Biology Reference
In-Depth Information
Early studies in erythropoiesis
Bright [9] is credited with being the first scientist to recognize that anemia was
a complication of kidney disease, but Jourdanet [10] has been credited as the
first scientist to observe the relationship between altitude and blood viscosity.
Jourdanet noted the similarity of symptoms reported by patients with altitude
sickness and the symptoms reported by patients who had experienced severe
blood loss. Several years later, Viault [11, 12] expanded knowledge of red
blood cells and the effect of altitude on them, and quantified the change in red
cell counts as altitude increased. On a train trip from the city of Lima, Peru to
the high-altitude tin mines of that country, he repeatedly sampled his blood,
blood of willing fellow travelers, and blood of a dog, rooster, and llama. Viault
noted an increase in his red blood cell count from 5
10
6
/mm
3
to 8
10
6
/mm
3
×
×
during the ascent to higher altitude.
Other early scientists continued studies in an attempt to understand the
mechanism of erythropoiesis in rabbits [13] and immigrants to the high
Alps [14, 15]. One theory proposed at the time to explain the polycythemia
seen at high altitudes was that low oxygen pressure directly stimulated bone
marrow to increase red blood cell production. This theory held for nearly 50
years.
In 1906, Carnot developed the concept of humoral regulation of erythro-
poiesis [16-18]. Serum from anemic rabbits was injected into normal rabbits,
and caused an increase in the red blood cell counts of the normal rabbits.
Carnot suggested that “hemopoietine” present in the serum of anemic rabbits
was responsible for the increase in cell numbers. Many other investigators
repeated these experiments in anemic rabbits or rabbits raised at high altitudes
[19-23].
For almost 30 years, researchers continued to repeat Carnot's work.
Because some investigators were successful and others were not, controversy
continued about the mechanism of erythropoiesis. Finally, Erslev [24] modi-
fied Carnot's original study: He injected large amounts of plasma from anemic
rabbits into normal rabbits and found that the number of nucleated red blood
cells in the bone marrow, the number of peripheral reticulocytes, and the
hematocrit of the normal rabbits increased. This study suggested that red blood
cell production is mediated by a humoral factor in rabbits. Four years later,
Jacobson et al. [25] demonstrated that this factor, EPO, was produced by the
kidney. Progress was being made in understanding the relationship between
oxygen supply and demand of the body and EPO and erythropoiesis; howev-
er, despite more than 100 years of research, nothing was known about the
structure of EPO or the
EPO
gene. Some debate continued whether EPO was
produced as an inactive precursor in the kidney that was activated in some
other tissue or organ.
