Chapter III: Part I: Experiments in Physiology (1)

EXPERIMENTS ON ANIMALS

I THE BLOOD

I.--BEFORE HARVEY

Galen, born at Pergamos, 131 A.D., proved by experiments on animals that the brain is as warm as the heart, against the Aristotelian doctrine that the office of the brain is to keep the heart cool. He also proved that the arteries during life contain blood, not [Greek: pneuma], or the breath of life:--

"Ourselves, having tied the exposed arteries above and below,
opened them between the ligatures, and showed that they were
indeed full of blood."

Though all vessels bleed when they are wounded, yet this experiment was necessary to refute the fanciful teaching of Erasistratus and his followers, of whom Galen says:--

"Erasistratus is pleased to believe that an artery is a vessel
containing the breath of life, and a vein is a vessel containing
blood; and that the vessels, dividing again and again, come at
last to be so small that they can close their ultimate pores,
and keep the blood controlled within them; yea, though the pores
of the vein and of the artery lie side by side, yet the blood
remains within its proper bounds, nowhere passing into the
vessels of the breath of life. But when the blood is driven with
violence from the veins into the arteries, forthwith there is
disease; and the blood is poured the wrong way into the
arteries, and there withstands and dashes itself against the
breath of life coming from the heart, and turns the course of
it--and this forsooth is fever."

For many centuries after Galen, men were content to worship his name and his doctrines, and forsook his method. They did not follow the way of experiment, and invented theories that were no help either in science or in practice. Here, in Galen's observation of living arteries, was a great opportunity for physiology; but the example that he set to those who came after him was forgotten by them, and, from the time of Galen to the time of the Renaissance, physiology remained almost where he had left it. Of the men of the Renaissance, Servetus, Cæsalpinus, Ruinius, and others, Harvey's near predecessors, this much only need be said here, that they did not discover the circulation of the blood; and that the claim made a few years ago to this discovery, on behalf of Cæsalpinus, by his countrymen, was not successful. But it is probable that Realdus (1516-1557) did understand the passage of blood through the lungs, but not the general circulation. He says:--

"The blood is carried through the pulmonary artery to the lung,
and there is attenuated; thence, mixed with air, it is carried
through the pulmonary vein to the left ventricle of the heart:
which thing no man hitherto has noted or left on record, though
it is most worthy of the observation of all men.... And this is
as true as truth itself; for if you will look, not only in the
dead body but also in the living animal, you will always find
this pulmonary vein full of blood, which assuredly it would not
be if it were designed only for air and vapours.... Verily, I
pray you, O candid reader, studious of authority, but more
studious of truth, to make experiment on animals. You will find
the pulmonary vein full of blood, not air or _fuligo_, as these
men call it, God help them. Only there is no pulsation in the
vein." (_De Re Anatomicâ_, Venice, 1559.)

Fabricius ab Aquapendente, Harvey's master at Padua, published his work on the valves of the veins--_De Venarum Ostiolis_--in 1603. He did not discover them. Sylvius speaks of them in his _Isagoge_ (Venice, 1555), and they were known to Amatus (1552), and even to Theodoretus, Bishop of Syria, who lived, as John Hunter said of Sennertus, "the Lord knows how long ago." But Fabricius studied them most carefully; and in anatomy he left nothing more to be said about them. In physiology, his work was of little value; for he held that they were designed "to retard the blood in some measure, lest it should run pell-mell into the feet, hands, and fingers, there to be impacted": they were to prevent distension of the veins, and to ensure the due nourishment of all parts of the body. It is true that he compared them to the locks or weirs of a river, but he understood neither the course nor the force of the blood: as Harvey said of him, "The man who discovered these valves did not understand their right use; neither did they who came after him"--_Harum valvularum usum rectum inventor non est assecutus, nec alii addiderunt; non est enim ne pondere deorsum sanguis in inferiora totus ruat; sunt namque in jugularibus deorsum spectantes, et sanguinem sursum ferri prohibentes._ Men had no idea of the rapidity and volume of the circulation; they thought of a sort of Stygian tide, oozing this way or that way in the vessels--Cæsalpinus was of opinion that it went one way in the daytime and another at night--nor did they see that the pulmonary circulation and the general circulation are one system, the same blood covering the whole course. The work that they did in anatomy was magnificent; Vesalius, and the other great anatomists of his time, are unsurpassed. But physiology had been hindered for ages by fantastic imaginings, and the facts of the circulation of the blood were almost as far from their interpretation in the sixteenth century as they had been in the time of Galen.

