research on animal testing

Ethical care for research animals

WHY ANIMAL RESEARCH?

The use of animals in some forms of biomedical research remains essential to the discovery of the causes, diagnoses, and treatment of disease and suffering in humans and in animals., stanford shares the public's concern for laboratory research animals..

Many people have questions about animal testing ethics and the animal testing debate. We take our responsibility for the ethical treatment of animals in medical research very seriously. At Stanford, we emphasize that the humane care of laboratory animals is essential, both ethically and scientifically.  Poor animal care is not good science. If animals are not well-treated, the science and knowledge they produce is not trustworthy and cannot be replicated, an important hallmark of the scientific method .

There are several reasons why the use of animals is critical for biomedical research: 

••  Animals are biologically very similar to humans. In fact, mice share more than 98% DNA with us!

••  Animals are susceptible to many of the same health problems as humans – cancer, diabetes, heart disease, etc.

••  With a shorter life cycle than humans, animal models can be studied throughout their whole life span and across several generations, a critical element in understanding how a disease processes and how it interacts with a whole, living biological system.

The ethics of animal experimentation

Nothing so far has been discovered that can be a substitute for the complex functions of a living, breathing, whole-organ system with pulmonary and circulatory structures like those in humans. Until such a discovery, animals must continue to play a critical role in helping researchers test potential new drugs and medical treatments for effectiveness and safety, and in identifying any undesired or dangerous side effects, such as infertility, birth defects, liver damage, toxicity, or cancer-causing potential.

U.S. federal laws require that non-human animal research occur to show the safety and efficacy of new treatments before any human research will be allowed to be conducted.  Not only do we humans benefit from this research and testing, but hundreds of drugs and treatments developed for human use are now routinely used in veterinary clinics as well, helping animals live longer, healthier lives.

It is important to stress that 95% of all animals necessary for biomedical research in the United States are rodents – rats and mice especially bred for laboratory use – and that animals are only one part of the larger process of biomedical research.

Our researchers are strong supporters of animal welfare and view their work with animals in biomedical research as a privilege.

Stanford researchers are obligated to ensure the well-being of all animals in their care..

Stanford researchers are obligated to ensure the well-being of animals in their care, in strict adherence to the highest standards, and in accordance with federal and state laws, regulatory guidelines, and humane principles. They are also obligated to continuously update their animal-care practices based on the newest information and findings in the fields of laboratory animal care and husbandry.  

Researchers requesting use of animal models at Stanford must have their research proposals reviewed by a federally mandated committee that includes two independent community members.  It is only with this committee’s approval that research can begin. We at Stanford are dedicated to refining, reducing, and replacing animals in research whenever possible, and to using alternative methods (cell and tissue cultures, computer simulations, etc.) instead of or before animal studies are ever conducted.

Organizations and Resources

There are many outreach and advocacy organizations in the field of biomedical research.

• Learn more about outreach and advocacy organizations

Stanford Discoveries

What are the benefits of using animals in research? Stanford researchers have made many important human and animal life-saving discoveries through their work. 

• Learn more about research discoveries at Stanford

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About Animal Testing

Humane Society International / Global

What is animal testing?

The term “animal testing” refers to procedures performed on living animals for purposes of research into basic biology and diseases, assessing the effectiveness of new medicinal products, and testing the human health and/or environmental safety of consumer and industry products such as cosmetics, household cleaners, food additives, pharmaceuticals and industrial/agro-chemicals. All procedures, even those classified as “mild,” have the potential to cause the animals physical as well as psychological distress and suffering. Often the procedures can cause a great deal of suffering. Most animals are killed at the end of an experiment, but some may be re-used in subsequent experiments. Here is a selection of common animal procedures:

• Forced chemical exposure in toxicity testing, which can include oral force-feeding, forced inhalation, skin or injection into the abdomen, muscle, etc.
• Exposure to drugs, chemicals or infectious disease at levels that cause illness, pain and distress, or death
• Genetic manipulation, e.g., addition or “knocking out” of one or more genes
• Ear-notching and tail-clipping for identification
• Short periods of physical restraint for observation or examination
• Prolonged periods of physical restraint
• Food and water deprivation
• Surgical procedures followed by recovery
• Infliction of wounds, burns and other injuries to study healing
• Infliction of pain to study its physiology and treatment
• Behavioural experiments designed to cause distress, e.g., electric shock or forced swimming
• Other manipulations to create “animal models” of human diseases ranging from cancer to stroke to depression
• Killing by carbon dioxide asphyxiation, neck-breaking, decapitation, or other means

What types of animals are used?

Many different species are used around the world, but the most common include mice, fish, rats, rabbits, guinea pigs, hamsters, farm animals, birds, cats, dogs, mini-pigs, and non-human primates (monkeys, and in some countries, chimpanzees). Video: Watch what scientists have to say about alternatives to animal testing .

It is estimated that more than 115 million animals worldwide are used in laboratory experiments every year. But because only a small proportion of countries collect and publish data concerning animal use for testing and research, the precise number is unknown. For example, in the United States, up to 90 percent of the animals used in laboratories (purpose-bred rats, mice and birds, fish, amphibians, reptiles and invertebrates) are excluded from the official statistics, meaning that figures published by the U.S. Department of Agriculture are no doubt a substantial underestimate.

Within the European Union, more than 12 million animals are used each year, with France, Germany and the United Kingdom being the top three animal using countries. British statistics reflect the use of more than 3 million animals each year, but this number does not include animals bred for research but killed as “surplus” without being used for specific experimental procedures. Although these animals still endure the stresses and deprivation of life in the sterile laboratory environment, their lives are not recorded in official statistics. HSI believes that complete transparency about animal use is vital and that all animals bred, used or killed for the research industry should be included in official figures. See some animal use statistics .

What’s wrong with animal testing?

For nearly a century, drug and chemical safety assessments have been based on laboratory testing involving rodents, rabbits, dogs, and other animals. Aside from the ethical issues they pose—inflicting both physical pain as well as psychological distress and suffering on large numbers of sentient creatures—animal tests are time- and resource-intensive, restrictive in the number of substances that can be tested, provide little understanding of how chemicals behave in the body, and in many cases do not correctly predict real-world human reactions. Similarly, health scientists are increasingly questioning the relevance of research aimed at “modelling” human diseases in the laboratory by artificially creating symptoms in other animal species.

Trying to mirror human diseases or toxicity by artificially creating symptoms in mice, dogs or monkeys has major scientific limitations that cannot be overcome. Very often the symptoms and responses to potential treatments seen in other species are dissimilar to those of human patients. As a consequence, nine out of every 10 candidate medicines that appear safe and effective in animal studies fail when given to humans. Drug failures and research that never delivers because of irrelevant animal models not only delay medical progress, but also waste resources and risk the health and safety of volunteers in clinical trials.

What’s the alternative?

If lack of human relevance is the fatal flaw of “animal models,” then a switch to human-relevant research tools is the logical solution. The National Research Council in the United States has expressed its vision of “a not-so-distant future in which virtually all routine toxicity testing would be conducted in human cells or cell lines”, and science leaders around the world have echoed this view.

The sequencing of the human genome and birth of functional genomics, the explosive growth of computer power and computational biology, and high-speed robot automation of cell-based (in vitro) screening systems, to name a few, has sparked a quiet revolution in biology. Together, these innovations have produced new tools and ways of thinking that can help uncover exactly how chemicals and drugs disrupt normal processes in the human body at the level of cells and molecules. From there, scientists can use computers to interpret and integrate this information with data from human and population-level studies. The resulting predictions regarding human safety and risk are potentially more relevant to people in the real world than animal tests.

But that’s just the beginning. The wider field of human health research could benefit from a similar shift in paradigm. Many disease areas have seen little or no progress despite decades of animal research. Some 300 million people currently suffer from asthma, yet only two types of treatment have become available in the last 50 years. More than a thousand potential drugs for stroke have been tested in animals, but only one of these has proved effective in patients. And it’s the same story with many other major human illnesses. A large-scale re-investment in human-based (not mouse or dog or monkey) research aimed at understanding how disruptions of normal human biological functions at the levels of genes, proteins and cell and tissue interactions lead to illness in our species could advance the effective treatment or prevention of many key health-related societal challenges of our time.

Modern non-animal techniques are already reducing and superseding experiments on animals, and in European Union, the “3Rs” principle of replacement, reduction and refinement of animal experiments is a legal requirement. In most other parts of the world there is currently no such legal imperative, leaving scientists free to use animals even where non-animal approaches are available.

If animal testing is so unreliable, why does it continue?

Despite this growing evidence that it is time for a change, effecting that change within a scientific community that has relied for decades on animal models as the “default method” for testing and research takes time and perseverance. Old habits die hard, and globally there is still a lack of knowledge of and expertise in cutting-edge non-animal techniques.

But with HSI’s help, change is happening. We are leading efforts globally to encourage scientists, companies and policy-makers to transition away from animal use in favour of 21st century methods. Our work brings together experts from around the globe to share knowledge and best practice, improving the quality of research by replacing animals in the laboratory.

Are animal experiments needed for medical progress?

It is often argued that because animal experiments have been used for centuries, and medical progress has been made in that time, animal experiments must be necessary. But this is missing the point. History is full of examples of flawed or basic practices and ideas that were once considered state-of-the-art, only to be superseded years later by something far more sophisticated and successful. In the early 1900’s, the Wright brothers’ invention of the airplane was truly innovative for its time, but more than a century later, technology has advanced so much that when compared to the modern jumbo jet those early flying machines seem quaint and even absurd. Those early ideas are part of aviation history, but no-one would seriously argue that they represent the cutting-edge of design or human achievement. So it is with laboratory research. Animal experiments are part of medical history, but history is where they belong. Compared to today’s potential to understand the basis of human disease at cellular and molecular levels, experimenting on live animals seems positively primitive. So if we want better quality medical research, safer more effective pharmaceuticals and cures to human diseases, we need to turn the page in the history books and embrace the new chapter—21st century science.

Independent scientific reviews demonstrate that research using animals correlates very poorly to real human patients. In fact, the data show that animal studies fail to predict real human outcomes in 50 to 99.7 percent of cases. This is mainly because other species seldom naturally suffer from the same diseases as found in humans. Animal experiments rely on often uniquely human conditions being artificially induced in non-human species. While on a superficial level they may share similar symptoms, fundamental differences in genetics, physiology and biochemistry can result in wildly different reactions to both the illness and potential treatments. For some areas of disease research, overreliance on animal models may well have delayed medical progress rather than advanced it. By contrast, many non-animal replacement methods such as cell-based studies, silicon chip biosensors, and computational systems biology models, can provide faster and more human-relevant answers to medical and chemical safety questions that animal experiments cannot match.

“The claim that animal experimentation is essential to medical development is not supported by proper, scientific evidence but by opinion and anecdote. Systematic reviews of its effectiveness don’t support the claims made on its behalf” (Pandora Pound et al. British Medical Journal 328, 514-7, 2004).

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Imagine a syringe being forced down your throat to inject a chemical into your stomach, or being restrained and forced to breathe sickening vapours for hours. That’s the cruel reality of animal testing for millions of mice, rabbits, dogs and other animals worldwide.

We’re giving the beauty industry a cruelty-free makeover with a wave of animal testing bans supported by hundreds of companies and millions of caring consumers worldwide.

We all dream of the day when cancer is cured and AIDS is eradicated, but is the continued use of mice, monkeys and other animals as experimental “models” of human disease actually holding us back from realizing the promise of 21st century science?

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Open Access

Ethical and Scientific Considerations Regarding Animal Testing and Research

* E-mail: [email protected]

Affiliations Physicians Committee for Responsible Medicine, Washington, D.C., United States of America, Department of Medicine, The George Washington University, Washington, D.C., United States of America

Affiliation Physicians Committee for Responsible Medicine, Washington, D.C., United States of America

• Hope R. Ferdowsian, 

Published: September 7, 2011

• https://doi.org/10.1371/journal.pone.0024059
• Reader Comments

Citation: Ferdowsian HR, Beck N (2011) Ethical and Scientific Considerations Regarding Animal Testing and Research. PLoS ONE 6(9): e24059. https://doi.org/10.1371/journal.pone.0024059

Editor: Catriona J. MacCallum, Public Library of Science, United Kingdom

Copyright: © 2011 Ferdowsian, Beck. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding: The authors are grateful to the National Science Foundation (grant SES-0957163) and the Arcus Foundation (grant 0902-34) for the financial support for the corresponding conference, Animals, Research, and Alternatives: Measuring Progress 50 Years Later. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: HRF and NB are employed by Physicians Committee for Responsible Medicine, which is a non-governmental organization which promotes higher ethical standards in research and alternatives to the use of animals in research, education, and training. Physicians Committee for Responsible Medicine is a nonprofit organization, and the authors adhered to PLoS ONE policies on sharing data and materials.

In 1959, William Russell and Rex Burch published the seminal book, The Principles of Humane Experimental Technique, which emphasized r eduction, r efinement, and r eplacement of animal use, principles which have since been referred to as the “3 Rs”. These principles encouraged researchers to work to reduce the number of animals used in experiments to the minimum considered necessary, refine or limit the pain and distress to which animals are exposed, and replace the use of animals with non-animal alternatives when possible. Despite the attention brought to this issue by Russell and Burch and since, the number of animals used in research and testing has continued to increase, raising serious ethical and scientific issues. Further, while the “3 Rs” capture crucially important concepts, they do not adequately reflect the substantial developments in our new knowledge about the cognitive and emotional capabilities of animals, the individual interests of animals, or an updated understanding of potential harms associated with animal research. This Overview provides a brief summary of the ethical and scientific considerations regarding the use of animals in research and testing, and accompanies a Collection entitled Animals, Research, and Alternatives: Measuring Progress 50 Years Later , which aims to spur ethical and scientific advancement.

Introduction

One of the most influential attempts to examine and affect the use of animals in research can be traced back to1959, with the publication of The Principles of Humane Experimental Technique [1] . William Russell and Rex Burch published this seminal book in response to marked growth in medical and veterinary research and the concomitant increase in the numbers of animals used. Russell and Burch's text emphasized r eduction, r efinement, and r eplacement of animal use, principles which have since been referred to as the “3 Rs”. These principles encouraged researchers to work to reduce the number of animals used in experiments to the minimum considered necessary, refine or limit the pain and distress to which animals are exposed, and replace the use of animals with non-animal alternatives when possible.

Despite the attention brought to this issue by Russell and Burch, the number of animals used in research and testing has continued to increase. Recent estimates suggest that at least 100 million animals are used each year worldwide [2] . However, this is likely an underestimate, and it is impossible to accurately quantify the number of animals used in or for experimentation. Full reporting of all animal use is not required or made public in most countries. Nevertheless, based on available information, it is clear that the number of animals used in research has not significantly declined over the past several decades.

The “3 Rs” serve as the cornerstone for current animal research guidelines, but questions remain about the adequacy of existing guidelines and whether researchers, review boards, and funders have fully and adequately implemented the “3 Rs”. Further, while the “3 Rs” capture crucially important concepts, they do not adequately reflect the substantial developments in our new knowledge about the cognitive and emotional capabilities of animals; an updated understanding of the harms inherent in animal research; and the changing cultural perspectives about the place of animals in society [3] , [4] . In addition, serious questions have been raised about the effectiveness of animal testing and research in predicting anticipated outcomes [5] – [13] .

In August 2010, the Georgetown University Kennedy Institute of Ethics, the Johns Hopkins University Center for Alternatives to Animal Testing, the Institute for In Vitro Sciences, The George Washington University, and the Physicians Committee for Responsible Medicine jointly held a two day multi-disciplinary, international conference in Washington, DC, to address the scientific, legal, and political opportunities and challenges to implementing alternatives to animal research. This two-day symposium aimed to advance the study of the ethical and scientific issues surrounding the use of animals in testing and research, with particular emphasis on the adequacy of current protections and the promise and challenges of developing alternatives to the use of animals in basic research, pharmaceutical research and development, and regulatory toxicology. Speakers who contributed to the conference reviewed and contributed new knowledge regarding the cognitive and affective capabilities of animals, revealed through ethology, cognitive psychology, neuroscience, and related disciplines. Speakers also explored the dimensions of harm associated with animal research, touching on the ethical implications regarding the use of animals in research. Finally, several contributors presented the latest scientific advances in developing alternatives to the use of animals in pharmaceutical research and development and regulatory toxicity testing.

This Collection combines some papers that were written following this conference with an aim to highlight relevant progress and research. This Overview provides a brief summary of the ethical and scientific considerations regarding the use of animals in research and testing, some of which are highlighted in the accompanying Collection.

Analysis and Discussion

Ethical considerations and advances in the understanding of animal cognition.

Apprehension around burgeoning medical research in the late 1800s and the first half of the 20 th century sparked concerns over the use of humans and animals in research [14] , [15] . Suspicions around the use of humans were deepened with the revelation of several exploitive research projects, including a series of medical experiments on large numbers of prisoners by the Nazi German regime during World War II and the Tuskegee syphilis study. These abuses served as the impetus for the establishment of the Nuremberg Code, Declaration of Helsinki, and the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research (1974) and the resulting Belmont Report [16] – [18] . Today, these guidelines provide a platform for the protection of human research subjects, including the principles of respect, beneficence, and justice, as well as special protections for vulnerable populations.

Laws to protect animals in research have also been established. The British Parliament passed the first set of protections for animals in 1876, with the Cruelty to Animals Act [19] . Approximately ninety years later, the U.S. adopted regulations for animals used in research, with the passage of the Laboratory Animal Welfare Act of 1966 [20] . Subsequent national and international laws and guidelines have provided basic protections, but there are some significant inconsistencies among current regulations [21] . For example, the U.S. Animal Welfare Act excludes purpose-bred birds, rats, or mice, which comprise more than 90% of animals used in research [20] . In contrast, certain dogs and cats have received special attention and protections. Whereas the U.S. Animal Welfare Act excludes birds, rats and mice, the U.S. guidelines overseeing research conducted with federal funding includes protections for all vertebrates [22] , [23] . The lack of consistency is further illustrated by the “U.S. Government Principles for the Utilization and Care of Vertebrate Animals Used in Testing, Research and Training” which stress compliance with the U.S. Animal Welfare Act and “other applicable Federal laws, guidelines, and policies” [24] .

While strides have been made in the protection of both human and animal research subjects, the nature of these protections is markedly different. Human research protections emphasize specific principles aimed at protecting the interests of individuals and populations, sometimes to the detriment of the scientific question. This differs significantly from animal research guidelines, where the importance of the scientific question being researched commonly takes precedence over the interests of individual animals. Although scientists and ethicists have published numerous articles relevant to the ethics of animal research, current animal research guidelines do not articulate the rationale for the central differences between human and animal research guidelines. Currently, the majority of guidelines operate on the presumption that animal research should proceed based on broad, perceived benefits to humans. These guidelines are generally permissive of animal research independent of the costs to the individual animal as long as benefits seem achievable.

