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Historically, attempts to advance medical research have depended heavily on violating the rights of vulnerable people and animals.

Fortunately, moral and scientific advancements have resulted in a serious reevaluation of how research is conducted.

Public demand has led to improved ethical standards in human research, and there have been some advancements in specific alternatives to the use of animals in research.

However, while the strides made to protect humans have been significant, the use of animals in research is still ethically problematic and based on the assumption that animal research is necessary and that human interests outweigh those of animals.

But there is a way forward.

 

The First Standards for Research Using Humans

Efforts to establish principles for the protection of human subjects in research began following the Second World War, after the Nuremberg Trials brought to light details of the experiments on concentration camp prisoners by Nazi physicians and researchers.

In 1947, the Nuremberg Code, which grew out of the trials, articulated protections against the coerced, torturous, and often deadly practices to which the prisoners had been subjected.

Although never formally adopted as a code of practice, the Nuremberg Code provided the foundation for later international and national policies on human subjects. The Nuremberg Code and subsequent codes of practice contain requirements around informed consent for research using human subjects, as well as considerations for the research such as the degree of scientific merit and the risks to the individual in relation to the expected humanitarian benefit.

The US Department of Health and Human Services maintains an International Compilation of Human Research Standards. Such standards have not prevented all abuses, but they do serve as guidelines that, if violated, can cost researchers funding, employment, and professional status.

 

The Belmont Report

In the US, the Belmont Report was issued in 1978 out of concern for human rights abuses in medical research. The report forms the ethical basis of the Federal Policy for the Protection of Human Subjects, often referred to as the “Common Rule.”

The Belmont Report specifies three core principles:

1. respect for persons;
2. beneficence (the obligation to show kindness and mercy and to act for the benefit of others); and
3. justice.

It emphasizes the importance of consent and of the special consideration of human subjects who are particularly vulnerable due to their inability to understand the potential risks and benefits of the research and/or to volunteer knowingly and willingly.

 

The Lack of Meaningful Standards for Research Using Animals

Despite organized animal protection movements dating back to at least the 18th century, there are no standards for animals that are comparable to those that apply to human subjects under the Belmont Report and the Common Rule. The lack of such standards means that today, for animal subjects, there is still no consideration of consent, and the assumption that underlies the use of animals in research is that they can be used and killed if anything will be learned in the process.

In fact, the Nuremberg Code’s suggestion that experiments using human subjects should be designed based on prior experimentation on animal subjects is still the norm.

For example, the US Food and Drug Administration’s application for clinical investigations of new drugs suggests the inclusion of a description of the drug’s pharmacological effects and mechanisms of action in animals, and if the drug has abuse potential, a description of dependency studies in nonhuman animals.

 

Weak and Inconsistent Protections for Animals Used in Research

The protections that do exist for animal subjects in research differ by species and vary widely across the world. The following articles from the journal of the Institute for Laboratory Animal Research address the strengths and weaknesses of protections for animals in various countries and regions:

AltTox.org, as part of its efforts to support alternatives to animal use in toxicity testing, maintains a list of links to international regulations and to national regulations in the US, EU, India, Japan, and Korea.

Inconsistencies in protections and reporting requirements between and within countries makes it difficult to assess the full scope of animal use in research.

For example, in the US, there is no requirement to count the individuals from species who are not legally considered “animals” for research purposes. See this discussion of the issue with regard to the omission of mice from the federal Animal Welfare Act.

 

The Establishment of the 3Rs

A commonly used framework in animal research is The Principles of Humane Experimental Technique, a report written by William Russell and Rex Burch and published in 1959. It is the product of an investigation of research techniques they undertook on behalf of the Universities Federation for Animal Welfare, a UK-based nonprofit organization.

The report outlines guiding principles for research using animal subjects; those guidelines have come to be known as the “3Rs”: Replacement, Reduction, and Refinement.

As scientists have increasingly accepted the fact that other animals are more like than unlike humans in our capacities to experience physical and psychological pain and pleasure, and that they warrant the same moral consideration, centers focused on the 3Rs have been founded around the world. The Bunddesinstitut für Risikobewertung and AltTox both have directories that list many of these centers.

One of the earliest and perhaps currently the most extensively developed 3Rs programs in the US is the Center for Alternatives to Animal Testing (CAAT) at the Johns Hopkins Bloomberg School of Public Health, which was founded in 1981.

In 1993, CAAT hosted the first World Congress on Alternatives and Animal Use in the Life Sciences, and it regularly holds workshops and symposia that bring together representatives from academia, industry, animal protection groups, and government regulatory bodies.

In 2009, CAAT joined with a similar project at the University of Konstanz in Germany to form CAAT-Europe. CAAT’s website hosts the quarterly open-access journal, ALTEX: Alternatives to Animal Experimentation, which was first published in 1984 by Fonds für versuchstierfreie Forschung, Zurich (now Animalfree Research, Berne).

