The Glands Regulating Personality - Louis Berman, M.D.
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These experiments, their nature, the manner in which they were
conducted, the character and age of the experimenter, and the results
claimed, were exquisitely good stuff for ridicule. Cartoonists and
reporters leaped upon the theme with the avidity of the true-blue
interviewer. Paris, where to be ridiculed is to be killed in public
with the most ignominious of deaths, reacted as only the French
temperament can react. The wits of the salons crackled, the
bourgeoisie chortled, the proletariat roared. The Elixir of Life had
been discovered and it was excellent sport.
But Brown-Sequard remained unshaken. He had all the roues of Paris
running to him, and consequent charges of quackery and charlatanism.
How much of these unsavory epithets really applied to him will not be
determined until we have a better acquaintance with his more intimate
life. A biography and collection of his letters is needed. But it is
certain that the general principles he arrived at, aided as much by
the wings of intuition as by the clues of incomplete and incompletely
controlled experiments, survive as the foundations of whatever we know
about the internal secretions, and all our present viewpoints. He
summed these up in 1891 as follows:
"All the tissues, in our view, are modifiers of the blood by means of
an internal secretion taken from them by the venous blood. From this
we are forced to the conclusion that, if subcutaneous injections of
the liquids drawn from these parts are ineffectual, then we should
inject some of the venous blood supplying these parts.... We admit
that each tissue, and, more generally, each cell of the organism,
secretes on its own account, certain products or special ferments,
which, through this medium (the blood), influence all other cells of
the body, a definite solidarity being thus established among all the
cells through a mechanism other than the nervous system.... All
the tissues (glands and other organs) have thus a special internal
secretion, and so give to the blood something more than the waste
products of metabolism. The internal secretions, whether by direct
favorable influence, or whether through the obstacles they oppose to
deleterious processes, seem to be of great utility in maintaining the
organism in its normal state."
The only part of this statement not conceded today is that relating to
the formation of internal secretions by tissues other than those of
which the cells are definitely glandular, that is secretory: as can be
determined under the microscope. Brown-Sequard added to the concept
of internal secretions, fathered by Claude Bernard, the idea of a
correlation, a mutual influencing of them and of the different organs
of the body through them. The nervous system had hitherto been
regarded as the sole means of communication between cells, by its
telegraphic arrangements of nerve filaments reaching out everywhere,
interweaving with each other and the cells. The Brown-Sequard
conception inferred the existence of a postal system between cells,
the blood supplying the highway for travel and transmission of the
post, the post consisting of the chemical substances secreted by
the glands. To be sure, the doctrine was only an inference, though
well-founded, of which the direct experimental proof was not to
be obtained until the researches of Bayliss and Starling. Yet to
Brown-Sequard belongs the immortal credit, if not of the originator,
at any rate of the resurrector of the idea of using gland extracts to
influence the body. The unwarranted hopes aroused by his enthusiastic
reports of rejuvenating miracles have long since been dissipated.
Moreover, they smeared the whole subject with a disrepute which clings
to certain narrow and unreasonable minds to this day. But as every
physiologist since has acknowledged, he was and remains the great
path-breaker in the conquest of the internal secretions.
THE HORMONES
The problem of the internal secretions was now attacked from another
angle. A great Russian physiologist, Pawlow, called attention to the
fact that the introduction of a dilute mineral acid, such as the
hydrochloric acid, normally a constituent of the stomach digestive
fluid, into the upper part of the intestine, provoked a secretion
of the pancreas, which is so important for intestinal digestion. He
explained the phenomenon as a reflex, a matter of the nerves going
from the intestine to the pancreas.
His pupil, Popielski, threw doubt upon so easy an explanation, by
proving that the same reaction could be elicited even after all the
nerve connections between the gut and the spinal cord were severed. If
the relation was a reflex, it would have to be classed now as one of
those local nerve circuits, which are pretty common among the viscera,
a local call and reply as it were, without mediation of the great long
distance trunk lines in the spinal cord and the medulla oblongata.
