In the holiday spirit, it’s time for #HematologyTweetstory 11: the Howell-Jolly Body!🎄A friend @UChicagoMed, Brian Nelson, sang “It’s A Holly Jolly Christmas” in 1st year med school, forever linking these erythrocyte bodies to Christmas for me. (Image Source: @ASH_hematology) 
William Henry Howell (1860-1945) collected post-nominal letters: MD, PhD, LLD, ScD. He trained @JohnsHopkins and returned there in 1893, 12 years after graduation & after periods on the faculty of @umichmedicine and @harvardmed. This painting of Howell is from 1911./2
Howell served 12 years as Dean of @HopkinsMedicine, and founded what is now the Bloomberg School of Public Health @JohnsHopkinsSPH. His major contribution to medicine was not the red cell body named after him, but something else important that you may have heard of.../3
In 1916, a 2nd year student working in Howell’s lab, Jay McLean (1890-1957), discovered a new anticoagulant. He called it “heparin” because he'd isolated it from dog liver ("ήπαρ", hepar = liver in Greek). McLean later had a successful career as a surgeon and radiotherapist./4
In 1922, after McLean graduated, Howell reported another new anti-coagulant, this one water soluble, which he also (confusingly) named heparin. The 2nd #heparin and its low-molecular-weight derivatives are the ones we use today. A pro-coagulant isolated from brain: "cephalin."/5
Howell did not do clinical trials of heparin; human studies were done by others. Key developments in turning heparin (from beef lung) into a drug took place in Toronto, at #ConnaughtLaboratories and @uoftmedicine. Heparin was first licensed by @US_FDA in the late 1930s./6
Howell’s name is forever paired with Justin Marie Jolly (1870 – 1953): a Frenchman born in Melun, now a southeastern suburb of Paris. Jolly studied with Louis-Charles Malassez, a pioneer of cell counting (I mentioned him in a recent @ASHClinicalNews on “Fathers of Hematology”)./7
Later Jolly became chief of lab medicine at Paris' Hôtel-Dieu, the oldest still-operating hospital in the world, which was reportedly founded in 651 C.E. Hôtel-Dieu = Hostel (or House) of God, reflecting the religious orientation of its founders. (No, not *that* House of God.)/8
Howell described RBC inclusions in 1890 in the "Journal of Morphology", while Jolly wrote about them in 1905 in "Sur la formation des globules rouges des mammifères". So it’s appropriate Howell’s name comes first – though in France, it is common only to refer to “Jolly bodies”.
Over the course of the 20th c. it became clear that in health, Howell-Jolly bodies are removed by the spleen. Mehdi Tavassoli & William Crosby in Boston described this "pitting" function of spleen in 1973 in @sciencemagazine, "Fate of the Nucleus of the Marrow Erythroblast"./10
What exactly are Howell-Jolly bodies? They are little basophilic remnants of nucleus that stick around after nuclear extrusion during RBC development. They're normally quickly removed by the spleen, the way a swimming pool filter removes floating insects. (Image: Carr & Rodak)/11
This 1972 #Shmoo-like EM image (Freeman et al @BloodJournal) shows how H-J bodies form. Sometimes a fragment of nucleus gets enveloped by nuclear membrane & pinched off from the main nucleus, just like the American Lost Battalion in the 1918 Meuse–Argonne offensive./12
The Lost Battalion story is quite interesting and has been made into an @AETV documentary. Yep, that’s a grown-up Ricky Schroeder from “Silver Spoons” - 1980s heartthrob. And now, back to our regularly scheduled program of hematology.../13
I imagine the process of Howell-Jolly body formation is physically a bit like those novelty gel stress balls that you can buy to squeeze when upsetting things happen, like introduction of a new mandatory online training module at your hospital./14
H-J bodies are commonly mistaken for Heinz bodies. But you don’t see Heinz bodies with Wright stains; you need a supravital stain or “Heinz body prep”. They're also mistaken for Pappenheimer bodies (a future topic) or other RBC inclusions. Nice image from medical-labs.net
For folks interested in reading more about #HowellJolly bodies, I can recommend @Baylor emeritus professor David Sears & Mark Udden’s 2012 article on H-J history. (Mark and I were on the ABIM Hematology committee – great guy. Mark served 2 full terms; I bailed out early.)/16