The concept of costs to individual animals can be further examined through the growing body of research on animal emotion and cognition. Studies published in the last few decades have dramatically increased our understanding of animal sentience, suggesting that animals' potential for experiencing harm is greater than has been appreciated and that current protections need to be reconsidered. It is now widely acknowledged by scientists and ethicists that animals can experience pain and distress [25] – [29] . Potential causes of harm include invasive procedures, disease, and deprivation of basic physiological needs. Other sources of harm for many animals include social deprivation and loss of the ability to fulfill natural behaviors, among other factors. Numerous studies have demonstrated that, even in response to gentle handling, animals can show marked changes in physiological and hormonal markers of stress [30] .

Although pain and suffering are subjective experiences, studies from multiple disciplines provide objective evidence of animals' abilities to experience pain. Animals demonstrate coordinated responses to pain and many emotional states that are similar to those exhibited by humans [25] , [26] . Animals share genetic, neuroanatomical, and physiological similarities with humans, and many animals express pain in ways similar to humans. Animals also share similarities with humans in genetic, developmental, and environmental risk factors for psychopathology [25] , [26] . For example, fear operates in a less organized subcortical neural circuit than pain, and it has been described in a wide variety of species [31] . More complex markers of psychological distress have also been described in animals. Varying forms of depression have been repeatedly reported in animals, including nonhuman primates, dogs, pigs, cats, birds and rodents, among others [32] – [34] . Anxiety disorders, such as post-traumatic stress disorder, have been described in animals including chimpanzees and elephants [35] , [36] , [37] .

In addition to the capacity to experience physical and psychological pain or distress, animals also display many language-like abilities, complex problem-solving skills, tool related cognition and pleasure-seeking, with empathy and self-awareness also suggested by some research. [38] – [44] . Play behavior, an indicator of pleasure, is widespread in mammals, and has also been described in birds [45] , [46] . Behavior suggestive of play has been observed in other taxa, including reptiles, fishes and cephalopods [43] . Self-awareness, assessed through mirror self-recognition, has been reported for chimpanzees and other great apes, magpies, and some cetaceans. More recent studies have shown that crows are capable of creating and using tools that require access to episodic-like memory formation and retrieval [47] . These findings suggest that crows and related species display evidence of causal reasoning, flexible learning strategies, imagination and prospection, similar to findings in great apes. These findings also challenge our assumptions about species similarities and differences and their relevance in solving ethical dilemmas regarding the use of animals in research.

Predictive Value of Animal Data and the Impact of Technical Innovations on Animal Use

In the last decade, concerns have mounted about how relevant animal experiments are to human health outcomes. Several papers have examined the concordance between animal and human data, demonstrating that findings in animals were not reliably replicated in human clinical research [5] – [13] . Recent systematic reviews of treatments for various clinical conditions demonstrated that animal studies have been poorly predictive of human outcomes in the fields of neurology and vascular disease, among others [7] , [48] . These reviews have raised questions about whether human diseases inflicted upon animals sufficiently mimic the disease processes and treatment responses seen in humans.

The value of animal use for predicting human outcomes has also been questioned in the regulatory toxicology field, which relies on a codified set of highly standardized animal experiments for assessing various types of toxicity. Despite serious shortcomings for many of these assays, most of which are 50 to 60 years old, the field has been slow to adopt newer methods. The year 2007 marked a turning point in the toxicology field, with publication of a landmark report by the U.S. National Research Council (NRC), highlighting the need to embrace in vitro and computational methods in order to obtain data that more accurately predicts toxic effects in humans. The report, “Toxicity Testing in the 21 st Century: A Vision and a Strategy,” was commissioned by the U.S. Environmental Protection Agency, partially due to the recognition of weaknesses in existing approaches to toxicity testing [49] . The NRC vision calls for a shift away from animal use in chemical testing toward computational models and high-throughput and high-content in vitro methods. The report emphasized that these methods can provide more predictive data, more quickly and affordably than traditional in vivo methods. Subsequently published articles address the implementation of this vision for improving the current system of chemical testing and assessment [50] , [51] .

While a sea change is underway in regulatory toxicology, there has been much less dialogue surrounding the replacement of animals in research, despite the fact that far more animals are used in basic and applied research than in regulatory toxicology. The use of animals in research is inherently more difficult to approach systematically because research questions are much more diverse and less proscribed than in regulatory toxicology [52] . Because researchers often use very specialized assays and systems to address their hypotheses, replacement of animals in this area is a more individualized endeavour. Researchers and oversight boards have to evaluate the relevance of the research question and whether the tools of modern molecular and cell biology, genetics, biochemistry, and computational biology can be used in lieu of animals. While none of these tools on their own are capable of replicating a whole organism, they do provide a mechanistic understanding of molecular events. It is important for researchers and reviewers to assess differences in the clinical presentation and manifestation of diseases among species, as well as anatomical, physiological, and genetic differences that could impact the transferability of findings. Another relevant consideration is how well animal data can mirror relevant epigenetic effects and human genetic variability.

Examples of existing and promising non-animal methods have been reviewed recently by Langley and colleagues, who highlighted advances in fields including orthodontics, neurology, immunology, infectious diseases, pulmonology, endocrine and metabolism, cardiology, and obstetrics [52] .

Many researchers have also begun to rely solely on human data and cell and tissue assays to address large areas of therapeutic research and development. In the area of vaccine testing and development, a surrogate in-vitro human immune system has been developed to help predict an individual's immune response to a particular drug or vaccine [53] , [54] . This system includes a blood-donor base of hundreds of individuals from diverse populations and offers many benefits, including predictive high-throughput in vitro immunology to assess novel drug and vaccine candidates, measurement of immune responses in diverse human populations, faster cycle time for discovery, better selection of drug candidates for clinical evaluation, and reductions in the time and costs to bring drugs and vaccines to the market. In the case of vaccines, this system can be used at every stage, including in vitro disease models, antigen selection and adjuvant effects, safety testing, clinical trials, manufacturing, and potency assays. When compared with data from animal experiments, this system has produced more accurate pre-clinical data.

The examples above illustrate how innovative applications of technology can generate data more meaningful to humans, and reduce or replace animal use, but advances in medicine may also require novel approaches to setting research priorities. The Dr. Susan Love Research Foundation, which focuses on eradicating breast cancer, has challenged research scientists to move from animal research to breast cancer prevention research involving women. If researchers could better understand the factors that increase the risk for breast cancer, as well as methods for effective prevention, fewer women would require treatment for breast cancer. Whereas animal research is largely investigator-initiated, this model tries to address the questions that are central to the care of women at risk for or affected by breast cancer. This approach has facilitated the recruitment of women for studies including a national project funded by the National Institutes of Health and the National Institute of Environmental Health to examine how environment and genes affect breast cancer risk. This study, which began in 2002, could not have been accomplished with animal research [55] .

Similarly, any approach that emphasizes evidence-based prevention would provide benefits to both animals and humans. Resource limitations might require a strategic approach that emphasizes diseases with the greatest public health threats, which increasingly fall within the scope of preventable diseases.

It is clear that there have been many scientific and ethical advances since the first publication of Russell and Burch's book. However, some in the scientific community are beginning to question how well data from animals translates into germane knowledge and treatment of human conditions. Efforts to objectively evaluate the value of animal research for understanding and treating human disease are particularly relevant in the modern era, considering the availability of increasingly sophisticated technologies to address research questions [9] . Ethical objections to the use of animals have been publically voiced for more than a century, well before there was a firm scientific understanding of animal emotion and cognition [15] . Now, a better understanding of animals' capacity for pain and suffering is prompting many to take a closer look at the human use of animals [56] .

Articles in the accompanying Collection only briefly touch on the many scientific and ethical issues surrounding the use of animals in testing and research. While it is important to acknowledge limitations to non-animal methods remain, recent developments demonstrate that these limitations should be viewed as rousing challenges rather than insurmountable obstacles. Although discussion of these issues can be difficult, progress is most likely to occur through an ethically consistent, evidence-based approach. This collection aims to spur further steps forward toward a more coherent ethical framework for scientific advancement.

Acknowledgments

The authors thank the conference speakers and participants for their participation.

Author Contributions

Conceived and designed the experiments: HRF NB. Contributed reagents/materials/analysis tools: HRF NB. Wrote the paper: HRF NB.

• 1. Russell WMS, Burch RL (1959) The principles of humane experimental technique. London: Methuen. 238 p.
• View Article
• Google Scholar
• 3. Ibrahim DM (2006) Reduce, refine, replace: the failure of the three R's and the future of animal experimentation. University of Chicago Legal Forum, 2006; Arizona Legal Studies Discussion Paper No. 06-17. Available: http://ssrn.com/abstract=888206 . Accessed 2011 Jan 7.
• 15. Lederer SE (1995) Subjected to science. Baltimore: The Johns Hopkins University Press. 192 p.
• 16. United States (1947) Nuremberg code. Trials of War Criminals before the Nuremberg Military Tribunals under Control Council Law No. 10. Washington, D.C.: U.S. Government Printing Office. Available: http://ohsr.od.nih.gov/guidelines/nuremberg.html . Accessed 2011 Jan 7.
• 17. World Medical Association (1964) Declaration of Helsinki. 18 th WMA General Assembly. Helsinki, Finland: Available: http://history.nih.gov/research/downloads/helsinki.pdf . Accessed 2011 Jan 7.
• 18. National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research (1979) The Belmont Report. Washington, D.C.: US Department of Health, Education, and Welfare. Available: http://ohsr.od.nih.gov/guidelines/belmont.html . Accessed 2011 Jan 7.
• 19. Parliament of the United Kingdom (1876) Cruelty to Animals Act 1876. Available: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1872363/ . Accessed 2011 Jan 7.
• 20. Animal Welfare Act. 7 U.S.C. §§ 2131–2159.
• 22. Institute of Laboratory Animal Resources, Commission on Life Sciences, National Research Council (1996) Guide for the care and use of laboratory animals. Washington, D.C.: National Academy Press. 140 p.
• 23. Office of Laboratory Animal Welfare (2002) Public Health Service policy on humane care and use of laboratory animals. Available: http://grants.nih.gov/grants/olaw/references/phspol.htm#PublicHealthServicePolicyonHumaneCareandUseofLaboratory . Accessed 2011 Jan 18.
• 24. Office of Laboratory Animal Welfare (2002) U.S. Government principles for the utilization and care of vertebrate animals used in testing, research and training. Available: http://grants.nih.gov/grants/olaw/references/phspol.htm . Accessed 2011 Jan 7.
• 25. Gregory NG (2004) Physiology and behavior of animal suffering. Oxford, U.K.: Blackwell Science. 280 p.
• 26. McMillan FD, editor. (2005) Mental Health and Well-Being in Animals. Oxford, U.K.: Blackwell Publishing Professional. 301 p.
• 27. Institute of Laboratory Animal Resources, Commission on Life Sciences, National Research Council (2009) Recognition and alleviation of pain and distress in laboratory animals. Washington, D.C.: National Academy Press. 196 p.
• 31. Panksepp J (2004) Affective neuroscience: the foundations of human and animal emotions. Oxford: Oxford University Press. 480 p.
• 32. Koob GF, Ehlers CL, Kupfers DJ, editors. (1989) Animal Models of Depression. Boston, MA: Birkhäuser. 295 p.
• 39. Shettleworth SJ (1998) Cognition, evolution, and behavior. Oxford, U.K.: Oxford University Press. 704 p.
• 40. deWaal F (2009) The age of empathy: nature's lessons for a kinder society. New York, NY: Random House, Inc. 304 p.
• 44. Burghardt GM (2005) The genesis of animal play: testing the limits. Cambridge, U.K.: MIT Press. 501 p.
• 49. Committee on Toxicity Testing and Assessment of Environmental Agents, National Research Council (2007) Toxicity testing in the 21st century: a vision and a strategy. Washington, DC: National Academy Press. 216 p.
• 55. Dr. Susan Love Research Foundation, National Cancer Institute Cancer Biomedical Informatics Grid (2009) Health of Women Study. Available: http://cabig.cancer.gov/action/collaborations/howstudy/ . Accessed 2011 Jan 10.
• 56. Beauchamp TL, Orlans FB, Dresser R, Morton DB, Gluck JP (2008) The Human Use of Animals: Case Studies in Ethical Choice, 2 nd ed. New York, NY: Oxford University Press. 287 p.

ADDRESS THE NHP CRISIS TODAY!

Immediate action needed.

DRUG DEVELOPMENT PIPELINE AT RISK

Advocating SOUND PUBLIC POLICY

in support of ethical and essential animal research.

PROTECTING VITAL ROLE ANIMALS PLAY

in biomedical research

FACILITATING DIALOGUE BETWEEN

our members and their congressional delegations on animal research issues

PRESERVING BIOMEDICAL RESEARCHERS'

abilities to use animals in ethical and responsible research

SUPPORTING HUMANE CARE & TREATMENT OF LABORATORY ANIMALS

in biomedical research, training, and education

PROVIDING OUR MEMBERS

with information and consultation on state and local issues

CREATING A FORUM FOR THE BIOMEDICAL COMMUNITY

to develop common positions on legislative and regulatory issues

PROTECTING THE ABILITY TO STUDY WHOLE LIVING ORGANISMS

in support of biomedical research

Founded in 1979, the National Association for Biomedical Research (NABR) is a 501(c)(6) non-profit association dedicated to sound public policy for the humane use of animals in biomedical research, education, and testing. NABR provides a unified voice for the scientific community on legislative, regulatory and legal matters affecting the responsible, humane, and ethical use of laboratory animals. Members include more than 340 universities, medical and veterinary schools, teaching hospitals, pharmaceutical and biotechnology companies, patient groups, and academic and professional societies who rely on humane and responsible animal research to advance global human and animal health. For more than 40 years, and as the only national, non-profit organization solely dedicated to advocating sound public policy for ethical and essential animal research, NABR has worked to safeguard the future of biomedical research. 

NABR Files Formal Petition Challenging the Listing of Long-Tailed Macaque by the IUCN 

Working with recognized, independent scientists, the National Association for Biomedical Research (NABR) filed an initial petition on June 15, 2023 with the International Union for Conservation of Nature (IUCN) challenging the recent designation of the long-tailed macaque ( Macaca fascicularis ) as endangered under IUCN listing criteria. This designation is a result of improperly used data that do not support the endangered species listing. NABR called for an immediate review. Read more by clicking here . 

After several weeks of discussions between NABR and the IUCN, on September 11, 2023, NABR filed a formal petition with the IUCN challenging its decision to uplist the status of the long-tailed macaque from “vulnerable” to “endangered.” Read NABR’s formal IUCN petition and the addendum  here.   Read NABR’s press release  here .

In October 2023, the IUCN formally accepted NABR’s petition. Read the press release  here . 

On February 1, 2024, NABR submitted an expanded petition to the IUCN concerning the long-tailed macaque status. The expanded petition can be found  here  and the press release about the expanded petition can be found  here .

Read NABR’s February 2024  response  to the authors of the study the IUCN relied on to uplist the status of long-tailed macaques to “endangered.”

NABR's IUCN Petition: Noteworthy Articles

Read  the August 1, 2023 article in the journal Science by Shanghai correspondent Dennis Normile about NABR’s IUCN petition. Normile also discusses a recent study in Biological Reviews according to which long-tailed macaques are hyperabundant in formerly wild environments where humans have started settling. He highlights the inherent contradiction between the IUCN’s “endangered” listing of long-tailed macaques on the one hand, and the scientific data presented in the Biological Reviews study and NABR’s petition on the other hand.

Read   the NABR press release announcing the December 21, 2023  American Journal of Primatology article that disputes information used to determine a faulty conservation status of long-tailed macaques the IUCN issued. You can also read the AJP article directly here . 

YOUR HELP NEEDED

The U.S. Fish and Wildlife Service is denying permits related to Cambodian origin nonhuman primates (NHPs) and samples. Roughly 60% of the preclinical animal models of the drug development process are Cambodian origin NHPs. This action has put the development of new drugs to treat thousands of diseases for which there is no treatment or cure at significant risk. Our message is simple: We are calling on the U.S. government to work with, not against, the biomedical research sector, to find solutions to remedy the disruption in the biomedical research supply chain. Thank you for helping us do that. 

Institutional Sign-on Letter

NABR is organizing an   institutional sign-on letter  to be sent to key members of Congress. The sign-on letter is   here , and we are asking as many organizations as possible to add their names. Some organizations have asked whether the U.S. Fish and Wildlife Service has issued any public notice regarding the denial of permits affecting Cambodian origin NHPs and samples. Unfortunately, there has been no public statement or public notice regarding this decision, which is one impetus for our correspondence to the government. At least 60% of the NHPs in the drug development pipeline are of Cambodian origin, which underscores the impact this decision has on the creation of new medications for thousands of diseases for which there is no treatment or cure.

If you would like to sign-on, please email   [email protected] .

 Individual Letters

NABR members have submitted more than 2,000 letters to Congress regarding the NHP crisis, so let’s keep the momentum going! Please broadly circulate the  link   [ speak4.app/lp/24d1d8/ ]  and encourage others at your organization to do the same. Alternately, you can click the "Take Action" bubble at the bottom right of your screen. The process is fast and easy, and it does make a difference. NABR is hearing from Capitol Hill staff who have taken an interest in this critical issue.

NHP Shortage News

March 1, 2024 Modern Approaches in Drug Designing :  https://crimsonpublishers.com/madd/pdf/MADD.000585.pdf  

December 26, 2023   The South Florida Sun Sentinel:  https://www.sun-sentinel.com/2023/12/26/international-organizations-monkey-business-will-slow-medical-research-opinion/   

September 4, 2023   The Washington Times :  www.washingtontimes.com/news/2023/sep/4/activists-are-trying-to-slow-down-lifesaving-medic/

August 4, 2023 BioSpace.com:  www.biospace.com/article/scientists-veterinarians-and-conservationists-offer-recommendations-to-address-the-shortage-of-long-tailed-macaques-required-for-continued-health-advancements-/

August 3, 2023 ScienMag.com: www.scienmag.com/scientists-veterinarians-and-conservationists-offer-recommendations-to-address-shortage-of-long-tailed-macaques-required-for-continued-health-advancements/

June 27, 2023   The San Joaquin Valley Sun : www.sjvsun.com/u-s/advocates-peta-pressuring-feds-to-bar-on-primate-use-for-dug-research/

June 15, 2023   The San Joaquin Valley Sun : www.sjvsun.com/business/report-false-designation-for-primate-could-block-ability-to-test-groundbreaking-drugs/

June 15, 2023   E&E News : www.subscriber.politicopro.com/article/eenews/2023/06/15/researchers-challenge-endangered-status-of-lab-primate-00102155

May 22, 2023   The Salina, Kansas Post : www.salinapost.com/posts/a5f331c8-afd1-49e0-b32c-f6e4ad0b2092

May 4, 2023   STAT+ :  www.statnews.com/pharmalot/2023/05/04/nih-primates-macaques-research-biomedical-animals-organs/  

May 4, 2023 NABR press release:   https://www.nabr.org/about-nabr/news/nas-report-affirms-necessity-nhp-models-and-highlights-shortage-crisis

May 4, 2023   The Wall Street Journal :  The U.S. Is Running Out of Research Monkeys

May 4, 2023  STAT+:   NIH systems for non-human primate research fall short, threatening biomedical research

May 4, 2023  AP News   Research monkey shortage undermines US readiness, panel says

March 27, 2023   www.openaccessgovernment.org :    https://www.openaccessgovernment.org/article/fostering-nonhuman-primate-nhp-brain-research-without-animal-sacrifice/155741/

March 20, 2023  UK Guardian : Fate of 1,000 trafficked lab monkeys at center of US investigation in limbo

March 6, 2023   Endpoints News :  Pharma industry lobbies Congress for solution to primate shortage after indictments for alleged smuggling

March 3, 2023  ScienceDirect:  Is biomedical research demand driving a monkey business?