II.--HARVEY (1578-1657)

The _De Motu Cordis et Sanguinis in Animalibus_ was published at Frankfurt in 1628. And it begins with these words: _Cum multis vivorum dissectionibus, uti ad manum dabantur_:--

"When by many dissections of living animals, as they came to
hand, I first gave myself to observing how I might discover with
my own eyes, and not from books and the writings of other men,
the use and purpose of the movement of the heart in animals,
forthwith I found the matter hard indeed, and full of
difficulty: so that I began to think, with Frascatorius, that
the movement of the heart was known to God alone. For I could
not distinguish aright either the nature of its systole and
diastole, or when or where dilatation and contraction took
place; and this because of the swiftness of the movement, which
in many animals in the twinkling of an eye, like a flash of
lightning, revealed itself to sight and then was gone; so that I
came to believe that I saw systole and diastole now this way now
the other, and movements now apart and now together. Wherefore
my mind wavered; I had nothing assured to me, whether decided by
me or taken from other men: and I did not wonder that Andreas
Laurentius had written that the movement of the heart was what
the ebb and flow of the Euripus had been to Aristotle.

"At last, having daily used greater disquisition and diligence,
by frequent examination of many and various living
animals--_multa frequenter et varia animalia viva
introspiciendo_--and many observations put together, I came to
believe that I had succeeded, and had escaped and got out of
this labyrinth, and therewith had discovered what I desired, the
movement and use of the heart and the arteries. And from that
time, not only to my friends, but also in public in my
anatomical lectures, after the manner of the Academy, I did not
fear to set forth my opinion in this matter."

It is plain, from Harvey's own words, that he gives to experiments on animals a foremost place among his methods of work. Take only the headings of his first four chapters:--

i. _Causæ, quibus ad scribendum auctor permotus fuerit._

ii. _Ex vivorum dissectione, qualis fit cordis motus._

iii. _Arteriarum motus qualis, ex vivorum dissectione._

iv. _Motus cordis et auricularum qualis, ex vivorum
dissectione._

He thrusts it on us, he puts it in the foreground. Read the end of his Preface:--

"Therefore, from these and many more things of the kind, it is
plain (since what has been said by men before me, of the
movement and use of the heart and arteries, appears inconsistent
or obscure or impossible when one carefully considers it) that
we shall do well to look deeper into the matter; to observe the
movements of the arteries and the heart, not only in man, but in
all animals that have hearts; and by frequent dissection of
living animals, and much use of our own eyes, to discern and
investigate the truth--_vivorum dissectione frequenti, multâque
autopsiâ, veritatem discernere et investigare_."

Finally, take the famous passage in the eighth chapter, _De copiâ sanguinis transeuntis per cor e venis in arterias, et de circulari motu sanguinis_:--

"And now, as for the great quantity and forward movement of this
blood on its way, when I shall have said what things remain to
be said--though they are well worth considering, yet they are so
new and strange that I not only fear harm from the envy of
certain men, but am afraid lest I make all men my enemies; so
does custom, or a doctrine once imbibed and fixed down by deep
roots, like second nature, hold good among all men, and
reverence for antiquity constrains them. Be that as it may, the
die is cast now: my hope is in the love of truth, and the
candour of learned minds. I bethought me how great was the
quantity of this blood. Both from the dissection of living
animals for the sake of experiment, with opening of the
arteries, with observations manifold; and from the symmetry of
the size of the ventricles, and of the vessels entering and
leaving the heart--because Nature, doing nothing in vain, cannot
in vain have given such size to these vessels above the
rest--and from the harmonious and happy device of the valves and
fibres, and all other fabric of the heart; and from many other
things--when I had again and again carefully considered it all,
and had turned it over in my mind many times--I mean the great
quantity of the blood passing through, and the swiftness of its
passage--and I did not see how the juices of the food in the
stomach could help the veins from being emptied and drained dry,
and the arteries contrariwise from being ruptured by the
excessive flow of blood into them, unless blood were always
getting round from the arteries into the veins, and so back to
the right ventricle--I began to think to myself whether the
blood had a certain movement, as in a circle--_coepi egomet
mecum cogitare, an motionem quandam quasi in circulo
haberet_--which afterward I found was true."

