Chapter IV: Part I: Experiments in Physiology (2)

"No less pregnant of future discoveries was the idea suggested
by this newly-found-out action of the hepatic tissue, the idea
happily formulated by Bernard as 'internal secretion.' No part
of physiology is at the present day being more fruitfully
studied than that which deals with the changes which the blood
undergoes as it sweeps through the several tissues, changes by
the careful adaptation of which what we call the health of the
body is secured, changes the failure or discordance of which
entails disease. The study of these internal secretions
constitutes a path of inquiry which has already been trod with
conspicuous success, and which promises to lead to untold
discoveries of the greatest moment; the gate to this path was
opened by Bernard's work." (Sir M. Foster, _loc. cit._)

But the work to be done, before all the clinical facts of the disease can be stated in terms of physiology, is not yet finished. In England, especial honour is due to Dr. Pavy for his life-long study of this most complex problem.

V

THE PANCREAS

Here again Claude Bernard's name must be put first. Before him, the diverse actions of the pancreatic juice had hardly been studied. Vesalius, greatest of all anatomists, makes no mention of the duct of the pancreas, and speaks of the gland itself as though its purpose were just to support the parts in its neighbourhood--_ut ventriculo instar substerniculi ac pulvinaris subjiciatur_. The duct was discovered by Wirsung, in 1642: but anatomy could not see the things that belong to physiology. Lindanus (1653) said, _I cannot doubt that the pancreas expurgates, in the ordinary course of Nature, those impurities of the blood that are too crass and inept to be tamed by the spleen: and, in the extraordinary course, all black bile, begotten of disease or intemperate living_. Wharton (1656) said, _It ministers to the nerves, taking up certain of their superfluities, and remitting them through its duct into the intestines_. And Tommaso Bartholini (1666) called it the _biliary vesicle of the spleen_.

This chaos of ideas was brought into some sort of order by Regnier de Graaf, pupil of François de Bois (Sylvius). De Bois had guessed that the pancreas must be considered not according to its position in the body, but according to its structure: that it was analogous to the salivary glands. He urged his pupil to make experiments on it: and de Graaf says:--

"I put my hand to the work: and though many times I despaired of
success, yet at last, by the blessing of God on my work and
prayers, in the year 1660 I discovered a way of collecting the
pancreatic juice."

And, by further experiment, he refuted Bartholini's theory that the pancreas was dependent on the spleen.

Sylvius had supposed that the pancreatic juice was slightly acid, and de Graaf failed to note this mistake; but it was corrected by Bohn's experiments in 1710.

Nearly two hundred years come between Regnier de Graaf and Claude Bernard: it is no wonder that Sir Michael Foster says that de Graaf's work was "very imperfect and fruitless." So late as 1840, there was yet no clear understanding of the action of the pancreas. Physiology could not advance without organic chemistry; de Graaf could no more discover the amylolytic action of the pancreatic juice than Galvani could invent wireless telegraphy. The physiologists had to wait till chemistry was ready to help them:--

"Of course, while physical and chemical laws were still lost in
a chaos of undetermined facts, it was impossible that men should
analyse the phenomena of life: first, because these phenomena go
back to the laws of chemistry and physics; and next, because
they cannot be studied without the apparatus, instruments, and
all other methods of analysis that we owe to the laboratories of
the chemists and the physicists." (Cl. Bernard, _Phys. Opér._,
p. 61.)

Therefore de Graaf failed, because he got no help from other sciences. But it cannot be called failure; he must be contrasted with the men of his time, Lindanus and Bartholini, facts against theories, not with men of this century. And Claude Bernard went back to de Graaf's method of the fistula, having to guide him the facts of chemistry observed by Valentin, Tiedemann and Gmelin, and Eberlé. His work began in 1846, and the Académie des Sciences awarded a prize to it in 1850:--

"Let this vague conception (the account of the pancreas given in
Johannes Müller's Text-book of Physiology) be compared with the
knowledge which we at present have of the several distinct
actions of the pancreatic juice, and of the predominant
importance of this fluid not only in intestinal digestion but in
digestion as a whole, and it will be at once seen what a great
advance has taken place in this matter since the early forties.
That advance we owe in the main to Bernard. Valentin, it is
true, had in 1844 not only inferred that the pancreatic juice
had an action on starch, but confirmed his view by actual
experiment with the juice expressed from the gland; and Eberlé
had suggested that the juice had some action on fat; but Bernard
at one stroke made clear its threefold action. He showed that it
on the one hand emulsified, and on the other hand split up, into
fatty acids and glycerine, the neutral fats; he clearly proved
that it had a powerful action on starch, converting it into
sugar; and lastly, he laid bare its remarkable action on proteid
matters." (Sir Michael Foster, _loc. cit._)

Finally came the discovery that the pancreas--apart from its influences on digestion--contributes its share, like the ductless glands, to the general chemistry of the body:--

"It was discovered, a few years ago, by von Mering and
Minkowski, that if, instead of merely diverting its secretion,
the pancreas is bodily removed, the metabolic processes of the
organism, and especially the metabolism of carbo-hydrates, are
entirely deranged, the result being the production of permanent
diabetes. But if even a very small part of the gland is left
within the body, the carbo-hydrate metabolism remains unaltered,
and there is no diabetes. The small portion of the organ which
has been allowed to remain (and which need not even be left in
its proper place, but may be transplanted under the skin or
elsewhere) is sufficient, by the exchanges which go on between
it and the blood generally, to prevent those serious
consequences to the composition of the blood, and the general
constitution of the body, which result from the complete removal
of this organ." (Prof. Schäfer, 1894.)

