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Chapter 1 : Paul Ehrlich and the Early History of Granulocytes

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Abstract:

Between 1878 and 1880, Paul Ehrlich (1854-1915), a medical student and then assistant physician at the Charité Hospital, Berlin, demonstrated, using acid and basic aniline coal tar dyes, that the different types of blood leukocytes could be distinguished on the basis of the staining properties of their granules ( Fig. 1 ). Ehrlich’s technique for staining blood films and his method of differential blood cell counting ended years of speculation regarding the classification of white cells. His discoveries were among the greatest advances in modern hematology, and the principles surrounding his methodology are applied to this day. Nevertheless, prior to Ehrlich there were several notable landmarks that led to a fuller understanding of white cells, their origin, and possible function. This chapter highlights many of the important achievements of Paul Ehrlich and others. It is not intended to be comprehensive. The priority of many of the observations described, particularly in pre-Ehrlich time, remains controversial to this day.

Citation: Kay A. 2017. Paul Ehrlich and the Early History of Granulocytes, p 3-15. In Gordon S (ed), Myeloid Cells in Health and Disease. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MCHD-0032-2016
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Image of Figure 1
Figure 1

Paul Ehrlich in 1878 (from Hirsch and Hirsch [ ]). The first description of the eosinophil appeared in the in 1879. Reprinted from ( ), with permission.

Citation: Kay A. 2017. Paul Ehrlich and the Early History of Granulocytes, p 3-15. In Gordon S (ed), Myeloid Cells in Health and Disease. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MCHD-0032-2016
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Image of Figure 2
Figure 2

(Left) William Hewson, the Father of Hematology. (Right) Alfred Donné, who introduced the microscope into clinical diagnosis and recorded one of the first descriptions of white cells in leukemia. Reprinted from ( ), with permission.

Citation: Kay A. 2017. Paul Ehrlich and the Early History of Granulocytes, p 3-15. In Gordon S (ed), Myeloid Cells in Health and Disease. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MCHD-0032-2016
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Figure 3

Alfred Donné’s microscopic images of blood from a patient with leukemia. (Top right) Red and white blood cells from a leukemic patient. (Lower right) “Mucous globules,” or white blood cells, from the same patient. The images were published in the supplement to in 1845 (left). Reprinted from ( ), with permission.

Citation: Kay A. 2017. Paul Ehrlich and the Early History of Granulocytes, p 3-15. In Gordon S (ed), Myeloid Cells in Health and Disease. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MCHD-0032-2016
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Figure 4

John Bennett published the first detailed description of leukemia. His illustrations show “colourless corpuscles” in the circulation. Reprinted from ( ), with permission.

Citation: Kay A. 2017. Paul Ehrlich and the Early History of Granulocytes, p 3-15. In Gordon S (ed), Myeloid Cells in Health and Disease. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MCHD-0032-2016
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Figure 5

Rudolf Virchow and an illustration taken from his volume (7th American edition, Robert M. de Witt, New York, NY, 1856): Fig. 63. A. Pus-corpuscles, a fresh, b after the addition of a little water, c–e after treatment with acetic acid, the contents cleared up, the nuclei which were in process of division, or already divided, visible, at e with a slight depression on their surface. B. Nuclei of pus corpuscles in gonorrhoea; a simple nucleus with nucleoli, b incipient division, with depressions (by many held to be nuclei) on the surface of the nuclei, c progressive bi-partition, d tri-partition. C. Pus-corpuscles in their natural position with regard to one another. 500 diameters. Reprinted from ( ), with permission.

Citation: Kay A. 2017. Paul Ehrlich and the Early History of Granulocytes, p 3-15. In Gordon S (ed), Myeloid Cells in Health and Disease. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MCHD-0032-2016
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Figure 6

(Left) Julius Cohnheim demonstrated that leukocytes passed through the apparently intact walls of the capillaries by amoeboid movement. (Right) Friedrich von Recklinghausen showed that the amoeboid properties of white cells were the result of both locomotion and contractility. Reprinted from ( ), with permission.

Citation: Kay A. 2017. Paul Ehrlich and the Early History of Granulocytes, p 3-15. In Gordon S (ed), Myeloid Cells in Health and Disease. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MCHD-0032-2016
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Figure 7

Gottlieb Gluge was possibly the first to describe granular cells, which he referred to as “inflammatory globules.” He proposed that blood corpuscles “metamorphosed” into inflammation globules. The cells shown in the top right panel were believed to represent stages in this process. However, they have the appearance of intact or degranulated eosinophils. Further examples of Gluge’s “inflammation corpuscles” are shown in the middle right and bottom panels. Reprinted from ( ), with permission.

Citation: Kay A. 2017. Paul Ehrlich and the Early History of Granulocytes, p 3-15. In Gordon S (ed), Myeloid Cells in Health and Disease. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MCHD-0032-2016
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Figure 8

Julius Vogel made extensive drawings of granular cells in inflammatory exudates. The right panels are examples of Vogel’s “pus corpuscles,” which he also refers to as “granular cells” or “Gluge’s compound inflammatory globules.” They bear a striking resemblance to eosinophils. Reprinted from ( ).

Citation: Kay A. 2017. Paul Ehrlich and the Early History of Granulocytes, p 3-15. In Gordon S (ed), Myeloid Cells in Health and Disease. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MCHD-0032-2016
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Figure 9

Thomas Wharton Jones made an extensive study of granular cells in a wide variety of species. His drawings show coarsely granular cells in the blood of human, horse, and elephant. Reprinted from ( ), with permission.

Citation: Kay A. 2017. Paul Ehrlich and the Early History of Granulocytes, p 3-15. In Gordon S (ed), Myeloid Cells in Health and Disease. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MCHD-0032-2016
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Figure 10

Max Schultze performed functional studies on finely and coarsely granular cells. The cells were observed on a warm stage at 38°C. Reprinted from ( ), with permission.

Citation: Kay A. 2017. Paul Ehrlich and the Early History of Granulocytes, p 3-15. In Gordon S (ed), Myeloid Cells in Health and Disease. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MCHD-0032-2016
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Image of Figure 11
Figure 11

Paul Ehrlich in 1908. Color plate from ( ). Triacid (orange G, acid fuchsin, and methyl green) was used as a differential leukocyte stain. Reprinted from ( ), with permission.

Citation: Kay A. 2017. Paul Ehrlich and the Early History of Granulocytes, p 3-15. In Gordon S (ed), Myeloid Cells in Health and Disease. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MCHD-0032-2016
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References

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