March 3, 2023  STAT+:   As a U.S. agency denies permits to import monkeys for research, industry starts pushing back

March 3, 2023   The Wall Street Journal :  Monkey Business Threatens U.S. Drug Discovery

January 20, 2023  The Dispatch: America's Primate Problem

June 23, 2022  Mother Jones :  A Plane of Monkeys, a Pandemic, and a Botched Deal: Inside the Science Crisis You’ve Never Heard Of

September 28, 2022  Bloomberg News:   Lab Monkeys Are the Latest Covid Shortage

August 31, 2020  The Atlantic:  America Is Running Low on a Crucial Resource for COVID-19 Vaccines

FAQs  on the FDA Modernization Act

Does the fda modernization act 2.0 end animal testing.

No. The FDA Modernization Act 2.0 does not eliminate animal testing nor does it state or imply that animal testing is unnecessary. It simply clarifies the definition under the Food, Drug and Cosmetic Act of a nonclinical test or study to include adjunct and complementary testing methods like organs-on-a-chip, micro-physiological systems and computer simulations. Animal models continue to be highly relevant to test the safety and efficacy of a drug as part of the approval process. NABR supports the use of alternative models to animal testing when scientifically feasible and when scientifically validated, and remains confident in the ability of FDA scientific reviewers to determine the best data that should be submitted in new drug applications.

The FDA states that many procedures intended to reduce animal tests are still in various stages of development[1,2]. Adjunct and complementary tests have a purpose, but ultimately testing must progress to a whole intact, living system, including a rodent and non-rodent species during preclinical drug trials[3,4,5]. Not conducting animal tests, when necessary, would likely subject humans and other animals to unreasonable risks.

What is the FDA Modernization Act 2.0?

The FDA Modernization Act 2.0, passed as part of the Omnibus appropriations legislation in December of 2022, amends the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355) to clarify methods manufacturers and sponsors can use to investigate the safety and efficacy of a drug by inserting language on “nonclinical tests,” where “nonclinical tests” are defined broadly as follows [6] :

• ·       A test or study that is most likely to predict human response based on scientific evidence and occurs before or during the clinical trial phase of the investigation of the safety and effectiveness of a drug. Such test or study may include the following:
• o   Cell-based assays
• o   Organ chips and microphysiological systems
• o   Sophisticated computer modeling
• o   Other human biology-based test methods
• o   Animal tests

It is important to note that the FDA previously had the authority to allow non-animal data to be considered during safety and efficacy reviews of new drugs and previously issued guidance regarding such. Ultimately, the FDA Modernization Act 2.0 may not materially change the current drug approval process at the FDA. In fact, a spokesperson for the FDA stated on the record that the new law does not change the regulatory process for drugs [7].

Why is animal testing important as part of the drug approval process?

The Food, Drug and Cosmetic Act was enacted in 1938 after the drug sulfanilamide, marketed for strep throat in the U.S. without human or animal research data establishing its safety or its efficacy, killed and sickened hundreds of people due to toxic levels of antifreeze it contained[8]. Additional animal research safety and efficacy data became required under the Act in 1963 to prevent incidents like the thalidomide incident in Europe and other parts of the world [9].

Animal testing followed by human clinical trials currently remains the best way to examine complex physiological, neuroanatomical, reproductive, developmental and cognitive effects of drugs to determine if they are safe and effective for market approval.

The overwhelming majority of drugs on the market today relied on safety and efficacy data from multiple animal models before being allowed to move to human clinical trials as demonstrated by the Foundation for Biomedical Research's Top 25 Drugs and Animal Model study [10].

NABR’s press statement on the FDA Modernization Act 2.0

NABR Files Expanded Petition Challenging the Listing of Long-Tailed Macaques by the IUCN

NABR April Webinar: “One Health and Animal Research: The Good, the Bad, and the Ugly”

NABR Press Release: LTM Conservation Status

The FY 2023 USDA Oversight Process

Nabr insights.

NABR contributes a great deal of time and resources towards developing and compiling industry relevant reports, webinars, and other informative documents for the benefit of its members. Please click the links below to access a variety of valuable resources and information in the   Member's Only  section.

Crisis Management Guide

Available for all NABR members. Download

Legal Resources for Managing Security at Private Residences

2022 NABR USDA Inspection Management Guide

Available for all NABR members. Explore

FOIA/Open Records

Available for all NABR members.

Legislation

Regulatory Comments

FY22 Appropriation Items

NABR Position Statement on Retirement/Adoption

DOT Secretary Pete Buttigieg on NABR’s complaint

Outgoing NIH Director Francis Collins Discusses Animal Research Ethics in Popular Podcast

FASEB Joins Partners to Support Biomedical Animal Research

Why Animal Research?

Animal research is a major contributor to almost all advances in human and animal health. The similarity in biological makeup between humans and some animals provides insight into diseases such as COVID-19, Diabetes, Cancer and many more. Animal testing also allows scientists to control factors such as temperature, lighting and diet, which is rather difficult and sometimes unethical during human trials. 

FAQ on Animal Research

Why is animal research necessary.

Modern medical research, including research using animals, is necessary to understanding disease and creating medicines to improve human and animal lives and reduce suffering.  Every known medical breakthrough known has a basis in animal research and all of the top 25 most prescribed drugs were developed with the assistance of animal models.  To learn more about the indispensable role of animal research, watch a brief PSA by the Foundation for Biomedical Research (FBR)  by clicking here .

Why is it even necessary to move animals?

Biomedical research is conducted in universities and commercial laboratories across the globe.  Important breakthroughs are typically dependent on collaborative efforts from different laboratories in many states and countries.

Successful research depends on a reliable source of healthy laboratory animals.  The best way of achieving this is through a global supply and transportation chain. Animals obtained from the same source have consistent genetics allowing scientists to better interpret data from animal studies.   Professional breeders with highly controlled environments produce disease free animals with special characteristics important in studying human disease.

A shared source of genetically defined and healthy animals dramatically reduces the total number of animals required for a research program.  A striking benefit of collaboration is the refinement of animal use.   By including collaborators with the highest expertise and the best modern methodology to conduct animal studies, better data is produced.

Without the ability to transport laboratory animals from licensed commercial breeders and between research facilities, each research site would have to breed its own animals.  This would be costly and would unnecessarily increase the number of animals for research.

How are animals transported?

Experienced and licensed professional transport companies are used to safely move laboratory animals. Animals are transported in vehicles equipped with temperature and humidity monitors and controls.  Travel routes are designed to take the shortest time reasonable to reduce travel stress.  To keep the journey as brief as possible, animals are frequently transported via airplane.

During transport, animals are provided with food, water and appropriate temperatures and conditions. Shipping containers are designed for proper ventilation and to protection animals from escape or injury.  Bedding materials are provided for comfort and are specific to the needs of each species.  Veterinarians specializing in the care of laboratory animals coordinate the shipping process, working with trained staff who monitor animals throughout the shipping process.

Why do we need to import nonhuman primates?

It is often in the best interests of an animal to be born and raised in areas with a climate well suited to the welfare of their species and where year-round outdoor housing is available.   Nonhuman primates most commonly used in research are native to tropical and subtropical regions, and breeding facilities in those regions can provide captive animals with a suitable environment.  These captive bred animals are reared to young adulthood before being moved to research facilities around the world.

Where do we get research animals?

The preferred source for research animals is a professional breeder. These producers are dedicated to supplying healthy, high quality animals to the research community.  Animals are obtained from licensed, inspected and accredited facilities that employ experienced handlers, caretakers, and veterinarians.  The research community demands high quality standards for food, water, sanitation and welfare for research animals, creating conditions that often exceed those of typical house pets.

Is it safe for animals?

The regulated transportation of laboratory animals is very safe.  Industry statistics show there is an error rate of less than 1% for either land or air transportation of animals.  Most of these errors do not impact the health or welfare of the shipment, so the actual impact on animal safety is even lower.

What would happen if we couldn’t transport animals in the future?

Without the ability to transport laboratory animals, research would be restricted to fewer locations and would lose the contributions of many talented scientists.  Further, scientists would not always be able to use the most appropriate model to study a disease or response to a medication, delaying or stopping much needed medical advances.

The development of new medicines would slow, or even stop, denying cures and treatments to the people who need them.  Research institutions would have to divert precious funding, manpower and laboratory space to breeding animals, taking resources away from important research.

Scientific collaboration across the world would be hampered by inconsistency in their research animals and difficulty interpreting data.  Without the ability to transport laboratory animals by air, the research community would be unable to provide the best possible conditions for shipping animals quickly and safely.  Without air transportation options, animals would often be subject to longer and more stressful transportation by land or sea.

Crisis Management

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Congressional and Legislative Action

Learn more about NABR's advocacy efforts, like the passage of the AETA.

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• Published: 03 March 2022

Openness about animal research increases public support

• Juan Carlos Mendez   ORCID: orcid.org/0000-0002-7251-0750 1 , 2 ,
• Brook A. L. Perry   ORCID: orcid.org/0000-0001-8598-1458 1 ,
• Rhyanne J. Heppenstall   ORCID: orcid.org/0000-0002-3137-8378 1 ,
• Stuart Mason 1 &
• Anna S. Mitchell   ORCID: orcid.org/0000-0001-8996-1067 1  

Nature Neuroscience volume  25 ,  pages 401–403 ( 2022 ) Cite this article

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• Long-term memory

Science engagement can be a daunting prospect. This is especially true for scientists whose work involves animal models, and particularly nonhuman primates. Here, we show that openly explaining our rationale for our neuroscience work involving nonhuman primates — and the legal and ethical regulations that govern animal experimentation — increased public support and understanding, which is crucial for this essential research to continue.

The use of animals in neuroscientific research has been essential to our current understanding of brain function, as well as for the development of therapies for neurological illnesses. Biomedical experimental findings on nonhuman primates (NHPs) are particularly transferable to humans, owing to their similar physiology and the anatomical resemblance of their brains to ours 1 . Although neuroscience has seen enormous advances since the middle of the twentieth century, research on animals (including NHPs) is still irreplaceable and support from policy makers and the public is crucial for its continuation. Thus, neuroscientists, supported by their funders and research institutions, need to keep raising awareness about the importance of their findings in animal models in creative and accessible ways.

Recognition of the need for transparency among researchers working with animals is increasing. In the UK, signatories of the 2014 Concordat on Openness on Animal Research committed to proactively and clearly communicate their research on animals with the media and the public 2 . This document has been signed by more than 120 research organizations, including our institution (University of Oxford) and our funders (The Wellcome Trust), and it has inspired countries worldwide to commit to similar agreements. An example of an effort along these lines is the creation of resources such as the Lab Animal Tour 3 , an interactive website with videos through which people can virtually access the animal facilities of four different research institutes of the UK, including the primate facility at the University of Oxford. The aims of this positive shift are to assuage the public on the ethical, moral and scientific justification for animal research, and to engage with regulators on the importance of biomedical research and the necessity for ensuring international collaboration 4 . Perhaps as paramount, these efforts should also inform about the scientists’ work toward the humane treatment of NHPs.

In Europe and the USA, scientists working with animals must comply with strict laws that ensure animal welfare remains a priority 4 , 5 . In the UK, any project involving NHP experiments must first undergo extensive ethical approval to be granted a license by the Home Office Secretary of State and is then continuously scrutinized. One of the guiding principles behind these animal research laws is adherence to the 3Rs: proposed in 1959 in the UK and subsequently adopted internationally, the 3R principles advocate for replacement (avoiding the use of animals if alternatives exist), reduction (minimizing the number of animals used) and refinement (methods that minimize suffering and improve welfare). However, the public seems to be unaware of most of these efforts: a poll conducted by IPSOS Mori ( https://www.ipsos.com/ ) 6 every 2 to 3 years to assess public attitudes toward animal research has consistently shown that less than 5% of the public is aware of the 3Rs. Similarly, this poll estimated that 38% of the population believe that cosmetic research on animals is legal in the UK, even though it has been banned since 1998 (and across the EU since 2013). Still, a recent petition submitted to the UK Government and Parliament 7 asking ‘to ban all UK animal testing, including for the development of cosmetics, household products and medicines’ reached more than 235,000 signatures. Perhaps this widespread misinformation is behind the finding by the Pew Research Center 8 that, whereas 89% of the community connected to the American Association for the Advancement of Science (AAAS) supports animal research, only 47% of the interviewed adults support it. Importantly, by the time this Comment is published, the Swiss government 9 will have submitted to public vote, in February 2022, an initiative seeking to ban all animal experimentation in the country for the fourth time. Thus, despite scientists and governments working continuously toward improving the standards of animal research, there is still strong opposition to it.

These facts imply that outreach efforts from scientists working with animals are still not reaching wide sectors of the public 10 , a notion reinforced by the finding that the characteristic that is most commonly associated with animal research organizations is that they are secretive 6 . In a way, this is understandable: there is a history of harassment and aggression toward researchers using NHPs that could deter many from being open about their work 11 . Nevertheless, governments have passed acts (such as the 2006 Animal Enterprise Terrorism Act in the USA) to protect researchers, and extreme violence against them is in decline 2 . Another reason for scientists’ reluctance to engage with the public could be the common belief that participating in scientific outreach does not bring any benefit to their career 12 . After all, there is little evidence that public engagement actually yields a positive impact 13 , particularly in the field of animal research 14 , 15 , 16 . Thus, if neuroscientists working with NHPs are to be encouraged to speak openly about their work, it is crucial to assess whether reaching out to the public is fruitful and ultimately benefits both the public and the scientists.

Periodical polls, such as those by IPSOS Mori 6 and the Pew Research Center 8 , normally collect the views of a large population sample (1,011 and 2,002 adult individuals, respectively, in their latest editions) over several days or weeks, with individuals in the sample changing every time the study is repeated. Thus, although these polls provide important insights about changes in opinion among the public throughout the years, it is difficult to gauge from them which factors led to which changes. For this, the effect of individual variables needs to be evaluated independently and, ideally, in the same sample. A few studies have analyzed how different informative strategies affect support for behavioral research experiments from visitors to primate zoo facilities 14 , as well as how much information visitors learn and understand 14 , 15 , 16 . Similarly, an online tool has been used to assess attitudes toward hypothetical experimental manipulations on pigs 17 . However, to our knowledge, there are no reports of attempts to measure the effect of science engagement activities on the attitudes of the audience toward neuroscientific research on animals.

As with many other human activities, the COVID-19 pandemic caused science engagement events to be moved online. This, in turn, brought new opportunities and advantages, as people from all over the world could now attend events that used to be restricted to locals and different types of interaction were facilitated: people could write their questions and discuss what was being presented at any time without needing to speak in public. Many of these events were recorded and then uploaded to video-sharing platforms, allowing for still more people to benefit from them. Moreover, researchers could share relevant links and documents with the audience and, importantly, create surveys to gauge their opinions.

We recently participated in two prominent public science festivals that were based in the UK but took place online: the IF Oxford Science and Ideas Festival 2020 and the British Neuroscience Association ‘Bring Your Own Brain’ 2021 Festival of Neuroscience. Our goal was to convey the rationale behind the use of NHPs in our neurophysiological and neuroimaging projects, which are aimed at elucidating the dynamics of cortico-thalamocortical interactions during learning, memory and decision-making, and understanding the effect of their disruption in neurological diseases. First, we explained the extensive regulatory and ethical approval that we must obtain to be authorized to carry out experimental procedures on NHPs in the UK. Then, we illustrated the different stages that the NHPs experience, from training to experimentation, showing real footage of the team members working with them. Importantly, we also highlighted our research on NHP welfare optimization and on the development of care refinements (for example, ref. 18 ). Finally, we explained some of our recent research findings to highlight the value of our work (for example, ref. 19 ). These 40-min presentations were recorded and are freely available to view on YouTube 20 , 21 , meaning they can continue to have an effect. Overall, our social media videos 20 , 21 , 22 have been viewed over 22,000 times.

Importantly, before we began our presentations, we asked participants ( n = 99) to voluntarily and anonymously answer two questions regarding their views on animal research (Fig. 1 ). Sixty-three participants completed this first couple of questions. These same questions were then repeated at the end of the event, plus an additional question that evaluated the effect of our presentation. Sixty-nine participants completed this second set of questions. In the beginning, most of the attendees (44%) declared that they felt ‘not very well informed’ about animal research, and only 13% claimed to be ‘very well informed’. These results mirror those by IPSOS Mori in the UK population (38 and 6%, respectively) 6 . After our presentation, the great majority (59%) felt that they were now ‘fairly well informed’, whereas those considering themselves uninformed dropped from an overall 57% to merely 17%.

Total per cent results of the online surveys completed before (early poll) and immediately after (late poll) our online science engagement event ‘Behind the Scenes of a non-human primate research lab’, attended by people over the age of 13 years from the IF Oxford Science and Ideas Festival 2020 and the British Neuroscience Association ‘Bring Your Own Brain’ 2021 Festival of Neuroscience.

Before our presentation, most people (71%) (Fig. 1 ) already thought that ‘animal research was necessary and could be done without cruelty’ and only one person (1%) thought that ‘animals should never be used for research’. This is in contrast with the 2018 IPSOS Mori poll that reported 38% of people agreed with the statement: ‘I think that animals should not be used in any scientific research because of the importance I place on animal welfare’ 6 . Perhaps this difference is due to our events appealing more to those already supportive of scientific research in animals. Another factor could be that the COVID-19 pandemic has caused an increase in approval for animal research, as shown by recent polls by Understanding Animal Research in the UK ( https://www.understandinganimalresearch.org.uk/ ) 23 and by the Foundation for Biomedical Research in the USA 24 . Critically, comparisons between different polls (for example, ref. 25 ) also reveal that when people are given more context about the rationale behind the use of animals in research, they tend to oppose it less and instead declare themselves to be undecided. This is in accordance with our own findings: by the end of our presentation, the proportion who originally thought that ‘animal research is necessary but cruel’ decreased from 27% to 17%, with individuals from this group who changed their mind now agreeing that ‘animal research can be done without cruelty’ or declaring themselves to be undecided.