Here, in this present study of "pancreatic diabetes," by Dr. Vaughan Harley and others, are facts as important as any that Bernard made out: in no way contradicting his work, but adding to it. The pancreas is no longer taken to be only a sort of salivary gland out of place: over and above the secretion that it pours into the intestines, it has an "internal secretion," a constituent of the blood: it belongs not only to the digestive system, but also, like the thyroid gland and the suprarenal capsules, to the whole chemistry of the blood and the tissues. So far has physiology come, unaided by anatomy, from the fantastic notions of Lindanus and the men of his time: and has come every inch of the way by the help of experiments on animals. Professor Starling's observations, on the chemical influence of the duodenal mucous membrane on the flow of pancreatic fluid, have advanced the subject still further.

VI

THE GROWTH OF BONE

The work of du Hamel proved that the periosteum is one chief agent in the growth of bone. Before him, this great fact of physiology was unknown; for the experiments made by Anthony de Heide (1684), who studied the production of callus in the bones of frogs, were wholly useless, and serve only to show that men in his time had no clear understanding of the natural growth of bone. De Heide says of his experiments:--

"From these experiments it appears--_forsan probatur_--that
callus is generated by extravasated blood, whose fluid particles
being slowly exhaled, the residue takes the form of the bone:
which process may be further advanced by deciduous halitus from
the ends of the broken bone."

And Clopton Havers, in his _Osteologia Nova_ (London, 1691), goes so far the wrong way that he attributes to the periosteum not the production of bone, but the prevention of over-production; the periosteum, he says, is put round the shaft of a bone to compress it, lest it grow too large.

Du Hamel's discovery (1739-1743) came out of a chance observation, made by John Belchier,[4] that the bones of animals fed near dye-works were stained with the dye. Belchier therefore put a bird on food mixed with madder, and found that its bones had taken up the stain. Then du Hamel studied the whole subject by a series of experiments. To estimate the advance that he gave to physiology, contrast de Heide's fanciful language with the title of one of du Hamel's papers--_Quatrième Mémoire sur les Os, dans lequel on se propose de rapporter de nouvelles preuves qui établissent que les os croissent en grosseur par l'addition de couches osseuses qui tirent leur origine du périoste, comme le corps ligneux des Arbres augmente en grosseur par l'addition de couches ligneuses qui se forment dans l'écorce._ Or take an example of du Hamel's method:--

"Three pigs were destined to clear up my doubts. The first, six
weeks old, was fed for a month on ordinary food, with an ounce
daily of madder-juice--_garence grappe_--put in it. At the end
of the month, we stopped the juice, and fed the pig in the
ordinary way for six weeks, and then killed it. The marrow of
the bones was surrounded by a fairly thick layer of white bone:
this was the formation of bone during the first six weeks of
life, without madder. This ring of white bone was surrounded by
another zone of red bone: this was the formation of bone during
the administration of the madder. Finally, this red zone was
covered with a fairly thick layer of white bone: this was the
layer formed after the madder had been left off.... We shall
have no further difficulty in understanding whence transudes the
osseous juice that was thought necessary for the formation of
callus and the filling-up of the wounds of the bones, now we see
that it is the periosteum that fills up the wounds, or is made
thick round the fractures, and afterward becomes of the
consistence of cartilage, and at last acquires the hardness of
bones."

[4] "An Account of the Bones of Animals being changed to a Red
Colour by Aliment only," by John Belchier, F.R.S., _Phil. Trans.
Roy. Soc._, 1735-36. There is a letter from Sir Hans Sloane, then
President of the Royal Society, to M. Geoffroy, member of the
French Academy:--"M. Belchier, chirurgien, membre de cette
Société, dînant un jour chez un Teinturier qui travaille en Toiles
peintes, remarqua que dans un Porc frais qu'on avoit servi sur
table, et dont la chair étoit de bon goût, les os étoient rouges.
Il demanda la cause d'un effet si singulier, et on lui dit que ces
sortes de Teinturiers se servoient de la racine de Rubia
Tinctorum, ou garence, pour fixer les couleurs déjà imprimées sur
les Toiles de coton, qu'on appelle en Angleterre callicoes." This
passage of dye into the bones of animals had been noted so far
back as 1573, by Antoine Mizald, a doctor in Paris--_Erythrodanum,
vulgo rubia tinctorum, ossa pecudum rubenti et sandycino colore
imbuit._

These results, confirmed by Bazan (1746) and Boehmer (1751), were far beyond anything that had yet been known about the periosteum. But the growth of bone is a very complex process: the naked eye sees only the grosser changes that come with it; and du Hamel's ingenious comparison between the periosteum and the bark of trees was too simple to be exact. Therefore his work was opposed by Haller, and by Dethleef, Haller's pupil: and the great authority of Haller's name, and the difficulties lying beyond du Hamel's plain facts, brought about a long period of uncertainty. Bordenave (1756) found reasons for supporting Haller; and Fougeroux (1760) supported du Hamel. Thus men came to study the whole subject with more accuracy--the growth in length, as well as the growth in thickness; the medullary cavity, the development of bone, the nutrition and absorption of bone. Among those who took up the work were Bichat, Hunter, Troja, and Cruveilhier; and they recognised the surgical aspect of these researches in physiology. After them, the periosteal growth of bone became, as it were, a part of the principles of surgery. From this point of view of practice, issued the experiments made by Syme (1837) and Stanley (1849): which proved the importance of the epiphysial cartilages for the growth of the bones in length, and the risk of interfering with these cartilages in operations on the joints of children. Finally, with the rise of anæsthetics and of the antiseptic method, came the work of Ollier, of Lyon, whose good influence on the treatment of these cases can hardly be over-estimated.

