406 CORRADO BAGLIONI 



of several inve;<ti<2;ators has hccii (li'ixcii to this field of rcscaich. A louj^h 

 estimate of the iiuinhcr of papcis puhlishcd within the last ten years on 

 this subject shows this number to be close to a thousand. It is impossible 

 to review and give reference to all these ])apers for reasons of conciseness 

 and limitation of space. The necessaiy omissions sliould not imply lack 

 of appreciation of the jiapers not cited; most of these references have 

 not been included because they are reported in previously i)ublished 

 reviews. 



The rapid progress in the past few years has stimulated many authors 

 to cover this field of research with excellent and specialized reviews. 

 Among the many good reviews may be mentioned Itano's (1957) review- 

 on human hemoglobins, Lehmann's (I960) review on abnormal hemo- 

 globins, Ingram's (1961b) book ''Hemoglobin and Its Abnormalities," 

 and Rueknagel and Neel's (1961) review on hemoglobinopathies. Gratzer 

 and Allison (1960) have recently reviewed the related field of the animal 

 hemoglobins. ]\Iost of these reviews report the historical developments 

 of the research in the particular field covered, so that no attempt will 

 be made to present a historical background in this review. 



The purpose of this review is to give the reader up-to-date informa- 

 tion on the latest developments of the genetic and chemical studies on 

 the human hemoglobins and to correlate the work of people active in 

 widely different disciplines: human genetics, biochemistry, hematology, 

 and biophysics. 



II. The Separation of Human Hemoglobins by 

 Chromatography and Electrophoresis 



Hemoglobin is a conjugated protein, consisting of a protein part 

 (globin) and of a prosthetic group (heme). Mammalian hemoglobins are 

 rather large molecules, made up of approximately 600 amino acids and 

 with a molecular weight of 66,000 dz 2,000. Hemoglobin is contained in 

 specialized cells, the red cells, which are nucleated in lower vertebrates 

 and anucleated in mammals. Red cells are easily obtained by bleeding 

 and hemoglobin solutions are usually prepared by lysis of the red cells 

 with hypotonic solutions, after washing away the serum proteins with 

 isotonic solutions. Over 95% of the soluble protein obtained in this way 

 from mammalian red cells is hemoglobin. This remarkable circumstance 

 and the ready availability of large quantities of red cells have made 

 hemoglobin one of the preferred objects of study for the protein chemist 

 for almost a century. 



Hemoglobins obtained from different animal species have been 

 analyzed by several investigators; the heme has been found to be 



