Problems with the Animal Model

Problems with the Animal Model


Mice, rats and other animals are not accurate models for predicting the human response. This claim is backed by copious amounts of scientific evidence!

Due to the large number of differences between species, including genetic, physiological, metabolic and psychological, animal-based research is far less reliable than flipping a coin! In reality, animal models can be used only as analogies for human systems.[i]

Different species often react differently to the same drugs or treatments. Penicillin is a great example. 

Penicillin can be:

- Fatal for guinea pigs and Syrian hamsters[ii]

- Effective in mice[iii]

- Metabolised too quickly in rabbits[iv]

- Teratogenic in rats (causes limb malformations in offspring[v])

- Effective in humans 

With such a variety of reactions to penicillin in many different species, how do we know which animal model will be predictive for humans? The answer is simple, we don't! This is one of the many issues in using animals to model human responses. Human-relevant research would provide a much more accurate result.

 

How predictive is unreliably predictive?

Only 5 in 5,000 compounds that enter preclinical drug safety testing make it to human trials, and only 1 of those five may be proven to be safe and effective enough to reach pharmacy shelves. This is a success rate of 0.02%.[vi] 

More than 9 out of 10 drugs deemed successful in animal tests fail in human trials.[vii] That’s a staggering 95% failure rate. Any other industry that boasts a 95% failure rate would be considered absurd.

This has also been acknowledged by the US FDA -“Currently, nine out of ten experimental drugs fail in clinical studies because we cannot accurately predict how they will behave in people based on laboratory and animal studies," Mike Leavitt, former Health and Human Services Secretary US Food and Drug Administration 2006.[viii]

One study published in the prestigious journal Nature in 2012, sent shockwaves through the scientific community. A team of highly respected researchers declared that they had been unable to reproduce the findings in 47 of 53 "landmark" cancer papers.[ix]

In 2003, a landmark study closely examined 25000 articles published in leading science journals. It measured the translation rate of basic research into clinically useful treatments. The result was astonishingly low: 0.004 percent, to be precise.[x]

The authors of the study state that even if their figure of 0.004% is out by a factor of 10 (to allow for all sorts of errors), the transfer rate of basic research into clinical use is very low. You could even go farther and say that if the figure of 0.004% is out by a factor of 100, the resulting figure of 0.4% success is still unacceptably low.

 

Examples of different research fields that highlight the failure of the animal model

  • Animal Experimentation is Ineffective for HIV and AIDS Research: HIV researchers have developed 90 vaccines that protect non-human animals from HIV infection; none of these vaccines are effective in humans.[xi] Useful AIDS research has been advanced in the vast majority of cases due to the use of human models.[xii]

 

  • Animal Experimentation is Ineffective for Stroke Research: Between 1993 and 2003, researchers developed fourteen neuroprotective treatments that were effective in non-human animals. All fourteen were ineffective in human patients.[xiii]

 

  • Animal Experimentation is Ineffective for Spinal Cord Injury Research: In a systematic review of animal-based research conducted to determine the viability of treatments for spinal cord injury, authors found that the highly variable results of the animal studies meant that human responses were impossible to predict. [xiv]

 

  • Animal Experimentation is Ineffective for Diabetes Research: Despite a considerable amount of literature published about type 2 diabetes (over 50 articles on rodent experimentation per month for the last 30 years) there are few treatments available for humans, and none of these prolongs life expectancy for patients[xv]. NOTE: In 2014, an estimated 422 million people had diabetes worldwide, which is 8.5% of the global population.[xvi] It is vital that relevant, human-based models are utilised for diabetes research.

 

  • Animal experimentation is ineffective for Sepsis Research: 150 cures developed for sepsis infections have been successful in mice. All of these failed and even caused the infection to worsen in some cases when used in humans.[xvii]

 


The poor predictive value that animal models have has three main negative impacts on people and science.

1. Animal-based research hurts humans too

Results from animal-based research are misleading when they are applied to humans and can lead to adverse effects in human clinical trials.

Unfortunately, these unforeseen side effects can even be fatal to people. Adverse drug reactions that weren't predicted in animal trials have been recorded as the 4th-6th leading cause of death in US hospitals.[xviii]

Examples:

  • In March 2006, six human volunteers were injected with the experimental drug, TGN1412, which had previously been tested on mice, rats, rabbits and monkeys with no adverse effects.[xix] For the human volunteers, the drug produced the opposite effect, and several were left with permanent organ damage. 

 

  • In 2003, trials of an Alzheimer’s vaccine cured the disease in “Alzheimer’s mice.” The trial had to be stopped after the substance caused brain inflammation in humans.[xx]

 

  • There are many more cases where animal experimentation has gone wrong, see some examples here.

