Page 9 - Flow Cytometry Protocols Fourth Edition

4 Howard M. Shapiro

space, it now referred to the membrane-bounded "elementary
particle" of biology.
Swift's 1726 narrative speaks of a breast cancer and a wen
( sebaceous cyst) at a time when no one had yet conceived of them
as representative of two types of abnormal growth, or that an
infected and inflamed wen also exemplified bacterial growth and a
proliferative response by the patient's immune cells. By the late
1800s, both the metabolic versatility and pathogenic capability of
microorganisms had been revealed by Louis Pasteur, Robert Koch,
and others, The cell theory had become accepted, and Rudolf
Virchow's famous quote, "Omnis cellula e cellula," embodied the
efforts of many pathologists to understand disease at the cellular
level.
Human blood cells had come to microscopists' attention; they
were relatively easy to procure, and could provide some informa-
tion about patients' overall state of health. Although anemias and
leukemias had been described by this time, their causes were
unclear; there were no known treatments for either, but their
diagnosis and prognosis could be indicated by changes in the
numbers of morphologically different cell types in the blood over
time. The term "cytometer," coined around 1880, described a
device in which cells within a defined volume of specimen could
be counted. "Cytometry" described the process. The cells most
often came from blood, giving us the "hemacytometer" and
"hemacytometry." "Flow" and "cytometry would not be com-
bined until the 1970s; there could be no instrumental alternatives
to microscopy until the 1950s.
A fascinating account of the development of cell biology from
medieval times until the twentieth century is given by the late Sir
Henry Harris in The Birth of the Cell [2]. I have written at length on
the history, technology, and philosophy of cytometry in my book
[ 1] and, more recently, in a chapter in the previous edition of this
compendium [ 3], a review/ overview [ 4], and two additional book
chapters [5, 6] A detailed retrospective view of the origins of
analytical flow cytometry, among other things, was also presented
by the late Leonard Ornstein [7].
Because light scattering and absorption by most cells were
insufficient to permit visual discrimination of internal details, syn-
thetic dyes began to be used by the 1860s to stain specimens, with
Paul Ehrlich providing much leadership. As a medical student in the
1870s, he recognized that different colored organic dyes with
different chemical affinities would be bound to different degrees
to different parts of different cells. This provided a basis for identi-
fying cells within mixed populations; Ehrlich's first practical success
was in classifying the different types of white blood cells using dye
samples provided by manufacturers. By 1880, he had experimented
with several stains containing mixtures of acidic and basic dyes, the