This is just amazing.
Ninety-two years and a few months ago, a US Army private died at what is now called Fort Riley, Kansas. It was July 1918, and the 21-year-old recruit had been sick for two days with a fever and a headache, an aching chest and a hard, hacking cough that didn’t bring anything up. He was admitted to the base infirmary, where they found his temperature was a scorching 105.4 degrees and his entire right lung was not functioning properly. He was diagnosed with pneumonia.
It was 10 years before Alexander Fleming would find the mold that produced penicillin, the first antibiotic, on a contaminated culture plate in his laboratory, and 25 years before World War II service-members would benefit from the compound. The medical staff at Fort Riley had almost nothing to offer the private except a primitive immunotherapy: serum refined from the blood of earlier victims of streptococcal pneumonia. It did nothing for him. He died on July 20, nine days after being admitted.
Because he was a member of the armed forces, the base hospital followed a directive that dated back to U.S. Surgeon General William Hammond in 1862: They performed an autopsy on his body, and recorded and preserved the results. Their diagnosis had been right: His lung tissue was positive for S. pneumoniae. But the damage done to his body by the infection and his immune system’s response to it was dramatic: The middle and lower lobes of his right lung, and both kidneys and his spleen, were inflamed and necrotic and speckled with hemorrhages.
In accordance with Hammond’s Civil War order, the medical staff wrote up the autopsy findings and preserved snips of the soldier’s tissues in blocks of paraffin, and sent them all to a repository that Hammond had ordered created: the Army Medical Museum, later called the Armed Forces Institute of Pathology, in the northwest corner of Washington, D.C. And there they sat, among many thousands of other records and samples, until a member of the institute’s staff delved into its archives 80 years after the soldier’s death.
The staff member’s name was Jeffery K. Taubenberger, a physician and virologist who was on a mission of detection: He wanted to recover the virus that had caused the Great Influenza, the pandemic that killed tens of millions in 1918. Medicine had never seen the virus, because flu viruses had not been identified until 1933, long after the circulating flu strain had mutated away from 1918’s viciousness. In the autopsy samples preserved at the Institute, he hoped to find traces of the virus that could be mechanically reassembled into a facsimile that would explain the epidemic strain’s extraordinary virulence.
Taubenberger asked the institute’s archivists to bring up to his lab any samples that dated from 1918. The private from Kansas was among them. There were two things in his record that made his case notable: He had died more than a month before the earliest known cases of the pandemic flu appeared in the United States, and he had been based at Fort Riley — which in 1918 was known as Camp Funston, and was said to be the site of the earliest cases of the 1918 flu anywhere in the world.
Taubenberger succeeded in his mission, using several of the 1918 samples. His first paper announcing the effort appeared in 1997 in Science and hit the small world of flu scientists with the force of a bomb, and he and his lab, now based at the National Institutes of Health, have been continuing the work ever since.
The Kansas private’s tissues, in the end, did not add to the effort. Analysis showed that he had in fact been infected with bacterial pneumonia, which commonly follows on flu infection and may have accounted for most of the deaths in 1918. But he did not have flu.
What he did have was much more interesting. His tissues — stored for decades and possibly never looked at until now — have provided what appears to be the earliest glimpse of the distorted, crescent-shaped erythrocytes for which his disease was named: sickle cell.
Taubenberger’s discovery is described in a letter that will be published in the December issue of Emerging Infectious Diseases but was put on the journal’s website Thursday evening. It describes how, in the cross-sections of the solder’s tissues, Taubenberger and his team members unexpectedly spotted sickle-shaped cells clustering in the blood vessels.
“It really struck me,” he told me in a phone conversation Friday. “So I went back to the chart, and looked, and the soldier was African-American. This was not a histological artifact.” According to the preserved record, the soldier was a member of Company F of the 806th Pioneer Infantry Regiment, a segregated labor unit organized at Camp Funston to provide support for white fighting troops.
(The soldier’s name is recorded — but because sickle cell is a hereditary disease, Taubenberger declined to release it. “This is someone’s relative,” he said, pointing out that revealing a genetic disease carried by someone 92 years ago could potentially breach the medical privacy of someone living today.)