Finally, perhaps the more straightforward proof that speaking openly is beneficial for both scientists and the public is that more than half of the attendees (Fig. 1 ) who participated in our polls thought that our presentation ‘positively changed their perception of animal research’.

Although it is evident that neuroscientists working with animals need to make their voices heard to achieve accurate representations of their work, it is also clear that we should pay attention to and address the concerns of the public. Results from polls and surveys such as ours suggest that when scientists are open about their work with NHPs, public support increases. Thus, the time is ripe for researchers to engage more globally and, crucially, to make use of technological advances to listen to and better engage their audiences, generating ongoing, mutually beneficial interactions.

Data availability

All data generated and analyzed in this study are included in this Comment.

Roelfsema, P. R. & Treue, S. Neuron 82 , 1200–1204 (2014).

Article   CAS   Google Scholar  

MacArthur Clark, J., Clifford, P., Jarrett, W. & Pekow, C. ILAR J. 60 , 34–42 (2019).

Article   Google Scholar  

Understanding Animal Research. 360° Laboratory Animal Tours, https://www.labanimaltour.org/ (accessed February 2022).

Mitchell, A. S. et al. Neuroimage 229 , 117700 (2021).

Homberg, J. R. et al. Neuron 109 , 2374–2379 (2021).

Ipsos MORI. Public Attitudes to Animal Research in 2018 (Department for Business, Energy & Industrial Strategy, 2018).

UK Government and Parliament. Ban Animal Testing - Fund, accept & promote alternatives to animal testing. petition.parliament.uk , https://go.nature.com/3JyDXdW (October 2021).

Pew Research Center. Major gaps between the public, scientists on key issues. pewresearch.org , https://go.nature.com/3LJ38wf (1 July 2015).

The Federal Council. Popular initiative “Yes to the ban on animal and human experiments – Yes to research that brings safety and progress”. admin.ch , https://go.nature.com/3GYVZUY (10 February 2022)

Bennett, A. J. & Ringach, D. L. Neuron 92 , 653–657 (2016).

Nat. Neurosci. 9, 1195 (2006).

Pham, D. NPJ Sci. Learn. 1 , 16010 (2016).

Weingart, P., Joubert, M. & Connoway, K. PLoS ONE 16 , e0254201 (2021).

Waller, B. M., Peirce, K., Mitchell, H. & Micheletta, J. PLoS ONE 7 , e44680 (2012).

Whitehouse, J. et al. PLoS ONE 9 , e113395 (2014).

Bowler, M. T., Buchanan-Smith, H. M. & Whiten, A. PLoS ONE 7 , e34505 (2012).

Schuppli, C. A., Molento, C. F. & Weary, D. M. Public Underst. Sci. 24 , 358–374 (2015).

Perry, B. A. L. et al. J. Neurosci. Methods 348 , 108992 (2021).

Pelekanos, V. et al. J. Neurosci. 40 , 7887–7901 (2020).

IF Oxford. Behind the scenes at a primate lab. youtube.com , https://youtu.be/ZO2NqgYZB7E (5 October 2020).

British Neuroscience Association. Behind the scenes of a primate lab. youtube.com , https://youtu.be/gCCXYAeNmRw (23 April 2021).

Wellcome Trust. Unravelling how the brain works. facebook.com , https://fb.watch/6bHEib6N7l/ (3 February 2019).

Williams, B. Public Attitudes to Animal Research Under COVID-19 (Understanding Animal Research, 2020).

Foundation for Biomedical Research. 2021 animal research poll. fbresearch.org , https://fbresearch.org/polls-2021/ (2021).

Speaking of Research. Unveiled: the moveable middle on animal research is larger than we thought. speakingofresearch.com , https://go.nature.com/34IAAm9 (16 June 2021).

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Acknowledgements

These outreach activities were supported by the University of Oxford ‘Enriching Engagement’ scheme, funded by the Wellcome Trust. The Thalamus, Cortex, and Cognition Lab is funded by the Wellcome Trust (110157/Z/15/Z). We thank the organizers of the IF Oxford Science and Ideas Festival 2020 and the British Neuroscience Association 'Bring Your Own Brain’ 2021 Festival of Neuroscience for hosting our online science engagement events. The University of Oxford Medical Sciences Interdivisional Research Ethics Committee (MS IDREC) indicated that formal ethical approval was not required as no personal information was collected in the survey responses.

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Juan Carlos Mendez, Brook A. L. Perry, Rhyanne J. Heppenstall, Stuart Mason & Anna S. Mitchell

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Mendez, J.C., Perry, B.A.L., Heppenstall, R.J. et al. Openness about animal research increases public support. Nat Neurosci 25 , 401–403 (2022). https://doi.org/10.1038/s41593-022-01039-z

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student opinion

Is Animal Testing Ever Justified?

The E.P.A. recently said it would move away from requiring the testing of potentially harmful chemicals on animals. Do you support the decision?

By Natalie Proulx

Find all our Student Opinion questions here.

On Sept. 10, the Environmental Protection Agency said it would move away from requiring the testing of potentially harmful chemicals on animals, a decision that was hailed by animal rights groups but criticized by environmentalists and researchers who said the practice was necessary to rigorously safeguard human health.

What are your thoughts on animal testing? Do you think it is ever justified? Why or why not?

In “ E.P.A. Says It Will Drastically Reduce Animal Testing ,” Mihir Zaveri, Mariel Padilla and Jaclyn Peiser write about the decision:

The E.P.A. Administrator Andrew Wheeler said the agency plans to reduce the amount of studies that involve mammal testing by 30 percent by 2025, and to eliminate the studies entirely by 2035, though some may still be approved on a case-by-case basis. The agency said it would also invest $4.25 million in projects at four universities and a medical center that are developing alternate ways of testing chemicals that do not involve animals. “We can protect human health and the environment by using cutting-edge, ethically sound science in our decision-making that efficiently and cost-effectively evaluates potential effects without animal testing,” Mr. Wheeler said in a memo announcing the changes. The E.P.A. has for decades required testing on a variety of animals — including rats, dogs, birds and fish — to gauge their toxicity before the chemicals can be bought, sold or used in the environment.

The article continues:

The practice of testing with animals has long prompted complex debates driven by passionate views on morality and scientific imperative. Reaction to Tuesday’s announcement was no different. “We are really excited as this has been something we’ve wanted for quite some time,” said Kitty Block, the president and chief executive of the Humane Society of the United States, an animal protection organization. “The alternatives are the future. They’re more efficient and save lives.” Kathleen Conlee, the vice president of animal research issues at the Humane Society, said the E.P.A.’s move is “broad-sweeping and significant.” “This is the first time a government agency has made such a commitment and timelined its specific goals along the way,” Ms. Conlee said. “There’s been a lot of positive action among other federal agencies, but we want to see all government agencies take this step.” Tracey Woodruff, a professor at the University of California, San Francisco’s school of medicine, said current alternatives to animal testing are somewhat useful. But Dr. Woodruff, who worked at the E.P.A. from 1994 to 2007, said only animal testing — a process honed over decades — was robust enough to gauge chemicals’ impacts on people of various ages, genetics and health backgrounds. “I definitely think we should be investing more in this research,” she said, referring to alternative testing. “But it’s really not ready for making decisions yet — at least the way that E.P.A. is making decisions.” Jennifer Sass, a senior scientist at Natural Resources Defense Council, an environmental advocacy group, said she was very concerned by the announcement. Dr. Sass said animals were still necessary to study chronic conditions, like cancer and infertility. Cells in a petri dish cannot yet replace whole living systems, she said. “The E.P.A.’s deadline is arbitrary,” Dr. Sass said. “Our interest isn’t in speed, it’s getting it right. We want proper animal testing because we don’t want harmful chemicals to end up in our food, air and water.”

Students, read the entire article, then tell us:

Do you support the decision by the E.P.A. to move away from requiring the testing of potentially harmful chemicals on animals? Or do you think animal testing is still necessary to regulate harmful substances that can have adverse effects on humans?

How important is it to you that the toxicity of chemicals and other environmental contaminants is rigorously studied and regulated? Why? Do you think not testing on animals hinders those efforts?

The Food and Drug Administration, the National Institutes of Health and the Department of Veterans Affairs are among the government agencies that still rely on animal testing. Do you think animal testing is important in these sectors or any others? Why or why not?

Do you think animal testing is ever justified? If so, what should be the criteria for when, how and on what animals testing is done?

Students 13 and older are invited to comment. All comments are moderated by the Learning Network staff, but please keep in mind that once your comment is accepted, it will be made public.

Natalie Proulx joined The Learning Network as a staff editor in 2017 after working as an English language arts teacher and curriculum writer. More about Natalie Proulx

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The FDA no longer requires all drugs to be tested on animals before human trials

Joe Hernandez

A staff member for Sen. Rand Paul takes photos of her puppy, Jefferson, before a 2021 press conference on the FDA Modernization Act. Anna Moneymaker/Getty Images hide caption

A staff member for Sen. Rand Paul takes photos of her puppy, Jefferson, before a 2021 press conference on the FDA Modernization Act.

A new U.S. law has eliminated the requirement that drugs in development must undergo testing in animals before being given to participants in human trials.

Animal rights advocates have long pushed for such a move, and some in the pharmaceutical industry have argued that animal testing can be ineffective and expensive.

Sen. Rand Paul, R-KY, who sponsored the FDA Modernization Act 2.0, said in a statement that the new law will help end the "needless suffering and death of animal test subjects" and will "get safer, more effective drugs to market more quickly by cutting red tape that is not supported by current science."

Shots - Health News

Drugs that work in mice often fail when tried in people.

PETA cheered the new law as a "radical shift" in how new drugs and treatments will be created.

Signed by President Biden in December as part of a larger spending package, the law doesn't ban the testing of new drugs on animals outright.

Instead it simply lifts the requirement that pharmaceutical companies use animals to test new drugs before human trials. Companies can still test drugs on animals if they choose to.

There are a slew of other methods that drugmakers employ to assess new medications and treatments, such as computer modeling and "organs on a chip," thumb-sized microchips that can mimic how organs' function are affected by pharmaceuticals.

But Aliasger Salem, a professor at the University of Iowa's College of Pharmacy, told NPR that companies opting to use these alternative testing methods as a replacement for animal testing must be aware of the methods' limits to ensure their drugs are safe.

"The companies need to be aware of the limitations of those technologies and their ability to identify or not identify potential toxicities," Salem said.

The Coronavirus Crisis

Mouse hunt: lab races to grow mice for covid-19 research.

"You don't want to shift to systems that might not capture all of the types of toxicities that have been seen in the past without ensuring that the methods that you have will capture that."

An FDA spokesperson told NPR that it will "implement all applicable provisions in the omnibus and continue to work with stakeholders to encourage the development of alternative testing methods."

This year's federal budget also includes $5 million for a new FDA program aimed at reducing animal testing by helping to develop and encourage industry to adopt new product testing methods, the spokesperson said.

EPA Chief Pledges To Severely Cut Back On Animal Testing Of Chemicals

The National Association for Biomedical Research , which supports testing drugs in animals, says animal testing in conjunction with human trials "remains the best way to examine complex physiological, neuroanatomical, reproductive, developmental and cognitive effects of drugs to determine if they are safe and effective for market approval."

The new law amends the U.S. Federal Food, Drug, and Cosmetic Act, which was originally passed in 1938.

• animal testing
• U.S. Food and Drug Administration

We’re calling on the FDA to save animals by modernizing drug testing

In an era defined by scientific and technological innovation, testing drugs on dogs, rats, monkeys and other animals is not only becoming increasingly outdated but causes immense animal suffering. Despite publicly indicating a commitment to non-animal test methods, the U.S. Food and Drug Administration’s regulations and guidance documents for pharmaceutical companies are unclear and continue to emphasize the use of animals for drug testing. There is evidence that some companies believe testing on animals is legally required as part of the drug approval process.

That’s why we’ve filed a petition with the FDA today, requesting that the agency take a series of steps to make it plain and clear that animal testing isn’t legally required for drug approval and that the agency encourage companies to use non-animal methods when available. The FDA is legally required to consider and respond to our petition.

The petition asks the FDA to make the following changes to its regulations and guidance documents, which are documents that provide additional information on how to comply with its regulations:

• Amend its regulations to make it clear that the FDA does not require animal testing for drugs. 
• Publish a new guidance document describing the non-animal test methods that can be used in place of animal tests. The document should be updated regularly as new non-animal methods become available.  
• Commit to adding text to all existing and future guidance documents regarding the regulation of drugs. The new text should encourage companies to use non-animal methods whenever possible and refer them to the new guidance document on accepted non-animal methods.  

Without these changes, the lack of clarity in FDA regulations will continue to perpetuate the status quo. That means tens of thousands of animals per year continue to suffer in archaic tests such as those we documented in an undercover investigation at a laboratory in 2022. The ambiguity surrounding whether animal testing is needed for drugs to gain approval is harmful in several ways. It creates confusion and discourages innovation. It may also negatively impact human health. 

We all agree that the FDA has a responsibility to make sure that drugs intended for people are safe and effective. This is all the more reason why the agency should promote the use of data from non-animal test methods based in human biology; animal testing is not a reliable predictor of safety or efficacy in humans. Animal testing has acknowledged scientific limitations, but innovative non-animal technologies will only continue to improve. Emerging technologies such as organ-on-a-chip models offer promising approaches that are based on human biology and yield more reliable results.  

We are not alone in our demand for the adoption of more humane testing methods. University centers devoted to non-animal methods are making the same case, and a pioneering 2007 National Research Council report spurred the creation of numerous governmental initiatives focused on the ultimate replacement of animals in toxicity testing. As a result of our longstanding political advocacy, Congress has also publicly supported and secured increased funding for alternatives to animal use. The time for change is now. You can help prevent countless animals from suffering by urging the FDA to update its drug testing regulations and embrace non-animal alternatives . 

By supporting our petition to modernize the FDA’s drug testing regulations and guidance documents, you can help us create a future where compassion and scientific advancement go hand in hand.

Sara Amundson is president of the Humane Society Legislative Fund. 

Taking Suffering Out of Science

About the author

Kitty Block is President and CEO of the Humane Society of the United States and CEO of Humane Society International, the international affiliate of the HSUS

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Get all of Kitty's latest updates delivered to your inbox.

Our fight against expanded use of monkeys in research heats up

New hope for 26 chimps who deserve life in a sanctuary, not a lab

Good news! Washington becomes 12th state to ban sale of animal-tested cosmetics

She worked in animal research. Now she’s blocked from commenting on it.

An animal rights activist is embroiled in a court fight with the National Institutes of Health for blocking her online comments on NIH research using monkeys.

For a long time, Madeline Krasno didn’t tell other animal rights advocates that she had worked in a monkey research lab as a college student. It had taken her years to understand her nightmares and fragmented memories as signs of post-traumatic stress disorder. And some activists could be vicious to former lab workers.

But four years after she graduated from the University of Wisconsin at Madison, Krasno started posting online about her experiences. Eventually, she started tagging the school in those posts and then commenting on its pages.

Many of those comments disappeared. As she would later learn, it was not a mistake or a glitch. Both the university and the National Institutes of Health were blocking her comments. Now with support from free speech and animal rights organizations, she is suing both institutions.

“They’re suppressing any kind of conversation on the issue,” Krasno said in an interview while walking her dog, Millie. (She said she thinks of Millie as a person — and a soul mate — not a pet.) “You can’t tell me that’s not a free speech violation.”

Two courts have told her that it’s not a violation, that the blocking of keywords such as “animal testing” and related hashtags is a legal way of managing online conversations — the same way a local government can avoid chaotic town halls by deciding who speaks and on what topics. Both rulings are now on appeal and could go to the U.S. Supreme Court.

“Courts are just starting to dig into the parameters of free speech online,” said lawyer Stephanie Krent of the Knight First Amendment Institute, who argued NIH’s case in front of the U.S. Court of Appeals for the D.C. Circuit last week. Courts have said officials — including former president Donald Trump — can’t muzzle criticism online. But they haven’t said what the limits are when the government is allowed to moderate.

The lab in Madison where Krasno worked was named after Harry Harlow, a pioneering psychologist whose work upended harmful beliefs that too much tenderness would soften children’s minds. On the contrary, he found , neglect and isolation were liable to make children grow up angry and violent; mothers who had been traumatized were liable to became neglectful or abusive toward their children.

He came to those conclusions through experiments on rhesus monkeys . Some were separated early from their mothers and given a choice between a doll made of cloth or one made of wire. Some were left for months in a box he called the “pit of despair”; female monkeys were forced to copulate by being tied to a device he called “the rape rack.”

Harlow’s name, along with that of a scientist who worked with him, are on NIH’s list of banned words. So are “animals,” “cruelty,” “monkeys,” “revolting,” “testing” and “torture.” After Krasno’s lawsuit was filed, “PETA,” “#stopanimaltesting,” “#stoptesting” and “#stoptestingonanimals” were taken off the list of banned words.

NIH said it chose those words because they were the ones most commonly used in off-topic, repetitive comments. For example, an Instagram post on sickle-cell anemia prompted more than five dozen comments that were variations on “#animalabuser,” although the research highlighted did not involve animal testing.

Krasno, now 33, worked in the Harlow lab decades after his death and was never directly involved in research. She was a student caretaker for the hours when scientists and their assistants were off-duty. Immediately, she says, she had some awareness that what she was seeing was wrong. On her first day at the lab, she was taken to the one cage that housed multiple macaques. Her supervisor gave her some peanuts and showed her how to hand the treats through the bars.

“They were so excited,” she said. “They’re living in basically dungeons — windowless rooms where the lighting half the time wasn’t working, where the drains weren’t working. A peanut is all they have to live for.”

Other monkeys were caged alone, she said. While mothers were not separated from their babies the way Harlow’s test subjects had been, Krasno said the mothers often rejected their offspring or failed to properly nurse them because they had not learned from older monkeys in the wild. Though they weren’t tied down, she said, female monkeys were clearly traumatized by being put into cages with unfamiliar males for breeding: “You would hear screaming.”

A spokesman for the school said that they have no evidence of mistreatment during Krasno’s time in the lab and that federal agencies provide oversight of animal research. The school settled an investigation with the U.S. Agriculture Department over alleged violations of the Animal Welfare Act in 2020 by paying a $74,000 fine, saying safety measures had been improved.

“Monkeys in the university’s facilities receive regular attention and care from specialized veterinarians” and “are housed socially with other monkeys … as research and safety allow,” said Chris Barncard, the spokesman. “Studying animals is an important way — in many cases, the only way — to answer crucial questions about basic biological processes and to ethically study diseases with often devastating consequences for humans and animals.”

