Last November, the UK government announced a bold plan to phase out animal testing in certain areas of research. Animal testing to detect skin irritations should be phased out this year, and some dog studies should be scaled back by 2030. The long-term vision is “a world where the use of animals in science is eliminated except in exceptional circumstances,” the government policy states.
Other countries are taking similar measures. Last April, the U.S. Food and Drug Administration (FDA) announced plans to make animal studies “the exception rather than the norm” in drug safety and toxicity testing within 3 to 5 years. That same month, the US National Institutes of Health (NIH) unveiled an initiative to reduce the use of animals in the research it funds. This year, the European Commission plans to publish a roadmap for ending animal testing in chemical safety assessments.
Concerns about ethics and animal welfare have long fueled efforts to limit the use of animals in research – and rapid advances in alternative scientific methods are now accelerating this change. These “new approach methodologies” (NAM) include devices called organs-on-chips, 3D tissue cultures called organoids, and computer models, such as artificial intelligence systems. The number of biomedical publications using only NAMs increased from around 25,000 to 100,000 between 2006 and 2022, according to an analysis of studies on seven diseases by Animal Free Research UK, an organization that promotes the replacement of animal testing. And China is investing heavily in this area: in 2024, it launched the Human Organ Physiopathology Emulation System, an infrastructure project dedicated to the development of NAMs, supported by an investment of 2,640 million yuan ($382 million).
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Proponents say NAMs may be better than animals at mimicking human biology and predicting whether new drugs are safe and effective. Organs-on-chips and organoids are often created with human cells, and computer models can be designed using human data. The move to alternative models is “long overdue,” says Donald Ingber, a bioengineer at the Wyss Institute for Biologically Inspired Engineering in Boston, Massachusetts, and co-founder of Emulate, a Boston biotechnology company specializing in organs-on-chips.
But NAMs are far from ousting all animal procedures in research, scientists say. Some biological systems are too complex and unpredictable to study without animals. And many of the alternative methods still need to be validated – to show that they represent the system they are modeling accurately and reproducibly enough to satisfy drug and chemical regulators. “Not all that [alternative] the models are ready for prime time,” says Ingber.
In decline
Efforts to replace, reduce, and refine the use of animals in research (known as the “3Rs”) have been growing for decades; in some places, animal use is already declining. UK data show that the number of scientific procedures on animals increased from 4.14 million in 2015 to 2.64 million in 2024. The total number of animals used in research and testing in the European Union and Norway fell by 5% between 2018 and 2022. (The number used in the United States is difficult to pin down because the law does not require reporting on rats, mice, and fish.)
In the UK, around 76% of animal experimental procedures are for basic and applied research: understanding organisms, modeling diseases and developing new therapies. Another 22% participate in regulatory procedures – primarily testing the toxicity and safety of new drugs and other chemicals before they can be used. About 67% of all procedures involve mice or rats (see go.nature.com/3mzfkgw).
But these and other animals have limits, particularly when it comes to understanding and intervening in human diseases. Drugs that work in animal models in preclinical trials often prove ineffective in humans. This is one of the main reasons why around 86% of experimental drugs fail in clinical trials, and why many researchers are focused on developing alternatives.
Take for example sepsis, a serious reaction to an infection. Researchers have developed more than 100 sepsis therapies that showed promise in rodent models but proved ineffective in clinical trials. This is due in part to differences between the immune systems of humans and rodents and the difficulty of mimicking a complex disease that varies from person to person in genetically similar inbred mice raised under uniform conditions.
Increasingly, researchers are considering NAMs as a way to help. Joseph Wu, a cardiologist and researcher at Stanford University in California, and his team developed an approach they dubbed “clinical trials on a plate.” This involves generating induced pluripotent stem cells (iPSCs) from a range of people with a health condition, using them to grow cells or organoids, and then testing whether potential drugs improve the functioning of the “diseased” models.