Here is why this is so important: Sickle cell disease was only described for the first time in 1910 — 100 years ago — in a single case written up by James B. Herrick, a physician from Chicago, in the Archives of Internal Medicine. His patient was a 20-year-old man from Grenada who had arrived in the US three months earlier to attend trade school and came to the doctor’s office complaining of heart palpitations, shortness of breath and jaundice, and periodic “billious” attacks and episodes of joint pain. Examining the man’s blood, Herrick found the corpuscles bent into strange crescent shapes.
“This case is reported because of the unusual blood findings, no duplicate of which I have ever seen described,” he wrote. “No conclusions can be drawn from this case. Not even a definite diagnosis can be made.”
It took until 1922 and a write-up of the fourth known case for the disease to be dubbed “sickle cell anemia.” The autopsy slides that Taubenberger uncovered and analyzed predate that by four years, and mark the first known image of the earliest cases. (Herrick’s first paper was published with a crude illustration.)
The Taubenberger team found something else in the analysis as well, something that gives the long-dead soldier’s case an urgent contemporary relevance. It is generally accepted that to develop sickle cell anemia — with its periodic crises of severe pain and mobile blood clots and its ongoing risks of organ damage and infection — patients must inherit two copies of the relevant gene, one from each parent. With only one copy, people are said to have only sickle cell trait, a state of silent carriage in which they do not suffer crises but can pass the gene down to their children.
But the Kansas soldier had only one copy of the gene. Yet, by his autopsy results — the clustered crescent cells in his blood vessels, the necrotic tissue and pinpoint hemorrhages — he suffered a sickle-cell crisis that contributed to his death. How could this be?
For several years, there has been an emerging concern that sickle cell trait can by itself precipitate debilitating and potentially fatal crises, especially in conditions of great exertion or low oxygenation. The highest-profile case to raise the question was the death of Dale Lloyd II, a Rice University freshman who died of exertional rhabdomyolysis — rapid muscle breakdown that releases toxins which choke off kidney function — after a football practice in 2006. Concern has grown so great that the National Collegiate Athletic Association agreed last April that all of its 167,000 student athletes must be tested for sickle cell trait before they can be eligible to play.
In the death of that anonymous Army private 92 years ago, Taubenberger sees a confirmation of that concern, and a warning. As a recruit and a laborer, the 21-year-old — the age of a young professional athlete today — was no doubt worked hard. When he developed pneumonia, the inflammation of his lungs would have kept him from absorbing all the oxygen his body required. Putting together the evidence, Taubenberger realized the pneumonia put the private into a sickle-cell crisis — and the crisis, along with the pneumonia, contributed to his death.
The finding not only fills in the story of the life and death of that anonymous young soldier; it provides evidence that could help save the lives of young men today. But it comes with a poignant footnote of its own. Taubenberger’s team could find no evidence that the slides of the private’s tissues, prepared in 1918, were ever viewed; his medical chart and autopsy account describe only the gross autopsy results and no microscopic ones. Chance, and the team’s interest in a geographically coincident disease, was all that brought them to light. There are millions more such slides and records held at the Institute, and most have never been evaluated.
And they may never be. The AFIP is scheduled for closure next September, part of an almost decade-long process of realigning and “disestablishing” military bases. Its current tasks will be assigned to a new institution, the Joint Pathology Center. The fate of its 150-year-old archive of the illnesses and deaths of military members — where the records will be housed, who will have access to them, how they may be studied — is still unknown.
UPDATE: I discussed this post in an interview with NPR’s Weekend Edition Sunday on Nov. 28, 2010.
Images of 1918 autopsy slides showing sickled red blood cells provided by Jeffery K. Taubenberger M.D., Ph.D., from Sheng Z-M et al., “Fatal 1918 Pneumonia Case Complicated by Erythrocyte Sickling,” Emerging Infectious Diseases, Dec. 2010 ahead of print. DOI: 10.3201/eid1612.101376