Advocacy for Adequate Translational Surgery in Large Mammals Open Access

Year 2035. Since the historic vote by European deputies in June 2025 banning the use of animals for scientific purposes – an initiative that had been narrowly rejected in 2021 [1], the landscape of European medical research has suffered a profound decline. Governments of the EU member states, the European Economic Area, Switzerland, and the UK have drastically reduced their investments in medical research, succumbing to the lobbying pressures and mandates of anti-animal experimentation organisations. The shift had already begun in 2025, initiated by the policies of the former US administration between 2025 and 2029, which radically dismantled funding for experimental research deemed “painful, bizarre, and wasteful” [2]. The EUR 50 tax per animal used for scientific purposes, initially implemented by European legislators in 2025 based on a French initiative [3], proved insufficient to satiate the ambitions of the anti-experimental research movements.

For nearly a decade now, major pharmaceutical companies have relocated their translational research to Asian countries with more lenient animal ethics regulations and less stringent adherence to the 3R principle. While the data produced are meticulously scrutinised, their reproducibility can no longer be verified due to the impossibility of access to animal models. Meanwhile, smaller companies have simply ceased to exist, unable to adapt to the shift toward “100% alternative methods.” Predicting interactions between different physiological systems using only organoids or microchips remains challenging despite the power of artificial intelligence; assessing new surgical medical devices on Drosophila or C. elegans – still exempt, for now, along with other invertebrates, from the ban on scientific use [4] – is impractical; and developing innovative drugs without in vivo evaluation is nearly impossible.

For the first time in over a century, international studies have, over the past 2 years, documented a decline in human life expectancy by an average of 3 years, attributed to the absence of novel therapies reaching the market. We must face reality: medical knowledge has reached a glass ceiling, and future research cannot progress as it did through the first quarter of this century. Certain diseases have been treated to the fullest extent possible, and emerging conditions will no longer be manageable with newly screened drugs. It is now impossible to adequately train future surgeons in in vivo operative techniques; their first experience will be on actual patients. The last COVID-29 pandemic, caused by SARS-CoV-3, struck exactly a decade after the 2019 outbreak, resulting in approximately 70 million deaths worldwide [5], ten times the toll of COVID-19. This catastrophe could not be averted, despite a 4-month global lockdown in 2030, due to the inability to develop a vaccine validated in a preclinical model.

Back to 2025. At the time of writing this editorial, the dystopian scenario outlined above has not (yet) materialised. The objective is not to incite fear or pessimism but to raise awareness of the critical risks associated with the complete eradication of preclinical research aimed at advancing future medical care. In this collection of three review articles, we explore the undeniable value of large mammal models in translational surgical research – a methodology that has already demonstrated its worth, as evidenced by the number of Nobel Prizes in Medicine and Physiology awarded in this field (43 out of 97 involving large mammal research, with nearly all laureates having relied on animal models) [6].

Our editorial focus centers on the three primary large mammal species utilised in 2025 (Fig. 1): non-human primates, pigs, and sheep (excluding small mammals such as rodents and rabbits by default). Dogs will also not be discussed, as ethical considerations have now largely precluded their use in translational surgical models. Each species presents specific advantages and limitations in translational surgery. Non-human primates (NHPs) are employed as a last resort when other species fail to yield optimal results (e.g., in neurosurgery, where their anatomy closely resembles that of humans). Pigs have limited utility in perinatal surgery but are highly valuable in digestive and endocrine surgery (particularly minipigs), cardiovascular surgery, and surgical training. Sheep have demonstrated significant translational value in orthopedics and reproductive surgery but hold little relevance in digestive or respiratory surgery.

Regardless of the model chosen, three fundamental principles must be meticulously adhered to by any responsible researcher:

• 1.

  Alternative methods must always be prioritised before resorting to animals for scientific purposes.

• 2.

  Preclinical research should only be conducted on animals if human studies are unfeasible – extensive clinical research must be thoroughly reviewed to prevent redundancy in experimental findings.

• 3.

  When animals are used for scientific purposes, they must be employed strictly in accordance with the universal 3R principle as suggested by Russel and Burch (Replacement, Reduction, and Refinement).

Thus, in 2025, animal models for surgical research still hold a critical place, in the absence of viable alternatives. The porcine surgical model has demonstrated its significant value in preparing surgical and para-surgical personnel for mass casualty scenarios related to terrorism. During the COVID-19 pandemic of 2020–2021, surgical students were able to continue honing their technical skills through animal models when non-urgent clinical procedures were suspended to prioritise intensive care management. In 2025, ChatGPT does not (yet) replace real-time surgical hemorrhage management; the pig, however, does [7].

Not to mention the highly probable emergence of xenotransplantation (which will be largely discussed in the review articles), which remains in its infancy today, much like the first human-to-human heart transplant performed in 1967 by Claude Barnard, where the first graft recipient survived only 18 days, compared to the current median survival of 12.5 years [8].

We must harness the strengths of large mammals in translational surgery wisely, fostering collaboration between preclinical and clinical researchers. Let us strive to advance medicine and surgery against all odds if we wish to prevent the decline of humankind. Let the scenario of 2035 – tomorrow – remain fiction.