VII

THE NERVOUS SYSTEM

As with the circulatory system, so with the nervous system, the work of Galen was centuries ahead of its time. Before him, Aristotle, who twice refers to experiments on animals, had observed the brain during life: for he says, "In no animal has the blood any feeling when it is touched, any more than the excretions; nor has the brain, or the marrow, any feeling, when it is touched": but there is reason for believing that he neither recognised the purpose of the brain, nor understood the distribution of the nerves. Galen, by the help of the experimental method, founded the physiology of the nervous system:--

"Galen's method of procedure was totally different to that of an
anatomist alone. He first reviewed the anatomical position, and
by dissection showed the continuity of the nervous system, both
central and peripheral, and also that some bundles of nerve
fibres were distributed to the skin, others to the muscles.
Later, by process of the physiological experiment of dividing
such bundles of fibres, he showed that the former were sensory
fibres and the latter motor fibres. He further traced the nerves
to their origins in the spinal cord, and their terminations as
aforesaid. From these observations and experiments he was able
to deduce the all-important fact that different nerve-roots
supplied different groups of muscles and different areas of the
skin.... An excellent illustration of his method, and of the
fact that we ought not to treat symptoms, but the causes of
symptoms, is shown very clearly in one of the cases which Galen
records as having come under his care. He tells us that he was
consulted by a certain sophist called Pausanias, who had a
severe degree of anæsthesia of the little and ring fingers. For
this loss of sensation, etc., the medical men who attended him
applied ointments of various kinds to the affected fingers; but
Galen, considering that that was a wrong principle, inquired
into the history, and found that while the patient was driving
in his chariot he had accidentally fallen out and struck his
spine at the junction of the cervical and dorsal regions. Galen
recognised that he had to do with a traumatism affecting the
eighth cervical and first dorsal nerve; therefore, he says, he
ordered that the ointments should be taken off the hand and
placed over the spinal column, so as to treat the really
affected part, and not apply remedies to merely the referred
seat of pain."[5]

[5] From an address on Galen, given by Sir Victor Horsley before
the Medical Society of the Middlesex Hospital. See _Middlesex
Hospital Journal_, May 1899.

Galen, by this sort of work, laid the foundations of physiology; but the men who came after him let his facts be overwhelmed by fantastic doctrines: all through the ages, from Galen to the Renaissance, no great advance was made toward the interpretation of the nervous system. Long after the Renaissance, his authority still held good; his ghost was not laid even by Paracelsus and Vesalius, it haunted the medical profession so late as the middle of the seventeenth century; but the men who worshipped his name missed the whole meaning of his work. This long neglect of the experimental method left such a gap in the history of physiology, that Sir Charles Bell seems to take up the experimental study of the nervous system at the point where Galen had stopped short; we go from the time of Commodus to the time of George the Third, and there is Bell, as it were, putting the finishing touch to Galen's facts. It is true that experiments had been made on the nervous system by many men; but a dead weight of theories kept down the whole subject. For a good instance, how imagination hindered science, there is the following list, made by Dr. Risien Russell, of theories about the cerebellum:--

"Galen was of opinion that the cerebellum must be the originator
of a large amount of vital force. After him, and up to the time
of Willis, the prevalent idea seems to have been that it was the
seat of memory; while Bourillon considered it the seat of
instinct and intelligence. Willis supposed that it presided over
involuntary movements and organic functions; and this view,
though refuted by Haller, continued in the ascendency for some
time. Some believed strongly in its influence on the functions
of organic life; and according to some, diseases of the
cerebellum appeared to tell on the movements of the heart....
Haller believed it to be the seat of sensations, as well as the
source of voluntary power; and there were many supporters of the
theory that the cerebellum was the seat of the sensory centres.
Renzi considered this organ the nervous centre by which we
perceive the reality of the external world, and direct and fix
our senses on the things round us. Gall, and later Broussais,
and others, held that this organ presided over the instinct of
reproduction, or the propensity to love; while Carus regarded it
as the seat of the will also. Rolando looked on it as the source
of origin of all movements. Jessen adduced arguments in favour
of its being the central organ of feeling, or of the soul, and
the principal seat of the sensations."

It is plain, from this list, that physiology had become obscured by fanciful notions of no practical value. If a better understanding of the nervous system could have been got without experiments on animals, why had men to wait so long for it? The Italian anatomists had long ago given them all the anatomy that was needed to make a beginning; the hospitals, and practice, had given them many hundred years of clinical facts; nervous diseases and head injuries were common enough in the Middle Ages; and by the time of Ambroise Paré, if not before, _post-mortem_ examinations were allowed. The one thing wanted was the experimental method; and, for want of it, the science of the nervous system stood still. Experiments had been made; but the steady, general, unbiassed use of this method had been lost sight of, and men were more occupied with logic and with philosophy.