In a 2020 study, Wu and his team grew iPSCs and then endothelial cells — which line blood vessels — from family members carrying a mutated gene that can cause a common form of heart failure. Using these cells, researchers were able to screen possible drugs and identify one that would help improve the cardiovascular function of two family members with the mutation and could be used more widely. According to Wu, integrating this method into a drug development pipeline could help reveal whether a drug works before animal testing, reduce the number of animals used, and increase the success of clinical trials.
Studies suggest that some NAMs are as good as, or better than, animal testing. Emulate has developed an organ-on-a-chip system called Liver-Chip, a device the size of a USB drive in which human liver cells are grown in tiny fluid-filled channels and used to test whether potential drugs could cause liver damage. A 2022 study by the company suggested that the chips could correctly identify compounds known to have caused liver damage with 87% accuracy, without falsely flagging harmless compounds as toxic. The chips also detected 12 of 15 liver-damaging drugs that were previously, using animal models, deemed safe enough to proceed to clinical trials.
In 2024, Liver-Chip was accepted into the FDA’s Innovative Science and Technology Approaches for New Drugs (ISTAND) pilot program, which supports the advancement of tools for drug development. If approved, pharmaceutical companies could use the chip to test for toxicity in place of animal models and submit the data as part of a drug approval application.
These chips, however, are highly specialized. Edward Kelly, a toxicologist at the University of Washington in Seattle, and colleagues have developed a kidney chip capable of replicating some aspects of acute kidney injury in humans and is currently being considered for the ISTAND program. But the device includes only one of the kidney’s more than two dozen cell types, he says. “It’s a reductionist approach, which allows us to study these cells in more detail. But understanding what’s happening in the whole human kidney still requires animal studies,” he says.
Organoid options
Another popular alternative to animal testing is organoids: 3D living systems that capture many features of real tissues or organs.
Over the past decade, researchers have created a wide range of organoids which can model human diseases, including cancers and genetic disorders such as cystic fibrosis, and has used them to research possible drugs and test their toxicity. In a 2021 study, researchers generated human liver organoids using iPSCs. They used them to create a toxicity screening tool that detected substances that hindered bile transport and mitochondrial function in the organoids. The test was found to be highly accurate when tested on 238 marketed drugs.
And a third alternative is computer models, in which researchers test how a drug behaves. in silico. In 2021, a team developed a tool to test whether a compound causes skin sensitization – an allergic reaction in humans. It is a standard part of safety testing of chemicals in industrial and household products and medicines, and usually requires animal testing. The team built a virtual test using data on about 430 chemicals from previous studies in humans, mice and labs, and showed that they could accurately identify chemicals with a 1% chance of causing a skin reaction. The tool was accepted as an approach for skin allergy testing last year by the Organization for Economic Co-operation and Development, which establishes internationally recognized guidelines for chemical safety testing.
Researchers hope AI can also help. Several regulatory agencies, including the FDA and the European Medicines Agency (EMA), are working to integrate AI tools into their chemical or drug safety assessment pipelines.
In 2023, researchers at the FDA’s National Toxicology Research Center in Jefferson, Arkansas, and their colleagues used clinical data on more than 8,000 rats treated with 138 compounds to create a generative AI model called AnimalGAN. In a simulated experiment involving 100,000 virtual rats, the team showed that the model could correctly classify the liver toxicity of three drugs with similar chemical structures. This approach is now part of a broader agency program to advance the use of AI tools in toxicology.
The pharmaceutical industry is increasingly investing in NAMs. Marianne Manchester, Global Head of Pharmaceutical Sciences at multinational pharmaceutical company Roche in Basel, Switzerland, says the company is conducting a growing number of studies using NAMs to test drug candidates in areas such as oncology and immunology. In 2023, the company launched the Institute of Human Biology, which develops human model systems, including organoids, to accelerate drug development. Animal data is still required for most new drug applications in the United States and Europe, but the company has waivers to use NAM data for 12 submissions to regulatory authorities, including the FDA and EMA, Manchester says. “There’s a lot more openness to considering these alternative approaches. »
Step-by-step approach
The UK and US government announcements for 2025 contained various commitments to accelerate the development and adoption of NAMs. The British government’s strategy — in line with other political and business groups — defined three “baskets” of animal testing and targets for their replacement.