Krasno had planned to go into primate conservation. Instead, after graduation she began working in animal sanctuaries. She would dream about being back in the lab, taking photographs — something she had never done when she worked there. She started going to therapy and was eventually diagnosed with PTSD, she said.

In 2017, Krasno posted on Instagram a photo of a tattoo she had gotten that said: “for patrick” — the name of the first baby monkey she cared for in the lab. And she started intermittently describing her experiences.

At first, it was her ideological allies who responded negatively, saying she was a psychopath for having worked in animal research. “Some of the worst things that have been said to me have come from animal rights activists,” Krasno said. But she noticed that when she tagged her alma mater in posts, the school removed the notation. Feeling she had hit a nerve, she started commenting on the school’s Facebook and Instagram pages. The comments disappeared. So did her comments on NIH’s pages.

A friend in she met through a vegan University of Wisconsin alumni Facebook group tried posting similar comments; they also disappeared. They filed Freedom of Information Act requests and learned that certain words were being automatically blocked. When those filters didn’t work, the university was manually removing Krasno’s comments.

With help from a friend at the Animal Legal Defense Fund, she sued the school and NIH; People for the Ethical Treatment of Animals (PETA), joined the NIH suit. In response, both institutions said that they were simply trying to keep their social media feeds from being overwhelmed by repetitive, irrelevant comments and that Krasno and other animal rights activists just happened to be the ones leaving them.

It’s “a seemingly coordinated campaign to flood [NIH’s] social media pages with off-topic commentary related to animal testing,” Justice Department attorney Jennifer Utrecht said during last week’s oral argument at the D.C. Circuit. “The people who are repeatedly violating the off-topic policy all have a particular viewpoint.” She said followers of an online chat on brain health and a social media campaign on retina issues were confused and annoyed by the repeated posts on animal rights.

Other posts blocked by NIH included external links, profanity, strings of numbers, the mention of cannabis and “#believemothers,” used by anti-vaccine activists.

But Krasno’s side argues that animal testing is so common that almost any scientific research can be linked to it, and any comment on it is arguably relevant. For example, as the animal advocates pointed out in their court filings , the sickle cell researcher has done work on rats .

“Most people would agree that a comment that the coronavirus vaccine was tested on animals would be on-topic,” attorney Caitlin Foley of the Animal Legal Defense Fund said. “But if that’s filtered out, they wouldn’t know speech was being censored.”

Appellate judges seemed to be divided over how to handle the comments.

If banning certain keywords violates the First Amendment, then content moderation would be “extremely difficult,” Judge Brad Garcia said. Judge Patricia Millett said having humans, rather than a computer program, read and curate threads was “unrealistic.” But Millett was also skeptical that the government had proved the bans are necessary. “I would not consider dozens, on internet threads, which can go on forever, flooding,” she said, adding, “I really am struggling with how ‘test’ is just clearly off-topic for NIH.”

Krasno said that if the lawsuits succeed, she plans to sue other universities that have engaged in similar deletion of animal rights advocacy.

“These are our tax dollars,” she said. “To say you can’t even talk about it in ways that most people are discussing issues — that’s just not fair.”

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Artificial intelligence resolves conflicts impeding animal behavior research

by University of Washington School of Medicine

Artificial intelligence software has been developed to rapidly analyze animal behavior so that behaviors can be more precisely linked to the activity of individual brain circuits and neurons, researchers in Seattle report.

"The program promises not only to speed research into the neurobiology of behavior, but also to enable comparison and reconcile results that disagree due to differences in how individual laboratories observe, analyze and classify behaviors," said Sam Golden, assistant professor of biological structure at the University of Washington School of Medicine.

"The approach allows labs to develop behavioral procedures however they want and makes it possible to draw general comparisons between the results of studies that use different behavioral approaches," he said.

A paper describing the program appears in the journal Nature Neuroscience . Golden and Simon Nilsson, a postdoctoral fellow in the Golden lab, are the paper's senior authors. The first author is Nastacia Goodwin, a graduate student in the lab.

The study of the neural activity behind animal behavior has led to major advances in the understanding and treatment of such human disorders as addiction, anxiety and depression.

Much of this work is based on observations painstakingly recorded by individual researchers who watch animals in the lab and note their physical responses to different situations, then correlate that behavior with changes in brain activity.

For example, to study the neurobiology of aggression, researchers might place two mice in an enclosed space and record signs of aggression. These would typically include observations of the animals' physical proximity to one another, their posture, and physical displays such as rapid twitching, or rattling, of the tail.

Annotating and classifying such behaviors is an exacting, protracted task. It can be difficult to accurately recognize and chronicle important details, Golden said. "Social behavior is very complicated, happens very fast and often is nuanced, so a lot of its components can be lost when an individual is observing it."

To automate this process, researchers have developed AI-based systems to track components of an animal's behavior and automatically classify the behavior, for example, as aggressive or submissive.

Because these programs can also record details more rapidly than a human, it is much more likely that an action can be closely correlated with neural activity, which typically occurs in milliseconds.

One such program, developed by Nilsson and Goodwin, is called SimBA, for Simple Behavioral Analysis. The open-source program features an easy-to-use graphical interface and requires no special computer skills to use. It has been widely adopted by behavioral scientists.

"Although we built SimBA for a rodent lab, we immediately started getting emails from all kinds of labs: wasp labs, moth labs, zebrafish labs," Goodwin said.

But as more labs used these programs, the researchers found that similar experiments were yielding vastly different results.

"It became apparent that how any one lab or any one person defines behavior is pretty subjective, even when attempting to replicate well-known procedures," Golden said.

Moreover, accounting for these differences was difficult because it is often unclear how AI systems arrive at their results, their calculations occurring in what is often characterized as "a black box."

Hoping to explain these differences, Goodwin and Nilsson incorporated into SimBA a machine-learning explainability approach that produces what is called the Shapely Additive exPlanations (SHAP) score.

Essentially, what this explainability approach does is determine how removing one feature used to classify a behavior, say tail rattling, changes the probability of an accurate prediction by the computer.

By removing different features from thousands of different combinations, SHAP can determine how much predictive strength is provided by any individual feature used in the algorithm that is classifying the behavior. The combination of these SHAP values then quantitatively defines the behavior, removing the subjectivity in behavioral descriptions.

"Now we can compare (different labs') respective behavioral protocols using SimBA and see whether we're looking, objectively, at the same or different behavior," Golden said.

"This approach allows labs to design experiments however they like, but because you can now directly compare behavioral results from labs that are using different behavioral definitions, you can draw clearer conclusions between their results. Previously, inconsistent neural data could have been attributed to many confounds, and now we can cleanly rule out behavioral differences as we strive for cross-lab reproducibility and interpretability," Golden said..

Journal information: Nature Neuroscience

Provided by University of Washington School of Medicine

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Animal Experiments in Biomedical Research: A Historical Perspective

Simple summary.

This article reviews the use of non-human animals in biomedical research from a historical viewpoint, providing an insight into the most relevant social and moral issues on this topic across time, as well as to how the current paradigm for ethically and publically acceptable use of animals in biomedicine has been achieved.

The use of non-human animals in biomedical research has given important contributions to the medical progress achieved in our day, but it has also been a cause of heated public, scientific and philosophical discussion for hundreds of years. This review, with a mainly European outlook, addresses the history of animal use in biomedical research, some of its main protagonists and antagonists, and its effect on society from Antiquity to the present day, while providing a historical context with which to understand how we have arrived at the current paradigm regarding the ethical treatment of animals in research.

1. Introduction

Animal experimentation has played a central role in biomedical research throughout history. For centuries, however, it has also been an issue of heated public and philosophical discussion. While there are numerous historical overviews of animal research in certain fields or time periods, and some on its ethical controversy, there is presently no comprehensive review article on animal research, the social controversy surrounding it, and the emergence of different moral perspectives on animals within a historical context. This perspective of animal use in the life sciences and its moral and social implications from a historical viewpoint is important to gauge the key issues at stake and to evaluate present principles and practices in animal research.

This review aims to provide a starting point for students and scholars—either in the life sciences or the humanities—with an interest in animal research, animal ethics, and the history of science and medicine. The reader interested in a more in-depth analysis on some of the topics reviewed is referred to the reference list for suggestions of further reading.

2. From Antiquity to the Renaissance

Humans have been using other vertebrate animal species (referred to henceforth as animals) as models of their anatomy and physiology since the dawn of medicine. Because of the taboos regarding the dissection of humans, physicians in ancient Greece dissected animals for anatomical studies [ 1 ]. Prominent physicians from this period who performed “vivisections” ( stricto sensu the exploratory surgery of live animals, and historically used lato sensu as a depreciative way of referring to animal experiments) include Alcmaeon of Croton (6th–5th century BCE) [ 2 , 3 ], Aristotle, Diocles, Praxagoras (4th century BCE), Erasistratus, and Herophilus (4th–3rd century BCE) [ 1 , 3 , 4 ]. The latter two were Hellenic Alexandrians who disregarded the established taboos and went on to perform dissection and vivisection on convicted criminals, benefiting from the favorable intellectual and scientific environment in Alexandria at the time [ 1 ]. All of these authors had a great influence on Galen of Pergamon (2nd–3rd century CE), the prolific Roman physician of Greek ethnicity who developed, to an unprecedented level, the techniques for dissection and vivisection of animals [ 3 , 5 ] and on which he based his many treatises of medicine. These remained canonical, authoritative, and undisputed until the Renaissance [ 1 , 6 ].

For most ancient Greeks, using live animals in experiments did not raise any relevant moral questions. The supposed likeliness of humans to their anthropomorphic deities granted them a higher ranking in the scala naturae (“the chain of being”), a strict hierarchy where all living and non-living natural things—from minerals to the gods—were ranked according to their proximity to the divine. This view of humans as superior would later influence and underline the Judeo-Christian perspective of human dominion over all nature, as represented by texts by Augustine of Hippo (IV century) and Thomas Aquinas (XIII Century), the most influential Christian theologians of the Middle Ages. For Augustine, animals were part of a natural world created to serve humans (as much as the “earth, water and sky”) and humankind did not have any obligations to them. For Thomas Aquinas, the mistreatment of another person’s animal would be sinful, not for the sake of the animal in itself, but because it is someone else’s property. Cruelty to animals was nevertheless condemned by Aquinas, as it could lead humans to develop feelings and actions of cruelty towards other humans. Also, for this theologian, one could love irrational creatures for the sake of charity, the love of God and the benefit of fellow humans (for selected texts, see reference [ 7 ]).

The belief amongst ancient Greek physicians that nature could be understood by means of exploration and experiment—and the medical knowledge thus obtained to be of clinical relevance in practice—would be replaced by other schools of medical thought. Most notably, the Empiric school (3rd century BCE–4th century) would reject the study of anatomy and physiology by dissection of cadavers or by vivisection, not only on the grounds of cruelty and the established taboos, but also for its uselessness. Empiricists believed pain and death would distort the normal appearance of internal organs and criticized the speculative nature of the conclusions drawn from experiments. Indeed, and despite taking an experimental approach to understand the human body and illness, the interpretations of physiological processes made by ancient Greeks who performed vivisections were often inaccurate. The theoretical frameworks by which physicians interpreted their experiments more often than not led them to misguided conclusions. Observations would be understood in light of such paradigms as the Hippocratic theory of the four humors or the Pythagorean theory of the four elements, along with others of natural or supernatural basis, and to which they added their own theoretical conceptions and observational errors [ 1 , 4 , 6 , 8 , 9 ]. The study of human or animal anatomy and physiology was hence deemed irrelevant for clinical practice. Beginning with the decline of the Roman Empire and continuing throughout the Middle Ages, physiological experiments—along with scientific activity in general—would fall almost entirely into disuse and medical knowledge would become dogmatic. In an increasingly Christianized Europe, there was little motivation to pursue scientific advancement of medical knowledge, as people became more concerned with eternal life than with worldly life, and returned to Pre-Hippocratic beliefs in supernatural causes for disease and in the healing power of faith and superstition. Therefore, and despite medieval physicians’ reverence for Galen and his predecessors, the experimental approach used by these classical authors had been sentenced to oblivion [ 3 , 8 , 9 , 10 , 11 ].

The use of animal experiments to satisfy scientific enquiry would only re-emerge in the Renaissance. Flemish anatomist Vesalius (1514–1564), through the course of his work as a physician and surgeon, realized that many anatomical structures thought to exist in humans—on account of them being present in other animals—were in fact absent [ 6 ]. This led him to break the established civil and religious rules and dissect illegally obtained human cadavers, and publish very accurate descriptions of the human anatomy, which challenged the authority of the classical authors. As Herophilus did centuries before (but not carried on by his successors) [ 1 ] Vesalius would also examine the similarities and differences between the internal structure of humans and other animals, thus setting the foundations of modern comparative anatomy.

Alongside the progress in anatomical knowledge made possible by experimenters defying the Catholic Church’s opposition to the dissection of human bodies, the Renaissance period also witnessed the resurgence of vivisection as a heuristic method for the understanding of animal physiology. Vesalius would again recognize the value of physiological experiments on animals as both a learning and teaching resource—he would vivisect animals for medical students as the finishing touch at the end of his courses—a view shared by his contemporary, and presumable student and rival, Realdo Colombo (1516–1559) [ 3 ]. Later, Francis Bacon (1561–1626), considered by many the founder of modern scientific methodology, would also approve of the scientific relevance of vivisection, stating that “the inhumanity of anatomia vivorum was by Celsus justly reproved; yet in regard of the great use of this observation, the inquiry needed (…) might have been well diverted upon the dissection of beasts alive, which notwithstanding the dissimilitude of their parts may sufficiently satisfy this inquiry” [ 12 ].

3. Seventeenth Century and the Dawn of the Enlightenment

Physiological experiments on animals carried on throughout the seventeenth century, in the period favorable to scientific progress now known as the Age of Enlightenment. René Descartes’s (1596–1650) description of animals as “machine-like” [ 13 ] was heavily criticized by many of his contemporaries, but nevertheless provided scientists a way to justify what would now be considered extremely gruesome experiments [ 3 , 14 , 15 , 16 ] in a time when anesthesia, for humans and animals alike, was not available. It has been argued, however, that Descartes’s views on animals were misinterpreted [ 17 , 18 ]—misconstructions that may not always have been free from malice, either by his contemporaries [ 19 ] or present-day critics [ 20 ]—as he did not explicitly state that animals were incapable of feeling pain and indeed recognized them to be able to do so insofar as it depends on a bodily organ, and even admitted animals to be capable of such sentiments as fear, anger, hope or joy [ 13 ]. Nonetheless, regardless of it being misinterpreted or not (for a discussion see [ 21 ]), Cartesian machinism would be recurrently evoked in defense of vivisection in the 17th and 18th centuries [ 14 , 15 , 16 ]. Malebranche, following his interpretation of Descartes, would explicitly justify vivisection on the grounds of it only being “apparently harmful” to animals [ 3 , 15 , 22 ]. Also, as someone deeply interested in physiology and medicine [ 23 , 24 ], and a “man of his time,” Descartes performed vivisections himself [ 15 , 16 , 21 ], an activity for which his—perhaps more apologetic than wholehearted—view of animals as soulless, senseless automata “absolved man from the suspicion of crime” [ 25 ].

As for other contemporary philosophers, Baruch Spinoza (1632–1677) did not deny animals’ ability to feel, but considered we should nevertheless “use them as we please, treating them in a way which best suits us; for their nature is not like ours” [ 26 ], whereas John Locke (1632–1704) fully recognized that animals could feel and stated that children should be brought up to abhor the killing or torturing of any living thing in order to prevent them from later becoming capable of cruel actions to fellow humans [ 27 ]. Immanuel Kant (1724–1804) would reject Cartesian mechanistic views, thus acknowledging sentience to other animals. However, Kant would not extend his concept of human intrinsic and inalienable dignity to other species. In his Of Duties to Animals and Spirits , and mirroring Thomas Aquinas’s views on the subject, he observed that “all animals exist only as means, and not for their own sakes, in that they have no self-consciousness, whereas man is the end (…) it follows that we have no immediate duties to animals; our duties towards them are indirect duties to humanity” [ 28 ]. Kant believed his anthropocentric philosophy provided the moral tradition and contemporary thought of his society; it was a philosophical underpinning, rather than an abstraction distant from the thoughts and feelings of the ordinary man [ 29 ]. Indeed, his argument that cruelty against animals would lead to cruelty to humans was—as it continues to be—popular amongst the public and scholars (e.g., [ 30 ]). In Duties to Animals, Kant would refer to William Hogarth’s (1697–1764) popular series “The Four Stages of Cruelty” ( Figure 1 ), a set of four engravings that depicted how cruel actions against animals could lead to moral degradation and crime. Regarding animal use in research, Kant would state that “Vivisectionists, who use living animals for their experiments, certainly act cruelly, although their aim is praiseworthy, and they can justify their cruelty, since animals must be regarded as man’s instruments; but any such cruelty for sport cannot be justified” [ 28 ]. While he believed actions that offended human intrinsic dignity were unacceptable—no matter how laudable their ultimate purpose should be—when it came to animals it would not be the actions themselves, but rather their justification that defined the acceptability of those actions. While the Enlightenment marked the beginning of the departure from Christian theocentrism, in the new anthropocentric view, animals continued to have no moral standing on their own. In perspective, it should be noted this was a time in which the slave market thrived and women were seen as inferior. However, the recognition of animals’ sentience in the new philosophical thought would later be instrumental for new ethical perspectives to arise on the moral status of animals.

“First Stage of Cruelty” by William Hogarth (1750), the first plate from “The Four Stages of Cruelty” series, which describes the escalating violent behavior that follows childhood cruelty to animals to an adulthood of criminal life. In this scene, two boys plunge an arrow into the rectum of a dog, while another boy, most likely the pet’s owner, pleads with them to stop. Meanwhile, some boys are burning the eye of a bird, while others tie bones to a dog’s tail. Also, some boys play “cock-throwing” (a popular sport in eighteenth-century England, consisting of throwing stones or bottles at a cockerel tied to a stake) while others hang fighting cats, and others even throw animals from windows. Source: © Victoria and Albert Museum, London.

Amidst the list of notable Western seventeenth-century physiologists using animals, the most noteworthy was undoubtedly William Harvey (1578–1657), physician to kings James I and Charles I, and one of the founders of modern science. In 1628, his groundbreaking Exercitatio Anatomica de Motu Cordis et Sanguinis in Animalibus (“An Anatomical Exercise on the Motion of the Heart and Blood in Living Beings”) was published, in which he provided the most accurate description of blood circulation and heart function of his time [ 31 , 32 , 33 , 34 ]. Using the results of meticulously planned experiments on live animals, as well as their interpretation through mathematics and physics, in this treatise, Harvey disproved many of Galen’s fifteen-hundred-year-old ideas [ 35 , 36 ]. In the tradition of his own academic lineage (he studied in Parma with the renowned anatomist Fabricius, a pupil of Colombo), Harvey was also a prolific and skilled comparative anatomist, whose studies on the anatomy of animals included species of several taxa, including mammals, fish, amphibians, reptiles and even insects [ 37 ].