Then, in 1811, came Sir Charles Bell's work. If any one would see how great was the need of experiments on animals for the interpretation of the nervous system, let him contrast the physiology of the eighteenth century with that one experiment by Bell which enabled him to say, "I now saw the meaning of the double connection of the nerves with the spinal marrow." It is true that this method is but a part of the science of medicine; that experiment and experience ought to go together like the convexity and the concavity of a curve. But it is true also that men owe their deliverance from ignorance about the nervous system more to experiments on animals than to any other method of observing facts.

1. _Sir Charles Bell_ (1778-1842)

The great authority of Sir Charles Bell has been quoted a thousand times against all experiments on animals:--

"Experiments have never been the means of discovery; and a
survey of what has been attempted of late years in physiology,
will prove that the opening of living animals has done more to
perpetuate error than to confirm the just views taken from the
study of anatomy and natural motions."

He wrote, of course, in the days before bacteriology, before anæsthetics; he had in his mind neither inoculations, nor any observations made under chloroform or ether, but just "the opening of living animals." He had also in his mind, and always in it, a great dislike against the school of Magendie. Let all that pass; our only concern here is to know whether these words are true of his own work.

They occur in a paper, _On the Motions of the Eye, in Illustration of the Uses of the Muscles and Nerves of the Orbit_; communicated by Sir Humphry Davy to the Royal Society, and read March 20, 1823.[6] This essay was one of a series of papers on the nervous system, presented to the Royal Society during the years 1821-1829. In 1830, having already published four of these papers under the title, _The Exposition of the Nervous System_, Bell published all six of them, under the title, _The Nervous System of the Human Body_.

[6] This paper includes an _Experimental Enquiry into the Action
of these Muscles_, giving an account of an experiment on the eye.

In his Preface to this book (1830) he quotes the earliest of all his printed writings on the nervous system, a pamphlet, printed in 1811, under the title, _An Idea of a New Anatomy of the Brain, Submitted for the Observation of the Authors Friends_. We have therefore two statements of his work, one in 1811, the other in 1823 and 1830. The first of them was written when his work was still new before his eyes.

Those who say that experiments did not help Bell in his great discovery--the difference between the anterior and the posterior nerve-roots--appeal to certain passages in the 1830 volume:--

"In a foreign review of my former papers, the results have been
considered as a further proof in favour of experiments. They
are, on the contrary, deductions from anatomy; and I have had
recourse to experiments, not to form my own opinions, but to
impress them upon others. It must be my apology that my utmost
efforts of persuasion were lost, while I urged my statements on
the grounds of anatomy alone. I have made few experiments; they
have been simple and easily performed, and I hope are
decisive....

"My conceptions of this matter arose by inference from the
anatomical structure; so that the few experiments which have
been made were directed only to the verification of the
fundamental principles on which the system is established."

If it were not for the 1811 pamphlet, the opponents of all experiments on animals might claim Sir Charles Bell on their side. But while his work was still a new thing, he spoke in another way of it:--

"I found that injury done to the anterior portion of the spinal
marrow convulsed the animal more certainly than injury to the
posterior portion; but I found it difficult to make the
experiment without injuring both portions.

"Next, considering that the spinal nerves have a double root,
and being of opinion that the properties of the nerves are
derived from their connections with the parts of the brain, _I
thought that I had an opportunity of putting my opinion to the
test of experiment, and of proving at the same time_ that nerves
of different endowments were in the same cord (nerve-trunk) and
held together by the same sheath.

"On laying bare the roots of the spinal nerves, I found that I
could cut across the posterior fasciculus of nerves, which took
its origin from the posterior portion of the spinal marrow,
without convulsing the muscles of the back; but that on touching
the anterior fasciculus with the point of the knife, the muscles
of the back were immediately convulsed.

"_Such were my reasons for concluding_ that the cerebrum and
cerebellum were parts distinct in function, and that every nerve
possessing a double function obtained that by having a double
root. _I now saw the meaning_ of the double connection of the
nerves with the spinal marrow; and also the cause of that
seeming intricacy in the connections of nerves throughout their
course, which were not double at their origins."

It is impossible to reconcile the 1830 sentences with this vivid personal account of himself; _I had an opportunity of putting my opinion to the test of experiment ... an opportunity of proving ... Such were my reasons for concluding ... I now saw...._ It is just what all men of science say of their experiments: the very phrase of Archimedes, and Asellius, and de Graaf. If Sir Charles Bell had been working at the facts of chemistry or of botany, who would have doubted the meaning of these words?

This same inconsistency of sentences occurs elsewhere in his _Nervous System of the Human Body_. In one place he says that he has made few experiments: _They have been simple, and easily performed, and I hope are decisive._ In another he says: "_After making several experiments on the cerebrum and cerebellum, I laid the question of their functions entirely aside_, and confined myself to the investigation of the spinal marrow and the nerves; _a subject which I found more within my power_, and which forms the substance of the present volume."

Next, take his account of the cranial nerves:--

"It was necessary to know, in the first place, whether the
phenomena exhibited on injuring the separate roots corresponded
with what was suggested by their anatomy....

"Here a difficulty arose. An opinion prevailed that ganglions
were intended to cut off sensation; and every one of these
nerves, which I supposed were the instruments of sensation, have
ganglions on their roots. Some very decided experiment was
necessary to overturn this dogma. (Account of the experiment.)
By pursuing the inquiry, it was found that a ganglionic nerve is
the sole organ of sensation in the head and face: ganglions were
therefore no hindrance to sensation; and thus my opinion was
confirmed.... _It now became obvious_ why the third, sixth, and
ninth nerves of the encephalon were single nerves in their
roots....

