We urge the UK Government to include sepsis as a priority topic in its strategy to phase out animal testing.
Sepsis kills more people in the UK annually than breast, bowel, and prostate cancer combined and affects tens of millions worldwide.1–3 Yet, despite decades of experiments using animals, targeted and effective treatments remain elusive. Indeed, hundreds of drugs that work in animals have proven ineffective in humans.4 With sepsis costing the UK an estimated £7.4–15.6 billion each year,5 there is an urgent need for effective therapies.
It is now widely recognised that sepsis models using animals poorly replicate human sepsis. Mice, for example, require large bacterial loads – much larger than loads detected in human patients – to trigger an inflammatory response. These large bacterial loads trigger an acute inflammatory response in mice, which directly contrasts with the milder, more prolonged inflammatory response observed in human patients.6–8 Crucial features of human sepsis, such as changes in blood pressure and flow, are absent in mice.8 Even the widely used caecal ligation and puncture method is flawed; outcomes vary with age, sex, strain, and technique, compromising reproducibility and cross-laboratory comparisons.7–11
External variables further undermine validity. Animals used are typically young, inbred, and kept in sterile conditions, while human sepsis affects genetically diverse populations, often infants, the elderly, and those with underlying conditions, living in unsterile environments.6,7,12–14 Moreover, animals often receive no supportive care, including fluids, pain relief, or ventilation, which are standard when treating humans.8,9,12,13 Untreated pain alters physiology, reducing model relevance.15,16 These studies also cause immense suffering. Animals endure pain, fever and organ failure before they are killed.
Recognising these issues, US agencies are already phasing out the use of animals to model human sepsis.17–20 The UK must not be left behind. The Government’s strategy to phase out animal testing presents a golden opportunity to accelerate the transition to human-relevant approaches in sepsis research.
We, the undersigned, urge the UK Government to align with scientific evidence and international progress by phasing out the use of animals to model human sepsis. To achieve this, we strongly encourage the inclusion of clear objectives and timely milestones in the UK strategy to end sepsis-induction experiments using animals and investment in superior non-animal methods that reflect the human condition.
References
1. Burki TK. Sharp rise in sepsis deaths in the UK. Lancet Respir Med. 2018;6(11):826. doi:10.1016/S2213-2600(18)30382-5
2. The UK Sepsis Trust. References & Sources. The UK Sepsis Trust. Accessed 21 August 2025. https://sepsistrust.org/about-sepsis/references-sources/
3. Rudd KE, Johnson SC, Agesa KM, et al. Global, regional, and national sepsis incidence and mortality, 1990–2017: analysis for the Global Burden of Disease Study. Lancet. 2020;395(10219):200-211. doi:10.1016/S0140-6736(19)32989-7
4. Collins F. Of mice, men, and medicine. NIH Director’s Blog. Published 19 February 2013. Accessed 21 August 2025. https://web.archive.org/web/20250218132403/https:/directorsblog.nih.gov/2013/02/19/of-mice-men-and-medicine/
5. Hex N, Retzler J, Bartlett C, Arber M. Whitewater Charitable Trust: The cost of sepsis care in the UK, final report. The UK Sepsis Trust. 2017. Accessed 21 August 2025. https://sepsistrust.org/wp-content/uploads/2024/11/YHEC-Sepsis-Report-17.02.17-FINAL.pdf
6. Verma S. Laboratory animal models to mimic human sepsis: a review. Res Rev J Zool Sci. 2016;4(2):1-6. http://www.rroij.com/open-access/laboratory-animal-models-to-mimic-human-sepsis-a-review-.php?aid=73496
7. Rittirsch D, Hoesel LM, Ward PA. The disconnect between animal models of sepsis and human sepsis. J Leukoc Biol. 2007;81(1):137-143. doi:10.1189/jlb.0806542
8. Buras JA, Holzmann B, Sitkovsky M. Animal models of sepsis: setting the stage. Nat Rev Drug Discov. 2005;4(10):854-865. doi:10.1038/nrd1854
9. Ward PA. New approaches to the study of sepsis. EMBO Mol Med. 2012;4(12):1234-1243. doi:10.1002/emmm.201201375
10. Ruiz S, Vardon-Bounes F, Merlet-Dupuy V, et al. Sepsis modeling in mice: ligation length is a major severity factor in cecal ligation and puncture. Intensive care Med Exp. 2016;4(1):22. doi:10.1186/s40635-016-0096-z
11. Joffre J. Preclinical model in sepsis: should we abandon the CLP? [Letter]. J Inflamm Res. 2023;16:1757-1759. doi:10.2147/JIR.S415972
12. Fink MP. Animal models of sepsis. Virulence. 2014;5(1):143-153. doi:10.4161/viru.26083
13. Esmon CT. Why do animal models (sometimes) fail to mimic human sepsis? Crit Care Med. 2004;32(5 Suppl):S219-22. doi:10.1097/01.ccm.0000127036.27343.48
14. Laudanski K, Stentz M, DiMeglio M, Furey W, Steinberg T, Patel A. Potential pitfalls of the humanized mice in modeling sepsis. Int J Inflam. 2018;2018:6563454. doi:10.1155/2018/6563454
15. Bara M, Joffe AR. The ethical dimension in published animal research in critical care: the public face of science. Crit Care. 2014;18(1):R15. doi:10.1186/cc13694
16. Nemzek JA, Hugunin KMS, Opp MR. Modeling sepsis in the laboratory: merging sound science with animal well-being. Comp Med. 2008;58(2):120-128.
17. Hays A. Major health agency slashes funding for sepsis experiments on animals after push from PETA. PETA. Published 18 June 2024. Accessed 21 August 2025. https://www.peta.org/blog/major-health-agency-slashes-funding-for-sepsis-experiments-on-animals/
18. Trunnell ER. Breaking: human-based research takes center stage at NIH. Science Advancement and Outreach (PETA). Published April 2025. Accessed 21 August 2025. https://www.scienceadvancement.org/reflections/human-based-research-takes-center-stage-at-nih/
19. PETA. PETA applauds end to cruel sepsis experiments on beagles, vows continued pressure to end all sepsis experiments on animals: PETA statement. PETA. Published 5 May 2025. Accessed 21 August 2025. https://www.peta.org/media/news-releases/peta-applauds-end-to-cruel-sepsis-experiments-on-beagles-vows-continued-pressure-to-end-all-sepsis-experiments-on-animals-peta-statement/
20. US Food and Drug Administration. Roadmap to reducing animal testing in preclinical safety studies. US Food and Drug Administration. Published 10 April 2025. Accessed 21 August 2025. https://www.fda.gov/files/newsroom/published/roadmap_to_reducing_animal_testing_in_preclinical_safety_studies.pdf