Harvey’s De Motu Cordis was highly criticized, since his experimental observations did not fit the prevalent theories of Western natural philosophy of his time (for an insight on the social, scientific and academic context surrounding Harvey see [ 33 , 37 , 38 ]), still heavily grounded on Galenic principles. Harvey’s findings would challenge firmly established beliefs, such as blood being continuously produced in the liver and transported through the veins to be consumed by other organs, while arteries were thought to be filled with air; the heart was believed to have a heating—rather than pumping—function, and blood was thought to flow between the ventricles across a permeable septum; the vascular system as a whole was thought to be open; the arterial and venous bloods were believed not to mix; and the mere concept of blood circulation was virtually unknown (however, his teacher Fabricius might already have envisaged the concept of blood circulation [ 34 ]. Also, blood circulation was already known in Chinese medicine sixteen centuries before Harvey [ 39 ]). From an epistemological point of view, such opposition also reflected a dispute between the empiricist and the rationalist approach to the understanding of nature, for Harvey professed “to learn and teach anatomy not from books but from dissection, not from the tenets of Philosophers but from the fabric of Nature” (from De Motus Cordi , cited in [ 32 ]). Not surprisingly, Descartes—although a researcher himself—disagreed emphatically with most of Harvey’s findings, since he believed that theories forged through philosophical reflection on metaphysics were superior to those resulting from experimental observation, thus considering experiments or interpretations that did not confirm his own natural philosophy as flawed [ 40 , 41 ]. He nevertheless praised Harvey’s discovery of circulation and the method of experiment and observation that had led to it, a support that would actually help to turn the tide amidst scholars in favor of Harvey’s observation-over-doctrine ideas and methodological approach on experimental physiology, thereby setting the ground for further developments in physiological knowledge [ 38 ].

Further advancements in physiology would be prompted by questions left unsolved by Harvey, many of them addressed by an ensemble of his colleagues and followers at Oxford who applied Harvey’s principle that life should be interpreted in light of new findings in physics in their physiological experiments on animals [ 42 , 43 , 44 , 45 ]. The Oxford Group included polymaths like Robert Hooke (1635–1703), John Locke (1632–1704), John Mayou (1640–1679), Richard Lower (1631–1691), Thomas Willis (1621–1675), Robert Boyle (1627–1691) and Christopher Wren (1632–1723), amidst several others. Most physiologists did not expect direct therapeutic applications to result from their experiments [ 45 ]. There were, however, a few exceptions, such as Lower’s attempts at intra and inter-species blood transfusions having in mind their medical application, or Johann Wepfer’s (1620–1695) use of animals as a proxy to humans to infer the toxicity of several substances [ 3 ], a practice that is still carried out to this day. Seventeenth-century physiology would mark the dawn of modern scientific inquiry in the life sciences. Animal experiments were now proving to be more informative and relevant for obtaining scientifically sound knowledge on basic biological processes than ever before. These advancements would eventually diminish the importance of Galenic dogmatic medicine—although some of its principles would still endure for many years—and ultimately pave the way for today’s evidence-based medicine.

The seventeenth century would also witness the advent of skepticism towards experiments on animals on scientific grounds. Physicians like Jean Riolan, Jr. (1580–1657) and Edmund O’Meara (1614–1681) began to question the validity of physiological experiments carried out on animals in such an extremely altered state as one endured under vivisection, although their hidden agenda was to restore the credibility of Galenic medicine [ 3 , 46 , 47 ]. This dispute between critics and advocates of the informative value of animal models of human physiology still echoes today, e.g., [ 48 ].

The moral acceptability of inducing suffering in animals on the physiologist’s workbench would also become an issue raised in opposition of vivisection before the end of the seventeenth century [ 3 ]. However, the acceptance of the animal-machine paradigm by many physiologists reassured them that their scientific undertakings were not cruel. Furthermore, even the many who acknowledged that animals suffered a great deal with experiments, nevertheless defended themselves against the accusation of cruelty by alleging that the suffering inflicted was not unjustified, but rather for the sake of humankind, in the same line of reasoning by which today animal research is still justified. Nevertheless, these scientists were often overwhelmed by the extreme ill treatment they forced themselves to carry out on fully conscious animals [ 3 , 45 , 49 ]. One such investigator was Robert Boyle, whose infamous experiments on live animals on an air pump (conceived by him and developed by Robert Hooke) consisted in registering how animals responded to increasingly rarefied air. While only two animal experiments in Boyle’s “pneumatic chamber” are described in his New Experiments Physico-Mechanical Touching the Spring of the Air and its Effects (1660)—he would nevertheless go on to publish further animal studies on physiology [ 50 , 51 ]. Public demonstrations of this experiment would become very popular in the eighteenth century, although it bore more of an entertaining, rather than educational, nature ( Figure 2 ).

“An Experiment on a Bird in an air pump”, by Joseph Wright of Derby (detail) (1768). In this brilliant artwork, the artist captures the multiple reactions elicited by the use of live animals as experimental subjects in eighteenth-century Britain, for which we can find a parallel in present day’s diverse attitudes on this topic, including shock, sadness, appreciation, curiosity and indifference. Currently in The National Gallery , London. Source: Wikimedia Commons .

4. Eighteenth Century and the Rise of Moral Consideration for Animals

Amongst the many remarkable physiologists of the eighteenth century, polymaths Stephen Hales (1677–1761) and Albrecht von Haller (1708–1777) stood out. Hales was responsible for the first measurement of pressure in the blood vessels, and for other important insights into cardiovascular and respiratory physiology [ 52 , 53 , 54 ]. He also gave landmark contributions to public health and other medical breakthroughs, including the invention of forceps. Von Haller was arguably the most prolific physiologist of his time, better known for his groundbreaking work on inflammation, neurophysiology, heart function, and hemodynamics [ 55 , 56 , 57 , 58 , 59 , 60 ]. Both researchers were disgusted by the gruesomeness of their own experiments and were concerned about their moral justification, but nevertheless carried on, certain of the need for the use of live animals for the comprehension of many basic physiological processes, which were yet far from being understood [ 3 , 49 , 61 , 62 ]. Other relevant landmarks of eighteenth-century biomedical science based on animal studies included the foundation of experimental pharmacology [ 63 ], electrophysiology [ 64 , 65 ], and modern embryology [ 66 ]. Despite these advancements in biological knowledge, the clinical relevance of animal studies continued to be challenged [ 3 , 61 , 62 ] and, indeed, direct benefits to human health from animal experiments would remain elusive throughout the eighteenth century [ 45 , 55 ] and well into the following century.

Opposition to vivisection had raised its tone since the beginning of the eighteenth century, prompted by the popularization of public displays of experiments on live animals—in particular the notorious demonstrations of Boyle’s notorious air pump experiments [ 3 , 61 , 62 ], which were seen as purposeless, and thus inherently cruel—but became more prominent in the second half of the century, particularly in northern Europe [ 3 , 61 , 62 , 67 ]. Anthropocentric views on human duties to animals began to become increasingly challenged by philosophers, from Voltaire’s (1694–1778) criticism of Cartesian machinism and the gruesomeness of animal experiments [ 68 ] to Jean-Jacques Rousseau’s (1712–1778), Jeremy Bentham’s (1748–1832) and Arthur Schopenhauer’s (1788–1860) criticism of those who viewed animals as mere “means to an end.” By referring to sentience rather than intelligence to grant animals inherent worth, these philosophers proposed a shift from an anthropocentric justification for our duties of kindness to animals, to human obligations towards other animals for the sake of the animals themselves [ 69 , 70 , 71 ]. Rousseau proposed that despite animals being unable to understand the concept of natural law or rights, they should nonetheless, as a “consequence of the sensibility with which they are endowed (…) partake of natural right.” While Bentham found the concept of natural right “nonsense” [ 72 ], he sanctioned the idea of granting animals moral standing for the sake of their sentience. As he would famously state: “The question is not, Can they reason? Nor, Can they talk? But, Can they suffer?” [ 71 ]. From his utilitarian philosophy standpoint ( i.e. , that a moral action is that which results in the highest overall wellbeing for all stakeholders), he deemed animal research acceptable, provided the experiment had “a determinate object, beneficial to mankind, accompanied with a fair prospect of the accomplishment of it,” thus admitting that humans had precedence over other animals, limited by the due consideration for their suffering [ 73 ]. Bentham’s utilitarianism continues to exert a great deal of influence in today’s debate on animal use in the life sciences.

Among philosophers and physiologists alike, the issue of discussion was now not if animals could feel or not and to what extent, but rather whether vivisection was justifiable based on the benefit for human beings derived from it. Thus, even when researchers had strong misgivings about the inflicted suffering of animals, benefit to humans remained a valid justification for them to pursue their scientific goals through vivisection [ 61 ]. While knowledge of bodily functions and pathology was still incipient at that time, eighteen-century physiologists differed from their seventeenth-century predecessors, as they believed that medical improvements could one day be achieved through advancing knowledge by the means of animal experimentation [ 62 ]. The same rationale—that human interests took precedence over animal suffering—would also be used by nineteenth-century physicians as an ethical justification for the use of animals.

5. The Nineteenth-Century Medical Revolution and the Upsurge of the Antivivisection Societies

By the beginning of the nineteenth century, medicine was undergoing a major revolution. The organization of medical practice was changing, with the construction of hospitals, the university training of medical doctors, and the invention of new instruments and methods for the medical profession [ 74 ]. There was also a growing acknowledgement by the medical community that most medical practice, up to that period, was based on unproven traditions and beliefs and that most therapies were not only ineffective but often worsened the patient’s condition. As a result, medical practice increasingly began to focus more on understanding pathology and disease progression, pursuing more accurate diagnosis and prognosis, and thus providing reliable and useful information to patients and families, as they realized this was often the best they could do at the time. This paradigm shift would help give more credit and recognition to medical doctors and scientists, who, at that time, were often viewed with disdain and suspicion by the general public. This gain in medical knowledge would, however, sometimes be at the expense of unapproved trials, invasive procedures, and no respect for what we would now call patients’ rights [ 75 , 76 , 77 ].

Another kind of medical revolution was taking place in the laboratories, one that would ultimately provide the consistent basic science on which twentieth-century modern medicine would set its foundations. This scientific revolution began with a political one. The French Revolution of the late eighteenth century would later, in the first-half of nineteenth century, set the grounds for the establishment of the Académie Royale de Médecine , a thriving academic environment where science—and physiology, chemistry, and pharmacy, in particular—would finally be incorporated into medicine. The acknowledgment of the great knowledge gap in physiology and pathology, and the openness to positivist views on scientific knowledge, led to the definitive abandonment of the quasi-esoteric and, up to that time, dominant vitalistic theories in physiology, which stated that a vital principle, the “soul”, was the main source of living functions in organisms, rather than biochemical reactions. This led to a generalization of the understanding of all bodily processes as an expression of physical and chemical factors, and to a greater relevance given to animal experiments for answering scientific questions ( Figure 3 ). At the Académie , animal experiments were being increasingly prompted by existing clinical problems, and carried out with the ultimate goal of developing new therapeutic approaches to tackle these issues. Importantly, the integration of veterinarians in the Académie was deemed valuable for their insight on such experiments [ 57 , 78 , 79 ]. Amidst many other prominent scientists, two physician–physiologists stood out for their contributions to experimental physiology, François Magendie (1783–1855) and, most notably, Magendie’s disciple, Claude Bernard (1813–1878) [ 67 , 80 , 81 , 82 , 83 , 84 ]. Bernard’s experimental epistemology, unlike his tutor’s more exploratory approach, advocated that only properly controlled and rigorously conducted animal experiments could provide reliable information on physiology and pathology of medical relevance, setting the landmark of experimental medicine [ 85 , 86 , 87 , 88 ]. Conciliating Descartes’s rationalism with Harvey’s empiricism, Bernard acknowledged the importance of ideas and theories for the formulation of hypotheses, safeguarding, however, that these were only useful if testable and only credible if substantiated through experimentation [ 80 , 89 ]. He seemed to have been aware of how important and groundbreaking his approach to medical knowledge would become, when in his opening remarks to medical students in his very first lecture he quoted himself from his seminal “Introduction to the Study of Experimental Medicine,” stating: The scientific medicine that I’m responsible to teach does not yet exist. We can only prepare the materials for future generations by founding and developing the experimental physiology which will form the basis of experimental medicine” [ 89 ].

“A physiological demonstration with vivisection of a dog,” by Émile-Édouard Mouchy. This 1832 oil painting—the only secular painting known of the artist—illustrates how French scholars valued physiological experimentation in service of scientific progress [ 90 ]. Notice how the struggling of the animal does not seem to affect the physiologist or his observers. Currently part of the Wellcome Gallery collection, London. Source: Wellcome Library .

From the 1830s and throughout the second half of the century, the concept of scientific medicine would also flourish amidst a distinct group of German/Prussian physiologists. Following the rationale that biology could be understood through the means of chemistry and physics, and through their pivotal animal experiments and the use of microscopy, these scientists vastly contributed to the development of anatomy, histology, pathology, embryology, neurophysiology, physiology and physics. The setting for this scientific and epistemological progress was the Anatomisches Museum in Berlin, where anatomist, zoologist, and physiologist Johannes Müller (1801–1858) offered workspace and supervision to brilliant students whose independent research he wished to encourage. Although lacking the money, space, and instruments available in the great German laboratories founded after 1850, the museum provided these young scientists—notably Theodor Schwann (1810–1882), Robert Remak (1815–1865), and Friedrich Henle (1809–1885) in the 1830s, and Carl Ludwig (1816–1895), Emil du Bois-Reymond (1818–1896), Ernst Brücke (1819–1892), Hermann von Helmholtz (1821–1894), and Rudolph Virchow (1821–1902) in the 1840s—a singular intellectual atmosphere for research. Henle and Virchow would become leaders of the 1840s’ medical revolution in Germany, promoting the reform of medicine by providing it with a scientific basis, while Brücke, Helmholtz, and Bois-Raymond’s focused on the development of physiology as an autonomous science [ 83 , 91 , 92 , 93 , 94 , 95 ]. Their contributions to medical knowledge through the nineteenth century, along with Magendie’s and Bernard’s pivotal works, would deeply influence their counterparts across the Western world in the latter decades of the nineteenth century. Thousands of students flocked to attend medical schools in Germanic universities (and French institutes, although to a lesser extent), many of them from across the Atlantic [ 85 , 88 , 91 , 96 , 97 ]. This, in turn, would lead to an unprecedented rise in animal research-based advancement in biological and medical knowledge in the late nineteenth century—with important consequences for public health and quality of life—as further discussed later in this text.

While the second half of the nineteenth century marked the beginning of scientifically meaningful and medically relevant animal research, this period also saw opposition to vivisection becoming a more widespread idea in Europe, especially in Britain. Although animal experiments were not yet regulated in the first half of the century, the development of British physiology research in the Victorian Era was losing pace to Germany and France, where unprecedented progress in medical knowledge was taking place. The openly antivivisectionist positions of influential jurists, politicians, literary figures, clergymen, distinguished members of the medical community, and even Queen Victoria, contributed to an unfriendly environment for animal-based medical research [ 90 , 91 ]. There was, however, also a matter of divergence of opinion between British anatomists and French physiologists on which was the best approach for obtaining medical knowledge. Taking advantage of the rising antivivisection trend, British anatomists explored the (undoubted) gruesomeness of Magendie’s experiments, along with some nationalistic partisanship and xenophobic feelings against France, in their defense of anatomical observation as the primary method for advancing physiology, to the detriment of experiment through vivisection. However, they seldom disclosed their own positive (or at least ambivalent) views on animal experiments as a means to corroborate findings achieved through anatomical exploration [ 90 , 98 , 99 ]. Magendie would become the arch-villain of the antivivisection movement. Despite the broad recognition of his contributions to science by most peers, he was also amongst the most infamous of his time for the disdain he held for his experimental subjects. This contestation was louder outside of France, where many of his fellow scientists, even those who approved of animal experimentation, described him as an exceptionally cruel person who submitted animals to needless torture [ 85 , 90 , 100 ]. His public presentations became the most notorious, particularly one he performed in England when he dissected a dog’s facial nerves while the animal was nailed down by each paw, and was left overnight for further dissection the following day [ 82 ]. A description of Magendie’s classes to medical students by an American physician added further to the widespread disgust directed towards his work:

This surgeon’s spring course of experimental physiology commenced in the beginning of April. I seldom fail of “assisting” at his murders. At his first lecture, a basketful of live rabbits, 8 glass receivers full of frogs, two pigeons, an owl, several tortoises and a pup were the victims ready to lay down their lives for the good of science! His discourse was to explain the function of the fifth pair of nerves. The facility was very striking with which the professor could cut the nerve at its origin, by introducing a sharp instrument through the cranium, immediately behind and below the eye. M. Magendie drew the attention of the class to several rabbits in which the fifth pair of nerves had been divided several days before. They were all blind of one eye, a deposition of lymph having taken place in the comes, from inflammation of the eye always following the operation alluded to, although the eye is by this section deprived of all its sensibility. Monsieur M. has not only lost all feeling for the victims he tortures, but he really likes his business. When the animal squeaks a little, the operator grins; when loud screams are uttered, he sometimes laughs outright. The professor has a most mild, gentle and amiable expression of countenance, and is in the habit of smoothing, fondling and patting his victim whilst occupied with preliminary remarks, and the rabbit either looks him in the face or ‘licks the hand just raised to shed his blood. During another lecture, in demonstrating the functions of the motive and sensitive fibers of the spinal nerves, he laid bare the spinal cord in a young pup, and cut one bundle after another of nerves. (…) Living dissection is as effectual a mode of teaching as it is revolting, and in many cases the experiments are unnecessarily cruel and too frequently reiterated; but so long as the thing is going on, I shall not fail to profit by it, although I never wish to see such experiments repeated. cit in Olmsted, 1944 [ 101 ]

All of Magendie’s experiments were carried out without anesthesia or analgesia (and animals would be left in agony for hours, or for students’ “hands-on” anatomical studies. While, in fairness, it should be recognized that anesthetics had not yet been discovered when Magendie performed the bulk of his work, even after this technique had become available, he and nearly all of his students continued to forgo anesthesia in their experiments [ 102 ]. Moreover, animal studies on the effects of anesthetics themselves (Bernard was responsible for significant contributions to the understanding of the physiology of anesthesia: for an overview, see references [ 103 , 104 ]) were performed, as well as anatomical studies that could well have been conducted with cadavers, with no need for animals to be exposed to such prolonged suffering. Magendie was so ill famed in Britain that his experiments were referenced in the House of Commons by Richard Martin (1754–1834) when he presented a bill for the abolition of bear-baiting and that would become the “Cruel Treatment of Cattle Act” of 1822, one of the first animal protection laws. He would be again evoked in the report favoring the regulation of animal experiments that led to the “Cruelty to Animals Act” of 1876, the first piece of legislation ever to regulate animal experiments. By that time, Magendie had been dead for over twenty years [ 82 , 90 , 100 ].