"Observing that there was a portion of the fifth nerve which did
not enter the ganglion of that nerve, and being assured of the
fact by the concurring testimony of anatomists, I conceived that
the fifth nerve was in fact the uppermost nerve of the spine....
This opinion was confirmed by experiment.... (Account of an
experiment on the dead body.) On dividing the root of the nerve
in a living animal, the jaw fell relaxed. Thus its functions are
no longer matter of doubt: it is at once a muscular nerve and a
nerve of sensibility. And thus the opinion is confirmed, that
the fifth nerve is to the head what the spinal nerves are to the
other parts of the body, in respect to sensation and volition."

The value of the experimental method could hardly be stated in more emphatic words. He supposed something, conceived it, had an opinion about it. Anatomy had suggested something to him. He put his opinion to the test of phenomena, that is to say, to the test of visible facts; and then his opinion was confirmed. As with the spinal nerve-roots, so with the fifth cranial nerve--his work was successful, because he followed the way of experiment.

He was by nature of a most complex and sensitive temperament, full of contrary forces--one man in 1811, another in 1830. In 1811 he wrote, _I now saw the meaning of the double connection of the nerves_; in 1830 he had come to hate the _stupid sterile materialism_ of the French school: he beheld anatomy falling behind physiology, and his Windmill Street school perishing to make way for the Hospital schools and for the University of London. He was before everything else a great anatomist: he stood up for the honour of anatomy against the new physiology, and for the honour of the Monroes and the Hunters against Magendie: he hated the notion that any man should proceed to experiments on function till the very last secrets had been got out of structure. He died a few years afterward. The 1830 writings are his last stand for the defence of his country, his school, and his beloved anatomy, against the methods of Magendie; who said of himself, "I am a mere street scavenger, _chiffonier_, of science. With my hook in my hand and my basket on my back, I go about the streets of science, collecting what I find."

This open conflict between Bell's first and last thoughts is a part of his character: he was brilliant, impulsive, changeable, inconsistent; and, what is more important, his honour kept him from trying to evade this trumpery charge of inconsistency; and he reprinted the 1811 Preface in the book that he published in 1830. Doubtless he would have picked his words more carefully if he had foreseen that one of the 1830 sentences would be wrested out of its place in his life's work, and used as false evidence against the very method that he followed.

His observations on the cranial nerves brought about an immediate change in the practice of surgery:--

"Up to the time that Sir Charles Bell made his experiments on
the nerves of the face, it was the common custom of surgeons to
divide the facial nerve for the relief of neuralgia, _tic
douleureux_; whereas it exercises, and was proved by Sir Charles
Bell to exercise, no influence over sensation, and its division
consequently for the relief of pain was a useless operation."
(Sir J. Erichsen.)

The relation of Magendie's work on the nerve-roots to Bell's
work need not be considered here. The exact dates of Bell's
observations are given by one of his pupils in the Preface to
the 1830 volume. Magendie finally proved the sensory nature of
the posterior nerve-roots: "The exact and full proof which he
brought forward of the truth which Charles Bell had divined
rather than demonstrated, that the anterior and posterior roots
of spinal nerves have essentially different functions--a truth
which is the very foundation of the physiology of the nervous
system--is enough by itself to mark him as a great
physiologist." (Sir M. Foster, _loc. cit._)

2. _Marshall Hall_ (1790-1857)

Reflex action had been studied long before the time of Marshall Hall. The Hon. Robert Boyle (1663) had observed the movements and actions of decapitated vipers, flies, silkworms, and butterflies. Similar observations were made on frogs, eels, and other lower animals, by Redi, Woodward, Stuart, Le Gallois, and Sir Gilbert Blane. According to Richet, it was Willis who first gave the name _reflex_ to these movements.

It cannot be said that these first studies of reflex action did much for physiology. But the following translation from Prochaska (1800) shows how they cleared the way for Marshall Hall's work, by the proof that they gave of the liberation of nervous energy in the spinal cord:--

"These movements of animals after decapitation must needs be by
consent and commerce betwixt the spinal nerves. For a
decapitated frog, if it be pricked, not only draws away the part
that is pricked, but also creeps and jumps; which cannot happen
but by consent betwixt the sensory nerves and the motor nerves.
The seat of which consent must needs be in the spinal cord, the
only remaining portion of the sensorium. _And this reflexion of
sensory impressions into motor impressions is not accomplished
in obedience to physical laws alone--wherein the angle of
reflexion is equal to the angle of incidence, and reaction to
action--but it follows special laws as it were written by Nature
on the spinal cord, which we can know only by their effects, but
cannot fathom with the understanding._ But the general law,
whereby the sensorium reflects sensory impressions into motor
impressions, is the preservation of ourselves."

It was not possible, in 1800, to go further, or to put the facts of reflex action more clearly: but this fine sentence gives no hint of the truth that guided Marshall Hall--that the "consent and commerce" of reflex action are to be found at definite points or levels in the spinal cord; that the cord no more "works as a whole" than the brain. The greatness of Marshall Hall's work lies in his recognition of the divisional action of the cord: he proved the existence of definite centres in it, he discovered the facts of spinal localisation, and thus foreshadowed the discovery of cerebral localisation. In his earlier writings (1823-33) he showed how the movements of the trunk and of the limbs are only one sort of reflex action; how the larynx, the pharynx, and the sphincter muscles, all act by the "consent and commerce" of the spinal cord. Later, in 1837, he demonstrated the course of nerve-impulses along the cord from one level to another, the results of direct stimulation of the cord, and other facts of spinal localisation. He noted the different effects of opium and of strychnine on reflex action; and he extended the doctrines of reflex action beyond physiology to the convulsive movements of the body in certain diseases.

