41 



during the exposure. 



BARRON: Yes. 



PATT: That, I think, is quite important. 



BARRON: You are absolutely correct. We have to demonstrate inhibi- 

 tion of -SH enzymes in the cell soon after irradiation. I am still hopeful of being 

 able to make such a demonstration when we start our work on synthesis of nu- 

 cleic acid components. I still believe they are -SH enzymes and that they are 

 very sensitive to oxidizing agents. 



CARTER: I don't want to take the part of defender of nucleic acids, but 

 I would like to get back to this business of what you have to measure when you 

 are talking about the relative sensitivity of nucleic acids to irradiation. I think 

 the criteria Dr. Barron discussed may be the least sensitive. In the case of bio- 

 logical activity of the transforming principle, it is known that minor changes in 

 the organization of the molecule brought about by heat, pH change, and ultraviolet 

 radiation are associated with loss of activity. 



MAZIA: Carter's statement raises the question, whether anyone has 

 irradiated solutions of transforming principle. This is the only means now 

 available where one could measure an effect on the biological activity of nucleic 

 acid. 



CARTER: Zamenhof has done some work in this regard. I have not 

 seen his published figures. 



CHARGAFF: I do not think he has worked with X-rays. He has studied 

 ultraviolet and similar things and some pH changes. I have the feeling that I 

 have seen a paper on it. 



CARTER: The ultraviolet has been done. Heat also causes inactiva- 

 tion. 



CHARGAFF: If 99 percent of the molecules have nothing to do with the 

 transforming principle, if the transforming principle is more sensitive to all 

 kinds of agents than the DNA present in the preparation, there could be inactiva- 

 tion because you have really hit the most sensitive part of the mixture. That is 

 a possibility. As long as we really don't know what makes the transforming 

 principle, it is hard to say. You see, the old finding of McCarty about inactiva- 

 tion of the transforming principle by ascorbic acid has stuck in my mind as 

 something very funny. I don't know whether that has been repeated. It has 

 never been shown in any event how ascorbic acid inactivates the transforming 

 principle. The analytical methods are too crude. You can analyze within plus or 

 minus 2 percent. You can account for 98 percent of your bases, but trace con- 

 stituents can still be present and escape detection for the moment. 



CARTER: For the most part, you knov/ from the chemical work that 

 those trace constituents are not protein. So what it comes back to is what is the 

 molecular identity of this material? 



CHARGAFF: It is undoubtedly true that it is the nucleic acid that has 

 the transformation activity, but whether this property is due only to a particular 

 sequence of the constituents or whether there is something else in its structure, 

 which we cannot describe yet, is unknown. 



