Asimov's New Guide to Science

by Isaac Asimov

  The nearest thing to an answer is the pituitary, a small gland suspended from the bottom of the brain (but not part of it). The name of the gland arose from an ancient notion that its function was to secrete phlegm, the Latin word for which is pituita (also the source of the word spit). Because this notion is false, scientists have renamed the gland the hypophysis (from Greek words meaning “growing under”—that is, under the brain), but pituitary is still the more common term.

  The gland has three parts: the anterior lobe, the posterior lobe, and, in some organisms, a small bridge connecting the two. The anterior lobe is the most important, for it produces at least six hormones (all small-molecule proteins), which seem to act specifically upon other ductless glands. In other words, the anterior pituitary can be viewed as the orchestra leader that keeps the other glands playing in time and in tune. (It is interesting that the pituitary is located just about in the center of the skull, as if deliberately placed in a spot of maximum security.)

  One of the pituitary’s messengers is the thyroid-stimulating hormone (TSH). It stimulates the thyroid on a feedback basis: that is, it causes the thyroid to produce thyroid hormone. The rise in concentration of thyroid hormone in the blood, in turn, inhibits the formation of TSH by the pituitary; the fall of TSH in the blood in its turn reduces the thyroid’s production; that stimulates the production of TSH by the pituitary, and so the cycle maintains a balance.

  In the same way, the adrenal-cortical-stimulating hormone, or adrenocorticotropic hormone (ACTH), maintains the level of cortical hormones. If extra ACTH is injected into the body, it will raise the level of these hormones and thus can serve the same purpose as the injection of cortisone itself. ACTH has therefore been used to treat rheumatoid arthritis.

  Research into the structure of ACTH has proceeded with vigor because of this tie-in with arthritis. By the early 1950s, its molecular weight had been determined as 20,000, but it was easily broken down into smaller fragments (corticotropins), which possessed full activity. One of them, made up of a chain of thirty-nine amino acids, has had its structure worked out completely, and even shorter chains have been found effective.

  ACTH has the ability of influencing the skin pigmentation of animals, and even humans are affected. In diseases involving overproduction of ACTH, human skin darkens. It is known that in lower animals, particularly the amphibians, special skin-darkening hormones exist. A hormone of this sort was finally detected among the pituitary products in the human being in 1955. It is called melanocyte-stimulating hormone (melanocytes being the cells that produce skin pigment) and is usually abbreviated MSH.

  The molecule of MSH has been largely worked out; it is interesting to note that MSH and ACTH share a seven amino-acid sequence in common. The indication that structure is allied to function (as, indeed, it must be) is unmistakable.

  While on the subject of pigmentation, it might be well to mention the pineal gland, a conical body attached, like the pituitary, to the base of the brain and so named because it is shaped like a pine cone. The pineal gland has seemed glandular in nature, but no hormone could be located until the late 1950s. Then the discoverers of MSH, working with 200,000 beef pineals, finally isolated a tiny quantity of substance that, on injection, lightened the skin of a tadpole. The hormone, named melatonin, does not, however, appear to have any effect on human melanocytes.

  The list of pituitary hormones is not yet complete. A couple of pituitary hormones, ICSH (interstitial cell-stimulating hormone) and FSH (follicle-stimulating hormone) control the growth of tissues involved in reproduction. There is also the lactogenic hormone, which stimulates milk production.

  Lactogenic hormone stimulates other postpregnancy activities. Young female rats injected with the hormone busy themselves with nest building even though they have not given birth. On the other hand, mice whose pituitaries have been removed shortly before giving birth to young exhibit little interest in the baby mice. The newspapers at once termed lactogenic hormone the “mother-love hormone.”

