Alternatives to Animal Testing

What is Animal Testing?

Animal testing, or animal experimentation, involves using non-human animals in experiments to study biological and behavioral processes. This practice includes a wide range of procedures, from observing natural behaviors to performing invasive procedures or administering substances to assess their effects on the body. Animal testing is used across various fields, including disease modeling, drug development, toxicology and much more.

History of Animal Testing

When did animal testing start?

Early records indicate that animal testing dates back to ancient Greek times where Greek scientists such as Aristotle and Erasistratus conducted experiments on living animals. In the 17th and 18th centuries, animal testing became more systematic, driven by advancements in anatomy and physiology.

What animals were used in the beginning and why?

Due to their anatomical and physiological similarities to humans, animals like pigs, goats, and monkeys were primarily used in early experiments, providing valuable insights into human biology.

Why is Animal Testing Done?

The 1938 United States Federal Food, Drug, and Cosmetics Act (FDCA) was passed after more than 100 people died in the United States after oral ingestion of “Elixir Sulfanilamide”, which contained poisonous diethylene glycol. No animal safety testing was required prior to 1938. Since then, animal testing had to be performed for all new drugs. Therefore, in vivo animal models and 2D in vitro cell culture models (mostly with cells derived from animals) have been at the center of the pre-clinical (or non-clinical) phases of drug development for decades.

Today, animal testing can be conducted for several reasons:

1. Understanding Biological Processes: Animal models provide a more controlled in vivo environment in which researchers can study complex biological systems and disease mechanisms. By helping researchers understand how diseases develop and progress, these models can help identify potential treatments for these diseases.
2. Safety Testing: All new drugs, chemicals, and consumer products must be tested for safety and toxicity before they are exposed to humans. Animals are often used in these tests to assess potential risks and side effects, ensuring that products are safe for human use. This step is crucial to prevent harmful substances from reaching the market and human consumption.
3. Drug Development: Animal models are used in pre-clinical phases of drug development to evaluate the efficacy and potential side effects of new drugs. Through animal testing, researchers can gather important data on how a drug interacts with biological systems, which guides the design of human clinical trials if pre-clinical phases are successful.
4. Regulatory Requirements: Many regulatory agencies, such as the United States Food and Drug Administration (FDA) and the European Medicines Agency (EMA), require data from animal testing for the approval of new drugs, chemicals, and consumer products. These regulations are in place to ensure that new products are thoroughly tested for safety and effectiveness before reaching the market and human consumption.

While animal testing has been a crucial component of scientific research and drug development, it remains a controversial topic due to ethical considerations and scientific limitations. With advancements in technology today, alternatives to animal testing can now be explored.

Applications of Animal Testing

In which fields is animal testing done?

Animal testing is used in scientific research to study complex biological processes, assess the safety and efficacy of new products, and provide critical training for future professionals. The following are key fields in which animal testing is commonly practiced:

1. Biomedical Research: In biomedical research, animal models are used to better understand the mechanisms of diseases, genetics, and developmental biology. Researchers utilize animals to investigate the causes and progression of various human diseases, including cancer, cardiovascular diseases, neurological disorders, and infectious diseases. Through these studies, scientists can gain insight into disease pathology and identify potential therapeutic targets that can potentially improve human health.
2. Pharmacology: Pharmacology relies heavily on animal testing to evaluate the effects of new drugs and treatments before they proceed to human clinical trials, such as determining the appropriate dosing, safety, and efficacy of drugs, ensuring that only the most promising candidates advance to human trials. This process is particularly important for developing treatments for conditions that currently lack effective therapies, such as certain cancers, rare diseases, and chronic illnesses.
3. Toxicology: Toxicology often relies on animal testing to assess the toxicity of chemicals found in pesticides, industrial products, pharmaceuticals, and household items. By exposing animals to different doses of these substances, toxicologists can evaluate potential risks to human health and the environment and establish safety standards and regulatory guidelines.
4. Cosmetics Testing: Animal testing has historically been used in the cosmetics industry to evaluate the safety of cosmetic products and their ingredients. This can include testing for skin and eye irritation, allergic reactions, and long-term health effects such as carcinogenicity. However, due to growing ethical concerns and the development of alternative methods to animal testing, many companies have moved away from animal testing for cosmetics.
5. Education: Animal testing is also employed in education, particularly in medical, veterinary, and biological sciences to train students hands-on in surgical techniques, anatomy, and physiology. Medical students may practice procedures on animal cadavers or live animals under controlled conditions to learn essential surgery skills. Similarly, veterinary students use animal models to practice diagnostic techniques, surgical procedures, and emergency care. While some educational institutions have begun to incorporate simulators and virtual reality as alternatives, animal testing remains a common practice in many training programs.

Animal testing has advanced our understanding of diseases to ensure the safety of new drugs and products. As science progresses, the adoption of alternatives to animal testing can be further explored to promote more scientific advancement and ethical responsibility.

