Which is More Dangerous: Wildlife Markets or Animal Research ? by Dr Andre Menache

The race is now on to develop a vaccine to deal with the COVID-19 pandemic. Developing a new vaccine is not without risk and so it is imperative that researchers use robust scientific methods in order to avoid some of the mistakes of the past. An important step in the right direction is to avoid using animal cells or animal viruses to manufacture human vaccines in the 21st century. A lack of technology is not the obstacle here. Rather, it is out dated manufacturing practices and a political culture that puts short term profits before public safety. This is particularly relevant in an era of personalized medicine: the opportunity to create vaccines that are more effective and with fewer side effects (1).     

By now we are all acutely aware of the risk of transmission of animal viruses in the context of wildlife markets and the consumption of wild animal products. Sadly, countries like China have issued only a temporary ban on such practices. Once the coronavirus pandemic eases up, it could be a return to business as usual in places where wild animal consumption is a tradition. There is, however, another cause for concern, in the form of medical research where animal viruses are involved in the production of human vaccines. To be clear, we are not talking about the use of animal viruses in the context of biological warfare, we are talking about vaccines manufactured by the pharmaceutical industry destined for general use in the human population.

The scientific research community has been taken by surprise by the speed at which the COVID-19 viral pandemic has spread throughout the world. Clinical trials are already underway, with scientists scrambling to find an effective vaccine. Some vaccine trials have received the official go-ahead without waiting for the results of the usual animal tests. Under normal circumstances, vaccine development can take up to 15 to 20 years, from start to finish, and includes giving the vaccine to various animal species to determine safety and efficacy.

With advancements in technology, industry and academia appear to have significantly reduced the timeline for the production of a future vaccine. Besides the questions surrounding the reliability and relevance of animal testing with regard to predicting human outcome, there is the equally important issue about which most people are completely unaware: the use of animal viruses in human vaccines (2). A current example is the use of a genetically modified chimpanzee virus grown in duck cell culture for use in human vaccines. This vaccine has already been administered to healthy human volunteers in the UK and Senegal as part of an early clinical trial (3).

As the saying goes, “history does not repeat itself, man repeats his mistakes”. It is worth taking a brief look at specific examples of the not so distant past to avoid repeating the same mistakes. Some of the early polio vaccine administered to millions of people between 1955 and 1963 was contaminated with the simian virus 40 (SV40). This virus originated in the monkey kidney cell cultures used to produce the vaccine. The SV40 virus is the most potent cancer causing virus known to science and is now thought to be responsible for the proliferation of certain rare human forms of cancer (4).

Vaccines containing animal viruses also share some of the risks associated with gene therapy. The death of 18 year old Jesse Gelsinger in September 1999 following experimental gene therapy was a wake-up call for the scientific research community on the risks of using viruses as a means transporting healthy genes into the cells of patients (5). Gelsinger died as a result of an immune overreaction caused by the virus. In a different clinical trial in 2003, it was reported that some of the children born with inadequate immune systems who received gene therapy (also based on a viral vector) showed some improvement, while others developed leukemia (cancer of the white blood cells) (6). In patients who have responded well to these treatments, the long term health effects are still unknown (7).

The above events highlight some of the major risks associated with using viruses (often of animal origin) as vectors of genes or in vaccines, and the risks of using animal tissues (monkey kidney, in the case of polio) as a means of cultivating the virus for subsequent human use. In the UK in 2000, polio vaccine manufactured using fetal calf serum was withdrawn following a massive public outcry in the wake of the Mad Cow Disease outbreak. Millions of doses of the vaccine had already been administered to infants in the UK when it was revealed that the fetal calf serum used in the vaccine was of UK origin (8). Although the risks were played down by the authorities, it should be noted that Mad Cow Disease is caused by prions, which are even smaller than viruses and were undetectable in blood products at the time.

In short, the COVID-19 pandemic is a wake-up call to all of society and industry to stop using animal tissues and animal viruses to manufacture vaccines destined for human use. It is also an opportunity to ditch the “animal model”, a concept that belongs to the 19th century. To try to reproduce a human disease, or test a human vaccine, in an animal is a perversion of science, a complete lack of understanding of what constitutes a complex system, such as the immune system. Each animal species is also an example of a complex system and therefore cannot serve as a model for another. Among humans, there are also important differences between individuals, in terms of susceptibility to COVID-19. Rather than experimenting with ferrets, monkeys or mice, it would be far more scientific to invest in high-performance technologies of the 21st century. 

One such example is the “MIMIC” (Modular IMmune In vitro Construct) which is an in vitro model of the human immune system (9). Advanced in vitro technologies (such as MIMIC, ‘organs on a chip’ and others) must by today’s standards, aim for a prediction rate of 85 to 90 % in order to be accepted at the regulatory level. Although animal tests are still required before human clinical trials, they fail spectacularly: 9 out of 10 drugs that appear safe and effective in animal tests subsequently fail in human trials, precisely due to a lack of safety or efficacy, according to the US Food and Drug Administration (10). 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 raise the bar in current 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 irresponsible scientific practices as well as the obsolete regulations that still impose them.

Dr Andre Menache BSc(Hons) BVSc MRCVS is a veterinarian who advises extensively on animal welfare matters.  He is director of Antidote Europe, based in France, a patron of Quaker Concern for Animals and a patron of and scientific adviser to the Animal Interfaith Alliance.   He has been president of Doctors and Lawyers for Responsible Medicine (UK) and general manager of The Federation of Animal Protection Societies in Israel.  He currently provides scientific support to several grass roots organisations. His full article can be read here.

References:

  1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2831634/
  2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4494222/
  3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6452431/
  4. https://www.ncbi.nlm.nih.gov/pubmed/10472327
  5. https://en.wikipedia.org/wiki/Jesse_Gelsinger
  6. https://www.ncbi.nlm.nih.gov/pubmed/14564000
  7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4274995/
  8. https://www.telegraph.co.uk/news/uknews/1371188/Polio-vaccine-withdrawn-after-mad-cow-contamination-fears.html
  9. https://www.ncbi.nlm.nih.gov/pubmed/19807200
  10. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4594046/

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