The first encompasses tests that can be quickly phased out because good substitutes exist, such as skin irritation tests which are to be abandoned this year in favor of computer, cellular or chemical tests.
The second includes procedures, the replacement of which will take more time. NAMs in this group include “pharmacokinetic” studies that analyze how the body moves and metabolizes a drug. The government says it will reduce such testing of dogs and non-human primates by at least 35% by 2030. The third basket, consisting of methods for which there are no good alternative methods, contains only one example: the use of fish to test for endocrine disrupting substances in environmental testing. (In this case, the goal is to develop alternative methods by 2035.)
As part of its April announcement, the FDA has published a roadmap reduce, refine and replace animals in drug testing. The program will initially focus on this approach to testing monoclonal antibodies because, according to the roadmap, animal studies are expensive and cannot predict human responses to these drugs. The NIH, meanwhile, announced last July that it would no longer offer funding opportunities “focused exclusively on animal models of human disease” as part of a broader program to encourage studies of NAMs.
One of the biggest obstacles to using NAMs in drug and chemical testing is validation. Researchers generally must submit data demonstrating that a model system is accurate and reproducible to national and international validation bodies, such as the EU Reference Laboratory for Alternatives to ANI. mal testing or the Interagency Coordinating Committee for the Validation of Alternative Methods in the United States. These help other agencies decide whether a model’s data is sufficient for future regulatory applications.
But this process can be costly and labor-intensive, says Natalie Burden, head of NAM strategy at the National Center for Animal Replacement, Refinement and Reduction in Research in London. And the necessary validation studies may differ from method to method.
The new UK and US strategies all focus on speeding up validation so that data from more alternative methods are accepted by regulators. The UK government said it would create a center for the validation of alternative methods that would link laboratories, policymakers and regulators in pursuit of this goal. Last September, the NIH announced the creation of a Validation and Qualification Network to accelerate regulatory approval of NAMs and announced that it was investing $87 million in a center to develop standardized organoid models.
The growing adoption of NAMs makes rigorous validation essential, says Kent Lloyd, a geneticist and director of the NAMs Testing Center at the University of California, Davis. “If we don’t hold NAMs to the same level of rigor and transparency that we expect from animal models, there will be harm,” he says.
Accelerate adoption
Many researchers have welcomed the latest initiatives to accelerate the adoption of animal-based alternatives, saying these techniques have not been adopted at a fast enough pace. “For years it was always thought that animals should be the priority,” says Valerie Speirs, a cancer biologist at the University of Aberdeen, UK. Speirs, Wu and other scientists expressed frustration with the slow pace of change and argued that peer reviewers and funders always favor articles or grant applications that include animal experiments.
But scientists also have concerns. Some announcements from funders and regulators risk giving the misleading impression that NAMs are more advanced than they actually are, Lloyd believes. And, he adds, drugs fail in clinical trials for reasons other than inadequate animal models. These include small sample sizes or other flaws in the design of animal experiments that can falsely suggest that a potential drug is effective – problems that NAMs can also have. “What concerns me is that there will be as many failures in clinical trials using NAMs as in clinical trials using animal models,” he says.
Some animal studies remain essential for the foreseeable future, researchers say. Biological systems, such as entire organs with complex networks of blood vessels and nerves, interacting endocrine and reproductive systems, or tissue aging, are difficult to recreate and study in organoids or organs-on-chips, says Robin Lovell-Badge, a biologist at the Francis Crick Institute in London.
Human behavior and cognition also remain virtually impossible to model on a laboratory plate, says Sarah Bailey, a neuropharmacologist at the University of Bath, UK. When it comes to understanding the complexity of biology, she says, “we will still need to use animals in fundamental scientific discoveries for some time to come.”
This article is reproduced with permission and has been published for the first time February 25, 2026.