The 5% Problem: How the Biomedical Community Responded to the Animal-to-Human Translation Crisis, and the Case for...

Area of Science:

• Biomedical Research
• Translational Science
• Drug Development

Background:

• A 2024 analysis revealed only 5% of animal-tested therapeutics gain human approval, reigniting debate on animal model predictivity.
• This review examines scientific interpretations of this finding and the evolving consensus on animal model validity.

Purpose of the Study:

• To analyze how the scientific community has responded to the low translation rate of animal models.
• To identify the emerging collective position on the utility of animal experimentation in therapeutic development.

Main Methods:

• A comprehensive literature search of public citation indexes for studies citing a key 2024 analysis.
• Classification of cited literature into five categories: defenses, critiques, methodological analyses, author's position, and non-animal method development.
• No new animal data were generated.

Main Results:

• Efforts to bolster animal study validity often decreased their translational signal.
• The low translation rate was consistent across diverse disease areas.
• Even proponents of animal models acknowledged poor translation, advocating for context-specific use.
• Non-animal methods (organoids, organ-on-chip, computational models) were frequently reported as superior to animal models.

Conclusions:

• Converging scientific, ethical, economic, and regulatory arguments support a proactive shift to human-relevant research methods.
• Deferring the transition to human-relevant methods is no longer justifiable.