ROUND TABLE DISCUSSION 521 
especially severe reactions in that the animals became quite ill after only the third or fourth day 
and died as early as the seventh day of force feeding. In the case of the other essential amino 
acids, these toxic reactions were not so severe. After 11 days of force feeding, the animals were 
sacrificed, seven days in the case of valine, the tumors excised, and tumors and carcasses weighed 
separately. Not much variation with regard to tumor growth was shown between the different 
groups. In addition, the carcasses of the animals on each of the deficient diets showed significant 
weight losses with but two exceptions, the exceptions being the animals fed the lysine-free and 
tryptophane-free diets, where slight net gains in carcass weight were noted despite the usual 
rapid tumor growth. This finding was further substantiated by nitrogen balance studies, which 
revealed that the tumor-bearing animals on these two diets suffered virtually no net nitrogen loss 
over the entire eleven day period. Normal animals on these same diets showed a very marked 
negative nitrogen balance, however, as did the tumor-bearing animals on the other deficient 
diets. From these results, one is almost inclined to the impression that, in the case of the lysine- 
free diets, for example, the tumor-bearing animal has in some mysterious way developed the 
ability to synthesize a portion of its lysine requirements, although what actually occurred may 
well have been due to a very highly efficient mobilization of nitrogen between carcass and tumor. 
L. MiLLer: While Dr. W1n17z is talking insucha fascinating way, I wish he would go on and tell us 
a little more about the manner in which these animals die in only a few days from forced feeding 
of an amino acid mixture deficient in leucine, isoleucine or valine. This may not seem as striking 
to some of you as it does to me, because quite obviously an animal that is getting adequate 
calories and vitamins and minerals can carry on for a very long time with relatively little difficulty, 
and the fact that forcing this amino acid mixture on these animals, which they won’t eat by 
themselves, incidentally—an expression of some sort of wisdom of nature—the fact that it leads 
to death in such a short time implies that there is a great deal more to amino acid balance, I 
think, than we really understand. 
Wrnitz: Yes, Dr. MILLER, this is undoubtedly very true. When you feed a diet that is completely 
devoid of only one of the essential amino acids, you are in effect imposing a more toxic condition 
than were you to supply no nitrogen source whatsoever. For example, were you to fast an animal 
overnight, don’t feed it anything but just fast it, a 200-gram animal would lose 10% of its 
body weight, or about 20 grams. Now were you to feed this same animal a nitrogen-free diet—just 
leave all the nitrogen out of an otherwise adequate diet—the animal loses weight, of course, but 
it doesn’t lose 20 grams per day; it uniformly loses only about 2 grams per day. So it takes an 
animal on a nitrogen-free diet a matter of ten days to lose the same amount of weight that a 
fasting animal loses overnight. Yet during all this time, the animal on the nitrogen-free diet 
appears healthy, happy and vigorous. If you were to add an amino acid mixture which lacks only 
one of the essential amino acids to this same nitrogen-free diet, this diet would now induce quite 
toxic effects. RosE observed this quite dramatically in this studies on the amino acid requirements 
of man, especially in his study on the isoleucine requirement wherein he fed his students diets 
deficient in this amino acid. After a few days on isoleucine-deficient diets, pronounced psycho- 
logical disturbances developed in these young men, who found it increasingly more difficult to 
tolerate the diet. In fact, their disturbed mental state became such that they actually pleaded 
with Rose to place them on a more tolerable diet. And all of this developed from an isoleucine 
deficiency in the diet. It’s really a remarkable phenomenon. 
H. RosenBerG: Rats will not take these mixed diets. How well do they take complete mixtures 
of amino acids? 
Wrnitz: Animals will, of course, accept these diets containing complete mixtures of amino 
acids—and very, very well—because when these diets are provided as the sole source of food, 
they will grow, undergo normal pregnancy, produce satisfactory litters and undergo normal 
lactation. This has been well established. It should also be pointed out that animals will accept, 
and again very well, nitrogen-free diets, although they will not grow on these diets. They 
will nevertheless ingest these diets at a remarkable rate. They will ingest them even more readily 
than they do a complete dietary mixture containing nitrogen, presumably because they are 
searching for a source of nitrogen. But should you give them a mixture from which only one 
essential amino acid has been left out, then they will soon reject it entirely. It now becomes 
necessary to force feed in order to study the effects induced by these diets. 
E. Roperts: Do they eat even a little bit of this mixture? 
Wrnitz: Just a very little bit and then they reject it. 
E. Roperts: That is sufficient signal so that they don’t eat any more? 
Winitz: Apparently so. But, it’s a very interesting thing, because if you now take this same 
mixture, in which you have only nine essential amino acids, and add the one that is missing, the 
animals will immediately accept the mixture and start eating again. 
WEsTALL: In view of the things that have just been said, it is extremely interesting that in the 
maple-syrup syndrome the first indication that these children might not be normal seems to 
occur at about the fourth day, when they have a disinclination to suck. The second point I would 
References p. 524 
