Editor: M. WINITZ 
Unt 
bo 
No 
like to say, too, that of all the metabolic diseases involving amino acids that we know so far, 
this one, which involves leucine, isoleucine and valine, is by far the most lethal, and many of the 
children with the disease die at about 11 to 12 days. 
SCHREIER: I should like to generalize, if I may. Any shortage of an essential factor in food—and 
the same thing applies to any overdosage—will initially appear in the appetite of the human 
being. If you have too little vitamin D children won’t eat and if you add too much they lose 
their appetites. Apparently it is due to something inborn. I further would like to add that if 
you give insufficient protein hydrolyzates to human premature infants, they don’t gain weight. 
If these are added to human milk, they will not grow better but rather they will show less growth 
and they will show a high excretion of several nitrogen products because of an imbalance, and 
you can find it in the blood. The amino acid missing, which is usually tryptophane, drops to a 
very low value. It almost cannot be found, and that may be the reason why there is no growth. 
E. Roperts: I am very much interested in this signal that goes to the central nervous system 
and is reflected in such a complex pattern as a refusal of the diet, on the basis of the absence of 
a single dietary constituent. I think that this certainly means that there must be centers in the 
brain which are constantly monitoring the total chemical composition in their environment and 
sending out signals which will then coordinate the activity of the organism with the environment 
on the basis of the findings. I think that is as clear as can be. And, therefore, I think there is a 
good reason for neurophysiologists to become interested in nutrition, which is a thing that is 
often furthest from their minds. 
SCHREIER: There are studies which show that the hunger of the human being and of animals is 
very well localized in the hypothalamus, and you can increase and decrease the hunger by in- 
creasing blood sugar—that is well known and an old phenomenon. MELInKorF found also that 
you can change the hunger feeling of the animal and the human being by increasing and de- 
creasing amino acids in blood. And the same thing, I think—I am not sure about it—holds with 
vitamin B,, which if given it in high doses, will immediately decrease the hunger feeling. 
L. MiLver: Decrease it? This is putting it right in the diet? 
SCHREIER: No, you inject it in high doses. 
H. RosENnBeERG: I would like to ask Dr. W1n1Tz, what is the time delay between tasting or con- 
suming an incomplete diet and the rejection? Is this a matter of tasting or is it actually con- 
sumed and monitored? 
Winitz: I think you have several effects combined. Appetite is probably one of them. Again, 
several years ago, we studied the physiological response to high concentrations of glucosamine 
in chemically defined diets. We carried out these studies because the work of QUASTEL, some 
years earlier, had indicated that p-glucosamine might be a good tumor inhibitor. What we 
attempted to do initially was use the p-glucosamine both as a dietary source of non-essential 
nitrogen and as a source of carbohydrate. However, it was soon found that the animals com- 
pletely rejected this diet, and as a result it became necessary to set up diets to which a source of 
non-essential nitrogen and glucose was added and which, in addition, contained varying amounts 
of glucosamine. It was now found that the animals would voluntarily ingest the diets, but that 
the amount of diet ingested varied inversely with the amount of glucosamine it contained. In 
fact, the variation of dietary intake with the glucosamine level was so quantitative and predict- 
able that it actually became possible for us to control the amount of weight that an animal would 
ultimately gain over a 50- or 60-day period, to within only a few grams, merely by employing 
a pre-determined and fixed level of p-glucosamine in the diet. The animals on the lowest p-glucos- 
amine diet—this was about 25 g of glucosamine per kg of dry weight of diet—ingested the diet 
in rather considerable amounts. But when the glucosamine level was raised to 150 g, the dietary 
intake fell off very markedly as, of course, did the growth. 
We felt that these ad libitum feeding experiments were not an adequate test of QUASTEL’s 
effect because at the high glucosamine levels, the dietary intake and hence the intake of glucos- 
amine was insufficient. So we subsequently undertook forced feeding studies with tumor-bearing 
animals, and we forced these animals, now, to take in larger quantities of these higher glucosamine 
diets than they would voluntarily inject per os. We found, in these experiments, that a high 
glucosamine intake had no effect on tumor growth. But more to the point of the present dis- 
cussion, we further found that animals, when force fed identical amounts of identical diets which 
differed only in the glucosamine level, showed exactly the same growth pattern, the same meta- 
bolic pattern, and the same degtee of nitrogen retention. So it appeared that the relation between 
dietary intake and glucosamine concentration was not due to any toxicity of the glucosamine 
per se. It rather looked like an appetite factor here. 
SCHREIER: May I try to answer, from the standpoint of human studies, the question raised 
by Dr. RosenBerG? If you leave a vitamin out of the diet, of course the taste of the diet remains 
entirely the same and children don’t notice it, so it would, depending on the missing vitamin, 
take several weeks or months before they stop eating. 
H. ROSENBERG: My question was really directed toward these rat experiments. I was just 
References p. 524 
