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Animal Testing and COVID-19

By Andre Menache, Scientific Advisor to Progressive Non-animal Research Society.

The Coronavirus pandemic called COVID-19 is an important opportunity to reassess the way we do medical research. Faced with this viral tsunami, scientists have not had time to find one or more animal species to serve as a ‘model’ to study this disease in the laboratory.

In the case of seasonal flu, doctors have well-known ways to lower rates of infection, such as vaccines and antiviral drugs, which can decrease the severity of symptoms and the duration of the disease. But faced with an emergency situation, researchers decided to test new treatments directly on patients. It should be noted that these are not untested medical drugs but rather drugs used for other diseases, or else different combinations of drugs already on the market.

This kind of human experimentation is called a ‘clinical trial’. Its purpose is to assess the efficacy of a treatment following the approval by ethics committees and the informed consent of the patient. A clinical trial is normally preceded by several ‘preclinical’ steps to assess the toxicity and efficacy of a new treatment. One of these steps is animal testing. This regulatory requirement dates back to the Nuremberg Codes of 1947 and is still the norm in national and international legislation today. Yet, according to the US Food and Drug Administration, out of ten medical drugs that have successfully passed the required tests on animals, nine will fail in clinical trials involving humans (due to lack of efficacy or to side effects not seen in animals). This represents a 90% failure rate or a 10% prediction rate based on animal tests.

It is interesting to note that scientists closely involved in the search for a treatment or a vaccine against COVID-19 also recognise the fact that animal tests are unreliable to predict human reactions. Let us quote some of them. According to Tal Zaks, medical director of Moderna, a successful biotech company in the United States: “I don’t think proving this in an animal model is on the critical path to getting this to a clinical trial” (1). Barney Graham, director of the National Institute of Allergy and Infectious Diseases (NIAID) also in the United States notes that standard laboratory mice do not catch this new Coronavirus, as humans do (2). Finally, Karen Maschke, editor of the journal Ethics & Human Research, pointed out that animal studies are often poor predictors of what will work in humans (3).

Of course, making a new vaccine is not without risk. This is the reason for using evidence-based technologies, as demonstrated by ‘personalised’ medicine and vaccines. Indeed, doctors and researchers note that we are not all equal to the risk of infection by this virus. Why are children far less susceptible than the elderly, for example? Crucially, the clinical information that is being collected constitutes the best data to develop personalised treatments and vaccines, more effective and with fewer side effects than conventional treatments.

This is a golden opportunity to get rid of the ‘animal model’, a concept that belongs to the 20th century, and to focus our efforts on the species in question, namely humans. To try to reproduce a human disease in an animal is a perversion of science, a complete misunderstanding of the complex system that we are and of the different complex systems that make up our organism, such as the immune system. Each animal species is a complex system and therefore cannot serve as a model for another. Even among humans, there are important differences between children and adults, men and women, in terms of susceptibility to COVID-19. Rather than experimenting with ferrets, monkeys or mice, it would be more intelligent – and far more scientific – to invest in high-performance technologies of the 21st century.

One example is the ‘MIMIC’ (Modular IMmune In vitro Construct). It is an in vitro model of the human immune system (4). “The information you get from this type of test is far and beyond what you’d get out of a mouse study,” says Michael Rivard, vice president of corporate development at VaxDesign, “both because it’s humans and because you can see the effect across a spectrum of genotypes” (5).

Advanced in vitro technologies (such as MIMIC, ‘organs on a chip’ and others) must aim for a prediction rate of 85 to 90 % in order to be accepted at the regulatory level, whereas the ‘animal model’ achieves a prediction rate of only 10% according to the FDA. A testing strategy based on a battery of in vitro tests using human material would be far more relevant than pursuing animal tests. It is time to change the current paradigm in biomedical research if we want to preserve our health in the face of emerging diseases of the 21st century. Perhaps the COVID-19 pandemic will help us to question some of our outdated scientific practices as well as the obsolete regulations that still impose them.

Dr. Andre MENACHE

BSc(Hons) BVSc MRCVSEBVS® European Veterinary Specialist in Animal Welfare Science, Ethics and LawMember of European College of Animal Welfare and Behavioural Medicine

Andre Menache holds degrees in zoology and veterinary medicine. Main areas of interest include animal experimentation and regulatory toxicology.

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Use of animal models a primitive outdated approach – all about money

By Pradmin Basu.

It is understandable that ‘scientists’ who use animals for their research are busy requesting grants for their ‘mouse bill’. My father, Dr. Prasanta Kumar Basu, did the same thing for years at the university of Toronto where he was director of research in dept of ophthalmology. This is a money game and not the noble pursuit for the betterment of the human condition that the public (and even many of the researchers themselves) are led to believe.