After Magendie’s death, the focus of antivivisectionists’ attention moved to Bernard’s works, which included cutting open conscious animals under the paralyzing effects of curare , or slowly “cooking” animals in ovens for his studies on thermoregulation [ 105 ]. Bernard’s line of work would eventually have a heavy personal cost. Tired of her husband’s atrocious experiments, his wife would divorce him—taking with her his two daughters, who grew up to hate him—and, joining the antivivisectionists’ ranks, set up rescue shelters for dogs. Even Bernard’s cause of death is attributed to years of work in a humid, cramped, and poorly ventilated laboratory. He would, however, die a national hero, being given the first state funeral ever to be granted to a scientist in France. In his later years, he would collect the highest academic and political honors, including a seat in the French senate [ 88 , 102 , 106 , 107 ].

Despite their utter disregard for animal suffering, Magendie and Bernard did not see themselves as the immoral senseless villains portrayed by their detractors, but rather as humanists. Indeed, their view that animals did not deserve the same moral consideration as humans made them condemn experiments in humans without previous work on animals, the general principle on which the use of animal models in biomedical science is still grounded. In a time when proper dosage, administration, and monitoring of anesthesia were still largely unknown, often leading to serious side effects and accidental deaths, Magendie would state, on the use of anesthetics in humans without previous and thorough tests on animals: “That is what I do not find moral, since we do not have the right to experiment on our fellows” [ 5 , 108 , 109 ]. The amorality of human experiments prior to animal testing in animals was also an ethical argument raised in favor of vivisection by Bernard [ 89 ], who wrote:

No hesitation is possible, the science of life can be established only by experiment, and we can save living beings from death only by sacrificing others. Experiments must be made either on man or on animals. Now I think physicians already make too many dangerous experiments on man, before carefully studying them on animals. I do not admit that it is moral to try more or less dangerous or active remedies on patients, without first experimenting with them on dogs; for I shall prove, further on, that results obtained on animals may all be conclusive for man when we know how to experiment properly. If it is immoral, then, to make an experiment on man when it is dangerous to him, even though the result may be useful to others, it is essentially moral to do experiments on an animal, even though painful and dangerous to him, if they may be useful to man.

British physiologists often refrained from experimenting on mammals, mostly on account of the public’s opposition to the gruesomeness of continental physiologists’ experiments. However, with the publication of Bernard’s book (1868) and John Burdon-Sanderson’s Handbook for the Physiological Laboratory (1873), the scientific relevance of animal experiments became increasingly acknowledged, providing a utilitarian justification for vivisection, despite the harm endured by animals, eventually resulting in the rise in animal studies in medical schools in Britain in the 1870s [ 5 , 88 , 99 ]. Furthermore, by this time, anesthetics were already available and used by British physiologists, leading RSPCA secretary John Colam to state that “laboratory practices in England were very different indeed from [those] of foreign physiologists.” While the usefulness of anesthetics to chemically restrain animals was certainly advantageous for researchers, pain relief was most likely the major reason behind their ready adoption by many physiologists in Britain, as the paralyzing properties of curare were already known and used for this purpose. In fact, even before the solidifying of the antivivisectionist struggle, British physiologists had set themselves guidelines for responsible research [ 110 , 111 ]. Nevertheless, many researchers still found the analgesic and anesthetic effect of these volatile agents to be a source of undesired variability, thus avoiding their use altogether [ 99 , 105 ].

The upsurge of animal research in Britain was accompanied by an intensification of the antivivisectionist struggle. In 1875, the first animal protection society with the specific aim of abolishing animal experiments was founded: the Victoria Street Society for the Protection of Animals Liable to Vivisection (later known as the National Anti-Vivisection Society), led by Irish feminist, suffragist, and animal advocate Frances Power Cobbe (1822–1904). Vivisection became a matter of public debate, only matched in Great Britain that century by the controversy around the 1859 publication of Charles Darwin’s (1809–1882) On the Origin of Species , in which he presented a strong scientific rationale for the acknowledgement of our close kinship with the rest of the animal world, giving both physiologists and antivivisectionists a strong argument for their cause, depending on the perspective.

As the original argument of antivivisectionists that animal research was inacceptable because it did not provide useful medical knowledge began to lose strength (however, it remained a recurrent accusation against animal research, see, for instance, [ 112 ]), the discussion shifted towards preventing unnecessary harm, rather than questioning the scientific value of animal experiments [ 99 ]. On the other hand, the use of anesthetics now allowed British scientists to argue that most physiological experiments involved little, if any, pain [ 105 , 110 , 113 ]. While this made some antivivisectionists ponder about their own standing on the use of animals in research—namely those who opposed vivisection on the grounds that the intense and prolonged suffering endured by animals on the physiologist table was intolerable—many others felt that the most relevant value at stake was the preservation of each animal life in itself, questioning if human benefit was sufficient reason for sacrificing animals [ 99 , 110 ]. Moreover, the claim that animals were rendered senseless to pain gave carte blanche to many physiologists to use as many animals as they pleased for research, teaching, and demonstrations, despite anesthesia often being improperly administered, thus failing to prevent suffering for more than the brief initial moments. A famous quote by George Hoggan (a former vivisectionist who was appalled to witness Bernard’s experiments and who would later co-found the Victoria Street Society ) illustrates the relevance of the new ethical issues that emerged: “I am inclined to look upon anaesthetics as the greatest curse to vivisectible animals” [ 5 , 99 ].

In the last decades of the nineteenth century, all of today’s most relevant arguments on the debate surrounding the use of animals for scientific purposes were already in place, as well as most of the rhetoric and means of action in defense of each position. These views included outright abolitionism and, on the opposite pole, scientists demanding to be allowed to work without restrictions; non-scientists accusing researchers to be self-biased and unable to think ethically about their work and, on the other side of the barricade, researchers disdaining the authority of non-scientists to criticize their work; the benefit for humankind argument vs . the questioning of the scientific and medical value of animal research on scientific grounds; public demand for stronger regulation vs . researchers’ appeals for more autonomy, freedom, and public trust; advocates of the justifiability of only applied research (but not basic research) vs. apologists of the value of all scientific knowledge, see [ 105 , 112 , 113 ].

Just like today, there were also those who valued both animal protection and scientific progress and, recognizing that each side had both relevant and fallacious arguments, found themselves in the middle-ground, where they sought ways for compromise and progress. Amongst these, the most notable was Charles Darwin, known for his affection to animals and abhorrence for any kind of cruelty, but also for his commitment to scientific reasoning and progress [ 111 , 114 , 115 ]. Additionally, Joseph Lister (1827–1912), one of the most influential physicians of his time, would decline a request by Queen Victoria in 1875 for him to speak out against vivisection. Lister was one of the few British surgeons that carried out vivisection, albeit only occasionally, and was acquainted with some of the most eminent continental physiologists. In his response letter to the Queen, he pointed out the importance of animal experiments for the advancement of medical knowledge, stressed that anesthetics should be used at all times, and also denounced the ill treatment of animals in sports, cruel training methods, and artificial fattening of animals for human consumption as being more cruel than their use in research [ 116 ].

With the controversy assuming growing complexity and relevance, two opposing bills were presented to the British parliament in 1875: the “Henniker bill,” named after its sponsor Lord Henniker and promoted by Frances Cobbe, and the “Playfair bill,” named after scientist and Member of Parliament, Lyon Playfair, and promoted by Charles Darwin himself, along with fellow scientists and friends. Despite coming from opposite ends , both bills proposed reasonable regulation of animal experiments, rather than demanding severe restriction or granting scientists unlimited rights to use animals. Somewhat surprisingly, the Playfair bill drafted by researchers was, in some aspects, more restrictive than Henniker’s by proposing, for instance, that animal experiments should only be performed for the advancement of physiology and not for teaching purposes. The crucial difference was that the Henniker bill called for all researchers and all kinds of experiments to be properly licensed and supervised, as it is today in Great Britain, while the Playfair bill proposed that the law should only be applied to painful experiments. In the absence of parliamentary consensus for either one or the other bill, a Royal Commission—properly balanced to include members of the RSPCA and a few eminent scientists, including T.H. Huxley—was appointed that same year to address this issue, which would result in the 1876 amendment of the 1835 Cruelty to Animals Act in order to regulate the use of animals for scientific purposes, being the first case of this kind of legislation in the world [ 99 , 111 , 117 , 118 ]. This bill would endure for 110 years, until the enactment of the 1986 Animals (Scientific Procedures) Act, and remain the only known legislation to regulate animal experiments for nearly 50 years, despite some attempts to pass similar bills in other Western countries, where antivivisectionism was growing, particularly in Germany, Switzerland, Sweden, and North America [ 14 , 119 ].

The recrudescence and spread of antivivisection feelings in the late nineteenth century was coincidental with the long-awaited beginning of direct clinical and public health benefit from animal research. Before the end of the century, the germ theory of infectious diseases— i.e. , that pathogenic microbes were the causative agent of such diseases, rather than internal causes, “miasmas” in the air or water, or even more esoteric explanations—would gain broad recognition by the medical community, mostly on account of the work of Louis Pasteur (1822–1895) and his German counterpart, Robert Koch (1843–1910), which was largely based on animal experimentation. This knowledge would have an immediate, profound, and enduring effect on public health, surgery and medicine. Although it had been earlier proposed by Ignaz P. Semmelweis (1818–1865) that puerperal fever was caused by infections resulting from poor hygiene of physicians [ 120 ], only after Joseph Lister’s paper On the Antiseptic Principle of the Practice of Surgery (1867)—prompted by Pasteur’s findings—was the importance of hand-washing and instrument sterilization before surgical procedures and child delivery finally acknowledged, leading to a drastic drop in deaths from puerperal fever and post-surgical sepsis. Until then, previous efforts to make hand-washing a standard procedure had been ridiculed by the medical class.

Pasteur, a professor of chemistry with a doctoral thesis on crystallography, would turn his attention to biology in 1848 [ 121 ]. He began by unraveling the biological nature of fermentation (the inhibiting effect of oxygen on fermentation is still called the “Pasteur effect”), moving on to devise solutions of great economic value by tackling wine and beer spoiling, as well as silkworm disease, all of which he properly identified as being caused by microbes. Together with Claude Bernard, a close friend, he would later develop the process of pasteurization to destroy microorganisms in food. Pasteur began hypothesizing that microbes could also be the causative agents of many diseases affecting humans and other animals. Together with his disciples, most notably Emile Roux (1853–1933), he would go on to identify Staphylococcus , Streptococcus , the “septic vibrio” (now Clostridium septicum ), the causative agents of anthrax ( Bacillus anthracis ) and chicken cholera ( Pasteurella multocida ), being the first to develop vaccines for these zoonotic diseases, as well as for Swine Erypselas, thus setting the foundations of modern immunology [ 122 ]. However, it would be Pasteur’s successful use of a therapeutic vaccine against rabies in humans that would grant him international celebrity status [ 107 , 122 , 123 , 124 ].

Pasteur’s work required the experimental infection of numerous animals, as well as inflicting surgical wounds to test antiseptic techniques and disinfectant products, which made him a prime target of antivivisectionists. Either by genuine conviction or pragmatic convenience, amongst the ranks of Pasteur’s critics for his use of animals, one could easily find opponents of vaccination and the germ theory. Pasteur would frequently receive hate letters and threats, mostly for his infection studies on dogs, although he also used chickens, rabbits, rodents, pigs, cows, sheep, and non-human primates ( Figure 4 ). Pasteur was, however, more sensitive to animal suffering than most of his French counterparts. Not only was he uneasy with the experiments conducted—although sure of their necessity—he would also always insist animals be anesthetized whenever possible to prevent unnecessary suffering. He would even use what we now call “humane endpoints” (for a definition, see [ 125 ]): in a detailed description of his method for the prophylactic treatment of rabies (from 1884), the protocol for infecting rabbits with the rabies virus (for ulterior extraction of the spinal cord to produce a vaccine), he stated that: “The rabbit should begin to show symptoms on the sixth or seventh day, and die on the ninth or tenth. Usually the rabbit is not allowed to die, but is chloroformed on the last day in order to avoid terminal infections and unnecessary suffering” [ 126 ]. Furthermore, he would become directly responsible for saving countless animals from the burden of disease and subsequent culling [ 5 , 107 , 113 , 127 , 128 ].

This full-page illustration of Pasteur in his animal facility was published in Harper’s Weekly in the United States, on 21 June 1884. At this time, there was moderate curiosity on Pasteur’s work in the US, which would intensify after his first successful human trials of a therapeutic vaccine for rabies in 1885. In the article, the reader is reassured that the use of dogs is both humane and justified in the interest of mankind. The use of other species, however, is barely mentioned [ 5 ]. Source: Images from the History of Medicine , U.S. National Library of Science.

Robert Koch, a practicing rural physician, would follow the tradition of the great German/Prussian physiologists of his time (and indeed was a student to many of them), providing invaluable contributions to medical knowledge through animal research, mainly in the field of bacteriology and pathology. His famous “Koch postulates” would play an important role in microbiology Along with his associates, Koch developed from scratch methods that are still used today, such as microphotography of organisms, solid medium culture, and staining or microbe quantification. They would go on to identify the causative agents of tuberculosis ( Micobacterium tuberculosis , also known as the “Koch bacillus”), cholera ( Vibrio cholera , albeit 30 years after Filippo Pacini, 1812–1883 [ 129 ]), and anthrax. The overlapping interest of Pasteur and Koch on anthrax would trigger a bitter rivalry between the two, fuelled by their different approaches to microbiology, as well as chauvinistic Germany–France rivalry [ 130 , 131 ]. Koch’s own school of microbiology housed many of the leading late-nineteenth, early-twentieth-century medical researchers. This included Emil von Behring (1854–1917) and Paul Ehrlich (1854–1915), both responsible for the first antitoxin for treatment of diphtheria—developed from horse serum—for which von Behring received the Nobel Prize in 1901. Von Behring would also develop an antitoxin for immunization against tetanus, along with Shibasaburo Kitasato (1853–1931), who had also studied under Koch. In 1908, Ehrlich would also be awarded the Nobel Prize for contributions to immunology, and would yet again be nominated for his contributions to chemotherapy and the development of Salvasaran (an effective treatment against syphilis), in particular [ 132 , 133 , 134 , 135 ]. The development and production of vaccines and antitoxins led to a dramatic increase in the number of animals used in research. The number of animals used by physiologists in the nineteenth century would be negligible in comparison with the several hundred used by Pasteur to develop, test, and produce vaccines, the thousands of mice used by Paul Ehrlich for the production of Salvasaran—his syphilis drug—and the millions of primates that would be used to produce Polio vaccines in the 1950s [ 5 ].

6. The Twentieth-Century Triumph of Science-Based Medicine

By the end of the nineteenth and beginning of the twentieth century, the pharmacopeia had effective, scientifically tested drugs, a landmark that allowed for an increasing number of people to understand the importance and validity of scientifically sound medical knowledge and, with it, the relevance of animal-based research (see [ 113 , 136 , 137 , 138 ]). One could still find as far as the end of the nineteenth century, however, physicians who disregarded the ideals of scientific medicine and vigorously stood by their traditional epistemological view of medicine and clinical practice, which they saw as more of a form of art than as a science. Many such physicians also opposed experiments on live animals and were members of antivivisection societies [ 77 , 139 , 140 , 141 ]. Nonetheless, the medical profession, medicine itself, and human health had now been irreversibly changed by science, and would continue to be pushed forward throughout the twentieth century to now.

The twentieth century would witness astonishing advances in medical knowledge and the treatment of disease. The discovery of vitamins, hormones, antibiotics, safe blood transfusion, new and safer vaccines, insulin, hemodialysis, chemo and radiotherapy for cancer, the eradication of small pox (and the near eradication of poliomyelitis), advanced means of diagnostic and new surgical techniques are but a very few examples of twentieth century’s medical achievements that have not only saved millions of lives—human and non-human—but also allowed countless humans and animals to live a “life worth living,” by the relief of disease-induced suffering. The advances of biomedical research to human health since the dawn of the past century are countless, with animal research playing a role in a number of important discoveries (for an overview, see [ 142 ]). Of the 103 Nobel Prizes in physiology or medicine given since 1901, on 83 occasions work conducted on vertebrate species (other than human) was awarded, while in another four instances, research relied heavily on results obtained from animal experiments in vertebrates conducted by other groups [ 143 ]. Another indirect measure of the impact that biomedical progress had on the twentieth century was the increase in life expectancy, which in some developed countries doubled between 1900 and 2000, and is still on the rise today [ 144 , 145 , 146 ].

By the 1910–1920s, antivivisection groups were fighting an increasingly difficult war for the public’s support. The argument that no medical progress could be obtained through animal research was becoming increasingly difficult to uphold and, as researchers pledged to avoid animal suffering whenever possible, criticism of animal experiments on the grounds of cruelty toned down. However, not all scientists had sufficient, if any, consideration for animal suffering, and research would continue to be unregulated in most countries. Nevertheless, the exaggerated claims, radical abolitionist views, and scientific denialism by more inflexible antivivisectionists would make them lose support from the general public and more moderate animal protection groups, leading to a decline—albeit not an end—to the antivivisection movement, until its resurgence in the 1970s. Confronted with a general lack of support, moreover in a period that would witness two great world wars and a serious economic recession—which would push the interests of animals further to the background—the line of action of antivivisectionists through most of the twentieth century focused on banning the use of dogs and other companion animals [ 5 , 147 , 148 , 149 , 150 ].

The toning down of the opposition to animal use in the life sciences had also something to do with the emergence of rodent species as a recurrent animal model in research. Unlike dogs or horses, rodents like mice and rats were seen as despicable creatures by most of the public, and therefore less worthy of moral consideration, which in turn deemed their use in research more acceptable [ 147 ]. While this came as an advantage to researchers, it is hard to say, however, if the actual weight of the public’s misgivings about the use of domestic animals was a relevant contributing factor for the ready adoption of rodent models, especially when considering their other numerous advantages as experimental animals when compared to other species. Firstly, they are small, easy to handle, and relatively cheap to house. Secondly, they are highly resistant to successive inbreeding and have a short lifespan and rapid reproduction rate [ 151 , 152 ].