  These pituitary hormones, associated with sexual tissues, are lumped together as the gonadotropins. Another substance of this type is produced by the placenta (the organ that serves to transfer nourishment from the mother’s blood to the blood of the developing infant and to transfer wastes in the opposite direction). The placental hormone is called human chorionic gonadotropin and is abbreviated HCG. As early as two to four weeks after the beginning of pregnancy, HCG is produced in appreciable quantities and makes its appearance in the urine. When extracts of the urine of a pregnant woman are injected into mice, frogs, or rabbits, recognizable effects can be detected. Pregnancy can be determined in this way at a very early stage.

  The most spectacular of the anterior pituitary hormones is the somatotropic hormone (STH), more popularly known as the growth hormone. Its effect is general, stimulating growth of the whole body. A child who cannot produce a sufficient supply of the hormone will become a dwarf; one who produces too much will turn into a circus giant. If the disorder that results in an oversupply of the growth hormone does not occur until after the person has matured (that is, when the bones have been fully formed and hardened), only the extremities—such as the hands, feet, and chin-grow grotesquely large—a condition known as acromegaly (Greek for “large extremities”). It is this growth hormone that Li (who first determined its structure in 1966) synthesized in 1970.

  THE ROLE OF THE BRAIN

  Hormones act slowly. They have to be secreted, carried by the blood to some target organ, and build up to some appropriate concentration. Nerve action is very rapid. Both slow control and fast control are needed by the body under various conditions, and to have both systems in action is more efficient than to have either alone. It is not likely that the two systems are entirely independent.

  The pituitary, which is a kind of master gland, is suspiciously close to the brain, almost a part of it. The part of the brain to which the pituitary is attached by a narrow stalk is the hypothalamus; and from the 1920s, it was suspected that there was some kind of connection.

  In 1945, the British biochemist, Geoffrey W. Harris, suggested that the cells of the hypothalamus produced hormones that could be taken by the bloodstream directly to the pituitary. These hormones were detected and termed releasing factors. Each particular releasing factor will bring about the production by the anterior pituitary of one of its hormones.

  In this way, the nervous system can, to an extent, control the hormone system.

  The brain, as a matter of fact, seems increasingly to be not merely a “switchboard” of nerve cells in superintricate arrangement, but is a highly specialized chemical factory that may turn out to be just as intricate.

  The brain, for instance, contains certain receptors that receive nerve impulses to which it ordinarily responds by producing the sensation of pain. Anesthetics such as morphine and cocaine attach themselves to the receptors and blank out the pain.

  Sometimes people, under the stress of strong emotion, do not feel pain when ordinarily they would. Some natural chemical must block the pain receptors on those occasions. In 1975, such chemicals were found and isolated from the brains of animals at a number of laboratories. They are peptides, short chains of amino acids, the shortest (enkephalins) made up of five amino acids only, while longer ones are endorphins.

  It may well be that the brain creates, fleetingly, large numbers of different peptides each of which modifies brain action in some way—easily produced, easily broken down. To understand the brain, it is likely that it will have to be studied intimately both chemically and electrically.

  THE PROSTAGLANDINS

  Before leaving the hormones, I should mention a group that have recently become prominent that are built up of neither amino acids nor a steroid nucleus.

  In the 1930s, the Swedish physiologist Ulf Svante von Euler isolated a fat-soluble substance from the prostate gland, which, in small quantities, lowered blood pressure and caused certain smooth muscles to contract. (Van Euler was the so
n of Nobel Laureate Euler-Chelpin and went on to win a share of the 1970 Nobel Prize for physiology and medicine for his work on nerve transmission.) Van Euler called the substance prostaglandin because of its source.

  It turned out to be not one substance but many. At least fourteen prostaglandins are known. Their structure has been worked out, and they are found all to be related to polyunsaturated fatty acids. It may be because of the need to form prostaglandins that the body, which cannot manufacture these fatty acids, requires them in the diet. They all have similar effects on blood pressure and smooth muscle but to different degrees, and their functions are not yet entirely elucidated.

  HORMONE ACTION

  How do hormones work?

