Blood. The Hormonal System

The success of the neuron theory was, like that of the germ theory, not absolute. It did not carry quite all before it. The electrical messengers coursing along the nerve were not the only controls of the body. There were chemical messengers, too, making their way through the blood stream.

In 1902, for instance, two English physiologists, Ernest Henry Starling (1866-1927)andWilliam Maddock Bayliss (1866-1924), found that even when all the nerves to the pancreas (a large digestive gland) were cut, it still performed on cue; it secreted its digestive juice as soon as the acid food contents of the stomach entered the intestine. It turned out that the lining of the small intestine, under the influence of the stomach acid, secreted a substance which Starling and Bayliss named "secretin." It was this secretin that stimulated the pancreatic flow. Two years later, Starling suggested a name for all substances discharged into the blood by a particular "endocrine gland" for the purpose of rousing some other organ or organs to activity. The word was "hormone" from Greek words meaning "to rouse to activity."

The hormone theory proved extraordinarily fruitful, for it was found that a large number of hormones, washing through the blood in trace concentrations, interlaced their effects delicately to maintain a careful balance among the chemical reactions of the body, or to bring about a well- controlled change where change was necessary. Already, the Japanese-American chemist, Jokichi Takamine (1854-1922), had, in 1901, isolated a substance from the adrenal glands which is now called epinephrine (or Adrenalin— a trade name) and this was eventually recognized as a hormone. It was the first hormone to be isolated and to have its structure determined.

One process that was quickly suspected of being hormone-controlled was that of the basal metabolic rate. Magnus-Levy had shown the connection between changes in BMR and thyroid disease, and the American biochemist, Edward Calvin Kendall (1886- ), was able, in 1916, to isolate a substance from the thyroid gland, which he called "thyroxine." This proved, indeed, to be a hormone whose production in small quantities controlled the BMR of the body.

The most spectacular early result of hormone work, however, was in connection with the disease, diabetes mellitus. This involved a disorder in the manner in which the body broke down sugar for energy, so that a diabetic accumulated sugar in his blood to abnormally high levels. Eventually, the body was forced to get rid of the excess sugar through the urine, and the appearance of sugar in the urine was symptomatic of an advanced stage of the disease. Until the twentieth century, the disease was certain death.

Suspicion arose that the pancreas was somehow connected with the disease, for in 1893, two German physiologists, Joseph von Mering (1849-1908)andOscar Minkowski (1858-1931), had excised the pancreas of experimental animals and found that severe diabetes developed quickly. Once the hormone concept had been propounded by Starling and Bayliss, it seemed logical to suppose that the pancreas produced a hormone which controlled the manner in which the body broke down sugar.

Attempts to isolate the hormone from the pancreas, as Kendall had isolated thyroxine from the thyroid gland failed, however. Of course, the chief function of the pancreas was to produce digestive juices, so that it had a large content of protein-splitting enzymes. If the hormone were itself a protein (as, eventually, it was found to be) it would break down in the very process of extraction.

In 1920, a young Canadian physician, Frederick Grant Banting (1891-1941), conceived the notion of tying off the duct of the pancreas in the living animal and then leaving the gland in position for some time. The digestive-juice apparatus of the gland would degenerate, since no juice could be delivered; while those portions secreting the hormone directly into the blood stream would (he hoped) remain effective. In 1921, he obtained some laboratory space at the University of Toronto and with an assistant, Charles Herbert Best (1899- ), he put his notion into practice. He succeeded famously and isolated the hormone "insulin." The use of insulin has brought diabetes under control, and while a diabetic cannot be truly cured even so and must needs submit to tedious treatment for all his life, that life is at least a reasonably normal and prolonged one.

Thereafter, other hormones were isolated. From the ovaries and testicles, the "sex hormones" (controlling the development of secondary sexual characteristics at puberty, and the sexual rhythm in females) were isolated by the German chemist Adolph Friedrich Johannes Butenandt (1903- ), in 1929 and the years thereafter.

Men such as Kendall, the discoverer of thyroxine, and the Polish-Swiss chemist, Tadeus Reichstein (1897- ), isolated a whole family of hormones, the "corticoids," from the outer portions (or "cortex") of the adrenal glands. In 1948, one of Kendall's associates, Philip Showalter Hench (1896- ), was able to show that one of these corticoids, "cortisone," had a beneficial effect on rheumatoid arthritis.

The pituitary gland, a small structure at the base of the brain, was shown, in 1924, by the Argentinian physiologist, Bernardo Alberto Houssay (1887- ), to be involved somehow with sugar breakdown. It turned out, later on, to have other important functions as well. The Chinese-American biochemist, Cho Hao Li (1913- ), in the 1930s and 1940s, isolated a number of different hormones from the gland. One, for instance, is "growth hormone," which controls the over-all rate of growth. When produced in excessive amounts, a giant result; in deficient amounts, a midget is produced.

The study of hormones, endocrinology, remains an extremely complicated aspect of biology in the mid-twentieth century, but an extremely productive one as well.