible to give reliable general rules for the validity of extrapolation from one species to another. [This] can often only be verified after the first trials in the target species [humans]. Extrapolation from animal models … will always remain a matter of hindsight.” [4]

Medical breakthroughs in the treatment of polio and diabetes are typically attributed to animal research, but in fact, they are just two examples of simply re-affirming what was learned first through studies of people.

3. Artificially induced diseases or injuries to an organism do not accurately mimic those that are naturally occurring.

Animals do not suffer from most of the naturally occurring human diseases that scientists use them to study. Rather, what’s studied in the lab is a “model” that scientists create by inflicting injury or abnormality to the animal, in the hope that it will parallel the disease state. Or, in the case of “transgenic” animals (also referred to as genetically modified), they insert or remove genes, or sections of genes, to hopefully recreate the disease state.

Animals do not get cystic fibrosis, muscular dystrophy, multiple sclerosis, sickle cell anemia, HIV, Parkinson ’s disease, or Alzheimer’s. Even cardiovascular occlusive disease, which is so prevalent in humans, is very rare in animals. Most disease states are unique to each species.

Yet animal researchers purport to study these diseases using animals all the time. What they do instead is study “models.”

For example, Parkinson’s disease is due to a deficiency of dopamine in the brain. To study it in animals, researchers create physical or drug-induced lesions in the animal’s brain that affect the brain’s level of dopamine. To study Alzheimer’s, scientists attempt to induce the dementia associated with the disease by administering drugs that alter brain chemistry, or damaging brain tissue, or through genetic modification.

Using this method, which essentially attempts to mimic the symptoms of a disease by tampering with the healthy body of an animal, researchers attempt to study the intricate etiology and course of disease. Such a system is fraught with problems, compounded by the fact that there is poor correlation between the animal and human to begin with.

“Humanized” transgenic animals have one or more human genes inserted into their own DNA, in an attempt to circumvent the problem of species-specific differences and create a more comparable model. But a transgenic mouse is still a mouse. Insertion of one gene, or even a segment of DNA, does not create a mini-human. Scientists have developed many transgenic “models” that continue to yield inaccurate results because the entire organism is still another species.

We are more than just a compilation of genetic material. The field of systems biology has demonstrated that the whole is greater than the sum of its parts, because there are innumerable interactions taking place between genes, and variability regarding which genes are even expressed. (Expressed genes are active genes. Not all genes in the body are active, or active at the same time).

As an example of the limitations of genetically modified animals, Science magazine published a study in 1997 wherein the National Cancer Institute tested 12 anti-cancer drugs on mice who were genetically engineered to grow human tumors. The effectiveness of the drugs was already known. The study showed that 30 out of 48 times the drugs were ineffective in mice, even though the mice had been genetically manipulated to grow “human” tumors. A stunning 63% of the time the mouse models with human tumors were wrong. [5]

The failure of animal models to yield accurate information about human diseases is readily acknowledged by many scientists and medical experts, yet this knowledge has not yet translated into replacing the use of animals in research, as it should.

Dr. Elias Zerhouni, former Director of the National Institutes of Health (NIH), said in his 2013 address to NIH Scientific Review Board: “We have moved away from studying human disease in humans. …With the ability to knock in or knock out any gene in a mouse, researchers have over-relied on animal data. The problem is that it hasn’t worked, and it’s time we stopped dancing around the problem. We need to refocus and adapt new methodologies for use in humans to understand disease biology in humans.” [6]

The current Director of the NIH, Dr. Francis Collins, has said “the use of animal models for therapeutic development and target validation is time consuming, costly, and may not accurately predict efficacy in humans. … With earlier and more rigorous target validation in human tissues, it may be justifiable to skip the animal model assessment of efficacy altogether. ” [7]

Evidence continues to mount that animal research is the wrong way to strive for progress in human medicine, but unfortunately, millions of animals continue to be used as the default method for research. The status quo method of using animals has been questioned, but not nearly enough. Until research moves to a fully human system, the flaws and inhumanity of animal research will persist.

Notes

[1] New England Journal of Medicine, as quoted in Bitter Pills, by Stephen Fried, Bantam Pub, 1998, p274.

[2] Taylor, LD, 2009, “Human vs. Rodent” Drug Discovery & Development : Vol. 12, No. 3, March, 2009, pp. 16-18.http://www.dddmag.com/articles/2009/03/human-vs-rodent

[3] Seok et al., 2013 J. Seok, Genomic responses in mouse models poorly mimic human inflammatory diseases Proc. Natl. Acad. Sci. U S A 2013) http://www.Ncbi.Nlm.Nih.Gov/Pubmed/23401516

[4] Volume II: Animal Models Svendensen and Hau (Eds.) CRC Press 1994 p6.

[5] Science, vol. 278, Nov. 7, 1997, p. 1041)

[6] Dr. Elias Zerhouni, Former NIH director, 2002 – 2008, NIH Record, June 4, 2013, http://nihrecord.od.nih.gov/newsletters/2013/06_21_2013/story1.htm

[7] Collins, Francis S., Director, National Institutes of Health, “Reengineering Translational Science: The Time Is Right,” http://stm.sciencemag.org/content/3/90/90cm17.full  6 July 2011, Vol. 3, Issue 90, page 1. 

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Posted on All-Creatures.org: August 21, 2024
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