  It seems certain that the hormones do not act as enzymes. At least, no hormone has been found to catalyze a specific reaction directly. The next alternative is to suppose that a hormone, if not itself an enzyme, acts upon an enzyme: that it either promotes or inhibits an enzyme’s activity. Insulin, the most thoroughly investigated of all the hormones, does seem to be definitely connected with an enzyme called glucokinase, which is essential for the conversion of glucose to glycogen. This enzyme is inhibited by extracts from the anterior pituitary and the adrenal cortex, and insulin can nullify that inhibition. Thus, insulin in the blood may serve to activate the enzyme and so speed up the conversion of glucose to glycogen. That would help to explain how insulin lowers the glucose concentration in the blood.

  Yet the presence or the absence of insulin affects metabolism at so many points that it is hard to see how this one action could bring about all the abnormalities that exist in the body chemistry of a diabetic. (The same is true for other hormones.) Some biochemists have therefore tended to look for grosser and more wholesale effects.

  There is the suggestion that insulin somehow acts as an agent to get glucose into the cell. On this theory, a diabetic has a high glucose level in his blood for the simple reason that the sugar cannot get into his cells and therefore he cannot use it. (In explaining the insatiable appetite of a diabetic, Mayer, as I have already mentioned, suggested that glucose in the blood has difficulty in entering the cells of the appestat.)

  If insulin assists glucose in entering the cell, then it must act on the cell membrane in some way. How? Cell membranes are composed of protein and fatty substances. We can speculate that insulin, as a protein molecule, may somehow change the arrangement of amino-acid side chains in the protein of the membrane and thus open doors for glucose (and possibly many other substances).

  If we are willing to be satisfied with generalities of this kind, we can go on to suppose that the other hormones also act on the cell membranes, each in its own fashion because each has its own specific amino-acid arrangement. Similarly, steroid hormones, as fatty substances, may act on the fatty molecules of the membrane, either opening or closing the door to certain substances. Clearly, by helping a given material to enter the cell or preventing it from doing so, a hormone could exert a drastic effect on what goes on in the cell. It could supply one enzyme with plenty of substrate to work on and deprive another of material, thus controlling what the cell produces. Assuming that a single hormone may decide the entrance or nonentrance of several different substances, we can see how the presence or the absence of a hormone could profoundly influence metabolism, as in fact it does in the case of insulin.

  The picture I have drawn is attractive but vague. Biochemists would much prefer to know the exact reactions that take place at the cell membrane under the influence of a hormone. The beginning of such knowledge came with the discovery in 1960 of a nucleotide like adenylic acid except that the phosphate group was attached to two different places in the sugar molecule. Its discoverers, Earl Wilbur Sutherland, Jr., and Theodore W. Rall, called it cyclic AMP. It was “cyclic” because the doubly attached phosphate-group formed a circle of atoms, and AMP stood for “adenine monophosphate,” an alternate name for adenylic acid. Sutherland received the 1971 Nobel Prize for physiology and medicine for this work.

  Once discovered, cyclic AMP was found to be widely spread in tissue, and to have a pronounced effect on the activity of many different enzymes and cell processes. Cyclic AMP is produced from the universally occurring ATP by means of an enzyme named adenyl cyclase, which is located at the surface of cells. There may be several such enzymes, each geared for activity in the presence of a particular hormone. In other words, the surface activity of hormones serves to activate an adenyl cyclase that leads to the production of cyclic AMP, which alters the enzyme activity within the cell, producing many changes.

  Undoubtedly, the details are enormously complex, and compounds other than cyclic AMP may be involved (possibly the prostaglandinsl=—but it is a beginning.

  Death

  The advances made by modern medicine in the battle against infection, against cancer, against nutritional disorders, have increased the probability that any given individual will live long enough to experience old age. Half the people born in this generation can be expected to reach the age of seventy (barring a nuclear war or some other prime catastrophe).