The work of Bayliss and Starling, two English physiologists, was
commenced then to test the hypothesis. They soon found that the
experiment could be so devised as to exclude any influence whatever on
the part of the nervous tissues, and yet result positively. Thus, if a
loop of intestine was so prepared as to be attached to the rest of the
body only by means of its blood vessels, all the nerves being cut,
putting some acid into it was still followed by a flow of pancreatic
juice, no less marked than when none of the parts about the piece
of gut had been disturbed. It was evident that the stimulus to the
pancreas was carried by way of the blood stream. That the stimulating
substance was not the acid itself, was shown by the failure of the
reaction to occur when the acid was injected directly into the blood
stream. Since there was this difference in the effects between acid in
the intestine and acid in the blood, it was manifest that the active
substance must be some material elaborated in the intestinal mucous
membrane under the influence of the acid. So they scraped some of the
lining of the bowel, rubbed it up with acid, and injected the filtered
mixture into the blood. They were rewarded by a flow of pancreatic
juice greater in amount than any obtained in their other experiments.
From the filtered mixture they isolated in an impure form, a solid
substance which, when introduced into the circulation, has a similar
action. To this, of which the exact chemical make-up is as yet an
unknown, they gave the name secretin.
Secretin and its properties they used to generalize as a perfectly
direct and amply demonstrable example of an internal secretion.
Metaphors are no less valuable in physiology than in poetry. They
declared that the internal secretions appeared to them to be chemical
messengers, telegraph boys sent from one organ to another through the
public highways, the blood (really more like a moving platform). So
they christened them all hormones, deriving the word from the Greek
verb meaning to rouse or set in motion. As a science is a well-made
language, a new word is an event. It sums up details, economizes
brain-work and so is cherished by the intellect. The study of the
internal secretions has advanced by leaps and bounds since it became
convenient to speak of them as hormones. Withal, the brilliant work of
Bayliss and Starling stands as the third great foundation stone,
the first Claude Bernard's and the second Brown-Sequard's, in the
architecture of the modern concepts of the internal secretions.
CHAPTER II
THE GLANDS: THYROID AND PITUITARY
The glands of internal secretion, the history of which, as tools of
thought, I reviewed in the previous chapter, have each an interesting
evolutionary story. Without some acquaintance with that story, the
rough outline of their physical architecture, and the particular work
they are called upon to perform in the body, no adequate understanding
of their influence upon types of human nature and personality is
possible.
THE THYROID GLAND
This gland consists of two maroon colored masses astride the neck,
above the windpipe, close to the larynx. These are bridged by a narrow
isthmus of the same tissue. They remind one of the flaps of a purse
opened up. The gland has always attracted much attention because its
enlargement constitutes the prominent deformity known as goitre.
To begin with, the thyroid was once a sex gland, pure and simple. In
the lowest vertebrates and in the homologous tissues of the higher
invertebrates, the fractions of the thyroid are intimately connected
with the ducts of the sexual organs. They are indeed accessory sexual
organs, uterine glands, satellites of the sex process. From Petromyzon
upward that relationship is lost, the thyroid migrates more and more
to the head region, to become the great link between sex and brain.
How alive that function still is, is grossly shown by the swelling of
the gland with sexual excitement, menstruation and pregnancy.
Relative to the body weight it is largest in the mammalia, and
smallest in the fishes. It therefore grows larger as the vertebrate
ascends in the scale. It has, in fact, developed in direct proportion
to and side by side with the fundamental, differentiating vertebrate
characteristics. Of these, the possession of a dry hairy skin instead
of a moist or mucus bearing, chitinous skin, the ownership of
an internal bony skeleton and a large skull, and a complicated
development of brain, are the diagnostic signs. Thyroid internal
secretion has a very definite controlling relation to all of them: to
skin, its hairiness, moisture and amount of mucus, to the growth and
size of the bones, especially the bones of the extremities and the
skull, and to intelligence and the complexity of the convolutions of
the brain. Injury to the thyroid, especially in growing animals, is
followed by profound retrogression or arrest of development in skin,
skeleton and brain.
In the fishes and the cyclostomes the thyroid is represented only by
some small scrubby patches, little larger than the heads of pins,
scattered along the aorta, the great blood vessels from the heart, and
out a little way along each gill. It becomes larger and more compact
among the amphibians and reptiles, but still remains quite small.
