GENERAL DISCUSSION 463 



tion of fibers ought not to be quite according to the normal pattern. And here the 

 striking thing is the orientation at an angle — often at a right angle — to the expected 

 one. The histologic technique is such that it leaves no question that these are truly 

 nerve fibers. In fact, the technique is so good as to give one every confidence in 

 the care with which the whole investigation has been carried out. 



Webb Haymaker (Armed Forces Institute of Pathology): One of the questions 

 was directed to me with regard to the fluorescent technique data by Dr. Calvo. It 

 was suggested that there perhaps were some holes knocked in some of these vessels, 

 and the extrusion of the labeled albumin came through these holes. To that I 

 would say this: This was a 6,000 r surface dose, and the first changes were seen 

 in two days. At that time, under the light microscope, we could find no mor- 

 phologic alterations in the blood vessels. Secondly, there were no hemorrhages. On 

 the basis of this and other data, I believe that Dr. Calvo would feel that this is 

 really a matter of permeability to a rather high molecule. I do not think there is 

 any way of comparing the experiments of Dr. Van Dyke, using soluble fluorescein, 

 with the technique which we use. His lesions were made with a 184 in. cyclotron 

 with far greater energy. I would suspect that if he had used 6,000 rad and 

 duplicated our experiment the soluble fluorescein would come through much more 

 rapidly than the protein molecules, the data on which we presented. 



Cornelius A. Tobias (University of California, Berkeley, California): First, I 

 wish to comment on the remarks Dr. Kruger made with respect to the dose-eflfect 

 relationship. You could see from the curve I presented, which had the dose volume, 

 that not all the points were exactly on the curve. Actually the relationship is 

 probably much more complicated than that. If you keep the volume the same and 

 give different doses, you have one relationship in which with lower doses, the 

 lesions appear later. Also, as Dr. Sourander has done, you can use the other ap- 

 proach, keeping the dose constant and changing the volume. This will give rise 

 to another curve. So we have actually more than one parameter to deal with. 

 Moreover, I believe now that different parts of the brain are somewhat different. 

 For example, in the cerebellum you get a slightly different dose-effect relationship 

 from that in the cerebrum. However, when you try to plot the relationship to the 

 time, the time slope of the curves obtained is about the same; whereas, the abso- 

 lute position of the curve in the dose-effect relationship is somewhat displaced. I 

 think we have heard possibly enough evidence today to realize that there must be 

 at least two different relationships. The relationship where the dose and time both 

 enter makes one strongly suspect the intereferency or the importance of circulation, 

 and of the capillarity and profusion by blood, of vascular accident, like hemorrhage 

 that may occur on a statistical basis. On the other hand, some of the data pre- 

 sented with respect to neurons have a more or less direct inner dose-effect rela- 

 tionship, as in the nuclei that Dr. Janssen counted. It may be due to a direct 

 effect, perhaps possibly even a direct effect of particles which hit the nuclei of the 

 cells. Dr. Clemente of U.C.L.A., Dr. Richards of our laboratory, and Dr. Gaffey 

 have undertaken ambitious programs, in which electrical activity will be studied 

 as the function of the location of the irradiation and the dose. The technique used 

 is imbedding electrodes in various locations, then placing the lesion with the high 

 energy beam at the various locations. For example, at the top of one of the sets 

 of electrodes. Then it probably is possible to stimulate and study electrical activity 