3. _Flourens_ (1794-1867)

Beside his work on the nervous system, Flourens studied the periosteal growth of bone, and the action of chloroform;[7] but he is best known by his experiments on the respiratory centre and the cerebellum. The men who interpreted the nervous system followed the anatomical course of that system: first the nerve-roots, then the cord, then the medulla oblongata and the cerebellum, and last the cerebral hemispheres; a steady upward advance, from the observation of decapitated insects to the localisation of centres in the human brain. Flourens, by his work on the medulla oblongata, localised the respiratory centre, the nerve-cells for the reflex movements of respiration:--

"M. Flourens a circonscrit ce centre avec une scrupuleuse
précision, et lui a donné le nom de noeud vital" (Cl. Bernard.)

[7] When Flourens died, Claude Bernard was appointed to his place
in the French Academy; and, in the _Discours de Reception_ (May
27, 1869), said, "It is twenty-two years since the discovery of
anæsthesia by ether came to us from the New World, and spread
rapidly over Europe. M. Flourens was the first man who showed that
chloroform is more active than ether."

Afterward came the discovery of cardiac and other centres in the same portion of the nervous system. Flourens also showed that the cerebellum is concerned with the equilibration of the body, and with the coordination of muscular movements; that an animal, a few days old, deprived of sensation and consciousness by removal of the cerebral hemispheres, was yet able to stand and move forward, but, when the cerebellum was removed, its muscles lost all co-ordinate action. (_Recherches Expérimentales_, Paris, 1842.) And from his work, and the work of those who followed him, on the semicircular canals of the internal ear, came the evidence that these minute structures are the terminal organs of equilibration: that as the special senses have their terminal apparatus and their central apparatus, so the semicircular canals and the cerebellum are the terminal apparatus and the central apparatus of the sense of equilibrium.

4. _Claude Bernard_ (1813-1878)

The discovery of the vaso-motor nerves, and of the control of the nervous system over the calibre of the arteries, was made by Claude Bernard at the outset of his work on the influence of the nervous system on the temperature.[8] The evidence of Professor Sharpey before the Royal Commission of 1875 shows how things had been misjudged, before Bernard's time, in the light of "views taken from the Study of Anatomy and Natural Motions":--

"I remember that Sir Charles Bell gave the increased size of the
vessels in blushing, and their fulness of blood, as an example
of the increased action of the arteries in driving on the blood.
It turns out to be just the reverse, inasmuch as it is owing to
a paralysis of the nerves governing the muscular coats of the
arteries."

[8] A full account of this discovery, and of its relation to the
experiments of Brown Séquard, Waller, and Budge, is given by Sir
Michael Foster in his life of Claude Bernard; and the question of
priority between Bernard and Brown Séquard need not be considered
here, for the experimental method was the only way open to either
of them. For an account of the work done, before Bernard, in this
field of physiology, see Prof. Stirling's admirable and learned
monograph, _Some Apostles of Physiology_ (Waterlow & Sons, London,
1902), p. 104.

Claude Bernard's first account of his work was communicated to the Société de Biologie in December 1851. The following description is taken from his _Leçons de Physiologie Opératoire_:--

"I will remind you how I was led to the discovery of the
vaso-motor nerves. Starting from the clinical observation, made
long ago, that in paralysed limbs you find at one time an
increase of cold, and at another an increase of heat, I thought
this contradiction might be explained by supposing that, side by
side with the general action of the nervous system, the
sympathetic nerve might have the function of presiding over the
production of heat; that is to say, that in the case where the
paralysed limb was chilled, I supposed the sympathetic nerve to
be paralysed, as well as the motor nerves; while in the
paralysed limbs that were not chilled, the sympathetic nerve had
retained its function, the systemic nerves alone having been
attacked.

"This was a theory, that is to say, an idea leading me to make
experiments; and for these experiments I must find a sympathetic
nerve-trunk of sufficient size, going to some organ that was
easy to observe, and must divide this trunk to see what would
happen to the heat-supply of the organ. You know that the
rabbit's ear, and the cervical sympathetic nerve of this animal,
offered us the required conditions. So I divided the nerve; and
immediately my experiment gave the lie direct to my theory--_Je
coupai donc ce filet et aussitôt l'expérience donna à mon
hypothèse le plus éclatant démenti_. I had thought that the
section of the nerve would suppress the function of nutrition,
of calorification, over which the sympathetic system had been
supposed to preside, and would cause the hollow of the ear to
become chilled; and here was just the opposite, a very warm ear,
with great dilatation of its vessels.

"I need not remind you how I made haste to abandon my first
theory, and gave myself to the study of this new state of
things. And you know that here was the starting-point of all my
researches into the vaso-motor and thermic system; and the study
of this subject is become one of the richest fields of
experimental physiology."

Waller, in 1853, studied the vaso-motor centre in the spinal cord; and Schiff, in 1856, found evidence of the existence of two kinds of vaso-motor nerves--those that constrict the vessels, and those that dilate them. This view was finally established in 1858 by Claude Bernard's experiments on the chorda tympani and the submaxillary gland.