Large and prominent among the birds and mammalia, it is largest and
most prominent among the primates and man. It is hence permissible to
think of the thyroid as a dictator of evolution, to crown it as the
vertebrate gland par excellence, and to call the typical vertebrate
brand marks secondary _thyroid_ characteristics in precisely the
sense of Darwin classing the horns of cattle as secondary _sexual_
characteristics.
In such enthusiasm for the thyroid as a determinant of evolution, its
pillar of cloud by day and column of fire by night, one should not
forget the other glands of internal secretion. In them all, we may
suppose, Life, tired of inventing merely prehensile, destructive and
reproductive organs, hit upon the happy thought of contrivances which
are in essence chemical factories to speed up the rate of variation
and so of a higher evolution.
CREATOR OF THE LAND ANIMAL
According to this conception the thyroid played a fundamental part in
the change of sea creatures into land animals. Experimentally, thyroid
has been used to transform one into the other. Thus the occasional
change of a Mexican axolotl, a purely aquatic newt, breathing through
gills, into the amblystoma, a terrestrial salamander, with spotted
skin, breathing by means of lungs, has long been known. Feeding the
axolotl on thyroid gland produces the metamorphosis very quickly, even
if the axolotl is kept in water. In the reptile house at the London
Zoological Gardens full-grown examples of the common black axolotl and
the pretty white variety are exhibited. Some are nearly three inches
long. Alongside are shown several examples of the amblystoma stage,
produced in one of the laboratories of Oxford University and at
the gardens by thyroid feeding. A variation of the thyroid in the
direction of increased secretion was probably responsible for the
first land animals.
THYROXIN, SECRETION OF THE THYROID
Under the microscope, as in the test tube, the thyroid shows
remarkable and unique features. Closed spherules lined by a single
layer of cells enclosing a gelatinous material known as colloid, which
stains deeply with acid dyes, comprise the units of its architecture.
Essentially, it may be pictured as a series of jelly bubbles secreted
by outlying cells.
A relatively high percentage of iodine is the unique distinctive fact
in its chemistry. Discovered by Baumann in 1895, the presence of the
element has focused the intelligence of chemists upon the gland,
with the consequent demonstration of arsenic also in it. It was soon
manifest that the secretion of the gland was dependent upon the
iodine content for its activity. Active extracts of the thyroid like
thyreoglobulin and iodothyrin were proven to contain iodine, and to
become inactive when the iodine was removed. Efforts to isolate the
iodine containing active principle in pure form were fruitless until
the work of Kendall at the Mayo Foundation. He obtained it as a white,
finely crystalline, odorless and tasteless substance, heat stable,
and analyzable. The free form separates as a sheaf of fine needles.
Kendall at first called it the a-iodine compound, then named it
thyroxin.
There are other internal secretions of the thyroid, with a function of
their own, that have no iodine. But they are secondary, and obscure.
Thyroxin is accepted today as the purified internal secretion of the
thyroid because all the effects of the whole gland may be elicited
with it. Thyroxin produces results with doses amazingly minute
compared with the quantity of whole gland necessary. Moreover, a dose
of thyroxin appears to last an organism in need of it over a period of
time; the other has to be administered continuously.
Studies with thyroxin carried on in recent years have rounded out the
whole concept of the business of the thyroid in the body economy.
One may sum it up by saying that the thyroid secretion is the _great
controller of the speed of living_. The more thyroid one has, the
faster one lives; the less one has, the more slowly one lives.
That is not to imply any direct proportion between the amount of
thyroid secretion in an individual, and the length of life to which he
is destined. The speed of living, in the chemical sense (which is the
fundamental sense), and the rate at which the chemical reactions go on
that constitute the process of life, are dependent upon the thyroid.
When the reactions go faster, more oxygen and food material are burned
up or oxidized, more energy is liberated, the metabolic wheel rotates
more quickly, the individual senses, feels, thinks and acts more
quickly.