CAAT deserves credit for being a pioneer in promoting alternatives to animal testing, and for contributing to the strides that have been made in adopting alternatives to using animals in toxicity testing—an area in which there has been more progress than in other spheres of research.

However, like other similar centers CAAT has embraced the underlying assumptions of the 3Rs that animals have no rights that preclude our use of them for our own purposes. And thus CAAT continues to consider improvement in animal welfare measures as acceptable “alternatives,” to animal testing.

CAAT defines these “alternatives” as “new methods that refine existing tests by minimizing animal distress, reduce animal usage, or replace whole animal tests.” Educational materials on the CAAT website perpetuate the myth of “humane” methods of animal research.

 

The Challenges of Transitioning to a More Just Research System

The inherent vulnerability of animals is given little if any ethical weight in research design. The extent to which animals in laboratories are considered disposable was made clear to the public when news outlets began reporting in early 2020 that university administrators were ordering researchers to kill mice in their laboratories in anticipation of workplace closures due to COVID-19.

One set of impediments to transitioning to a more just research system is the number of individuals, educational institutions (including 3Rs centers), corporations, and government agencies involved in research using animal subjects, how attached they are to that model, and how lucrative it is for those involved.

In addition to the scientists in academia whose positions and salaries depend on their getting grants for research involving animals, and the industry researchers whose livelihoods depend on selling products developed through research involving animals, the breeding and selling of animal subjects is an industry unto itself. One trade projection suggests that the global market for laboratory animals will grow from $5.9 billion in 2018 to $7.8 billion in 2023.

To be ultimately successful, research institutions focused on alternatives face the challenges of replacing the current structure of supply and demand—in addition to designing and validating alternatives—and of shifting the research paradigm away from the unfounded presumption that research using animal models is a necessary part of developing treatments for humans.

Recently, a new Canadian center has taken up those challenges, rejecting animals as permissible or adequate models for human health and disease.

 

Canadian Centre for Alternatives to Animal Methods

Founded in 2017 by Dr. Charu Chandrasekera and based at the University of Windsor, the Canadian Centre for Alternatives to Animal Methods (CCAAM), along with its subsidiary, the Canadian Centre for the Validation of Alternative Methods in toxicity testing, is devoted solely to the replacement mandate of the 3Rs.

A former animal researcher, Dr. Chandrasekera notes in the Centre’s welcome video that 95 percent of drugs found to be safe and effective in animal trials fail in human clinical trials.

In a TEDx talk, Chandrasekera further discusses this fact, as well as the issues of

  • diseases that have been “cured” in other animals but not in humans (e.g., Alzheimer’s);
  • drugs that are safe and effective in humans but toxic in other animals (e.g., aspirin);
  • why animals are insufficient models for human physiology;
  • how animal replacement technologies work; and
  • why they are ethically essential.

Under Dr. Chandrasekera’s leadership, CCAAM’s explicit aim in meeting human health needs is to shift the research paradigm to one in which “human biology serves as the gold standard.”

CCAAM characterizes its educational initiatives, which range from replacing animal dissection in high school classes to training and degree programs in human-centered methodologies at the undergraduate and graduate levels, as teaching students to “think outside the cage.”

The alternative methods CCAAM teaches and explores include both traditionally available methodologies, such as noninvasive imaging and population studies, and cutting-edge technologies. These new technologies include generating adult stem cells from skin biopsies and turning them into organoids or 3D-bioprinted tissues, configuring those products to create “disease in a dish” and “toxicity on a chip” models that mimic the functioning of human organ systems at smaller scale, and using computational models made possible by artificial intelligence.

By refusing to see Reduction and Refinement as “necessary” to research, CCAAM positions itself to make significant contributions to a just knowledge system.

 

A Belmont Report for Animals

A Belmont Report for Animals would recognize that animals overwhelmingly bear the burdens of research without accessing the benefits. The ethical benefits of such an approach include a substantial shift in the balance of burdens to benefits for animals involved in research.

Phoenix Zones Initiative CEO Hope Ferdowsian and her colleagues have developed a proposal for a Belmont Report for Animals. Read more about it here.

The ethically significant capacities of animals and their vulnerability as research subjects warrant more protections from the harms of research than current regulatory schemes and guidelines provide.

Adopting a Belmont Report for Animals would take into account animals’ preferences, interests, and vulnerabilities, and would thus have a significant impact on using animals for research.

Nothing less than ethically-grounded, principled guidelines, similar to those found in the Belmont Report, can adequately address the ethical inconsistencies and inadequacies of research with animals. It would also force us to continue to hold human research to the highest ethical research standards possible.

 

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