In the world of biomedical science, we are witnessing a paradigm shift. At Replacing Animal Research, our mission is clear: we want to move away from using animals to model human disease and toward a future built on human biology.

We regularly discuss how we use language in our internal communications meetings, and this week we had an interesting conversation around the meaning of ‘human-relevant’ research.  This phrase potentially has a different meaning to someone working in complex biological research than it would to a non-researcher (such as myself).

When ‘modern’ still means ‘animal’

The most common umbrella term used today is NAMs (New Approach Methodologies). To add confusion, NAMs has also been used to describe ‘Non-Animal Methods’, alongside a similar phrase, NATs (Non-Animal Technologies).  However, the definition has blurred. Today, many researchers and organisations use ‘NAMs’ (New Approach Methodologies) to include any modern, high-tech research method, including animal-based models.

Then there are other terms that are used to describe methods based on human biology, these include human-relevant, human-centred, human-based, and human-specific.

These terms seem to me, and probably to many of you, perfect for describing technologies like organ-on-a-chip, organoids or even computer modelling of the human body. They emphasise that human tissue or data is the central point of reference.

It was therefore interesting to be reminded that in scientific circles, some of these words are used to describe methods that use animals or animal tissue to mimic the response of a human. As an example, in  some scientific literature, ‘human-relevant’ is used to describe:

• Humanised Mice: These are mice genetically engineered to carry human genes or injected with human stem cells. Scientists call them human-relevant because they contain human biological components, yet the overall system remains that of a rodent.

• Genetically Modified Pigs: Because a pig’s organs are similar in size to a human’s, they are frequently described as ‘human-relevant’ for heart research or organ transplantation (xenotransplantation) studies.

• Non-Human Primates (NHPs): Due to their close evolutionary proximity to us, monkeys are often cited as the ultimate ‘human-relevant’ model for researching complex brain disorders.

Human derived vs human relevant

To put this into context, we need to think about scientific research in terms of models. Any research to benefit our knowledge of human-biology or human disease can be gained directly from humans, or by using a research model to mimic the human body or a response. Cells, Organ-on-chip, computer simulations, and animals can all therefore be a ‘model’ of the human body.

After the communications meeting, I read around and found an interesting article that argues that ‘human-derived’ does not mean ‘more predictive’, ‘validated’ or even more ‘human-relevant’ than an existing animal model. The author gives examples of modern models that use human-derived cells and organoids, which are immature, lacking complexity or unvalidated  (meaning the model has not gained regulatory approval for safety tests or it has not been sufficiently used by others to show it is a reproducible model for research purposes).

He has a point. Many cell-based models are still in development and do not (yet) accurately model the human body, but that does not mean they have no use; it is very dependent on the research question, the data needed,  and the accuracy of the specific elements of the model that are needed to answer it. These models may not yet be ‘validated’ because they are new. The animal models they replace, or may replace, have been around for years and likely have more evidence behind them. But many of these lack accuracy or high levels of translation (to predict outcomes in people). So, we should not be comparing new, human-specific models to previous animal models, but to the human condition. . Animal models should not be the ‘gold-standard’ just because they have been around a long time.

The one point some articles miss when comparing alternative, non-animal models in development to existing animal models, is the context. This must all be viewed and discussed through the lens of ‘replacement’. We live in a world where it is mandated from the highest level that we need to be avoiding and replacing animal use with ‘scientifically satisfactory’ alternatives, regardless of how well established the animal models are.  This might take a bit of effort and thinking outside the box to achieve, but that is kind of the point.

I understand why an animal ‘model’ with a relatively high predictivity for human responses may be considered a ‘human-relevant model,’ but it still feels disingenuous to call a mouse ‘human-relevant’ because it carries a human gene.

Good science without animals

Ultimately, we are working towards better science, without animals. So, when we use ‘human-relevant’ at Replacing Animal Research, we aren’t talking about using an animal to model the human body. We mean:

Human-derived: Based on human cells, tissues, and data (such as Organ-on-a-Chip or AI-driven human data modelling).

Non-animal: Research that does not rely on animals, animal tissue, or animal-derived products (like Foetal Bovine Serum).

The terminology may change, but to us, this is the gold standard.  

What do you think about the term ‘human-relevant’? How do you perceive it? How do you use it? Leave us a message.