Thread by @DavidSteensma

There is an interesting history behind these cells, so familiar to hematologists & pathologists: ring (formerly 'ringed') sideroblasts. While most commonly associated with #MDS or inherited disorders like #XLSA, they can also result from ethanol or TB drugs - even hypothermia./1

Sideroblasts and siderocytes - red cells and their precursors with iron granules in the cytoplasm visualized by a chemical reaction - were first described by Hans Grüneberg in 1942, a Jewish refugee from Germany working in London @ucl from 1933. /2

In 1955, Sven-Erik Björkman, working in Jan Gösta Waldenström's hematology unit @lunduniversity (thus far this tweetorial has 100% umlaut surnames!) noticed 4 of his anemic patients had weird sideroblasts: the iron granules encircled the nucleus. One of them developed leukemia./3

Others recognized this too, so "sideroblastic anemia" was born. In 1982, this group - hematopathologists from the US, Paris, and London - created the "French-American-British Co-Operative Group Classification of #MDS. (I got this image from John Bennett @UofR who led the #FAB.)/4

The #FAB recognized some forms of MDS had lots of ring sideroblasts, others not so many. A then-fellow working with Georges Flandrin, Surender Juneja (now he's a Professor @PeterMacCC in Melbourne) looked at 100 cases of MDS and counted the distribution of ring sideroblasts./5

Juneja found a little gap between ~15% and 20% ring sideroblasts - so the FAB decided 15% would be the ring(ed) sideroblasts cutoff. For 37 years and counting it has been. @mrinal90151372 and I looked at ~1000 cases @MayoClinic some years back and found this was an artifact./6

In 2008 the WHO changed #FAB's term "ringed" sideroblast to "ring", recognizing that "ring" was the term originally used by Björkman. In 2016, WHO decided #MDS with ring sideroblasts could include cases with as few as 5% ring sideroblasts if a mutation in #SF3B1 was present. /7

In 2008, an International Working Group led by Ghulam Mufti @KingsCollegeNHS and John Bennett decided ring sideroblasts were "erythroblasts in which there are a minimum of 5 siderotic granules covering at least a third of the nuclear circumference." /8 ncbi.nlm.nih.gov/pubmed/18838480

But where does "sideroblast" come from? The root is the Greek σίδᾱρος which meant "iron" (similar words were used for "blacksmith shop" or "sword"). The Latin cognate is sīdus or sideris, which was used for terms relating to stars or constellations./9

Until it was replaced Earth Rotation Angle (ERA) about 15 years ago, astronomers often used Sidereal Time: time measured by the stars. I worked in the astronomical observatory @Calvin_Uni circa 1990 (prob. the best job I've ever had) & we had a clock that looked like this one./10

The connection between iron and the stars is that until our ancestors learned to smelt, the purest forms of iron fell from the sky - "falling stars" - in the form of meteorites. For example this "thumbprinted” iron meteorite (Group IIAB) I own fell in eastern Siberia in 1947./11

It was such a spectacular fall (Sikhote-Alin) that the Soviets commemorated it in this postage stamp. #Sikhote @APS_stamps /12

The "blast" part of sideroblast is also Greek; the uncommon word βλαστός designated a bud, sprout, germ, embryo... basically something immature but growing, which summarizes well how we use the term "blast" in hematology. /13

There's another twist to this story that I find fascinating. In hematopathology, we use the "Prussian Blue" reaction to identify iron, including ring sideroblasts. Prussian Blue is a dark blue pigment produced by oxidation of ferrous ferrocyanide salts. Why "Prussian"? /14

Circa 1704, a Swiss colormaker, Johann Jacob Diesbach, was trying to make an improved red-colored pigment from cochineal (a crimson extract of New World insects). Diesbach wasn't having much success, so he went to visit one of chemistry's strangest characters./15

Johann Conrad Dippel was from Castle Frankenstein (!) near Darmstadt in Hesse. Dippel was an alchemist and heterodox theologian. Diesbach's dying process required iron sulfate, and potash as an acid source. Dippel at the time was doing a lot of work with animal blood.../16

Just like those old Reese's peanut butter/chocolate commercials, Dippel's animal blood got in Diesbach's potash, and instead of red he got a purplish-blue pigment, potassium hexocyanoferrate -- one of the earliest synthetic pigments./17

Diesbach was smart enough to recognize this was important and could replace the expensive lapis lazuli. After the synthesis method was reported to @royalsociety the pigment became a sensation./18

The "Prussian" part comes from correspondence involving Gottfriend Leibniz, then head of the Prussian Academy of Sciences. As "Parisian blue" the same substance became a popular pigment in the art world, e.g. used in this famous painting by #Hokusai./19 metmuseum.org/blogs/now-at-t…

Why was Dippel using animal blood? He was trying to create an "elixir of life" - an immortality agent. Alas, Dippel's Oil turned out to be most useful as an insect repellant. But there is one final twist to this story./20

There were rumors Dippel (who styled himself "Frankensteinensis") was doing some sinister stuff back home in #CastleFrankenstein: trying to reanimate corpses. A century later, a young woman named Mary Wollstonecraft Godwin Shelley was touring nearby with her husband Percy./21

It seems likely that this gifted writer heard about the sinister reputation of Dippel & his Burg Frankenstein, and her fertile imagination transformed this "blast" of an idea into one of the all-time classic novels, "Frankenstein", published in 1820 - the first "Gothic" tale./22

So the next time you see the "Frankenstein monster" of a #ringsideroblast under the microscope with its canvas-worthy brilliant blue granules, keep in mind that you are looking at star-stuff. /23End @ASH_hematology @BritSocHaem @mrinal90151372