Domesticated rats ( Rattus norvegicus ) were the first rodent species to be used for scientific purposes. Their use in physiological research dates to as early as 1828, but only in the first decades of the twentieth century did they become a preferred tool in research, after the development in 1909 of the first standard rat strain, the Wistar Rat , from which half of all rats used in laboratories today are estimated to have descended (for a historical perspective, see [ 153 , 154 ]) ( Figure 5 ). The mouse ( Mus musculus ) had also been used in the nineteenth century, famously by Gregor Mendel in his 1850s studies on heredity of coat color, until the local bishop censored mouse rearing as inappropriate for a priest, which made him turn to using peas instead [ 155 ]. The mouse would be again picked up in the beginning of the nineteenth century by Lucien Cuénot (1866–1951) to demonstrate that mammals also possessed “genes” (a vague concept at the time) that followed the laws of Mendelian inheritance, and would since then become a privileged model in the study of genetics, a field that would grow exponentially after the discovery of the DNA structure in 1953 by James Watson (born 1928) and Francis Crick (1916–2004). In 1980 John Gordon and Franck Ruddle developed the first transgenic mouse [ 156 ], and in 1988, the first gene knockout model was produced, which granted Mario R. Capecchi (born 1937), Martin J. Evans (born 1941), and Oliver Smithies (born 1925) the 2007 Nobel Prize. In 2002, the mouse became the second mammal, after humans, to have its whole genome sequenced. These, along with other technologies, have opened unlimited possibilities for the understanding of gene function and their influence in several genetic and non-genetic diseases, and have made the mouse the most commonly used animal model in our day (for a historical overview of the use of the mouse model in research, see [ 157 , 158 ]), with prospects being that it will continue to have a central role in biomedicine in the foreseeable future.

Two outbred laboratory rats, of the Lister Hooded (Long–Evans) strain. Rodents are the most commonly used laboratory animals, making up nearly 80% of the total of animals used in the European Union, followed by cold-blooded animals (fish, amphibian and reptiles, making up a total of 9.6%) and birds (6.3%) [ 159 ] Photo: Francis Brosseron, reproduced with permission.

7. Animal Liberation and the Pathway for a More Humane Science

Opposition to animal experiments resurged in the second half of the twentieth century, in particular after the 1975 publication of Animal Liberation by Australian philosopher Peter Singer (born 1946) [ 160 ]. Singer offered a strong philosophical grounding for the animal rights movement, by arguing that the use of animals in research—as well as for food, clothing or any other purpose—is mostly based on the principle of speciesism (coined by Richard Ryder in 1970 [ 161 ]), under which animals are attributed a lower moral value on the sole basis of belonging to a different species [ 162 ], which he considers to be no less justifiable than racism or sexism. His argument, however, does not stem from the premise that animals have intrinsic rights. As a preference utilitarian—and unlike hedonistic utilitarians like Bentham and Mill who argued we should act in order to maximize net happiness—Singer proposed that our actions should aim to do what on balance “furthers the interests of those affected” [ 163 ]. Holding that the interest of all sentient beings to both avoid pain and have positive experiences deserves equal consideration, he thus argues that it is difficult to justify animal research, since it generally does not hold to Bentham’s “ Each to count for one and none for more than one ” postulate. Furthermore, it is usually unfeasible to prospectively quantify how many may benefit directly from a given animal experiment. According to Singer, by using the principle of equal consideration of interests, one should give priority to relieving the greater suffering. Singer does not propose we should assume different species suffer similarly under the same conditions but, on the contrary, that care should be taken when comparing the interests of different species as, for instance, a human cancer patient, for his higher cognitive skills, can suffer a great deal more than a mouse with the same disease [ 164 ]. For this reason, he does not consider animal research to always be morally wrong in principle, and even admits that in certain occasions it may be justifiable, albeit these situations are, in his view, exceptional [ 165 ].

The animal rights movement would, however, receive from American philosopher Tom Regan (born 1938) a more uncompromising view of our duties to animals than Singer’s utilitarianism, one that would question the use of animals in research—or in any other way—altogether, regardless of the purpose of research. In Regan’s book The Case for Animal Rights (1983), he proposed we should extend the Kantian concept of intrinsic value to all sentient beings. This perspective inherently affords vertebrates rights, despite their incapacity to understand or demand such rights, as it is also the case—Regan argues—of small infants and the severely mentally handicapped. Hence, the respect for the life and wellbeing of sentient animals should be taken as absolute moral values, which can only be violated in very specific and extreme cases—such as self-defense. Regan’s moral philosophy hence only allows for an abolitionist view on animal research—since no “ends” can justify the “evil means” of sacrificing an animal in the face of the inviolable dignity of sentient beings [ 166 ]—and has become the main theoretical reference for the animal rights movement.

From the impact of Singer’s and Regan’s works in society and the academic world, “animal ethics” would emerge as a whole new field of philosophical and bioethical studies, and, with it, new and diverse ethical views on animals—including on animal research—and of our duties towards them. However, despite the diversity of philosophical views on the use of animals, the public debate on animal research would become polarized between animal rights activists and animal research advocates. While the first would uphold an uncompromising abolitionist stand, one could also find on the opposite side several persons who did not regard animal research as a moral issue at all [ 167 ]. Furthermore, and despite the debate in the philosophical ground remained civilized—even between diametrically opposed perspectives, see, for example, [ 168 ]—in the “real world” the antagonism began to build up. In the 1970s, animal rights extremist groups began resorting to terrorist actions, thus becoming a serious problem for researchers and authorities in several Western countries still today. These actions more often consist of trespassing, raiding animal facilities and laboratories, damage to property, harassment and death threats to researchers, their families and neighbors. It has also sometimes escalated into kidnapping, car and mail bombings, arson of homes and research facilities, mailing of AIDS-contaminated razorblades, and violence against scientists and their family members [ 169 , 170 ]. These actions, which have been classified as unjustifiable and damaging to the animal rights cause by Tom Regan himself [ 171 ], made researchers close themselves within their community and avoid speaking publicly about their work [ 172 , 173 , 174 ], which in turn left pro-research advocacy to emotion-appealing campaigns, of the likes of the Foundation for Biomedical Research’s “Will I be alright, Doctor?” film [ 175 ], or the advertisement depicted in Figure 6 .

A large advertisement published in the 13 May 1991 edition of The Hour (p. 9), and part of a campaign in defense of animal research, sponsored by the United States Surgical Corporation. While the value of Pasteur’s work is undeniable, there is, however, no scientific grounding for the claim that only by experimenting on dogs would a vaccine for rabies have been developed, or that other animal models or even non-animal methods could not have been used to achieve this in over a century. These dramatic and biased portraits of animal research are now more uncommon, as an increasing number of scientists acknowledge the need to be more candid and open to objective discussion over the possibilities and limitations of animal research, and of the scientific process altogether.

In spite of the emergence of the animal rights movement, animal research for biomedical purposes was—as it continues to be—seen as morally acceptable by the majority of the public [ 176 , 177 ]. It became, however, increasingly evident that animal suffering was morally and socially relevant, and that an ethical balance between the benefits brought about by biomedical progress and the due consideration to animal wellbeing should be sought. However, whilst antivivisection movements would only re-emerge in the late 1970s [ 5 , 178 ], the need for a more humane science had already been acknowledged and addressed within the scientific community as early as the 1950s.

Following the first edition of the Universities Federation for Animal Welfare’s Handbook on the Care and Management of Laboratory Animals (1954), the organization’s founder Charles Hume commissioned that same year a general study on humane techniques in animal experimentation to zoologist and classicist (and overall polymath) William Russell (1925–2006) and microbiologist Rex Burch (1926–1996), under a project chaired by immunologist Peter Medawar (1915–1987), Nobel Prize laureate in 1960 [ 179 , 180 , 181 ]. From this work, Russell and Burch would develop the tenet of the “Three Rs”— Replacement, Reduction, Refinement —principles that would be extensively developed in their seminal book, The Principles of Humane Experimental Technique [ 182 ]. In this book, the authors argued “humane science” to be “best science,” going so far as to state that “If we are to use a criterion for choosing experiments to perform, the criterion of humanity is the best we could possibly invent.” Replacement was defined as “any scientific method employing non-sentient material [to] replace methods which use conscious living vertebrates”; Reduction as the lowering of “the number of animals used to obtain information of a given amount and precision”; and Refinement as the set of measures undertaken to “decrease in the incidence or severity of […] procedures applied to those animals which have to be used,” later including also the full optimization of the wellbeing of laboratory animals, also seen as a basic requirement for the quality of science [ 179 ]. They also challenged the commonly held belief that vertebrate animals—and mammals in particular—are always the most suitable models in biomedical research, a reasoning they called the high-fidelity fallacy . Despite receiving a warm welcome, Russell and Burch’s work would remain largely ignored well into the 1970s. In 1978, physiologist David Henry Smyth (1908–1979) would again bring the Three Rs to the light of day and encompass them under the concept of alternatives [ 67 , 183 ], which he defined as “all procedures which can completely replace the need for animal experiments, reduce the numbers of animals required, or diminish the amount of pain or distress suffered by animals in meeting the essential needs of man and other animals” [ 184 ]. More than a restatement of the Three Rs, this definition had the added value of placing onto researchers the burden of providing convincing evidence for the necessity of using animals [ 183 ], a particularly important statement from the then-president of the UK’s Research Defence Society.

The Three Rs approach would provide an ethically and scientifically sound framework on which a reformist approach to the use of animals in biomedicine could be grounded. It would also set the stage for a more moderate advocacy of animal rights to appear: while remaining incompatible with an abolitionist animal rights perspective, this paradigm grants animals something like a right to protection from suffering, or at least certain suffering beyond a defined threshold [ 185 ], preserving the central idea that there are absolute and non-negotiable limits to what can be done to animals. This welfarist perspective stems from a utilitarian view that animals can be used as means to an end as long as their interests—as far as they can be ascertained—are taken into account, but also accepting that the lives and wellbeing of human beings must be granted greater consideration than animals’. Utilitarian philosopher Raymond G. Frey (1925–2012) offered a philosophical view compatible with the current paradigm, by acknowledging that what we do to animals matters morally, since animals’ sentience and ability to control their lives grants them moral standing and a rightful place in the “moral community.” However, when weighing the interests of humans against animals’ interests (or between animals, or humans), he held that the main question should not lie on one who has moral standing or not, or to which degree, but rather on whose life may be more valuable. In Frey’s view, the value of life “is a function of its quality, its quality of its richness, and its richness of its capacities and scope for enrichment.” Hence, as a result of their higher cognitive capabilities, human lives are typically richer than animal lives, being therefore generally more valuable [ 186 ].

A “welfarist–reformist” approach has been accepted as a compromise by some prominent animal rights advocates who, while maintaining the long-term goal of a full end to all animal experiments, believe that it is by successive short-term improvements of the status quo that their goal can be achieved; see [ 178 , 187 , 188 ]. This position—also endorsed by influential animal advocacy groups like the Humane Society of the United States, or the UK’s FRAME—has, however, been highly criticized by less compromising animal rights advocates, like Regan and Gary Francione (born 1954), who believe reformist attitudes validate and perpetuate the exploitation of animals [ 171 , 189 , 190 ].

The 1980s and the 1990s would witness considerable progress in the development and acknowledgment of the Three Rs, to the satisfaction of William Russell and Rex Burch, who lived to see the “rediscovery” of their principles and the emergence of a whole new field of research inspired by their groundbreaking work [ 179 , 191 ]. As Peter Medawar had predicted in the 1960s, the number of animals used in research would peak in the 1970s and start to decline thereafter, although the number of biomedical papers has since then more than doubled [ 181 , 192 , 193 , 194 , 195 , 196 ]. This data is, however, limited to the Western world, as statistics on animal use in emerging countries such as India and China are unavailable [ 197 ], and there is no way to assess if (and, if so, to what extent) the decline in numbers of animals used in Western countries may be attributed to the outsourcing of animal experiments to these emerging countries. In recent years, the rise in the use of genetically modified animals has led to the stabilization of what would otherwise be a continuously downward trend [ 198 , 199 ] ( Figure 7 ).

This schematic illustration (adapted with permission from an original by Professor Bert van Zupthen) attempts to describe trends in the use of animals for scientific purposes in the Western world across time. It depicts the emergence of the first vivisection studies by classical Greek physicians, the absence of animal-based research—along with most medical and scientific research—across the Middle Ages, its resurgence in the Renaissance onwards, and the rapid increase in animal studies following the rise of science-based physiology and medicine in the nineteenth century. The curves represented are nevertheless conjectural, as there are no reliable statistics on animal use for most of the period covered. Even nowadays it is hard to estimate trends in animal research, as data from several developed countries is insufficient (for instance, in the United States, rodents, fish and birds are not accounted for in the statistics). The available data, however, suggest that the number of animals used in research and testing in the Western world peaked in the 1970s, and decreased until the late 1990s, or early 2000s, to about half the number of 30 years earlier, and stabilizing in recent years. While many, if not most, researchers do not foresee an end to animal experiments in biomedicine, the European Commission has nevertheless set full replacement of animal experiments as an ultimate goal [ 204 ], and the Humane Society of the United States has the optimistic goal of full replacement by the year 2050 [ 192 ].

In 1999, the Declaration of Bologna, signed in the 3rd World Congress on Alternatives and Animal Use in the Life Sciences, would reaffirm that “ humane science is a prerequisite for good science, and is best achieved in relation to laboratory animal procedures by the vigorous promotion and application of the Three Rs ” [ 200 ]. The Three Rs would also become the overarching principle of several legislative documents regulating animal use in science since the 1980s (including the latest European legislation [ 201 ]). Most recently, biomedical researchers in both industry and academia have also acknowledged the central importance of the Three Rs and the need for more transparency regarding animal use in biomedical research through the Basel Declaration [ 202 , 203 ]. More important, there are currently thousands of scientists devoted to the progress of animal welfare and development of alternatives to animal use in the life sciences.

8. Conclusion

The historical controversy surrounding animal research is far from being settled. While the key arguments in this debate have not differed significantly since the rise of antivivisectionism in nineteenth-century England—and even before—we have since then moved a long way forward in regards to the protection of animals used in research and transparency regarding such use. While animal experiments have played a vital role in scientific and biomedical progress and are likely to continue to do so in the foreseeable future, it is nonetheless important to keep focusing on the continuous improvement of the wellbeing of laboratory animals, as well as further development of replacement alternatives for animal experiments.

Acknowledgments

The author thanks Francis Brosseron ( Lycée Français du Porto ) for the photograph in Figure 5 , Bert van Zutphen (Emeritus Professor, Utrecht University) for the original picture that has been adapted for Figure 7 , and I. Anna S. Olsson, Manuel Sant’Ana (IBMC, University of Porto) and four anonymous referees for their valuable comments on this manuscript.

Conflict of Interest

The author declares no conflict of interest.

References and Notes

Dogs play a key role in veterinary college’s brain cancer trial

• Marjorielee Christianson

21 May 2024

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Lucy, with her boundless puppy-like energy even at 12 years old, is more than just a pet to Susan Ketcham. She's now part of a research project that could transform the way we treat brain cancer – in both dogs and humans.

This study at Virginia Tech's Virginia-Maryland College of Veterinary Medicine explores an innovative therapy called histotripsy. It's a leap forward from traditional cancer treatments, harnessing the power of focused ultrasound to break down tumors with precision. 

When Lucy began experiencing seizures last July, Ketcham, a clinical nurse specialist, knew something more serious was the cause. The diagnosis of a brain tumor was devastating, but Ketcham was determined to explore all treatment options available. She discovered the histotripsy trial during her search and quickly reached out.

"Being in human medicine myself," said Ketcham. "I work in operating rooms and am very familiar with focused ultrasound, so I was eager to learn more."

Collaborative mission, translational impact

The trial is led by John Rossmeisl , the Dr. and Mrs. Dorsey Taylor Mahin Professor of Neurology and Neurosurgery, and Rell Parker , an iTHRIV scholar and assistant professor of neurology and neurosurgery.

Also on the team is Lauren Ruger , a postdoctoral associate in Eli Vlaisavljevich’s lab in the Department of Biomedical Engineering and Mechanics where histotripsy is extensively researched. She's adapting the equipment used in the study to make it safe and effective for their canine patients.

“I had wanted to be a veterinarian when I was younger before deciding to become an engineer,” said Ruger. “So I love having the opportunity to use my skills as an engineer to influence animal health.”

This trial offers an essential stepping stone in developing less invasive treatment options for brain cancer and is supported by the Focused Ultrasound Foundation and the Canine Health Foundation, highlighting the widespread commitment to results across species.

Hope for histotripsy

“Histotripsy uses acoustic energy, or sound waves, to modify tissue,” said Rossmeisl. “The intent is to cause a mechanical disruption of the tissue – killing cancer cells." 

The technology was developed by researchers at the University of Michigan in the early 2000s. 

The advantage is precision. Unlike traditional surgery, histotripsy can focus its impact on the tumor itself. "We could potentially treat these hard-to-reach brain tumors we normally can’t access with traditional surgery,” said Parker.

"We really don't have great ways to treat brain cancers in patients,” said Rossmeisl. “Even when you do surgery, radiation, or chemotherapy alone or in combination, usually, you're not creating a cure." 

However, there is hope that histotripsy could be used to activate the body’s immune response and have it attack cancer cells, called the abscopal effect. Clinicians also see fewer side effects compared to other traditional treatment options.

About the procedure

The study currently still involves surgery to access brain tumors, which is the gold standard of care for this type of diagnosis. This allows for direct targeting of the tumor with the histotripsy transducer, delivering focused sound waves for precise treatment.

“When we do the surgery, we can see the tumor via ultrasound,” Parker said. “We can see that we're treating the appropriate cells, and then we also do an MRI to ensure that we've targeted the right area.” 

After the histotripsy treatment, surgeons carefully remove the treated tumor. This tissue provides crucial insights into the technique's effect on cancer cells, helping researchers refine the technology for future applications.

“It gives us the advantage of being able to look at the tissue that's been broken down to ensure that we're getting the desired effect from the histotripsy therapy,” said Ruger.

While the science is complex, the stories of patients like Lucy are reminders of why this work matters. "The recovery was quick, the incision was small," Ketcham said. "She's back to her playful self, and knowing she's helped advance science and technology is amazing."

Parker added: "We’re happy to say that the procedure has been safe for our patients, and we've been able to treat them appropriately."

Looking toward the future of treatment

A long-term goal of this study is to develop a completely non-invasive treatment that would eliminate the need for surgery. The team is in the early stages of exploring this possibility, citing several challenges to realizing a solution that could be widely available. 

“Transmitting ultrasound through the bones of the skull is very difficult,” said Ruger. “And then accurately focusing it in only the areas you want to treat with histotripsy adds another layer of complexity.”

However, the technique can be successfully applied through the skin, explained Rossmeisl. "That would be a paradigm changer. We would make surgically treating tumors a lot more widely available.”

“Even though I love neurosurgery,” he added. “Anytime I can do something that doesn't require putting the patient through a complex and invasive procedure and get them home quicker, that's always a good thing.”

To learn more about eligibility criteria or enroll your dog in the trial, please contact John Rossmeisl at [email protected] or 540-231-4621 or Mindy Quigley, clinical trials coordinator at  [email protected] or 540-231-1363.  

Andrew Mann

540-231-9005

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