For decades, animal experimentation was considered the “gold standard” of biomedical research, but today a growing number of well-known scientists and researchers begin to challenge that assumption. It is clear that the underlying molecular, cellular, and physiological mechanisms of animals being distinct from humans can lead to poor predictions in humans. This unreliability is the result of several factors, including translation issues between basic scientific findings in a laboratory setting compared to human applications due to the complexity of many human diseases.
Human disease complexity makes the disparity between animal experimentation and humans even more significant and can complicate and delay the process of drug development because animal model results are not necessarily predictive of human clinical responses. For example, the rapid and successful development of at least nine vaccines and several drugs for COVID-19 in less than one year has been possible mainly because certain animal studies were skipped, though we do not know in detail the extent to which human-relevant methods contributed to this achievement. There is a widening gap in the science needed to understand the underlying biological processes that contribute to human disease––animal experimentation alone cannot fill this gap. Innovative technologies and methods that recapitulate human biological functions must be developed and leveraged to solve this key issue. Fortunately, the National Institutes of Health (NIH) can help foster the development of these technologies through policy change.
Why NIH?
NIH is at the forefront of medical research in the United States. A portion of NIH’s mission is to “seek fundamental knowledge about the nature … of living systems and the application of that knowledge to enhance health, lengthen life, and reduce illness and disability.” The agency identifies goals relevant to the development of new and alternative research and testing methods—replacement options to traditional animal experimentation such as in silico models and organ chips. The funding NIH provides to researchers helps support “fundamental creative discoveries… [and] innovative strategies,” as well as develop scientific resources that can “expand the knowledge base in medical and associated sciences.”
The acceptance and development of human-relevant alternatives to animal experimentation can help NIH protect human health by producing the most relevant science for humans. Modern science is now at a point where non-animal techniques, such as organoids and organ chips, can provide much-needed insight into human systems. The mission and goals put out by the NIH make furthering the shift to human-relevant methods in research and testing paramount. Supporting the use and development of human-relevant methods contributes to fundamental discoveries and innovative strategies for medical science. This fosters the entrepreneurial nature of scientists and their participation in the creation of more human-centered methods. By placing human-relevant research on an equal playing field (or above) animal experimentation, more solutions may be found for challenges confronting complex human diseases such as cancer, Alzheimer’s, and Parkinson’s disease.
NIH provides funding opportunities to researchers in the form of grants and contracts. These funding opportunities help further NIH’s mission and meet its goals by supporting research across disciplines that can and will enhance the health and lives of humans. In the current grant and contract process, there are available pathways to streamline the acceptance and development of human-relevant research and testing methods. Many scientists are entrepreneurial in nature. By creating incentives such as grant and contract opportunities for these new techniques, NIH will help foster innovation and more quickly develop additional research methods by tapping into the entrepreneurial spirit of scientists.
The NIH has an annual budget of more than $40 billion to fund medical research. Approximately 10% of the NIH’s budget funds intermural research projects undertaken by NIH scientists, while more than 80% supports extramural research including more than 50,000 competitive grants across universities, medical schools, and other research institutions. More than 300,000 researchers across 2,500 organizations and universities receive NIH funding. In 2019, NIH had more than $31 billion for funding across all institutes. The total amount of funding is not only split between the different institutes, but also between research grants, research and development contracts, fellowships, training grants, construction, and other awards. Nearly all of the funding budget was allocated for the 49,092 research grants awarded. There are several ways that NIH’s funding process can be altered to turn towards increased funding of human-relevant methods such as cell-based or computer models.
Although NIH does fund certain endeavors that are human-relevant focused, such as certain projects at the Wyss Institute, a major barrier to the development and use of human-relevant methods remains a lack of funding. For example, despite the interest that NIH shows in human-relevant models, 71% of the grant applications submitted to NIH between FY2008 and FY2015 involved mouse models. Human-relevant models continue to progress and build traction. Human-relevant research deserves to be prioritized regarding funding, granting, and publications.
Looking Forward
As technology advances at a rate never previously seen in human history, there is a critical need to rapidly evolve our research methods to better understand complex human diseases. This need is scientifically recognized––expansion and diversification of research methodologies that better recapitulate human biological response is crucial.
Improving the NIH grants and contract process to encourage the use of human-relevant methods would show NIH’s intent to support new developments and drive researchers to further the development, use, and reporting of new technologies. Small policy changes by NIH could effectively lead to an influx of applications leveraging human-relevant technologies and help move human health and biomedical research forward. Animal experimentation is not the only available option for research. Non-animal, human-relevant, models can be used where animal experimentation hit barriers or are simply not predictive. NIH should fund human-relevant methods and maintain its high standards for those who develop and use these methods.