Copyright
©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
Decoding Alexander the Great’s gastrointestinal cause of death using artificial wisdom: An artificial intelligence-human inquiry into a medical mystery
An-Lai Zhou, Joelle Yee-Hui Chiang, Kai Siang Chan, Nicole Tan, Vishal G Shelat
An-Lai Zhou, Department of General Medicine, Tan Tock Seng Hospital, Singapore City 308433, Singapore
An-Lai Zhou, Joelle Yee-Hui Chiang, Kai Siang Chan, Vishal G Shelat, Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore City 308232, Singapore
Joelle Yee-Hui Chiang, Department of General Surgery, Singapore General Hospital, Singapore City 169608, Singapore
Kai Siang Chan, Vishal G Shelat, Yong Loo Lin School of Medicine, National University of Singapore, Singapore City 117597, Singapore
Nicole Tan, Faculty of Medicine, Monash University, Melbourne 3800, Victoria, Australia
Vishal G Shelat, Department of General Surgery, Tan Tock Seng Hospital, Singapore City 308433, Singapore
Co-first authors: An-Lai Zhou and Joelle Yee-Hui Chiang.
Author contributions: Zhou AL and Chiang JYH contributed to data acquisition, analysis and interpretation, and manuscript writing; Tan N contributed to data acquisition, analysis and interpretation, and manuscript drafting; Chan KS contributed to data analysis and interpretation, manuscript drafting, critical revisions, and final approval; Shelat VG conceived and designed the study, and contributed to data interpretation, critical revisions of the manuscript, and final approval.
Institutional review board statement: This study does not involve human participants or human data and hence do not require institutional review.
Informed consent statement: This study does not involve human participants or human data and hence do not require informed consent.
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
STROBE statement: The authors have read the STROBE Statement—a checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-a checklist of items.
Data sharing statement: This project does not involve any data or its sharing with any parties or persons.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: An-Lai Zhou, MD, Doctor, Department of General Medicine, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, Singapore City 308433, Singapore.
zhouanlai99@gmail.com
Received: July 7, 2025
Revised: August 4, 2025
Accepted: October 27, 2025
Published online: December 14, 2025
Processing time: 156 Days and 19 Hours
BACKGROUND
ChatGPT was developed in November 2022 with studies showing its impressive performance in academic examinations, serving as a promising tool to answer questions even on controversial topics. Artificial intelligence (AI) achieving surface-level performance does not necessarily equate to a deep understanding of human cognition. The development of artificial wisdom, therefore, necessitates a shift from simply mimicking intelligent behavior to modeling the underlying mechanisms of human wisdom, including emotional understanding, ethical considerations, and contextual awareness. Several theories exist behind the death of Alexander the Great, but no definitive conclusion has been made.
AIM
To evaluate whether a hybrid approach, combining generative AI (ChatGPT) with human clinical judgment, can meaningfully reassess the cause of death of Alexander the Great.
METHODS
This is a cross-sectional study using ChatGPT (version 4 Pro). A search was performed with search terms describing the symptoms experienced by Alexander the Great and possible causes of his death: West Nile virus (WNV) encephalitis, poisoning, acute pancreatitis due to excessive alcohol consumption, typhoid fever, and malaria. The historical data and symptomatology were analyzed, weighing evidence and context in a manner akin to human wisdom.
RESULTS
The most likely cause of death of Alexander the Great, as generated by ChatGPT, was typhoid fever complicated by Guillain-Barré syndrome (GBS). The hypothesis was based on the alignment between Alexander’s reported symptoms, such as prolonged high fever, severe abdominal pain, neurological decline, and the known clinical presentation of typhoid fever. However, after carefully reviewing the sources mentioned by ChatGPT, many did not back up the idea that typhoid caused GBS and instead pointed to Campylobacter jejuni as the more likely trigger. Other possible causes of death suggested by ChatGPT including acute pancreatitis from excessive alcohol consumption, infectious causes (WNV encephalitis, malaria), and poisoning were less likely.
CONCLUSION
While ChatGPT initially concluded typhoid fever with GBS as the most plausible cause of death, expert reappraisal of the sources and pathophysiology suggested that C. jejuni-associated GBS was more likely. This study exemplifies how incorporating AI’s pattern recognition with human scrutiny can yield responsible interpretations of historical records.
Core Tip: While ChatGPT is an impressive tool, its conclusions still require human validation. Although ChatGPT identified typhoid fever with Guillain-Barré syndrome (GBS) as the most likely cause of Alexander the Great’s death, cross-checking both the available literature and the sources cited by ChatGPT revealed that Campylobacter jejuni, a more common and well-established cause of GBS, better fits the clinical and historical presentation. This study shows how artificial wisdom, which combines artificial intelligence with human judgment, can support more contextually accurate interpretations in historical medical investigations.