Likening one energy machine to another, the thyroid may be compared
to the accelerator of an automobile. That is a rough and superficial
comparison because an accelerator lets in more of the fuel to be
burned up, while the thyroid makes the fuel more combustible. It thus
resembles more the primer, for a rich mixture of gasoline and air
burns at a greater velocity than a poor one. But the action of thyroid
could really be simulated only by some substance that could be
introduced into the best possible of gasoline mixtures, to increase
its combustibility by a hundred per cent or more. For that is what
thyroid will do to our food. Nor has it only this destructive or
combustion side. Withal there is at the same time a constructive
action, for the process frees energy to be used for heat, motion or
other need. The thyroid, therefore, in addition to its role as an
accelerator, acts, too, as the efficient lubricator for energy
transformations. So we see it as accelerator, lubricator and
transformer of our energies.
THE GLAND OF ENERGY PRODUCTION
The isolation of thyroxin has made possible the determination of the
influence of the thyroid hormone upon the evolution of energy in any
higher animal organism. There is, for every individual, a constant,
known as the metabolic rate, or the combustion rate, a reading of the
rate at which his cells are consuming material for heat. The metabolic
rate is thus a gauge of the energy pressure within the organism.
It may be calculated by measuring the amount of carbon dioxide gas
exhaled during a unit of time, and the number of calories of heat
radiated by the skin simultaneously. A simplified device has lately
rendered it practicable to make actual determinations by a few
five-minute readings of the rate of oxygen absorption by the lungs.
Plummer, also connected with the Mayo Foundation, has shown that what
would amount to less than a grain of the thyroxin would more than
double the amount of energy produced in a unit of time. To be exact,
one milligram of thyroxin increases the metabolic rate two per cent.
That illustrates some of the power of the internal secretion of the
thyroid and its importance to normal life.
THE MOBILIZATION OF ENERGY
But not only is the height of pressure of energy in the cells
controlled by the thyroid. The mobility of that energy is also
controlled. Without it, rapid and large fluctuations of energy output,
and elasticity and flexibility of energy mobilization for any sudden
mental or muscular act, let alone an emergency, become impossible. A
woman suffering with myxedema, the condition described by the English
physician Gull as a cretinoid state supervening in the adult life
of woman, has an insufficient amount of thyroxin in her blood and
tissues. She is clumsy and awkward and will stumble when endeavoring
to walk upstairs. Any effort is almost paralyzed because the range
of fluctuation of energy, the ability to mobilize energy, in turn
dependent upon an ability to increase the metabolic rate, is limited.
In slang phrase, she cannot step on it. Her existence is set to go at
a rate in the neighborhood of forty per cent below the normal. By the
administration of thyroxin, her metabolic rate can be raised to any
desired figure, the spark can be adjusted, so to speak, to any point
we like, and it can be so maintained for years.
In the normal animal, to be sure, the internal secretion of the
thyroid is not absolutely essential to life. So it contrasts with the
hormone of the minute parathyroids placed so closely to it, a minimum
dose of which is absolutely a prerequisite for continued life. The
fundamental chemical reactions within the cells occur in the complete
absense of thyroxin. But they go on in a relatively fixed, rigid and
unvarying way, confined within the narrow limits of a constant figure.
Under such conditions, the level of energy production is bound to be
low, and to remain low, and the modus of its mobilization slow and
unwieldy. With thyroid is introduced the trick of _catalysis_, or the
speeding up of the vital chemical reactions, through the agency of an
_intermediate_ which accelerates the process. It is par excellence the
great catalyst of energy in the body. (A catalyst is an intermediary
like the trace of water, which will bring about an explosion between
dry oxygen and hydrogen that without it have stayed inert with the
strongest currents of electricity.) Thus it supplies a mechanism not
only for quantity output of that subtle reality we label energy, but
also an apparatus for varying the available amount of it, and for
permitting the maximum range in ease and rapidity of its utilization.
The thyroid is still another device of life for procuring more and
more variation and differentiation, its goal, as far as we can peer
through the opalescent screen upon which its manifestations quiver.
From another point of view, the thyroid may be looked upon as the
organ evolved for maintaining the same amount of iodine in the blood
as there is in sea water. Sea water was our original habitat, since,
like Venus, we have all come up out of the sea.
