Pituitary Master

(See Cover)

Above and behind the mouth cavity, tucked into a cradle of bone at the base of the human brain, lies a reddish nugget of tissue, no bigger than a big pea in normal adults--the pituitary gland. Galen, the famed physician of antiquity, and Vesalius, the great anatomist of the Renaissance, knew it. They thought it gave saliva. In 1783 an Irishman named Charles O'Brien died at the age of 22. He was 8 ft. 4 in. tall. A curious physician bought his body for $2,500, dissected the head, found a pituitary gland almost as big as a hen's egg. Modern endocrinologists regard it as the "master gland" of the body.

Scientific research into the pituitary was not pushed until the 1920s, when Herbert McLean Evans of the University of California caused rats to become giants by injecting them with crude pituitary extract. He dwarfed rats by pituitary removal, then with pituitary injections restored them to normal size. He made it clear that the reddish little gland was intimately concerned with one of the most important of biological processes--growth. Since then the veil of ignorance has been gradually lifted.

Last week the American Association for the Advancement of Science held its winter convention in Richmond, Va. With an attendance of 7,000 and 1,800 papers to be presented, the multiple preoccupations of science had to share the spotlight. On hand to see that the pituitary got its share of attention, however, was a pituitary master: Dr. Oscar Riddle of the Carnegie Institution's Station for Experimental Evolution at Cold Spring Harbor, Long Island.

With a great deal of fruitful work behind him on animal pigmentation, on the physiology of reproduction, on the nature and functional basis of sex, and on bionomics,* Dr. Riddle ranks as one of the half-dozen top biologists of the U. S. He also knows more about the pituitary and its functions than anyone else in the U. S., with the possible exception of California's Evans.

At an age (61) when many scientists of bright repute have relaxed their efforts and slipped into the role of inspiring figureheads and advisers to younger men, Oscar Riddle remains in the front line of research.

Dr. Riddle's great contribution to biology is the recognition and analysis of the major pituitary hormone prolactin, discovered in 1932. This substance is the stuff that makes mothers motherly. In Richmond last week Dr. Riddle and two of his ablest co-workers--Robert Wesley Bates, 34, and James Plummer Schooley, 34--summarized their work on prolactin. Dr. Riddle is also, more than any other U. S. biologist, a crusader for the propagation of biologic truth among plain people, and at a dinner for biologists he steamed them up on the opportunities and obligations of biology teachers.

Front Lobe. The pituitary gland consists of three parts, two lobes and a narrow middle. In the smaller rear lobe, two hormones have been fairly well identified (alpha-hypophamine and beta-hypophamine), which appear respectively to influence uterine contractions and blood pressure. Biochemist James Bertram Collip of Montreal's McGill University discovered a hormone of the middle pituitary (appropriately called intermedia) which affects, though it does not exclusively control, the blood sugar level.

But the hormones secreted by the larger front lobe make the pituitary the "master gland." Yet no one knows just what or how many hormones the front lobe secretes. The trouble is that--although a few front lobe hormones have been freed of all but small traces of impurities--a living body's response under test may be due not to the hormone tested but to an "impurity."

Moreover, some responses are not due to one hormone, but to the combined action of two or more. This phenomenon is called "synergism." The work of Evans and others convinced many a gland man that the pituitary secreted a "growth hormone." Riddle's researches, however, tend to show that growth is a synergic response to two hormones, thyrotropin and prolactin. He also believes that this same pair get together in another synergism to maintain body heat.

The pituitary spurs other glands to produce hormones of their own, and in some cases these secretions may return to act on the pituitary. Thus primary, secondary and tertiary responses can be traced to the gland.

When these sources of confusion were less well understood than now, it was fashionable to attribute every pituitary reaction to a separate hormone. Riddle exposed some of these as "ghosts." He believes the number of definitely established front-lobe hormones to be small--five at most. These possible five are 1) thyrotropin, the thyroid-stimulator; 2) adrenotropin, which acts on the adrenals; 3) and 4), "FSH" and "LH" which affect the ovaries or testes; 5) prolactin.

Mother Love. Six years ago, by a repeated complicated procedure called "isoelectric precipitation," the Riddle laboratory crew obtained a pituitary substance which did not noticeably affect the thyroid or the sex glands, but which had a marked effect on the mammary glands. It started milk production not only in normal female guinea pigs but also in spayed females and males. In pigeons it thickened the crop sac, which provides a liquid ("pigeon milk") with which pigeons feed their young. Riddle called this new hormone prolactin.

Prolactin caused chickless hens and virgin rats to mother chicks and ratlets with great affection. This earned prolactin the nickname of "mother love" hormone. The implication of the discovery was that mother love, though doubtless fortified and colored in women by training and tradition has a physiological basis in a chemical substance--probably large protein molecules. (Dr. Riddle found that prolactin and other front-lobe hormones are disintegrated by trypsin, an enzyme which has the special property of "digesting" proteins.)