As Dr. Ray Greek (one of several authorities opposed to animal research) said to UBC’s animal care committee in July 2017, the technology exists to replace animal research and that:

“even pharmaceutical companies want to move away from testing on
animals as only 1 out of every 10 drugs coming out of research and
development on animals makes its way to market”
http://adavsociety.org/dr-ray-greek-speaks-to-ubcs-animal-care-committee/

Furthermore, Dr. Greek stated that “the stumbling block for immediate change is from the world of academia, as universities are entrenched in the lucrative government grant system.1“

If we really are serious about “benefiting human health” we need to put our funding where it really counts into proper technological models and  dispose of outdated, primitive approaches that are more than 100 years old.

1 http://adavsociety.org/dr-ray-greek-speaks-to-ubcs-animal-care-committee/

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New Pathways for Medical Research

By Maidie Hilmo, PhD

In what direction is medical research going? It is clear from a step into the Willerth lab at the University of Victoria that the answer is quite simply: advanced technology. The brilliant Dr. Stephanie Willerth holds joint appointments in the Division of Medical Sciences and the Department of Mechanical Engineering.

She and her team have been a pioneering force in making significant progress in 3D bioprinting differentiated stem cells directly applicable to the neural tissues in patients with spinal cord injuries, Parkinson’s, and Alzheimer’s.

Incubator for producing bio ink

The process involves several steps starting with human stem cells cultured from blood draws obtained from UBC (UVic is one of the co-partners of the UBC Faculty of Medicine), which are then differentiated into stem cells, and then further into neural stem cells, subsequently printed with bio ink, and then eventually matured to show the characteristics of, for example, Alzheimer’s.

Engineered 3D bioprinted tissues from stem cells from people with and without the disease can be compared, which can help with diagnosis and identifying treatment options as well as repairing damaged neural tissue. The efficacy of different drugs can also be tested with greater immediacy and accuracy without involving lab animals. It is one of her goals to get the right drugs into people. In more outdated experimental methods some 95% of pharmaceutical drugs that are tested on animals fail in human clinical trials and never make it to market.

Dr. Willerth and the RXI bioprinter

Dr. Willerth found that using human cells and tissue engineering can generate tissues that better replicate human biology. Early in her career, she was struck by the differences between the biology of mouse and human stem cells. Animal blood just does not replicate that from the human immune system.

In the meantime, if you want to slow and possibly reverse the symptoms of Alzheimer’s, you might try yoga. In an article Dr. Willerth co-published, neuronal cultures from human induced pluripotent stem cells led to findings that supported the positive effects of yoga on inhibiting Alzheimer’s. Future research might focus on how specific movements and meditative practices affect neuroprotective biomechanisms, especially those involved in Kirtan Kriya yoga originating in India. It would be interesting to know if engaging in some forms of painting, calligraphy, or music involving “physical, mental, and spiritual activities” might also work!

The scope of Dr. Willerth’s interests is further demonstrated by her collaboration with Dr. Ryan Flannigan and his team at UBC who managed, for the first time, to 3D print viable sperm cells from the testicular biopsy of a 30 year old man who had none in his ejaculate. This sort of research offers hope for couples wanting to start a family since male infertility can be about 50% as likely as not to be the deterrent in such cases.

Ever current with developing needs, as her extensive list of publications indicates, she has been involved in developing biomedical engineering strategies during the Covid crisis and investigating 3D tissue models to help study viruses and vaccine development. Her inspired students even 3D printed over 5000 face masks that have been used locally by medical personnel and even dentists. An interesting side effect of the pandemic is that research is trending away from static traditional methods involving years of experimenting on animals to evaluate drugs by moving in the direction of better technological modalities. If sourced and used wisely for the benefit of all, these offer real solutions.

Of course, there are still legal and political hurdles to overcome before such new technologies can become the go-to methods. Dr. Willerth is enthusiastic about the proposed bio-printing lab at the new St. Paul’s Hospital in Vancouver. She would like to see a combined patient treatment and research facility in Victoria where the former could be treated on the main floor and research could be done on an upper floor.

For the moment, Dr. Stephanie Willerth and her team, including students, are a shining light illuminating the path forward.

Note:
For a list of Dr. Stephanie Willerth’s publications, see:
https://www.engr.uvic.ca/~willerth/publications
Most recently in April, 2022, see: “Protocols for printing 3D neural tissues using the BIO X equipped with a pneumatic printhead” at https://star protocols.cell.com/protocols/1609
And in the supplement to the May issue of Cytotherapy 24(5):S155-S156: “Tissue Engineering, Embryonic, Organ and Other Tissue Specific Stem Cells: PARTNERING TO ADVANCE THE DEVELOPMENT OF TISSUE THERAPEUTICS WITH MICROFLUIDIC 3D BIOPRINTING”
For the video about the 3D printing of testicular cells, see:
https://globalnews.ca/video/8730746/canadian-researchers-print-3d-testicular-cells/