The more intimate study of the composition of the blood has revealed
the most astonishing parallelism between it and the compounds of sea
water. The blood is sea water, to which has been added hemoglobin as
a pigment for carrying oxygen to the cells not in direct contact with
the atmosphere, nutrients to take the place of the prey our marine
ancestors gobbled up frankly and directly, and white cells to act as
the first line of defense. To keep the concentration of iodine in the
blood a constant, the thyroid evolved, since there is no iodine in
most foods and very little in those which do contain it.
That a minimum amount of iodine in the food is necessary to health is
shown by the existence of goitre regions. Around some of the Great
Lakes in the United States, for instance, the water does not contain
enough iodine. As a result, numerous cases of goitre occur. Iodine in
the form of sodium iodide in small doses will act as a prophylactic.
The amount of iodine in the blood is about one or two parts to ten
millions, and that of the liver is about three or four parts to ten
millions. Since the liver is the most complex and active chemical
factory in the body, its appropriation of a greater amount of iodine
for itself is understandable.
When thyroxin is administered in a single dose, there is a distinct
lag in the absorption of it by the tissues. A single dose does not
generate its maximum effect until the tenth day. This effect continues
for about ten days. Then there is a gradual decrease in the intensity
of reaction for another ten days. So that the length of time a single
administration of thyroxin functions within the body is about three
weeks. Again we have occasion to notice a protective device of the
cells. Since the presence of thyroxin in the tissues determines the
rate at which they burn themselves up, it is obvious that if there
were no mechanism for retarding its action, and at need varying it,
they really would set fire to themselves. That is to say, if the
tissues held a maximum of the thyroid internal secretion, and had to
take up more and more as it was fed out to them by the thyroid through
the blood, the pressure of energy production would attain the state of
a boiler without a safety valve. Even if self-destruction were avoided
by the ingestion of the largest quantities of energy-bearing foods,
rest for the cells would be difficult, if not impossible.
The thyroxin in the tissues diminishes after a period of great
exertion, the thyroxin probably being carried back to the thyroid
gland and kept there as reserve until further demand. So it has been
discovered that during the winter months, the thyroid glands of beef,
sheep and hogs all contain much less iodine than during the summer
months. During the winter months, manifestly, more energy is required
to maintain body temperature, hence the gland surrenders more of its
secretion to the tissues and so keeps less of it itself. There must
be, too, a certain wearing out of the potency of the iodine with time.
Even dead inorganic catalysts, made of simple elements, wear out after
having been used time and time again.
Though the thyroid is the supreme energizer, life is incompatible with
a certain excess of it. Death can be produced by successive daily
injections of its internal secretion. But it has, besides the
energizing effect, certain formative and nervous influences equally
marvelous. As illustrations, there are the cases of thyroid
deprivation in human beings, cretinism and myxedema, as well as
those in which it is believed there occurs an excess of the
thyroid secretion in the blood and tissues, the condition of
_hyper_thyroidism.
CRETINISM AS THYROID DEFICIENCY
Not that there is any arresting contrast of startling difference
between the phenomena presented by different species. The younger the
animal, the grosser the morbid symptoms witnessed. The animal fails to
grow. The bones and cartilage, except of the skull, fail to develop.
The abdomen projects and becomes large and flabby. The sex organs
atrophy. There is sterility. Pregnant rabbits abort, hens produce
very small eggs or none at all. These are the results of removing the
thyroid in animals.
Apathetic, indifferent, dirty, awkward, apparently idiotic, describe
the human cretins. Their skin is rough and coarse, peeling in sheets.
In some it is considerably knarled and creased as in the aged, and in
others swollen, hard and resistant. The hair becomes shaggy and rough,
losing all luster, and tends to grow irregularly and fall out. The
temperature becomes subnormal and an anemia supervenes. There is a
distinct reduction in the resistance to infections and intoxications.
Cretinism in the human is a condition in which the burning taper we
call Life flickers and smoulders and smokes. Thirty years ago it
was an example of the most hopeless idiocy. Whole populations were
afflicted with it. But neither man of science, nor bigot-fanatic,
assured by the Divine Confidence of its meaning as a visitation,
believed it could be modified an iota. Today, that inept word "cure"
may be applied to our power of attack upon it, provided it is
permitted to attack early enough. Modification, in the direction of
the most surprising betterment, is the miracle that has been wrought.