Busy Hormone. Prolactin also inhibits the activity of the sex glands, which is obviously nature's way of quieting the distraction of sex urges when parental behavior and responsibility are called for. And either alone or in concert with other hormones, it maintains the weight of abdominal organs; controls basal metabolism (heat production) ; promotes appetite; and probably also affects the metabolism of carbohydrates and fat.

Clinicians have given prolactin to human mothers to stimulate milk production. Result: some successes, some failures. In the failures, however, the mammary tissue of the mother was usually itself deficient. The job of preparing the mammary tissue for nursing seems to belong to the sex hormones estrone and progesterone. Prolactin's job is to start milk secretion after the breasts are ready.

Charting & Checking. The station at Cold Spring Harbor is a cluster of buildings beside a tranquil bay off Long Island Sound. There Dr. Riddle and his co-workers have painstakingly tested prolactin and other front-lobe hormones on normal animals, fasting animals, animals without pituitaries, without thyroids, without adrenals.

They have measured the crop-sac response of pigeons so closely that it serves as a quantitative test for prolactin in samples sent there by other laboratories. Dr. Bates, who took part in the original discovery of the hormone, has specialized in this "biological assay." Dr. Schooley has worked out a pituitary removal technique for pigeons, going in through the pharynx at the back of the throat, which leaves the back lobe of the gland intact so that almost all the birds survive the operation.

In Dr. Riddle's opinion, the higher vertebrates have a dual control system, the brain and the pituitary. That they are closely associated is shown by the ability of prolactin to produce a psychological phenomenon, maternal behavior. How hormones work on the brain and nervous system remains a stubborn mystery. The fact of their association, however, shows that mind and body are not separate, that a living organism is one "body-mind." Says he: "The mind has been firmly placed in an evolutionary frame. . . . The consciousness of dog and man has evolved . . . in the same unbroken way that the function of the digestive or glandular system has evolved."

Crusader. Oscar Riddle was born in Cincinnati, Ind., got his Ph.D. at the University of Chicago, after returning from a natural history expedition to South America's Orinoco River, was well on the way to becoming an ichthyologist when a lecture on evolution gave a new turn to his career. He went to the Carnegie Institution's station at Cold Spring Harbor in 1912 as a research associate, and, except for a Wartime sojourn in France, has stayed there ever since.

When Dr. Riddle talks most earnestly about glands, he is apt for emphasis to indicate their location on his own person, and his eyes begin to sparkle. He smokes a great many de-nicotinized cigarets down to ragged little stubs. In his enthusiasm he lunches in his laboratory on sandwiches, coffee and condensed cream, perhaps with the bloody carcass of a rat in the sink at his elbow and surrounded by jars of pickled pigeon specimens. He used to play golf but has given it up, used to be a bachelor, but gave that up also almost at the age of 60, when he married in 1937.

His only hobby nowadays is the propagation of biologic truth--which, says Oscar Riddle, provides man with his "just hope for grandeur and power, and happiness." No cloistered, secretive scientist, he constantly sallies forth to preach the necessity of wider understanding of biological research.

"Every biologist," he says, "knows that his science--the life-sciences--can extend the mental horizon, give better health, improve the economic status and promote the social understanding of any people or nation that will teach the subject adequately to its youth. The peoples of India or China are restrained far more by ignorance of simple biological truth than by unfamiliarity with letters, arithmetic or the rules of trade."

Because the majority of young people do not get past high school, Dr. Riddle wants increased emphasis on science and particularly biology in the primary and secondary schools, where it is weakest and growing weaker.

He is exasperated because opposition to the teaching of evolution has not died out, although it is accepted as an ABC fact by every biologist of standing, and modern biology is unintelligible without it. As a horrendous example of pussyfooting, he quotes the declaration of a Philadelphia school principal:

"The old theory of evolutionists as to whether man is descended from the monkey has been over these many years.* Such teaching is discredited and is not representative of science and so will not be found in our textbooks. The public schools teach biology. In this study, the difference of the species is indicated."

As a result of such attitudes as this, says Dr. Riddle, "an eviscerated straw man is set up in place of the reality. . . . Many millions of our present and future citizens are robbed of a biological outlook, or they get one that is warped and unrecognizable."

After three decades of research on the heredity mechanism of the genes and chromosomes he has a strong opinion on the first thing that biology should teach humanity: "All men are created unequal. No politics or poetry or dogma in this; just a straight clean fact of prime importance to decent thinking on human social problems; and possibly a fact that must be learned, digested and assimilated . . . before unreason ceases to be a threat to all forms of democratic government."

* The relation of living things to one another and to their environment.

*Consensus of anthropologists is that man is descended from a generalized type of Dryopithecus, an extinct ape whose fossil remains have been widely found.

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