The _Leçons de Physiologie Opératoire_ were published in 1879. Twenty years later, Sir Michael Foster says of Bernard's work:--

"It is almost impossible to exaggerate the importance of these
labours of Bernard on the vaso-motor nerves, since it is almost
impossible to exaggerate the influence which our knowledge of
the vaso-motor system, springing as it does from Bernard's
researches as from its fount and origin, has exerted, is
exerting, and in widening measure will continue to exert, on all
our physiological and pathological conceptions, on medical
practice, and on the conduct of human life. There is hardly a
physiological discussion of any width in which we do not sooner
or later come on vaso-motor questions. Whatever part of
physiology we touch, be it the work done by a muscle, be it the
various kinds of secretive labour, be it the insurance of the
brain's well-being in the midst of the hydrostatic vicissitudes
to which the changes of daily life subject it, be it that
maintenance of bodily temperature which is a condition of the
body's activity; in all these, as in many other things, we find
vaso-motor factors intervening. And if, passing the insecure and
wavering line which parts health from illness, we find ourselves
dealing with inflammation, or with fever, or with any of the
disordered physiological processes which constitute disease, we
shall find, whatever be the tissue specially affected by the
morbid conditions, that vaso-motor influences have to be taken
into account. The idea of vaso-motor action is woven as a
dominant thread into all the physiological and pathological
doctrines of to-day; attempt to draw out that thread, and all
that would be left would appear as a tangled heap."

5. _Cerebral Localisation_

Finally, moving upward along the anatomy of the nervous system, physiology came to study the motor-centres and special sense-centres of the cerebral hemispheres. The year 1861 may fairly be said to mark the beginning of the discovery of these centres, when Broca, at a meeting of the Anthropological Society of Paris, heard Aubertin's paper on the connection between the frontal convolutions and the faculty of speech. But, of course, some sort of belief in cerebral localisation had been in the air long before Broca's time. Willis (1621-1675), who was contemporary with Sir Isaac Newton, had written of the brain as though its convolutions, or "cranklings" as he called them, showed that its work was departmental:--

"As the animal spirits for the various acts of imagination and
memory ought to be moved within certain and distinct limits, or
bounded places, and these motions to be often iterated or
repeated through the same tracts or paths, for that reason these
manifold convolutions and infoldings of the brain are required
for these divers manners of ordinations of the animal
spirits--to wit, that in these cells or storehouses, severally
placed, might be kept the species of sensitive things, and as
occasion serves, may be taken from thence."[9]

[9] For an account of Willis' work on the nervous system, see Sir
Victor Horsley's _Fullerian Lectures_, 1891. Willis was the first,
or one of the first, to recognise the fact that the cerebral
ventricles are nothing more than lymph-cavities.

And Gall, a century after Willis, had collected and published, in support of his system of phrenology, many cases and _post-mortem_ examinations showing the differentiation of the work of the brain. Gall is a warning for all time against the dangers of deduction; he had but one idea, and he drove it to death; but the clinical and pathological facts which he amassed, in the hope of establishing a set of doctrines out of all relation to facts, are as true now as ever; and, if he had been content to go the way of induction, and to set himself to the accumulation of facts, he might have become a great physiologist. In his knowledge of the anatomy of the brain, and in the dissection of the brain, he was far ahead of the men of his time; but he followed his own imaginings, and left nothing that could last, except those cases and pathological instances that are buried in the ruins of his system. But there they are, and are still of value. For example, Gall's case of loss of speech, after an injury involving the speech-centres, ought to have commanded the attention of all physiologists: but it came to nothing, because he used it to support his doctrine of organs and bumps, and it shared the fate of that doctrine. Phrenology is gone past recall; it died of that congenital disease, the deductive fallacy; but there was a time when it might have been turned to the service of science.

The excitement that Gall aroused by the spread of his ideas shows that some belief in cerebral centres was waiting for development. All men are by nature phrenologists; the commonplace excuses that are offered for lapses of memory, venial offences, and inherited weaknesses, all appeal to the comfortable notion that the offender is not wholly perverted, and that some very small and strictly localised group of cells is at fault. And it is probable that the physiology of the central nervous system, with its present strong tendency toward psychology, will some day be back, at a far higher level, above the point where phrenology went wrong. As Mme. de Staël said, _L'esprit humain fait progrès toujours, mais c'est progrès en spirale_. But the question, whether the general desire for a rational system of psychology will ever commend itself to physiology, belongs to the future. All that is of present concern is the steady, continuous, and successful advance, by the way of induction, and by the help of experiments on animals, toward a clear and accurate statement of the departmental work of the brain.

It is one of many instances how science and practice work together, that the modern study of these centres began not in experiment but in experience. The first centres that were thus studied were the speech-centres; and the observation of them arose out of the cases recorded by Bouillard in 1825, and Dax in 1836. Clinical observation, and _post-mortem_ examination, found the speech-centres; physiological experiments had nothing to do with it; and phrenology had, as it were, found them, and then lost them. But at once, so soon as practice gave the word to science, physiology set to work. These clinical facts had been there all the time; loss of speech had gone with disease or injury of "Broca's convolution" ever since man had been on the earth, and nobody had seen the significance of this sequence. Then, after 1861, everything was changed; and in a few years physiology had mapped out a large part of the surface of the brain, and had charted the motor-centres.

