How Using Animals in Experiments Fails Both Humans and Animals
by Dr. Hope Ferdowsian
March 21, 2023
When making daily medical decisions with patients, doctors follow a hierarchy of medical evidence in recommending lifestyle changes, medicines, vaccines, surgery, and other medical interventions.
The top level of evidence includes systematic reviews and meta-analyses—filtered information that draws together unfiltered information from other types of medical studies, such as randomized controlled trials and cohort studies.
Another big question medical professionals ask is related to generalizability: Is the research population in this study similar enough to the patient or patient population that the doctor is treating?
For example, If I have a 65-year-old woman with heart disease sitting in front of me in clinic, I’m not going to rely on a study that only focuses on men with heart disease. Similarly, if I have a 70-kg man with heart disease, I’m not going to reach for a study of mice, who weigh 30-40 grams and have a range of anatomical and physiological differences from the person I’m treating.
There Is a Problematic Reliance on Animal Experimentation
This hierarchy of evidence is also important to how we evaluate animal research more broadly.
When doctors and scientists have examined how animal experimentation translates to human outcomes, they have found serious problems. When researchers have analyzed published animal studies through systematic reviews and meta-analyses, they have shown that animal studies do not reliably match human data.
In drug development, for example, animal data does not correspond well with human data.
Studies in animals repeatedly show that there is no clear relationship between human bioavailability (the proportion of a drug that enters the bloodstream and can have an effect) and animal bioavailability, including in dogs, nonhuman primates (such as monkeys), and rodents—all animals who are commonly used in research.
As a result of the mismatch between human and animal data, high rates of false negatives (a wrong negative result) and false positives (a wrong positive result) are common, which increases the risk for harmful events in humans and delays in drug discovery.
The External Flaws with Using Animals in Experiments
There are several threats to external validity when using animals in experiments:
1. Humans and other animals develop different diseases and disease progression.
For example, most animals do not experience heart disease like humans do. Certain cancers aren’t found in animals in the same ways they are found in humans. There are also major differences in anatomy and physiology across species.
As my colleague likes to say, “human adults aren’t 70-kilogram mice.”
2. Whether human or nonhuman, an individual’s health status matters as to how they develop disease.
An individual’s health status—whether we’re talking about a human, a dog, a cat, or another animal—also matters as to how they develop disease. And, as noted below, laboratory environments adversely affect the physical and mental health of animals.
3. Animal experiments don’t represent the diversity or heterogeneity that we see in the human population.
In animal experiments, the animals used are often very homogeneous. For example, many of the mice and rats who are used often come from the same genetic lines.
4. There are also differences in outcome measures (what we’re trying to determine in research).
For example, how can we adequately assess for side effects such as headaches and other subjective and self-reported symptoms in animals in laboratories if they can’t tell us about their pain in the same way that most human adults and many human children and adolescents can?
5. Lab experiments involving animals also don’t account for human epigenetic effects.
Epigenetic effects are the huge effects of our behaviors and the environment on genetic expression from birth to death, which affects our disease risk and progression.
6. Lab experiments using animals don’t account for human genetic variability.
Animal experimentation can’t replicate the human genetic variability that we see in the US and across the globe. But more modern technologies, such as MIMIC® (Modular IMmune In vitro Construct), can.
Problems Intrinsic to Using Animals in Research
Animal experimentation also fails because of intrinsic problems.
We also can’t separate the experimental outcomes that we’re interested in from the acute and cumulative trauma of laboratory life.
When they are used for laboratory experiments, animals experience the traumatic effects of breeding and captivity, family separation, other broken bonds, social isolation, and fear, anxiety, pain, and discomfort—from birth to death.
These traumas result in changes to their physical and mental health and wellbeing.
Animals can even develop depression and posttraumatic stress disorder (PTSD). I’ve written or talked about this fact in my book, in popular science magazines, in academic papers, in Medical Grand Rounds, and in Congressional testimony.
We now know that traumatic experiences and physical and psychological suffering affect the manifestation of multiple diseases. In humans and other animals, traumatic experiences, including family separation, prolonged isolation, and captivity ultimately affect the brain, the heart, the immune system, and virtually every other system of the body.
These problems interfere significantly with the interpretation of laboratory results, and there is no way to reliably correct for these problems in individuals who are sensitive and capable of complex joy and suffering. Animals aren’t tools.
The Future of Modern, Ethical Research
The current paradigm of animal experimentation fails both people and animals.
Fortunately, after horrific research scandals in the US, we now have The Belmont Report to guide human research. The Belmont Report emphasizes key principles, including respect for autonomy, and duties to do good (beneficence), avoid harm (nonmaleficence), and exercise justice.
The Belmont Report provides special research protections for vulnerable populations, including children and individuals who are incarcerated. These ethical advancements have also prompted advancements in science.
My colleagues and I have written (see here and here for examples) about how the time has come for a Belmont Report for animals—a more ethical and just system—to align with advancements in our values and ethics and to stimulate better science.
The adoption of a Belmont Report for animals would essentially eliminate laboratory animal research as we know it, create more effective innovation and progress for humans, and move us forward to a more just research paradigm.
Dr. Hope Ferdowsian is an internal medicine, preventive medicine, and global public health physician and president of Phoenix Zones Initiative.