Stop sacrificing mice and other guinea pigs in experimentation. A possible future, thanks to new technologies: organ chips, 3D cell cultures, computational models, organoids, artificial intelligence. A pilot project has been started in the USA. In Italy, scientists are ahead (but regulatory issues exist). In the meantime, however, animal testing remains essential
It doesn’t have a name, just a number engraved on a metal earring. It is a laboratory mouse, one of the 365,130 animals used in 2023 in Italy for scientific purposes, according to official data from the Ministry of Health. He lives in a cage, under artificial light, fed at fixed times. Then he is sedated, exposed to a new molecule, and often killed to analyze his liver, kidneys, brain. It seems like the story of Algernon, the brilliant mouse from Daniel Keyes’ novel (Flowers for Algernon). But it is not fiction: it is the daily reality of preclinical medicine, for over seventy years. A reality which, in many cases, also turns out to be scientifically ineffective. This is confirmed by the Ecvam 2025 report from the Joint Research Center (JRC) of the European Commission: «About 90 percent of experimental drugs that pass animal tests fail during clinical trials on humans, mainly due to ineffectiveness or unexpected toxicity».
In the United States, the Food and Drug Administration (FDA), the American regulatory agency, has launched a pilot program financed by Trump: some pharmaceutical companies will be able to start clinical trials based solely on alternative methods to animal testing. They are the so-called NAMs (New approach methodologies): organ chips, 3D cell cultures, organoids, computational models and artificial intelligence. In essence, these are technologies developed during the preclinical phase to simulate the human body in vitro or on the computer, replicating physiological functions and specific cellular responses without resorting to living beings.
A concrete example? The liver chip developed by Emulate Inc., a Boston biotech: a microdevice containing human liver cells, capable of precisely reproducing liver functions. In tests, it achieved 87 percent accuracy in identifying toxic molecules and 100 percent accuracy for safe ones. Unthinkable levels for animal models, which are notoriously inconsistent.
But it’s better not to be dazzled by institutional marketing. «In 2024, around 775 thousand animals were officially used for scientific purposes in the United States» declared Giuliano Grignaschi, general secretary of “Research4Life” and head of animal welfare at the State University of Milan, on the occasion of Biotech Week 2025. «But it is a partial figure, because in the USA, unlike Europe, mice, rats and zebrafish are not registered, despite representing 80-90 percent of laboratory animals. The real number is between 8 and 10 million specimens per year. So no, the USA has not abandoned animal testing.”
The Italian Medicines Agency (Aifa) also maintains a cautious position. «Beware of the American advertising hype: these methodological approaches must be validated and guarantee safety for patients», warns Pierluigi Russo, scientific technical director. «Some of these technologies are like electric car batteries: products that multinationals are ready to sell».
Brussels, at least on paper, has moved. The JRC has published a European roadmap to gradually replace the use of animals in regulatory testing without binding deadlines for member states.
“The European Commission has declared its commitment through political action in the framework of the European Research Area (ERA),” explains an expert from the JRC. «And Horizon Europe will allocate 50 million euros to NAMs in the 2026-27 program».
A pioneer in Europe was the Dutch government, which already in 2016 launched a national plan with billions of investments to become a leader in alternative methods. But, almost ten years later, the finish line is still far away.
According to the JRC, Italy is in a solid position to support the transition towards non-animal approaches. Izsler, the experimental zooprophylactic institute of Lombardy and Emilia-Romagna, is based in Brescia. It is a public body supervised by the Ministry of Health and a national reference center for alternative methods. Cited in the Ecvam report among the most active players, Izsler develops protocols, monitors validated methods and trains scientific operators.
«There is a big difference between basic research and the regulatory field», he explains to Silvia Dotti, veterinary medical director of Izsler and head of the Reference Centre. «In the field of basic and preclinical research, NAMs can already be used, especially in toxicology and chemical risk assessment».
In fact, at Izsler, methods based on three-dimensional cell cultures and 3D printers capable of reconstructing portions of human tissue in vitro are developed. Molecules are tested on these mini-organs, cellular reactions are observed and even molecular alterations are mapped. Without sacrificing a single animal. But as Dotti warns, «in the regulatory context everything becomes complicated: here the methods must be validated at a European level, and the path – between bureaucracy, studies, certifications – is long and very expensive».
The private sector is also in turmoil. At Evotec, a multinational active in the research and development of new drugs, alternative methods are tested, including for example 3D cultures and human stem-derived cells to evaluate the hepatic, cardiac and neuronal toxicity of potential drugs. «We invest around 3 million euros a year, but we need a lot of scientific evidence to demonstrate that NAMs can completely replace animal testing and ensure that regulatory authorities accept them. It will still take a lot of time and a coordinated effort from the scientific community”, Maria Pilla, CEO of Aptuit Verona, one of the group’s largest offices, tells Panorama.
In theory, however, the law is already on the side of the animals. Legislative Decree 26 of 2014, which transposes European Directive 2010/63, requires compliance with the 3R principle, an acronym that stands for Replacement, Reduction, Refinement: that is, replace the animal if possible, reduce its use when necessary and perfect techniques to reduce suffering and stress. In essence, all this translates into an obligation for researchers: before starting experiments on animals, they must demonstrate that they have no better alternatives. And each project must pass the scrutiny of an ethics committee authorized by the Ministry of Health. A legislation designed to “protect sentient animals, which feel pain and fear just like us”, recalls Grignaschi.
It’s a shame that Italy stumbles precisely on the application. «We have introduced absurd bans: we deny the breeding of some laboratory animals, but we allow their use. So we have to import guinea pigs from abroad, stressing them out in transportation. And Europe opened an infringement procedure against us that is still ongoing”, explained Grignaschi.
But it is not just a problem of regulatory coherence. It is political and cultural. «China and India are investing heavily in cutting-edge research», Grignaschi warned. “And a growing number of researchers are migrating to those countries.” The transition is possible, but structural resources and continuity are needed. «Public centers like ours receive funds from the Ministry of Health dedicated to the development of these methods, as required by Legislative Decree 26/2014, and the investment must be constant to guarantee a scientifically valid path over time», explains Dotti.
A timid signal arrived with the 2026 economic budget: article 65 provides for an increase of 10 million per year for experimental zooprophylactic institutes starting from next year.
A breath of fresh air, sure. But intended – states the text – to cover “the increase in the cost of services as well as recurring health emergencies”, not to push the NAMs revolution. Ultimately, caution is justified: this type of chip does not replicate the entire organism, nor does it foresee all the interactions between complex systems. And so, at least for now, Algernon remains in his cage. To do his duty.
