“The Queen has been horribly shocked by the details of some of these animal research practices and is very keen to bring them to an end.”
– Queen Victoria, 1895
Animals have been used throughout history to better understand anatomy, physiology, and medicine; debates on the ethics of animal experimentation have been going on since the 17e Century.
Queen Victoria’s view was countered by Claude Bernard, a French physiologist, in 1865. He argued that animal experimentation was ethical because of the benefits to medicine and human life. Barnard said,
“Animal experiments are completely conclusive for toxicology and human hygiene. The effects of these substances are the same on humans as on animals, with a few differences. »
While we should respect Mr. Bernard as a pioneer of science, in the case of animal testing he was dead wrong.
In 1959, the “three Rs” for animal research were developed and are still used today:
- Replacement (replacement of animal use with alternative research methods)
- Reduction (minimize the use of animals where possible)
- Refining (reduction of suffering and improvement of animal living conditions)
In 2007, the National Research Council of the National Academy of Sciences called for animal testing to be further reduced and recommended the use of new technologies that could eventually eliminate the need for animal testing. Unfortunately, we are very far from achieving this goal.
Animal research, a necessary evil?
The scientific establishment has presented animal testing as a necessary evil where the benefits to human health far outweigh ethical and other concerns.
There has been surprisingly little scientific scrutiny of the effectiveness of animal testing. It is generally supported without critical examination of its validity and a lack of data on how animal experiments predict human outcomes.
The answer is not very good. While there are very well-known cases where animals and humans have reacted similarly to drugs, such as penicillin, there are many others where species responses have differed, for example,
- Isotretinoin (Accutane) caused birth defects in rabbits, monkeys, and humans, but not in rats and mice;
- Corticosteroids cause birth defects in animals, but not in humans, and
- Thalidomide did not cause birth defects in many animal species, but did in humans.
Why the discrepancy?
Laboratory procedures greatly affect the outcome of animal experiments: animals are kept in cages for their entire lives, causing distress and abnormal behavior. This can lead to changes in neurochemistry, gene expression, and elevation in blood pressure and heart rate. In other words, animals are stressed, which can significantly affect test results.
Human diseases are not the same as animal diseases; the experimental animal model does not necessarily reflect the human condition. For example, a drug that showed promise in stroke research in which a set of animal experiments was considered to meet the “gold standard” failed in clinical trials. This has been a recurring theme in drug research – drugs that show promise in animals have no beneficial effects in humans, even after years or even decades of testing.
A 2007 review looked at the outcomes of treating several diseases, including osteoporosis and stroke, as they transition from animal studies to clinical studies. The results were consistent only half the time; in other words, animal studies were no more likely to predict benefit in humans than flipping a coin.
These differences are most likely due to differences between the physiology, behavior, genetics, and pharmacokinetics (the processing of chemicals or drugs in the body) of animals and humans. And these differences are found within the same species. For example, studies have shown that the same strain of rats purchased from two suppliers may exhibit different test results.
why is it important
The problem isn’t just that animal testing isn’t accurate; it can also be harmful to humans. On the one hand, researchers are misled by animal tests that show a drug is safe and effective, and clinical trial volunteers have their hopes dashed when this is not the case in humans. .
Alternatively, drugs may be discontinued due to animal test results that do not apply to humans. An example is Gleevec, a very effective drug for treating chronic myeloid leukemia which has shown liver damage in dogs and serious adverse effects in 5 other species. The drug was reportedly discontinued based on the results of animal testing. It was only allowed to continue clinical trials because results in human cells showed no liver damage.
There are three major alternatives to animal testing that have been developed over the past decades:
- Human cell lines: Cells from the inside of a person’s cheek or skin can be transformed into stem cells, cells that are not fully developed. These stem cells can be cultured and self-renewing in petri dishes and developed into any type of cell under investigation. They also have the genetic fingerprint of the person from whom they were taken, enabling the ultimate in personalized medicine.
- Organoid systems: Human cell lines in Petri dishes do not fully model the diversity of cells and their three-dimensional relationships in our organs. Organoid systems are closer organ models that recreate complex cellular diversity and the actual architecture of the organ. Currently, organoid systems have been developed for the human lungs, intestine, blood vessels, pancreas and brain.
- Computational toxicology: Uses artificial intelligence to analyze chemical structures to predict toxicity, serving as a first pass to identify more promising or threatening chemical structures.
All three of these methods have shown results that surpass traditional animal testing. For example, a recent study used computational methods to define chemical similarity and showed better reproducibility than animal testing. Results from another study using an intestinal organoid model showed how inflammation can disrupt cellular metabolism and contribute to Crohn’s disease.
Obstacles to acceptance
The two main obstacles to the acceptance of alternatives to animal testing are bureaucratic and scientific entrenchment. For science grounding, the good news is that eventually scientists stuck in the old ways will move on and hand it over to a new generation of scientists. The biggest problem is how to speed up regulatory change, move the bureaucracy.
Animal testing is firmly embedded in our regulatory process. The FDA, EPA, and USDA have strict animal testing requirements that have proven remarkably resistant to change. There are some steps in the right direction, but no significant change has occurred. In 2000, the National Toxicology Program established the Interagency Center for the Evaluation of Alternative Toxicological Methods. In 2008, the EPA launched Toxicology in the 21st Century (Tox21), a research center presented as a pioneer in this field. Although the two centers have done many workshops and done some interesting studies, the EPA is still a long way from the goal set by its administrator in 2019 to eliminate animal testing by 2035.
The EPA has not accepted alternatives to animal testing in the regulatory process, except for a change in 2021 that allowed researchers to forego testing chemicals on animal skin in certain circumstances. The FDA doesn’t do much better, only allowing alternatives to animal testing in a few cases in drug development and food safety.
Some scientists believe that we are entering a phase of scientific revolution where the old paradigm of animal testing does not work, but science does not easily abandon its old ways. This is due to the intransigence of those in positions of power in universities, federal agencies and research centers who believe that the techniques they have used all their careers are the only correct ones and should continue to be used. .
Accelerating change is critical for many reasons, including getting more accurate results in a timely manner. Remember that animal studies are time consuming and very expensive. The new methods are accelerating the time in which answers about whether a drug is effective in humans or whether a chemical can harm humans can be obtained. These faster responses will not only result in significant cost savings, but also in saving lives for animals and people.
Sources: The Human Flaws and Harms of Animal Testing
Why animal studies are often poor predictors of human responses to exposure
Alternatives to Animals