SUMMARY AND DISCUSSION 189 



one of 16 different amino acids, we get ten to the fourth power different possible 

 combining regions, and we conclude that the specilicity of antibodies should 

 be far from perfect, that there would not be an infinite number of possible anti- 

 bodies but only a finite number. 



I might point out that even if we have the same four amino acid residues in 

 the combining region, there is the possibility of backing them up differently. 

 That is, by moving these four around to different positions, with the use of 

 more protein material as structural material behind, we can produce, with these 

 same four residues as the face plates, a very large number of different kinds of 

 combining regions. 



This gives us the possibility of an essentially infinite number of different 

 kinds of combining regions, not ten to the fourth power. Ten to the fortieth 

 would sound more reasonable. 



Professor Haurowitz: I would like to talk quite briefly in self defense and 

 then ask two questions. 



Until a few years ago I would have agreed with Professor Pauling that there 

 are perhaps ten to the fortieth antibody molecules. Peptide chains at that time 

 were believed to existin liJiT infinite number of conformations. At present we 

 know that they cannot be distorted beyond a certain limit and we know by 

 the work of Pauling, Corey and others that there are preferential states of 

 stability and states of least energy, for instance, the alpha helix or the pleated 

 sheet. If we assume for the sake of simplification, that just alpha helixes can 

 exist, then we find that there cannot be ten to the forty different arrangements 

 for amino acids, but only about ten to the four. 



There are two other questions. One of them is concerned with Dr. Itano's 

 paper on hemoglobin. It is not surprising that normal hemoglobin and sickle- 

 cell hemoglobin are different in solubility and therefore in crystalline shape 

 but what is astounding is that the solubility should be so enormously dependent 

 on one single CO or one single O2 molecule bound to the hemoglobin molecule. 

 The hemoglobin of the horse crystallizes in large platelets which are rather 

 easily soluble. If we saturate it with oxygen, we get a needle-like shape which 

 is much less soluble. Thus not only the crystal shape but also the solubility 

 changes drastically on oxygenation. In some cases, as in normal adults, the 

 solubility decreases on oxygenation. In the case of sickle-cell hemoglobin, the 

 solubility increases in oxygenation. I would be happy if I knew any explanation 

 for these changes. In no field of protein research are we so in the dark as in the 

 problem of solubility. We cannot explain why certain globulins are soluble in 

 water and other globulins are not, why some plant proteins are soluble in 80 

 percent alcohol and others are not. This is one of the main problems, I think, 

 of protein chemistry. 



I have another question which I would like to address to Dr. Anfinsen and, 

 perhaps. Dr. Donohue. Dr. Anfinsen mentioned that tyrosine has a particular 