 

2. Misleading results from animal-based research may cause us to discard treatments that could help humans

Examples:

  • Therapies that were nearly abandoned due to misleading results from animal-based research include Tamoxifen (one of our most effective drugs against certain types of breast cancer), which caused liver tumours in rats.[xxi]

 

  • The now-highly-regarded leukaemia drug Gleevec caused severe liver toxicity in dogs.[xxii] Fortunately, the manufacturers persisted with the development of this drug because it seemed so promising in human cell culture tests. 

 

  • Approximately 95% of experimental drugs fail in clinical studies because we cannot accurately predict how they will behave in humans based on laboratory and animal studies.[xxiii] We can only imagine how many of these could be useful human treatments if they weren’t tested on the wrong model first! In other words, of all those drugs which were cast aside because they were NOT successful on animals, how many might have worked in humans? Have we inadvertently discarded a potential cure for cancer or any other major illness?

 

3. Human patients will continue to suffer while time, money and other resources are wasted on animal-based research

The average cost to develop a new drug is USD 2.558 million,[xxiv] and if proven effective, can take 12 years to reach human patients.[xxv]

Time and time again, misleading results from animal-based research have resulted in findings that aren’t useful for humans. No wonder it takes so long and costs so much to get a useful drug onto shelves.

Examples:

  • Smoking does not cause cancer in mice and rats.[xxvi] Humans were misled by animal studies for years and were wrongly led to believe that smoking did not cause cancer. It was population studies that led to the discovery that smoking causes cancer.

 

  • A recent article by a tobacco industry consultant reported that results from years of cigarette inhalation studies on rats, mice, hamsters, dogs, and nonhuman primates did not show significant increases in cancerous tumour development and were “clearly at variance with the epidemiological evidence in smokers, and it is difficult to reconcile this major difference between observational studies in humans and controlled laboratory studies now in five different animal species.”[xxvii]  

 

  • It took over thirty years of diabetes research using rodents before “we” discovered that the internal structure and function of the human pancreatic islet cell, which is central to the development of diabetes, is dramatically different from that in the “well-studied rodent”.[xxviii]

 

  • One of the researchers, Per-Olof Berggren, adjunct professor at the Diabetes Research Institute and professor at the Rolf Luft Center for Diabetes Research at Karolinska Institutet in Stockholm, Sweden, stated that: “We can no longer rely on studies on mice and rats. It is now imperative that we focus on human islets. At the end of the day, it is the only way to understand how they function.” [xxix]

 

  • AIDS/HIV research has been carried out on non-human primates for decades, yet all of approximately 85 HIV vaccines that succeeded in animals failed in humans.[xxx]

 

  • In the last decade, zero new drugs have been developed that can treat Alzheimer’s effectively.[xxxi] This is likely due to the reliance that Alzheimer’s research has on animal models and 99.6% of Alzheimer’s drugs that test successfully in animals, fail in human trials.[xxxii]

 

  • Cancer research using rodents has proven over the past 30 + years, to be a massive waste of time. Even the head of America’s most prominent cancer institute has admitted so. “We have cured mice of cancer for decades – and it simply didn’t work in humans.” Dr Richard Klausner, former director of the US National Cancer Institute.[xxxiii]

 

To help humans, resources being wasted on invalid animal experiments needs to be redirected to relevant and accurate human-based research methods!

 

This short animated film by Doctors Against Animal Experiments Germany helps highlight further why animal experiments don't help people:

 

 


[i] T. Ryan Gregory, “The Failure of Traditional Arguments in the Vivisection Debate,” Public Affairs Quarterly 14, no. 2 (April 2000): 166.

[ii] Robert H. Green, “The Association of Viral Activation with Penicillin Toxicity in Guinea Pigs and Hamsters' Yale Journal of Biology and Medicine 3 (1974): 166-7.

[iii] Robert Gaynes, “The Discovery of Penicillin—New Insights After More Than 75 Years of Clinical Use”, Emerging Infectious Diseases 23, no. 5 (2017): 850.

[iv] Harare DM, Rake C, McKee C, M., MacPhillamy HB: The toxicity of penicillin as prepared for clinical use. Am J M Sc 1943, 206:642-652.

[v] Greek, R., & Shanks, N. FAQs About the Use of Animals in Science: A handbook for the scientifically perplexed. 2009.

[vi] Sandra Kraljevic, Peter J. Stambrook & Kresimir Pavelic, “Accelerating Drug Discovery”, European Molecular Biology Organization Reports 5, no. 9 (2004): 837.

[vii] Moshe Shalev, “New FDA recommendations to speed drug development,” Lab Animal 35, no. 3 (Mar 2006): 13.

[viii] Shalev, “New FDA recommendations,” 13.

[ix] C. Glenn Begley and Lee M. Ellis, “Raise standards for preclinical cancer research,” Nature 483 (2019): https://doi.org/10.1038/483531a

[x] William Crowley, “Translation of basic research into useful treatments: how often does it occur?” The American Journal of Medicine 114, no. 6 (2003): 503.