Where is animal testing required?

Many regulatory agencies, such as the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA), require animal testing data for the approval of new drugs, chemicals, and consumer products to ensure their safety and efficacy.

Why Consider Alternatives to Animal Testing? : Ethical Criticisms

Animal testing has long been a subject of ethical debate, raising significant concerns about the treatment and welfare of animals used in research and testing. While animal models have contributed significantly to scientific advancements, the ethical implications of causing harm to animals for the sake of research cannot be overlooked. This section explores the key ethical criticisms of animal testing and highlights the moral dilemmas and push for more humane alternatives to animal testing.

1. Animal Welfare: One of the primary criticisms of experimenting on animals revolves around the animals’ welfare. Many animal experiments involve invasive techniques, prolonged confinement, and exposure to harmful substances, leading to significant physical and psychological distress. Thus, the welfare of these animals is often compromised and the potential benefits to humans do not justify the animals’ suffering. Concerns about this pain, suffering, and distress of animals in research has led to the exploration of alternatives to animal testing.
2. Moral Status: Debates about the moral status of animals question the ethical implications of using them for human benefit. Some ethicists argue that animals possess intrinsic value, and human interests should not automatically take precedence over animal well-being. These arguments imply that animals deserve moral consideration comparable to that given to humans.
3. Rights of Animals: The argument for animal rights advocates for the intrinsic rights of animals that should protect them from exploitation and harm. Advocates for animal rights contend that animals, like humans, have the right to live free from suffering and exploitation. This perspective suggests that animals are sentient beings capable of experiencing pain and pleasure, and therefore should not be used as tools for experimentation.
4. Public Opinion: Growing public awareness and opposition to animal testing has intensified the call for more humane alternatives. As society becomes more informed about the conditions under which animals are tested, there is increasing demand for more ethical research practices. Public opinion can often influence policy and funding decisions, leading to greater investment in the development of non-animal testing methods, such as in vitro testing, computer modeling, and the use of human cell cultures.
5. Scientific Validity: Another criticism of animal testing is the question of scientific validity. Some critics argue that animal models do not always accurately predict human responses due to largely physiological and genetic differences between species, raising concerns about the reliability and relevance of data obtained from animal testing. Relating back to the above criticisms, this suggests that the suffering of animals may not always translate into meaningful or applicable results for human health.
6. Legal and Regulatory Pressure: There is growing legal and regulatory pressure to reduce or even eliminate animal testing. Various laws and guidelines, such as the European Union's REACH regulation and the U.S. National Research Council's Toxicity Testing in the 21st Century, advocate for minimizing animal use and promoting alternative methods to animal testing. These legal frameworks reflect a shift towards more ethical and scientifically advanced approaches to research and testing.
7. Alternatives to Animal Testing: The development of alternatives to animal testing, such as organ-on-a-chip technology, 3D tissue cultures, and advanced computer simulations, offer promising avenues to reduce reliance on animal testing. These alternatives can potentially provide more accurate and ethical means of studying diseases and evaluating the safety and efficacy of new treatments.

The ethical criticism of animal testing encompasses a range of concerns related to animal welfare, moral status, and the intrinsic rights of animals. Growing public opposition and advancements in alternative testing methods further highlight the need for more humane and scientifically valid approaches to research. The ongoing debate underscores the importance of balancing scientific progress with ethical responsibility, ensuring that the welfare of animals is considered alongside the pursuit of human health and safety.

Why Consider Alternatives to Animal Testing? : Scientific Criticisms & Limitations

The limitations of in vivo animal models as predictors for human efficacy and safety have become increasingly evident. More than 95% of clinical trials for new drugs fail, with a significant proportion of failures attributed to a lack of efficacy or unacceptable toxicity that was not predicted by animal testing in pre-clinical drug development. This staggering failure rate has prompted not only ethical but scientific scrutiny of animal testing as a reliable model for human biology, including the following:

1. Species Differences: One of the most significant criticisms of animal testing is the inherent biological differences between species. Even closely related species can have vastly different metabolic processes, immune responses, and overall physiology, leading to significant discrepancies in how animals and humans respond to the same substance. These interspecies variations make it difficult to extrapolate data from animal studies to humans, thus contributing to the poor translation of pre-clinical results to clinical outcomes.
2. Predictive Validity: The predictive validity of animal models, or how accurately these models predict human responses, is often questioned. While animal studies can provide insights into biological mechanisms and potential effects, they do not always replicate the complexities of human disease or accurately predict how a drug will perform in human trials. There is no true animal equivalent to humans, leading researchers to use models that only partially mimic the human condition. As a result, drugs that are promising in animal models often fail to demonstrate the same efficacy or safety in humans, contributing to the high attrition rate in drug development.
3. Reproducibility: Reproducibility is critical in scientific research, yet variability in animal experiments can often lead to inconsistent results. Factors such as genetic differences between animal strains, differences in housing and handling conditions, and variations in experimental protocols can all influence the outcomes of animal studies. This variability can make it difficult to reproduce results across different laboratories or even within the same laboratory over time, diminishing the reliability of animal testing as a predictive tool and leading to misguided decisions in drug development.
4. Technological Advances: The rise of new technologies offers alternative approaches that can provide more precise and relevant data than traditional animal models. David Ingber at the Wyss Institute was the first to develop a lung-on-a-chip in 2007. Since then, numerous single-organ and multi-organ systems have been developed for research and commercial applications, enabling a higher level of control over the cellular microenvironment in a culture to investigate diseases and pathophysiologies. Additionally, advances in 3D bioprinting allows researchers to create more complex, human-relevant models of tissues and organs to mimic human physiology more closely than animal models. Finally, computational modeling and machine learning approaches can predict drug responses based on human data, further reducing the reliance on animal testing. As these technologies continue to develop, they hold the potential to improve the efficiency and success rate of drug development while addressing the ethical and scientific limitations of animal testing.

The scientific limitations of animal testing as predictive models for human biology underscore the need for alternative approaches. While animal models have historically played a crucial role in advancing biomedical research, their inherent species differences, issues with predictive validity, and reproducibility challenges highlight their shortcomings. As technological advancements continue to offer more accurate and human-relevant data, embracing these innovations not only addresses ethical concerns but also promises to improve the efficiency and success rate of bringing safe and effective drugs to market.

Alternatives to Animal Testing

On December 29, 2022, President Biden signed the FDA Modernization Act 2.0 into law after it passed the US Senate (29 Sep. 2022) and the House of Representatives (23 Dec. 2022) with bipartisan support. The new law updates the Federal Food, Drug, and Cosmetic Act from 1938, which required that all drugs must be tested on animals prior to human clinical trials.

The FDA Modernization Act 2.0 replaced the word “animal” with “nonclinical tests, which is a term that “means a test conducted in vitro, in silico, or in chemico, or a non-human in vivo test that occurs before or during the clinical trial phase of the investigation of the safety and effectiveness of a drug, and may include animal tests, or non-animal or human biology-based test methods, such as cell-based assays, microphysiological systems, or bioprinted or computer models”.

On February 6, 2024, the U.S. House of Representatives introduced the FDA Modernization Act 3.0, which proposes to reduce and replace the use of animals in nonclinical research in an effort to improve the predicitivity of nonclinical drug testing.

Significant improvements in technology over the past 20 years were needed to enable drug development without sacrificing animals in each of the following research areas:

BMSEED's Mission: Alternatives to Animal Testing

BMSEED’s mission is to provide innovative products that contribute to the elimination of animals in pharmaceutical research and drug development. Our goal is to make pre-clinical research more effective in accurately predicting clinical outcomes than animal models.

Our core technology is the reliable manufacturing of proprietary stretchable microelectrode arrays (sMEAs). Our MEASSuRE platform greatly improves the validity of in vitro experiments by replicating the electrical and mechanical environment of cells in vivo in a controlled environment in vitro, both for 2D and 3D cultures. By providing a biomimetic environment for cells and tissues, sMEAs can more closely mimic the human body and offer more accruate human-relevant data early in the pre-clinical research process to reduce the failure rates in human clinical trials.

sMEAs can monitor electrical activity in cultured tissues, providing valuable data for neurological research and drug testing. This is important for in vitro research because bioelectrical and biomechanical cues affect phenotype and function in hiPSC-derived lineages. In the absence of biophysical (i.e., electrical or mechanical) cues, cells in vitro will differ from their in vivo counterparts.  For instance, Nunes et al. demonstrated that electrical stimulation of hiPSCs improved cardiomyocyte (CM) structure, induced sarcomere maturation, and enhanced electrophysiological properties compared to a non-stimulated control. Tulloch et al. demonstrated that cyclic mechanical stretch of hESCs promoted a 2-fold increase in cardiomyocyte differentiation yield and matrix fiber alignment, a 2.2-fold increase in cardiomyocyte hypertrophy, and a 21% increase in proliferation rates compared to unstretched controls. These mounting evidences indicate that cardiomyocytes differentiated from stem cells with added electrical or mechanical stimulation are more representative of the native phenotype within the adult myocardium.

Conclusion

Shifting toward alternatives to animal testing represents a significant advancement in scientific research and ethical responsibility. By embracing innovative technologies and methodologies as alternatives to animal research, researchers can enhance the accuracy, efficiency, and ethical standards of their studies. However, despite significant progress, challenges remain in the widespread adoption of alternatives to animal testing, such as the need for further validation, standardization, and regulatory acceptance. Collaborative efforts between academia, industry, and regulatory bodies are essential to advance the development and implementation of alternative methods to animal testing, ultimately reducing the dependence on animal models. Learn more about BMSEED's stretchable microelectrode array technology as an alternative to animal testing.