The patient had a host of mysterious symptoms: pain in his bowels and back, fever and gout. He got better, then worse, then better again before finally succumbing to his illness.
The reason behind the death of Oliver Cromwell, the 17th-century English Protestant military and political leader, has confounded historians for more than 350 years. Last year, the University of Maryland School of Medicine asked Sanjay Saint, a professor of internal medicine at the University of Michigan, to solve it.
Saint believes that Cromwell died not of poisoning, as some have posited, but from a one-two punch of malaria and typhoid fever
"Malaria was very common in England at that time and would have explained many of his clinical manifestations, but not all, which is why I think his second disease was typhoid fever," Saint said. With typhoid fever, "patients can get better, and then worse, better and then worse and then die just as you think they're going to recover, and they often die of perforation of the bowels, and I think that's what did him in."
Saint made his presentation in late October at UM's Historical Clinicopathological Conference, a melding of medicine and history that takes on the unexplained deaths of figures from antiquity and attempts to diagnose their illnesses. The conference, now in its 23rd year, has examined the mysterious deaths of Christopher Columbus, Joan of Arc, Mozart and Edgar Allan Poe.
Philip A. Mackowiak, a history of medicine scholar-in-residence at the UM School of Medicine, called organizing the conferences his "labor of love." Mackowiak chooses a historical figure who has a good amount of information available about their symptoms before death. He doesn't tell the diagnostician which person they will be diagnosing.
"It was pretty easy to figure out who it was," Saint said. "Once you see Lees of Oyl or the most powerful person in England, then you're able to find that out."
Lees of Oyl, the term in the 17th century for oily-looking deposits in a spleen, indicate sepsis, Saint explained.
Cromwell remains a controversial figure, and is credited with helping to execute King Charles I for alleged treason and bring about rule by Parliament. He was an avid Protestant and staunchly opposed to the Catholic Church. Cromwell led an invasion of Ireland and is viewed unfavorably there. He became chief of state, under the title Lord Protector of the Commonwealth, and died in 1658.
Cromwell was also a source of tension for the new colony of Maryland, which was then overseen by Cecil Calvert, the second Baron Baltimore. Calvert was a Catholic at a time when wars were being fought between Protestants and Catholics throughout Europe, and his father, George Calvert, had envisioned Maryland as a haven for English Catholics escaping the wars. After Cromwell took power, Calvert passed an act indicating Maryland would be neutral on the subject of Christianity, said Burt Kummerow, the historian-in-residence for the Maryland Historical Society.
"Cromwell could have undone Maryland very quickly," Kummerow said. "Cecil Calvert was obviously a brilliant politician because he rode this tide. He was able to keep this charter that had been given to the Calvert family [from the king of England]. It's a pretty amazing achievement."
Saint dug into books written by historians, peer-reviewed literature, and other documents to glean information on Cromwell's symptoms, including "The Death of Oliver Cromwell" by H.F. McMains, who theorized that Cromwell was poisoned. Other people have believed Cromwell died of kidney stones or of malaria.
"None of them adequately explained it, in my opinion," Saint said.
Cromwell's symptoms throughout the years indicated that he had a type of malaria that reoccurs, but isn't typically fatal, Saint said. A bout of malaria, known back then as ague, likely weakened him before he contracted typhoid fever, he said.
"We're now sort of reliant on lab data, CAT scans, MRIs, other types of imaging studies," Saint said. "There was none of that, it was really just based on the clinical symptoms."
Typhoid fever is a bacterial infection caused by exposure to Salmonella typhi through contaminated water or food. The infection causes high fever, headache, abdominal pain, and constipation or diarrhea. Today, vaccines exist but don't protect in all cases.
Cromwell didn't show signs of a few typical symptoms of typhoid fever, according to the historical record. His autopsy — which Saint said was more like an embalming than a modern procedure— did not show an enlarged spleen, though it did note the Lees of Oyl. There's no record of Cromwell's having rose spots, or a rash typical of typhoid fever. And the autopsy didn't show a perforation of the intestine, which Saint believes killed Cromwell.
Saint had a few theories for the discrepancy. First, in about a third of typhoid cases, the spleen is of a normal size. Rose spots also only occur in about a third of typhoid cases, he said, or they could have been missed because Cromwell's physicians did not ask him to undress. And intestinal perforation can be tiny and easy to miss.
Saint ruled out kidney stones because he said they didn't fit with Cromwell's symptoms, and poisoning because it doesn't typically cause fever. Endocarditis, an inflammation of part of the heart, wouldn't result in Cromwell's appearing to get better before dying, Saint said.
Mackowiak praised Saint's diagnosis but said he thought endocarditis also might have been a factor, given Cromwell's history of boils, which indicate a recurrent staph infection. Mackowiak arranged for a supercomputer to help diagnose Cromwell as well, and for musicians to play 17th-century English music at the Historical Clinicopathological Conference.
The conference, Mackowiak said, was a unique melding of history and medicine, which don't usually mix.
"It teaches student doctors and reminds doctor doctors how to go about making diagnoses," he said, "but it also teaches history, and people who are devoted to science hunger for liberal arts stuff, and rarely are the two combined in any serious way in any of the publications."