[xi] Aysha Akhtar, “The Flaws and Human Harms of Animal Experimentation,” Cambridge Quarterly of Healthcare and Ethics (2015): 412.

[xii] Gregory, “The Failure of Traditional Arguments,” 165-6.

[xiii] Stephen H. Curry, “Why Have So Many Drugs with Stellar Results in Laboratory Stroke Models Failed in Clinical Trials? A Theory Based on Allometric Relationships,” Annals of the New York Academy of Sciences, 993 (2003): 69.

[xiv] Aysha Z. Akhtar, John J. Pippin, and Chad B. Sandusky, “Animal Studies in Spinal Cord Injury: A Systematic Review of Methylprednisolone,” ATLA, 37 (2009): 55.

[xv] P. Charukeshi Chandrasekera and John J. Pippin, “Of Rodents and Men: Species-Specific Glucose Regulation and Type 2 Diabetes Research,” ALTEX 31 (2013): 157-8.

[xvi] World Health Organization, Global Report on Diabetes (2016) http://apps.who.int/iris/bitstream/10665/204871/1/9789241565257_eng.pdf

[xvii] Junhee Seok et al., “Genomic responses in mouse models poorly mimic human inflammatory diseases,” Proceedings of the National Academy of Sciences USA, 110, no. 9 (2013): 3511.

[xviii] Jason Lazarou, Bruce H. Pomeranz, and Paul N. Corey, “Incidence of adverse drug reactions in hospitalized patients: a metaanalysis of prospective studies,” The Journal of the American Medical Association, 279, no. 15 (1998): 1203.

[xix] Aysha Akhtar, Animals and Public Health: Why Treating Animals Better is Critical to Public Health (Basingstoke, Hampshire: Palgrave Macmillan, 2012): 147-8.

[xx] Arthur Allen, “Of Mice or Men: The Problems with Animal Testing,” Slate (2006) https://slate.com/technology/2006/06/does-animal-testing-work.html

[xxi] Philip Carthew et al., “Tamoxifen Induces Short-Term Cumulative DNA Damage and Liver Tumors in Rats,” Cancer Research 55 (1995): 544.

[xxii] Martin H. Cohen et al., “Approval Summary for Imatinib Mesylate Capsules in the Treatment of Chronic Myelogenous Leukemia,” Clinical Cancer Research 8 (2002): 936.

[xxiii] John Arrowsmith, “A Decade of Change,” Nature Reviews Drug Discovery 11, no. 1 (2012): 17-8.

[xxiv] Joseph A. DiMasi, Henry G. Grabowski, and Ronald W. Hansenc, “Innovation in the pharmaceutical industry: New estimates of R&D costs,” Journal of Health Economics 47 (2016): 31.

[xxv] California Bilmedical Research Association, New Drug Development Process, https://ca-biomed.org/wp-content/uploads/2018/02/FS-DrugDevelop.pdf

[xxvi] Christopher R. E. Coggins, “A review of chronic inhalation studies with mainstream cigarette smoke in rats and mice,” Toxicologic Pathology 26, no. 3 (1998): 307-314.

[xxvii] C.R.E. Coggins, “A Minireview of Chronic Animal Inhalation Studies With Mainstream Cigarette Smoke,” Inhalation Toxicology 14 (2002): 1001.

[xxviii] Diabetes Research Institute, “Researchers find Striking Differences between Human and Animal Insulin-Producing Islet Cells,” https://www.diabetesresearch.org/differences-between-human-and-animal-insulin-producing-islet-cells? ; Over Cabrera et al., “The unique cytoarchitecture of human pancreatic islets has implications for islet cell function,” PNAS 103, no. 7 (2006): 2334.

[xxix] Diabetes Research Institute, “Researchers find Striking Differences,” https://www.diabetesresearch.org/differences-between-human-and-animal-insulin-producing-islet-cells?

[xxx] Jarrod Bailey, “An Assessment of the Role of Chimpanzees in AIDS Vaccine Research”, ATLA 36 (2008): 419.

[xxxi] Jeffrey L. Cummings, Travis Morstorf, and Kate Zhong, “Alzheimer’s disease drug-development pipeline: few candidates, frequent failures”, Alzheimer's Research & Therapy 6, no. 37 (2014): 1.

[xxxii] Cummings et al., “Alzheimer’s disease,” 1; Camryn Berk and Marwan Sabbagh, “Successes and Failures for Drugs in Late-Stage Development for Alzheimer's Disease,” Drugs Aging 30, no. 10 (2013): 13.

[xxxiii] Thomas H. Maugh, “Cancer Drugs Face Long Road From Mice to Men”, LA Times (May 6, 1998) https://www.latimes.com/archives/la-xpm-1998-may-06-mn-46795-story.html


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