If obesity is always due to one very specific diencephalic deficiency, it follows that the only way to cure it is to correct this deficiency. At first this seemed an utterly hopeless undertaking. The greatest obstacle was that one could hardly hope to correct an inherited trait localized deep inside the brain, and while we did possess a number of drugs whose point of action was believed to be in the diencephalon, none of them had the slightest effect on the fat-center. There was not even a pointer showing a direction in which pharmacological research could move to find a drug that had such a specific action. The closest approach were the appetite-reducing drugs - the amphetamines----- but these cured nothing.
Mulling over this depressing situation, I remembered a rather curious observation made many years ago in India. At that time we knew very little about the function of the diencephalon, and my interest centered round the pituitary gland. Froehlich had described cases of extreme obesity and sexual underdevelopment in youths suffering from a new growth of the anterior pituitary lobe, producing what then became known as Froehlich's disease. However, it was very soon discovered that the identical syndrome, though running a less fulminating course, was quite common in patients whose pituitary gland was perfectly normal. These are the so-called “fat boys” with long, slender hands, breasts any flat-chested maiden would be proud to posses, large hips, buttocks and thighs with striation, knock-knees and underdeveloped genitals, often with undescended testicles.
It also became known that in these cases the sex organs could he developed by giving the patients injections of a substance extracted from the urine of pregnant women, it having been shown that when this substance was injected into sexually immature rats it made them precociously mature. The amount of substance which produced this effect in one rat was called one International Unit, and the purified extract was accordingly called “Human Chorionic Gonadotrophin” whereby chorionic signifies that it is produced in the placenta and gonadotropin that its action is sex gland directed.
The usual way of treating “fat boys” with underdeveloped genitals is to inject several hundred International Units twice a week. Human Chorionic Gonadotrophin which we shall henceforth simply call HCG is expensive and as “fat boys” are fairly common among Indians I tried to establish the smallest effective dose. In the course of this study three interesting things emerged. The first was that when fresh pregnancy-urine from the female ward was given in quantities of about 300 cc. by retention enema, as good results could be obtained as by injecting the pure substance. The second was that small daily doses appeared to be just as effective as much larger ones given twice a week. Thirdly, and that is the observation that concerns us here, when such patients were given small daily doses they seemed to lose their ravenous appetite though they neither gained nor lost weight. Strangely enough however, their shape did change. Though they were not restricted in diet, there was a distinct decrease in the circumference of their hips.
Remembering this, it occurred to me that the change in shape could only be explained by a movement of fat away from abnormal deposits on the hips, and if that were so there was just a chance that while such fat was in transition it might be available to the body as fuel. This was easy to find out, as in that case, fat on the move would be able to replace food. It should then he possible to keep a “fat boy” on a severely restricted diet without a feeling of hunger, in spite of a rapid loss of weight. When I tried this in typical cases of Froehlich's syndrome, I found that as long as such patients were given small daily doses of HCG they could comfortably go about their usual occupations on a diet of only 500 Calories daily and lose an average of about one pound per day. It was also perfectly evident that only abnormal fat was being consumed, as there were no signs of any depletion of normal fat. Their skin remained fresh and turgid, and gradually their figures became entirely normal, nor did the daily administration of HCG appear to have any side-effects other than beneficial.
From this point it was a small step to try the same method in all other forms of obesity. It took a few hundred cases to establish beyond reasonable doubt that the mechanism operates in exactly the same way and seemingly without exception in every case of obesity. I found that, though most patients were treated in the outpatients department, gross dietary errors rarely occurred. On the contrary, most patients complained that the two meals of 250 Calories each were more than they could manage, as they continually had a feeling of just having had a large meal.
Once this trail was opened, further observations seemed to fall into line. It is, for instance, well known that during pregnancy an obese woman can very easily lose weight. She can drastically reduce her diet without feeling hunger or discomfort and lose weight without in any way harming the child in her womb. It is also surprising to what extent a woman can suffer from pregnancy-vomiting without coming to any real harm.
Pregnancy is an obese woman's one great chance to reduce her excess weight. That she so rarely makes use of this opportunity is due to the erroneous notion, usually fostered by her elder relations, that she now has “two mouths to feed” and must “keep up her strength for the coming event. All modern obstetricians know that this is nonsense and that the more superfluous fat is lost the less difficult will be the confinement, though some still hesitate to prescribe a diet sufficiently low in Calories to bring about a drastic reduction.
A woman may gain weight during pregnancy, but she never becomes obese in the strict sense of the word. Under the influence of the HCG which circulates in enormous quantities in her body during pregnancy, her diencephalic banking capacity seems to be unlimited, and abnormal fixed deposits are never formed. At confinement she is suddenly deprived of HCG, and her diencephalic fat-center reverts to its normal capacity. It is only then that the abnormally accumulated fat is locked away again in a fixed deposit. From that moment on she is suffering from obesity and is subject to all its consequences.
Pregnancy seems to be the only normal human condition in which the diencephalic fat-banking capacity is unlimited. It is only during pregnancy that fixed fat deposits can be transferred back into the normal current account and freely drawn upon to make up for any nutritional deficit. During pregnancy, every ounce of reserve fat is placed at the disposal of the growing fetus. Were this not so, an obese woman, whose normal reserves are already depleted, would have the greatest difficulties in bringing her pregnancy to full term. There is considerable evidence to suggest that it is the HCG produced in large quantities in the placenta which brings about this diencephalic change.
Though we may be able to increase the dieneephalic fat banking capacity by injecting HCG, this does not in itself affect the weight, just as transferring monetary funds from a fixed deposit into a current account does not make a man any poorer; to become poorer it is also necessary that he freely spends the money which thus becomes available. In pregnancy the needs of the growing embryo take care of this to some extent, but in the treatment of obesity there is no embryo, and so a very severe dietary restriction must take its place for the duration of treatment.
Only when the fat which is in transit under the effect of HCG is actually consumed can more fat be withdrawn from the fixed deposits. In pregnancy it would be most undesirable if the fetus were offered ample food only when there is a high influx from the intestinal tract. Ideal nutritional conditions for the fetus can only be achieved when the mother's blood is continually saturated with food, regardless of whether she eats or not, as otherwise a period of starvation might hamper the steady growth of the embryo. It seems that HCG brings about this continual saturation of the blood, which is the reason why obese patients under treatment with HCG never feel hungry in spite of their drastically reduced food intake.