  The rarity of survival to old age in earlier eras no doubt accounts in part for the extravagant respect paid to longevity in those times. The Iliad, for instance, makes much of “old” Priam and “old” Nestor. Nestor is described as having survived three generations of men; but at a time when the average length of life could not have been more than twenty to twenty-five, Nestor need not have been older than seventy to have survived three generations. That is old, yes, but not extraordinary by present standards. Because Nestor’s antiquity made such an impression on people in Homer’s time, later mythologists supposed that he must have been something like two hundred years old.

  To take another example at random, Shakespeare’s Richard II opens with the rolling words: “Old John of Gaunt, time-honored Lancaster.” John’s own contemporaries, according to the chroniclers of the time, also considered him an old man. It comes as a slight shock to realize that John of Gaunt lived only to the age of fifty-nine. An interesting example from our own history is that of Abraham Lincoln. Whether because of his beard, or his sad, lined face, or songs of the time that referred to him as “Father Abraham,” most people think of him as an old man at the time of his death. One could only wish that he had lived to be one. He was assassinated at the age of fifty-six.

  All this is not to say that really old age was unknown in the days before modern medicine. In ancient Greece, Sophocles, the playwright, lived to be ninety; and Isocrates, the orator; to ninety-eight. Flavius Cassiodorus of fifth-century Rome died at ninety-five. Enrico Dandolo, the twelfth-century doge of Venice, lived to be ninety-seven. Titian, the Renaissance painter, survived to ninety-nine. In the era of Louis XV, the Due de Richelieu, grandnephew of the famous cardinal, lived ninety-two years; and the French writer Bernard Le Bovier de Fontenelle managed to arrive at just a month short of one hundred years.

  This emphasizes the point that although the average life expectancy in medically advanced societies has risen greatly, the maximum life span has not. We expect very few individuals, even today, to attain or exceed the lifetime of an Isocrates or a Fontenelle. Nor do we expect modern nonagenarians to be able to participate in the business of life with any greater vigor. Sophocles was writing great plays in his nineties, and Isocrates was composing great orations. Titian painted to the last year of his life. Dandolo was the indomitable leader of a Venetian war against the Byzantine Empire at the age of ninety-six. (Among comparably vigorous oldsters of our day, the best example I can think of is George Bernard Shaw, who lived to ninety-four, and the English mathematician and philosopher Bertrand Russell, who was still active in his ninety-eighth year, when he died.)

  Although a far larger proportion of our population reaches the age of sixty than ever before, beyond that age life expectancy has improved very little over the past. The Metropolitan Life Insurance Company estimates that the life expectancy of a sixty-year-old American male in 1931 was just abou
t the same as it was a century and a half earlier—that is, 14.3 years against the estimated earlier figure of 14.8. For the average American woman, the corresponding figures were 15.8 and 16.1. Since 1931, the advent of antibiotics has raised the expectancy at sixty for both sexesby two and a half years. But on the whole, despite all that medicine and science have done, old age overtakes a person at about the same rate and in the same way as it always has. We have not yet found a way to stave off the gradual weakening and eventual breakdown of the human machine.

  ATHEROSCLEROSIS

  As in other forms of machinery, it is the moving parts that go first. The circulatory system—the pulsing heart and arteries—is the human’s Achilles’ heel in the long run. Our progress in conquering premature death has raised disorders of this system to the rank of the number-one killer. Circulatory diseases are responsible for just over half the deaths in the United States; and of these diseases, a single one, atherosclerosis, accounts for one death out of four.

  Atherosclerosis (from Greek words meaning “mealy hardness”) is characterized by grainlike fatty deposits along the inner surface of the arteries, which force the heart to work harder to drive blood through the vessels at a normal pace. The blood pressure rises, and the consequent increase in strain on the small blood vessels may burst them. If this happens in the brain (a particularly vulnerable area), one has a cerebral hemorrhage, or stroke. Sometimes the bursting of a vessel is so minor that it occasions only a trifling and temporary discomfort or even goes unnoticed, but a massive collapse of vessels will bring on paralysis or a quick death.