Since my recent "tweetorial" about the history of ring sideroblasts & Prussian blue seems to have been well received, I thought I’d follow up with the fascinating and sordid history of the term, “Refractory Anemia” (RA). (This ugly #MDS image is from a book I edited years ago.)/1 
Iron salts had been used since the 17th century to treat “chlorosis” – i.e., the green sickness, characterized by weakness and pallor. Thomas Sydenham (1624–1689) is usually given credit for first rational use. Here's a classic painting of a young woman fainting from chlorosis./3
Some flowery language from Sydenham about iron: “To the worn out or languid blood it gives a spur or fillip whereby the animal spirits which lay prostrate and sunken under their own weight are raised and excited.” (I wish I could give more of my patients a 'filip'.)/4
So iron salts, sometimes supplemented by quinine (especially if there were associated fevers), became an accepted treatment for anemia in the late 19th century, when RBCs could finally be measured reliably using a new tool from France called a hemocytometer./5
Then, in 1926, Minot & Murphy in Boston treated pernicious anemia pts. with raw liver, with remarkable results. This is often considered the beginning of "modern hematology" and they got a Nobel prize for it in 1934. Later the active ingredient in liver was identified as B12./6
Anemia that didn’t respond to iron salts or raw liver soon became known as “refractory” anemia. Later, Lucy Wills (she just got a Google doodle for her 131st birthday!) discovered another anemia-treating factor - it became known as folate - and that too was thrown in the mix./7
In 1938, Cornelius Parker Rhoads (1898-1959) and his junior colleague William Halsey Barker (1907-1949) published in JAMA a series of 100 patients seen at the Hospital of the @RockefellerInst in New York who had “refractory anemia”. (Warning: things will soon take a dark turn.)/8
Rhoads and Barker presented these data at the June 1937 @AmerMedicalAssn 88th annual meeting. The abstract discussion was led by Minot (mentioned above) and George Whipple, who had shared the 1934 Nobel Prize with Minot & Murphy for his work on anemia in animals./9
Minot was impressed, and he emphasized both the potential for confusion of this new "refractory anemia" with good old pernicious anemia, and underscored the importance of dedicated research institutes such as the @RockefellerInst, which were new in the US./10
I'm less impressed. I looked through these 100 patients and I think 40 of them had anemia of cancer or anemia of inflammation, 27 had aplastic anemia, 23 had AML, and 8 had hemolytic anemia. Maybe 4 had what we would consider MDS? But the refractory anemia term stuck./11
There were other candidate names for unexplained anemia. For instance, beginning in the 1920s the broad term “di Guglielmo syndrome” (coined in Italy) was applied to any anemia that no one really understood, especially if there were a lot of immature cells in the marrow./12
And at my alma mater @UChicagoMed, Matthew Block and Leon Oris Jacobson recognized that anemia could sometimes turn into leukemia, and coined the term “preleukemic anemia.” That got some use also./13
But refractory anemia was the most commonly employed term. I found more than 400 papers indexed on PubMed between 1938 (Rhoads and Barker) and 1976 (the #FAB classification of AML, which included something they called "RAEB") that employed the RA term in different contexts./14
Now let's talk a bit about Cornelius Parker “Dusty” Rhoads (of course that was his nickname!)/15
A few years before his 1937 presentation to the AMA on refractory anemia, Rhoads became a controversial figure as a result of his behavior during an extended research project in Puerto Rico in 1931. He worked in San Juan as part of a visiting research team from New York. /16
The principal focus of this "Commission for the Study of Anemia" was to learn how to better combat common causes of anemia in the Caribbean, such as endemic hookworm and tropical sprue; some novel observations were made. Here's Rhoads looking snazzy in his uniform./17
Rhoads didn't get along with the Puerto Rican laboratory staff in San Juan. The locals did not enjoy being referred to as "experimental animals" (!) and they felt condescended to by the New York-based investigators. Not everyone had recovered from the Spanish-American War.../18
The animosity spilled outside of the lab, and came to a boiling point after an alcohol-fueled party in San Juan in November 1931. Rhoads became incensed after returning to his car following this party to find the air had been let out of the tires and his briefcase stolen./19
Maybe he was a little drunk, maybe he was just an idiot. Regardless, in a fit of pique, Rhoads went back to his lab and wrote an angry letter to a friend back in New York, Fred W. "Ferdie" Stewart (1894-1991), later chief of pathology at @MSKCC_OncoNotes #MSKCC./20
Rhoads wrote, "I can get a damn fine job here and am tempted to take it. It would be ideal except for the Porto Ricans. They are beyond doubt the dirtiest, laziest, most degenerate and thievish race of men ever inhabiting this sphere..."/21
"....It makes you sick to inhabit the same island with them. They are even lower than Italians. What the island needs is not public health work but a tidal wave or something to totally exterminate the population. It might then be livable. " Pretty bad, right? It gets worse. /22
The coup de grace: "I have done my best to further the process of extermination by killing off 8 and transplanting cancer into several more..." Whoa!! This NY researcher is claiming to have injected cancer cells into Puerto Rican research subjects. A madman. @Lin_Manuel /23
Rhoads left this letter unsent on his desk (maybe he really was drunk) and went home. The following morning it was noticed by a Puerto Rican lab assistant, who passed it on to Harvard-trained Puerto Rican nationalist leader Pedro Albizu Campos. Here's a picture of #Campos./24
Campos, recognizing the political bombshell potential of the letter, sent copies of it to newspapers and numerous international organizations in order to highlight perceived abuses of the colonial occupiers./25 (COMING NEXT: THE AFTERMATH)