The story of Broca's convolution is told in Hamilton's _Text-Book of Pathology_:--

"In 1825, Bouillard collected a series of cases to show that the
faculty of speech resided in the frontal lobes. In the year 1836
M. Dax, in a paper read to the Medical Congress of Montpellier,
stated as a result of his researches that, where speech was lost
from cerebral causes, he believed the lesion was invariably
found in the left cerebral hemisphere, and that the accompanying
paralysis of the right side of the body is consequent upon this.
This paper for long lay buried in the annals of medical
literature, but was unearthed years afterwards by his son, and
presented to the French Academy. Bouillard's views were also
disinterred by Aubertin, and in the year 1861 were brought by
him before the notice of the Anthropological Society of Paris.
Broca, who was present at the meeting, had a patient under his
care at the time who had been aphasic (without power of speech)
for twenty-one years, and who was in an almost moribund state.
The autopsy proved of great interest, as it was found that the
lesion was confined to the left side of the brain, and to what
we now call the third frontal convolution. Broca was struck with
the coincidence; and when a similar case came under his care
afterwards, unaware of what had been done by Dax, he postulated
the conclusion that the integrity of the third frontal
convolution, and perhaps also part of the second, is essential
to speech. In a subsequent series of fifteen typical cases
examined, it was found that the lesion had destroyed, among
other parts, the posterior part of the third frontal in
fourteen. In the fifteenth case the destruction had taken place
in the island of Reil and the temporal lobe."

After 1861, physiology took the lead, and kept it. But, through all the work, science and practice have been held together; the facts of experimental physiology have been and are tested, every inch of the way, by the facts of medicine, surgery, and pathology. The infinite minuteness and complexity of the investigation, and its innumerable side-issues, are past all telling. They who are doing the work, in science and in practice, have always had in their thoughts the fear of fallacies in the interpretation of these highest forms of life. Sir William Gowers, fourteen years ago, wrote as follows of the earlier workers:--

"Doubt was formerly entertained as to the existence of
differentiation of function in different parts of the cortex,
but recent researches have established the existence of a
differentiation which has almost revolutionised cerebral
physiology, and has vastly extended the range of cerebral
diagnosis. The first step of the new discovery was constituted
by the clinical and pathological observations of Hughlings
Jackson, which suggested the existence, on each side of the
fissure of Rolando, of special centres for the movements of the
leg, arm, and face. These observations led to the experiments of
Ferner, which resulted in the demonstration of the existence in
the cortex of the lower animals of well-defined regions,
stimulation of which caused separate movements, or evidence of
special sense excitation, while the destruction of the same
parts caused indications of a loss of the corresponding
function. Hence he came to the conclusion that these regions
constitute actual motor and sensory centres. Ferrier had,
however, been anticipated in many of these results by two German
experimenters, Fritsch and Hitzig, whose results, differing a
little in detail, correspond closely in their general
significance. Many other investigations of the same character
have since been made, of which those of Munk are especially
important. The original observations of Hughlings Jackson left
little doubt that the general facts, learned from experiments on
animals, are true of man; and this conclusion has been to a
large extent confirmed by pathological and clinical observations
directed to the verification on man of the pathological results.
To this verification the labours of Charcot and his coadjutors
have largely contributed. But the verification has already made
it probable that some differences exist between the brain of man
and that of higher animals (even of monkeys), and that the
conclusions from the latter cannot be simply transferred to the
former."

Many and great difficulties, beyond this danger of the fallacy of "simple transference," beset every step of the work: it required the right use of the most delicate and susceptible instruments and tests, and the right understanding of anatomy, microscopic anatomy, comparative anatomy, organic chemistry, electricity, and physics: every moment of advance must be guarded, every word must be weighed. Among the earlier difficulties, was the failure of almost all the physiologists, before Hitzig, to produce muscular action by excitation of the cerebral cortex. Longet, Magendie, Flourens, Matteuci, Van Deen, Weber, Budge, and Schiff, had all failed. Hitzig (_Untersuchungen über das Gehirn_, Berlin, 1874) had observed, in man, that it was easy to produce movements of the eyes by the passage of the constant current through the occipital region.[10] Taking this fact for a starting-point, he used a very low current, and thereby succeeded in producing certain definite muscular movements by stimulation of the cortex in animals. Of Hitzig's work, Sir Victor Horsley says:--

"It was not till 1870 that the next absolute proof (after Bell's
work in 1813) was obtained of the localisation of function, so
far as the highest centres of the nervous system were concerned.
In that year Fritsch and Hitzig discovered that electrical
excitation, with minimal stimuli, of various points of the
cortex, caused those storehouses, of which Willis spoke, to
discharge, and to reveal their function by the precise
limitation of the groups of muscles which they were able to
throw into action. These researches were abundantly confirmed
and greatly extended by Professor Ferrier, and thus has been
constructed in the history of this subject the most recent great
platform or stage of permanent advance."[11]

[10] That the surface of the brain is not sensitive of such
stimulation, that it does not perceive its own substance, was
known to Aristotle. The fact is so familiar that there is no need
to quote evidence of it, beyond that of Sir Charles Bell: "I have
had my finger deep in the anterior lobes of the brain, when the
patient, being at the time acutely sensible, and capable of
expressing himself, complained only of the integument."

[11] Horsley, _Fullerian Lectures_, 1891, _loc. cit._

The thirty years since Hitzig's work cannot be put here, for they would take a volume to themselves. There have been differences of interpretation of this or that fact, diversities of results, and problems too hard to solve, and other difficulties, such as befall all the natural sciences; but these imperfections amount to very little, when the whole result comes to be reckoned. The marvel is that the work is so nearly perfect, seeing its immeasurable complexity.