The giant leap: Moonwalking into 21st Century non-animal science and medicine

Brinda Poojary / Neha Raghuvanshi | Updated on July 20, 2021

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Transitioning to more humane and human-relevant technologies to better understand human diseases

On 20th July 1969, Neil Armstrong became the first human to set foot on the moon, describing the occasion as "one giant leap for mankind". Since then, July 20th has been marked as Science Exploration Day in the world of science and space, and astronauts aboard the International Space Station (ISS) continue to make great strides in science.

Among other outcomes, science in space has helped to advance our use of tissue chips (thumb-drive-sized devices with human cells in a 3D matrix that simulate organ functions) used on the ISS to learn more about the effects of microgravity on human health and to apply that knowledge to enhance human health on earth. We need to keep the same pace of progress here on earth, where unfortunately major funding remains concentrated on research and testing techniques for drugs and pesticides among other chemicals, primarily still relying on animal models.

Using promising emergent technologies, scientists have demonstrated the superiority of non-animal methods to the conventional use of animals in drug efficacy or safety testing. One of the first evidences of the link between Zika virus and microcephaly was found using brain organoids.

According to a recent study by a scientist GA Van Norman, around 89 percent of novel medicines fail in human trials, with half of those failing owing to unanticipated toxicity in humans that went undetected in animal studies. Aspirin, for example, shows embryo toxicity in rats and rhesus monkeys and if tested in the current regulatory regime, would not be approved yet it is the most used drug for humans since decades.

Animal experimentation maintains millions of animals in confinement throughout their lives, ranging from small fish, rats, mice, and rabbits to bigger animals like dogs and non-human primates, subjected to varying degrees of physical and psychological discomfort. The majority of animals employed in the most invasive types of studies are subjected to stressful procedures without any painkillers.

The Prevention of Cruelty to Animals Act of 1960, Chapter IV, lays forth the regulations governing animal testing. It specifies explicitly in section 17 (2) (d) that experiments on animals should be avoided where there are alternatives. The Government of India, under Chapter IV of the PCA also established the Committee for the Purpose of Control and Supervision of Experimentation on Animals (CPCSEA) to oversee animal experiments small and large through ethics committees established in each institution and through its large animal experimentation monitoring committee. The need to phase out animal testing is urgent, not just for ethical reasons, but also to establish a strategy that better protects the health of humans, wildlife, and the environment. The concept of one health.

Cost of animal testing

Animal testing to predict human diseases is costly, time-consuming, and frequently poor in it translation to humans. Response to substances differ considerably between species due to biological differences. As a result, the reliability of animal studies is compromised by physiological and genetic differences. The failure to bridge the gap between reproducibility and data translation has major consequences, as seen by wasted resources spent on early compound development and significant financial losses owing to attrition at a later stage.

Moreover, economic variables such as costs of animals and their care, the upkeep of space and equipment, and the availability of qualified personnel bring other limitations on the use of laboratory animals into clear view, supporting the momentum toward their replacement with accurate, swift and less expensive non-animal methods.

Towards sustainable pathways

Using systems like cell cultures, organ cultures, tissue slices, stem cells, established cell lines, and primary cell cultures, a new generation of scientists has embraced a future for science and medicine. Among other steps, they have pioneered in the application of approaches like Adverse Outcome Pathways (AOPs)- based on toxicology testing of chemicals on our understanding of biological pathways as a way of reducing uncertainty in risk assessment for chemicals. In addition, computer modelling approaches have proven both lightning fast and accurate. Moreover, many cell-based in vitro methods may be automated using robots for “high throughput screening”—all at a fraction of the time needed to conduct animal experiments. So far, these methods have been applied mostly to chemical safety; however, the same approaches are equally relevant for medical research and drug discovery.

Currently, non-animal methodologies are in a nascent stage in India, with animal models widely used in more than two thousand facilities throughout the country. The BioMed21 Collaboration by Humane Society International is a targeted effort that unites a diverse group of stakeholders representing civil society, research funding, academic, regulatory, corporate, and other communities, all committed to the diversification of research methods to ensure that India can easily and fully these new technologies.

These stakeholders recognize the human relevance of non-animal methods as well as translational limitations of the current paradigm in biomedical research and drug discovery. Through BioMed21, Humane Society International/India in collaboration with the Atal Incubation Centre -Centre for Cellular and Molecular Biology launched the Centre for Predictive Human Model Systems in 2019, to work towards the promotion of more human relevant non-animal model systems. The year before that, in 2018, the Indian Council of Medical Research established an ICMR Centre for Excellence in Human Pathway-Based Biomedicine and Risk Assessment to advance similar goals.

The Road ahead

New breakthroughs in science, combined with our deeper understanding of the serious limitations of animal models, present us with an urgent challenge. We must repurpose our resources away from unreliable approaches toward more accurate, human biology-based and relevant technologies. This paradigm shift in research and testing will require increased investment in research institutions committed to the advancement of non-animal tests. We must also make stronger investments in capacity-building in this sector, including the establishment of more Centres for Excellence to coordinate stakeholder commitments to the development, promotion, and validation of non-animal models in India. This Science Exploration Day, let us move together towards more humane and human-relevant technologies to better understand human diseases even as we uphold the welfare of animals so dependent upon our mercy.

(Dr Brinda Poojary (PhD) is the Science Advisor (Research and Toxicology) at Humane Society International/India. She is part of several committees that promote non – animal methodologies in biomedical research and safety testing, including under the Indian Council of Medical Research (ICMR) and Indian Pharmacopeia Commission (IPC).

Neha Raghuvanshi is a content writer with Humane Society International/India, and has authored research papers on economics and sustainability.)

Published on July 20, 2021

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