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Jared Diamond proposed that germs, along guns and steel, have shaped our modern world and current pandemic is a good example. But diseases, apart from germs, have also contributed in altering the current of world history, often permanently. A thread....
German Emperor Wilhelm I & chancellor Otto van Bismarck had forged German nation(with Blood and Iron). In contrast, Crown Prince Frederick III and his wife Princess Vicki, daughter of Queen Victoria of UK, were outspoken liberal and admirer of the British constitutional monarchy.
Prince was a chronic pipe-smoker and in 1887 developed hoarseness of voice, which was diagnosed initially as chronic catarrh. However, in spite of various treatment (scrapping of membrane to cauterisation), there was no respite.
Soon a vocal cord growth developed. Team of german surgeons suspected cancer & recommended total laryngectomy. Given the stature of patient, an 'expert' opinion of Dr. Mackenzie (later Sir) of London was sought. He biopsied lesion for microscopy, a novel diagnostic test of era.
Rudolf Virchow, father of the cellular pathology, was known for his expertise in microscopic examination (here dressed in red robe and talking with Prince, in 1878). After microscopic examination, he diagnosed it as 'pachydermia verrucosa laryngis' with no evidence of malignancy.
In spite of multiple treatment protocols attempted for one year (including tracheotomy), disease kept on progressing. In March 1888, expectorated tissue bits were examined by Dr. Waldeyer ( after whom Waldeyer tonsillar ring is named), and a diagnosis of cancer was rendered.
Soon Wilhelm I passed away and Frederick III was anointed as Emperor. Tumour progressed further, killing Emperor in 99 days, thus bringing young, disabled yet militaristic Kaiser Wilhelm II to throne. He was antithesis of his father. His reckless behaviour lead to World war 1.
Autopsy of Frederick III was carried out by Virchow, Waldeyer and Langerhans (remember pancreatic ilets and dendritic cells), which revealed carcinoma with suspected cervical lymph node metastases.
Controversy of missed diagnosis had raged since then, and multiple recent reconstructions, have proposed that is might have been verrucous carcinoma, a rare and difficult diagnosis. Even after 100 years, diagnosis was missed in ~50% of patients. https://tinyurl.com/2rwhptkw
2. From daughter to grand-daughter of Queen Victoria. One of the sons of Queen Victoria suffered from hemophilia( also called Royal disease), X chromosome linked disorder leading to excessive bleeding after minor trauma.
Her grand-daughter, Princess Alix (later Alexandra Feodorovna), was married to Nicolas III Romanav, who became Czar of Russia at relatively young age. Tragedy struck when Crown Prince Alexei was diagnosed as having the Royal disease.
Disease of son weighed on the mind of Czar & Czarina, while Russia was convulsed with multiple violent revolutions. Chaos were was amplified by WWI (lead by grandson of Victoria, Kaiser). Finally in 1917, Czar was forced to abdicate and whole Royal family was murdered.
In 2007, grave of Alexie was found. DNA analysis showed presence of pathogenic mutation in F9 gene, predicted to have caused hemophilia B or Christmas disease (named after a patient, not holiday). His sister, Anastasia, was a carrier, like his mother. https://tinyurl.com/n30wlmj7
3. Carlo Maria di Buonaparte, was a Corsican freedom fighter turned representative at the court of Louis XVI of France. At the age of 39 years, he developed gastric ailments and soon died, leaving behind a poor family of nine. Autopsy showed presence of a gastric tumour.
Death made his son, Napoleon (15 years), to suspect correctly that his lifespan may also be short one. His boundless energy, military genius and urgency for achieving greatness at a young age lead to meteoritic rise in anarchic post-revolutionary France, becoming Emperor in 1804.
At his zenith, he dominated most of the Europe. But Empire collapsed after battle of Waterloo & he was exiled to St.Helena. In 1821, just before death, he predicted that he will most likely die like his father. Demise fortified British dominance, allowing expansion of colonies.
Autopsy findings proved him right and showed gastric tumor (T3N1M0, Stage IIIB, by current staging) with features similar to his father's tumor. His sister was also diagnosed with gastric tumor, thus raising a possibility of hereditary cancer. https://tinyurl.com/2gcw563k
Although the exact genetic etiology cannot be ascertained, two major candidates are 1. CDH1 (E-cadherin) mutation causing hereditary diffuse cancer and 2. IL-1β polymorphims with increased risk for development of cancer in H. pylori infected relatives of gastric cancer patients.
Interpretation of historical records can be subjective. Famous 'madness of George II' following loss of American colonies, was initially attributed to acute intermittent porphyria. But recent reanalysis has questioned this theory and proposed he suffered from bipolar disorder.
On a lighter note, the Crown on Netflix is an engaging drama but try to imagine prequel with Queen Victoria. It will be the Crown meets Game of Thrones. WWI can be called 'War of Cousins' (Wilhelm II vs George V) and it was definitely far more savage than ' Battle of Bastards'!!
