The global SARS-CoV2 pandemic is generating a powerful need for drug and vaccine development, and time is of the essence. Therefore, this is an ideal moment to leverage novel approach methodologies (NAM) that avoid the use of animals for evaluating the efficacy, safety, and quality of potential discoveries to drastically decrease drug and vaccine development times and alter the course of this devastating, worldwide infection.
When faced with a time-sensitive predicament such as vaccination and treatment of COVID-19, traditional animal-based testing methods are too lengthy and have been shown to have poor success rates for species-specific pathogens as well as drug development based on the distinct attributes of human biology.
Alternative approaches for SARS-CoV-2:
When addressing the unique features of SARS-CoV-2, the virus that causes COVID-19, there are many aspects that must be prioritized. First, there is the glaring lack of an animal disease model reference. SARS-CoV-2 is most closely representative of coronaviruses in Asian bats and reptiles. But these are not well suited as lab animals, and data garnered from them does not translate seamlessly to the pathology found in humans.
When lacking an animal model, pivoting to the use of nonhuman primates (NHP) or even great apes is a classic strategy; however, historically, this has not provided much insight for HIV or hepatitis C, as shown by the US National Academy of Sciences (NAS) research with great apes. Another approach is to breed or genetically modify lab animals, for example mice, to increase susceptibility, as was performed for the earlier SARS virus.
The time-saving capacity of NAM:
The implementation of testing alternatives to traditional methods, for example, those using synthetic skin as opposed to live animals, can generate data in as little as a few minutes to a few hours, compared with the weeks or even months required of animal testing. Fast testing times afford researchers the ability to test five or six products with alternative testing in the same time it takes to study one product with animal testing.
Fortunately, the healthcare industry has been transitioning to NAM for the past 20 years, with public funding programs driving the development of animal-free technologies. For instance, NAM is capable of predicting genotoxicity (a fundamental aspect of carcinogenicity) within days, human antibodies for specific virus epitopes can be demonstrated in molecular biology laboratories within weeks, and a multitude of human cell-based organoids are available to test virus infectivity as well as the biological processes mandating them.
The European Medicines Agency (EMA) has created an expert group to lead the way toward implementing NAM approaches for accelerated drug development. The global pandemic brings to light the vitality of diversification in drug discovery strategies while revealing the shortcomings of the limited-scope approach of an industry built upon animal testing, which has historically invested a significant amount of resources into the single technology of animal experimentation.
Government financial investment trends endorsing NAM:
The pivotal NAS report on the future of toxicity testing in the twenty-first century catalyzed a chain of events culminating in roadmaps by leading agencies to limit and ultimately abandon animal testing entirely.
In September 2019, US Environmental Protection Agency Administrator Andrew Wheeler announced a directive to prioritize efforts to decrease animal testing, fueled by a $4.25 million investment provided to five universities for researching the development and use of NAM test methods and strategies that “reduce, refine, and/or replace vertebrate animal testing.” This aggressive reduction in animal testing was further bolstered by the parameters of reducing mammal study requests and funding by 30% by the year 2025, in order to completely eliminate them by 2035. The agency’s Science to Achieve Results Program awarded grants to:
- Johns Hopkins University for the development of a human-derived brain model to assess the mechanism by which environmental chemicals may cause developmental neurotoxicity
- Vanderbilt University to test their organ-on-a-chip to examine the blood-brain barrier and potential brain injury post organophosphate exposure
- Vanderbilt University Medical Center to use their Endo Chip technology to study how pre-existing diseases affect cellular responses to environmental toxicants, specifically regarding reproductive disorders in women
- Oregon State University to develop in vitro testing for fish species to screen chemicals in complex environmental mixtures
- The University of California Riverside to use human cells to generate a cost-effective endpoint to characterize potential skeletal embryotoxicants
Scientific research outcomes supporting the efficacy and speed of NAM:
A second notable report from an NAS committee targeted drug efficacy for countermeasures to biological terrorism weapons. Within these two NAS reports, an indisputable recommendation was provided to shift focus solely onto NAM to achieve speed and predictivity in outcomes.
Alongside these highly visible government actions, the private industry moved from predominantly animal-based efficacy testing in the 1980s to primarily animal-free efficacy research methods. Academia and industry-driven use of NAM for target discovery promptly followed suit. Cell culture–based methods, in combination with modern molecular biology and stem cell technology, play a significant role, but the implementation of computational research (in silico models) has recently expanded as well, in synchrony with increasing evidence of the limiting shortcomings of animal models.
Corporate ethical considerations promoting NAM:
Aside from the clear financial investment trends, efficacy, and speed-related research outcome drivers supporting NAM, companies must consider the ethical and social impacts of continuing animal testing in a climate rapidly evolving beyond this practice. The results from a survey of managers’ perceptions of corporate ethics and social responsibility and the actions that may affect the success of a company indicated that many managers and professionals have unified views about the ethical and social responsibility reputations of companies. These factors directly impact their attitudes toward the organizations and have a significant effect on their intended behaviors within them.
The shift away from animal testing methods is widespread across several different industries and is seen in public attitudes regarding animal testing for medical products. An October 2018 Ipsos Mori poll identified a public shift toward increased questioning of animal research, with 60% of surveyed individuals reporting they are interested in learning more about alternatives. Also, the poll showed the proportion of the public who believe animal testing for medical products is important for human health has decreased from 46% in 2016 to 41% in 2018.
As Harvard Business School professor Lynn Sharp Paine states in her book Value Shift: Why Companies must Merge Social and Financial Imperatives to Achieve Superior Performance,
“We now understand that ethics and economic advantage often go hand in hand. As research is beginning to document, companies that bring ethical discipline to bear on their activities and tap into the moral capabilities of their people start to reap a variety of economic benefits from doing so. Many of these benefits follow from the very simple fact that given a choice, most people prefer to work for and do business with companies that are honest, fair, reliable, and considerate.”
