IX. GENETICS AND HUMAN HEMOGLOBIN CHEMISTRY 459 



B. THE CONTROL OF THE SYNTHESIS OF FETAL AND ADULT HEMOGLOBIN 



Hb-F is the principal component of human fetus hemoglobin. The 

 synthesis of Hb-A starts, however, early in fetal life; Hb-A has been 

 detected in fetuses of 13 weeks (Walker and Turnbull, 1955). The level 

 of Hb-A raises to about 10% by 22 weeks and to an extremely variable 

 20% at birth. The Hb-F level is fairly constant from the twenty-fourth 

 to the thirty-second week of fetal life and then falls at a rate of 2.5 to 

 4% per week, Hb-F being substituted by Hb-A (Cook et al, 1957). 



The level of Hb-F at birth in infants of different gestational ages 

 has been detemiined by Cook et al. (1957) ; the concentration of Hb-F 

 decreases with increasing gestational age of the newborns (Fig. 13). 

 Babies born prematurely have higher levels of Hb-F, while babies bom 

 after term have lower levels of Hb-F; i.e., babies born 4 weeks after 

 teiTn seem to have Hb-F levels comparable to those of 4-week-old babies 

 born at the nonnal term. Betke (1958) has also studied the fall of 

 Hb-F concentration in newborns and has come to the conclusion that 

 the Hb-F level falls as a function of gestational age and that birth 

 has a negligible effect upon the variation of Hb-F level. 



Hb-F is present for a variable time after birth (Chernoff and Singer, 

 1952; Jonxis and Visser, 1956); the Hb-F level decreases to about 1% 

 or less by the end of the first year of adult life. The disappearance of 

 Hb-F takes significantly longer than the time predicted on the basis of 

 a complete cessation of Hb-F synthesis (White and Beaven, 1959) ; 

 the production of Hb-F decreases after birth and is very limited in 

 normal adults. 



In the course of fetal differentiation, eiythropoietic activity resides 

 in different morphological sites. Hemoglobin containing cells appear first 

 in the mesenchyme of the embryo; the liver and the spleen are the next 

 active erythropoietic sites until birth (Maximow and Bloom, 1957). The 

 bone marrow is the main center of red cell production around birth; 

 after birth, active bone marrow disappears from the long bones and the 

 erythropoietic activity is limited to the red mari'ow of the steiTium and 

 vertebrae (Maximow and Bloom, 1957). 



No correlation has been established between the morphological sites 

 of erythropoiesis and the switch from Hb-F synthesis to Hb-A synthesis. 

 Betke (1958) has shown that Hb-F and Hb-A are both present in red 

 cells obtained from liver and bone marrow of human fetuses. Thomas 

 et al. (1960) have determined the hemoglobin types synthesized by fetal 

 spleen, liver, and bone marrow; these hematopoietic tissues synthesize 

 both Hb-A and Hb-F, although in a different ratio. More Hb-A is syn- 

 thesized in bone marrow preparations than in spleen or liver prepara- 



