Will organ-on-chip replace animal testing?

An opinion piece by Dr. Martin Raasch CEO and co-founder of Dynamic42 in light of recent announcements by the FDA and NIH.

Will advanced in vitro models such as organ-on-chip replace animal testing? A question that has been asked before but has increased in relevance with recent announcements in the U.S. and the publication of a pro-animal testing campaign in Germany.

On April 10th 2025 the FDA announces to replace animal testing in the development of monoclonal antibody therapies and other drugs with more effective, human-relevant methods.

Just a few weeks later, on April 29th, this was followed by the National Institutes of Health (NIH) announcing to prioritize human-based research technologies and reduce animal use in NIH-funded projects.

Meanwhile in Germany more than 100 German scientists, publicly declare in the magazine SPIEGEL on April 24th, their support for animal experiments. They call for a clear separation of animal testing and agriculture in the Animal Welfare Act and emphasize the necessity of animal testing in basic research, especially for complex diseases such as epilepsy and cancer. They say that despite advances in alternative methods such as cell cultures and AI, animal testing remains essential for understanding complex organisms and drug safety.

There are several aspects in the discussion that need critical reflection. Here is just some exemplary food for thoughts without any claim to completeness:

• • In contrast to pharmaceutical drug development, basic research is not obliged to test on animals.
  • Cancer research has one of the highest failure rates when it comes to transferring preclinical candidates to clinical settings. Here, up to 95 % fail after showing promising results in animals. Argumentation does not add up with the numbers we see. Just more animal testing in that area will not cure cancer.
  • Besides the scientists that signed the article, there are different opinions within the scientific community on the subject of animal testing. The article and number of supporting researchers could give the impression that there is a broad consensus, which is not the case.
  • The debate is missing focus on longterm developments. The opinion piece and the positioning could give the impression that it sticks to short-term solutions and does not sufficiently promote innovative research into alternative methods.

We observe this not just in Germany. The debate is often polarised, missing out on diverse perspectives and being perceived as a simple either or decision. However, to move forward, we need to see that a hybrid phase is the natural progression (3Rs).

Even when looking at the announcement made by the FDA, the plan isn’t to remove animal experimentation from the equation but rather act according to the 3R principle to replace, reduce and refine. In detail, it states “The FDA’s animal testing requirement will be reduced, refined, or potentially replaced using a range of approaches…”. Such methods will include AI-based computational models, New Approach Methodologies (such as organ-on-chip) as well as pre-existing safety data from other countries.

So should we instead of asking “Will organ-on-chip replace animal testing?” rather ask “How can we make drug testing safer and advance biomedical research?”.

While this title isn’t clickbait, I believe it effectively captures the essence of the situation. Scientist should be able to choose the system that provides them with the results that are most relevant to their research. The reality is that animals, despite resembling a very complex system, are not always human relevant and results in fact can be harmful when used for toxicity testing for humans.

So, when can organ-on-chip systems be used instead of animals?

Ethical considerations

• • Organ-on-chip systems can replace animals when testing on humans or animals is ethically unfeasible.

Industry applications

• • Pharmaceutical companies can use organ-on-chip systems to test drug efficacy, dosage, and toxicity.
  • Cosmetic industry, consumer products as well environmental toxins

Research applications

• • Research that involves the human immune system, esp. inflammation and infection
  • Research that focussed on very specific questions, involving one or only few organs, pathways, certain gene or protein functions particularly if they are not conserved in animals
  • Studies on rare human diseases where animal models do not accurately replicate the condition
  • Personalized medicine research, using patient-specific cells to predict individual drug responses
  • Investigating human-specific pathogens and diseases that do not infect animals similarly
  • Studying the blood-brain barrier and neurological disorders where animal models fall short
  • Assessing the chronic effects of drugs and chemicals over extended periods without ethical constraints

So generally speaking, organ-on-chip systems can replace animals whenever a specific research question doesn’t require the full complexity of a living organism.

The question remains, can organs-on-chip truly replace animals? The answer is currently no, as long as we can’t create a whole body-on-chip that links all the organs, incorporates a complex immune system, microbiome, and other crucial bodily components. This is a vision for the future. However, if we ask, “Can we reduce animal experiments?”, the answer is certainly yes. Not just for the sake of having fewer animals used in research, but also to reduce the financial, ethical and administrative burden on scientists, and ultimately to produce more human-relevant results.

And, eventually, every transition goes along with a decision to let go of what’s become obsolete…

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