How Organoids and AI Are Replacing Animal Testing

Back to the Future

Humanity’s relationship with animals began long before formal science. As early as 17,000 years ago, cave paintings in places like Lascaux, France, suggest that early humans carefully observed the animals they lived alongside. Instead of idle sketches they may have been an early form of biological recording. While hunting, early humans gained comparative anatomical insights, laying rudimentary foundations for medicine and survival.

Lascaux painting. Сourtesy of Prof Saxx—Public Domain

Over the millennia, ancient civilizations like Egypt and China began cataloguing natural remedies, many derived from animals, though without clear records of systematic testing. Nevertheless, experimentation likely occurred. In Egypt, the Ebers Papyrus listed hundreds of animal-based treatments. Later in Greece, Aristotle was acknowledged as the first to elevate mere observation into controlled manipulation of animals. An ancient Greek philosopher turned physician Galen later conducted primitive therapeutic trials on roosters and twelve centuries later a famous Arab surgeon Ibn Zuhr tested surgical techniques on animals before applying them to humans.

• With the First Industrial Revolution (circa 1760–1840), economic expansion fueled a surge in human and animal welfare—and scientific curiosity. Tools like the stethoscope and blood pressure gauges emerged alongside medical physiology. Animals (dogs, pigs, and rodents) became subjects of these technological inquiries.
• The Second Industrial Revolution (late 19th to early 20th century) underlined a milestone change. The growth of the synthetic chemistry industry demanded rapid screening of compounds, spurring the systematic use of animals as human surrogates. Safety, efficacy, and mechanism of action all required preclinical animal studies. This era birthed toxicology and pharmacology, and with it, specialized institutions and companies dedicated to breeding research animals.
• Post–World War II science expanded into what some call the Third Industrial Revolution. In this period, in vivo and later in vitro tissue animal testing became deeply embedded in drug development and biomedical research. Rodents, dogs, cats, and rabbits populated labs, powering advances in endocrinology, toxicology, pathology, and more.
• By the 1980s, animal bioassays proliferated thanks to improved surgical techniques, telemetry, and miniaturization of sensors. Newly introduced conscious, acclimated animal models replaced anesthetized ones.

Yet, despite progress, a recurring question remained whether animals could truly predict human outcomes.

In the 1970s and 1980s, the molecular revolution began to reshape biomedical research. Scientists pivoted from whole-animal models to molecular and cellular systems. DNA sequencing, target-directed drug discovery, and in vitro assays began replacing traditional bioassays. This reflected a transition from phenotype-based observation to mechanism-driven testing.

Then, the 21st century resulted in the Fourth Industrial Revolution in life sciences, driven by genetics. Following the Human Genome Project and the rise of CRISPR and other gene-editing technologies, genetically altered (GA) animal models spiked in use. Mice, rats, and fish became instrumental in modeling human diseases, enabling scientists to insert human genes and disease mutations for study. These models helped refine drug targets and reduce the need for prolonged toxicology studies, especially via specialized strains like the P53 knockout mouse.

Beginning with the formation of 19th-century animal protection societies, the movement culminated in the 1966 US Laboratory Animal Welfare Act and similar international laws introducing formal oversight.

With the introduction of the 3Rs—Replacement, Reduction, and Refinement—ethical standards became embedded in biomedical research. But new technology brought paradoxes—while molecular tools and in silico computational models reduced animal use, GA technology increased it, albeit in different species and for more targeted purposes.