The National Animal Resource Facility for Bio-medical Research, or NARFBR, is projected to be an "animal house" that will breed and supply animals—ranging from rodents to primates— for use in biomedical testing. Slated to be built on 102.69 acres of land at Genome Valley in Hyderabad at an estimated cost of ₹338.58 crore, the facility aims to be fully operational by 2019.
New drug entities that have been developed and tested in animals fail at a rate of more than 90%.
First tabled back in 2003, NARFBR is currently operating out of the existing National Centre for Laboratory Animal Sciences. We should be asking several fundamental questions before it moves any further: How predictive and human-relevant are tests on nonhuman animals? What are the ethical considerations? Are there available non-animal alternatives or ones that could be further developed? What is the global context? And why should the government put money into developing a new facility for research animals, when there is already a functioning centre?
Let's tackle the effectiveness of animal testing first, which is under scrutiny, as scientists increasingly question its ability to accurately predict 'real-world' outcomes in humans. Differences in fundamental biology (genetics, metabolism, immune system, etc.) mean that substances can have substantially different effects on animal species—or even different strains within the same species. This makes extrapolation from rodents or dogs to humans a high-risk gamble. Drug development is an expensive process and becoming ever more expensive as new drug entities that have been developed and tested in animals fail at a rate of more than 90%. The United States Food and Drug Administration first reported this very high failure rate in 2004, but has been confirmed subsequently in a number of follow-up studies.
As former U.S National Cancer Institute Director Dr. Richard Klausner points out:
"The history of cancer research has been a history of curing cancer in the mouse. We have cured mice of cancer for decades—and it simply didn't work in humans."
Renowned primatologist, ethologist and anthropologist Jane Goodall takes this point a step further inReason for Hope, writing:
"[A] great deal of animal experimentation has been misleading and resulted in either withholding of drugs, sometimes for years, that were subsequently found to be highly beneficial to humans, or to the release and use of drugs that, though harmless to animals, have actually contributed to human suffering and death."
Now to the ethical dimension. While no figures are available regarding animal use in Indian laboratories, worldwide it is estimated that more than 115 million animals are used in laboratory experiments every year. Each one of these animals has been subjected to physical pain as well as psychological distress, with many subject to extreme suffering. Experimental manipulations can include physical restraint, food and water deprivation, the infliction of wounds and burns, as well as exposure to drugs, chemicals or infectious disease at levels that cause illness, pain, distress and death.
Globally, the combination of these ethical and scientific considerations has led to an increasing consensus that we must replace or reduce the experimental use of animals to the bare minimum. Back in 2004, when India was first proposing the NARFBR, the United Kingdom was establishing a National Centre for the Replacement, Refinement & Reduction of Animals in Research. In 2010, a European Union Directive on the protection of animals used for scientific purposes was revised, which further strengthened the legal requirement to develop alternatives to animal use and to apply these to the fullest possible extent. More recently (2016), the Netherlands published a road map for ending animal use in regulatory testing by 2025 and the US Society of Toxicology has now organised three special conferences on toxicology that point to a future of no animal use.
To enable and further these aims, there is an increasing focus on developing non-animal technologies. A cornerstone of this 21st century approach is an understanding of fundamental human (not mouse, rabbit or dog) biology in states of health and disease. This biological understanding is captured in a framework called adverse outcome pathways or AOPs. Technologies based on human-specific models have the potential to test for disruptions in key aspects of these AOPs at multiple biological levels (molecular, cell, tissue, organ, etc.), and thereby better predict the effectiveness of new drugs on humans.
There is compelling evidence that such non-animal approaches and technologies are the future, and as such there are massive financial and practical motivations for leading the way. Here are just a few of the large-scale, human-focused research efforts under way in developed countries:
- US Tissue Chip for Drug Screening: A five-year, US$142 million collaboration between the US National Institutes of Health, the Food and Drug Administration and the military to develop human tissue chips that accurately model the structure and function of human organs to help predict drug safety in humans more rapidly and effectively
- EUToxRisk: A six-year, €30 million European project aimed at driving toxicological animal testing towards a toxicological assessment based on human cell responses and a comprehensive understanding of chemical adverse effects
- BD2K: A US$55.5 million 'big data to knowledge project' aimed at supporting and the development of innovative tools to maximize and accelerate the integration of 'big data' and data science into biomedical research
- StemBANCC: A five-year, €55.6 million project aimed at engineering human stem cells for biological assays of novel drugs and predictive toxicology
India and Indian entrepreneurs are world leaders in information technology and have a great opportunity to pull ahead of other countries. Indian companies are making promising strides in bioinformatics that aim to combine powerful computing algorithms with biological data to better predict human biology, disease and treatment. Shouldn't Make in India be taking note, and planning a strategy that allows India to lead the way in alternate technologies with transformative potential over a longer period?
By channelling funding away from poorly predictive animal models and towards genuinely path-breaking research into human-focused, non-animal technologies, we can both understand human disease biology better, and put animal cruelty behind us.
A lot has changed since NARFBR was proposed in 2003. Non-animal technologies have developed dramatically, awareness of the drawbacks of animal testing has increased, and legislation to protect animal welfare has been introduced. Here in India, it's been prohibited to test cosmetic products on animals since 2013, and to import cosmetics that have been tested on animals since 2014. And as of last year, the cruel 'Draize test' (which measure eye and skin irritation on rabbits) and repeat testing of drugs already tested abroad, have both been banned.
Yet no national centre is currently tasked with providing Indian scientists and companies with access to critical, modern infrastructures—such as internationally validated non-animal test methods—or working to develop the next generation of such technologies to advance this field further. This is why we at Humane Society International/India recommend repurposing funds toward an Indian Centre for Excellence in Human Pathway-Based Biomedicine and Risk Assessment. By channelling funding away from poorly predictive animal models and towards genuinely path-breaking research into human-focused, non-animal technologies, we can both understand human disease biology better, and put animal cruelty behind us. Which side of history do we want to be on?