This vehement passage, which goes with a rush like that of the blood itself, is a good example of the width and depth of Harvey's work--how he used all methods that were open to him. He lived to fourscore years; "an old man," he says, "far advanced in years, and occupied with other cares": and, near the end of his life, he told the Hon. Robert Boyle that the arrangement of the valves of the veins had given him his first idea of the circulation of the blood:--

"I remember that when I asked our famous Harvey, in the only
discourse I had with him, which was but a while before he died,
what were the things which induced him to think of the
circulation of the blood, he answered me that when he took
notice that the valves in the veins of so many parts of the body
were so placed that they gave free passage of the blood towards
the heart, but opposed the passage of the venal blood the
contrary way, he was invited to imagine that so provident a
cause as Nature had not so placed so many valves without design;
and no design seemed more probable than that, since the blood
could not well, because of the interposing valves, be sent by
the veins to the limbs, it should be sent by the arteries, and
return through the veins, whose valves did not oppose its course
that way."

But between this observation, which "invited him to imagine" a theory, and his final proofs of the circulation, lay a host of difficulties; and it is certain, from his own account of his work, that experiments on animals were of the utmost help to him in leading him "out of the labyrinth."

III.--AFTER HARVEY

1. _The Capillaries_

The capillary vessels were not known in Harvey's time: the _capillamenta_ of Cæsalpinus were not the capillaries, but the [Greek: neura] of Aristotle. It was believed that the blood, between the smallest arteries and the smallest veins, made its way through "blind porosities" in the tissues, as water percolates through earth or through a sponge. The first account of the capillaries is in two letters (_De Pulmonibus_, 1661) from Malpighi, professor of medicine at Bologna, to Borelli, professor of mathematics at Pisa. In his first letter, Malpighi writes that he has tried in vain, by injecting the dead body, to discover how the blood passes from the arteries into the veins:--

"This enigma hitherto distracts my mind, though for its solution
I have made many and many attempts, all in vain, with air and
various coloured fluids. Having injected ink with a syringe into
the pulmonary artery, I have again and again seen it escape
(become extravasated into the tissues) at several points. The
same thing happens with an injection of mercury. These
experiments do not give us the natural pathway of the blood."

But, in his second letter, he describes how he has examined, with a microscope of two lenses, the lung and the mesentery of a frog, and has seen the capillaries, and the blood in them:--

"Such is the divarication of these little vessels, coming off
from the vein and the artery, that the order in which the vessel
ramifies is no longer preserved, but it looks like a network
woven from the offshoots of both vessels."

He was able, in a dead frog, to see the capillaries; and then, in a living frog, to see the blood moving in them. But, in spite of this work, it took nearly half a century before Harvey's teaching was believed by all men--_Tantum consuetudo apud omnes valet_.

2. _The Blood-pressure_

Harvey had seen the facts of blood-pressure--_the great quantity of blood passing through, and the swiftness of its passage_--but he had not measured it. Keill's experiments on the blood-pressure (1718) were inexact, and of no value; and the first exact measurements were made by Stephen Hales, who was rector of Farringdon, Hampshire, and minister of Teddington, Middlesex; a Doctor of Divinity, and a Fellow of the Royal Society. His experiments, in their width and diversity, were not surpassed even by those of John Hunter, and were extended far over physiology, vegetable physiology, organic and inorganic chemistry, and physics; they ranged from the invention of a sea-gauge to the study of solvents for the stone, and he seems to have experimented on every force in Nature. The titles of his two volumes of _Statical Essays_ (1726-1733) show the great extent of his non-clerical work:--

Volume I. _Statical Essays, containing Vegetable Statics, or an
Account of some Statical Experiments on the Sap in Vegetables,
being an Essay towards a Natural History of Vegetation; also, a
Specimen of an Attempt to Analyse the Air, by a great Variety of
Chymio-Statical Experiments._

Volume II. _Statical Essays, containing Hæmostatics, or an
Account of some Hydraulic and Hydrostatical Experiments made on
the Blood and Blood-vessels of Animals; also, an Account of some
Experiments on Stones in the Kidneys and Bladder, with an
Enquiry into the Nature of those anomalous Concretions._

"We can never want matter for new experiments," he says in his
preface. "We are as yet got little further than to the surface
of things: we must be content, in this our infant state of
knowledge, while we know in part only, to imitate children, who,
for want of better skill and abilities, and of more proper
materials, amuse themselves with slight buildings. The farther
advances we make in the knowledge of Nature, the more probable
and the nearer to truth will our conjectures approach: so that
succeeding generations, who shall have the benefit and advantage
both of their own observations and those of preceding
generations, may then make considerable advances, when _many
shall run to and fro, and knowledge shall be increased_."

His account of his plan of measuring the blood-pressure, and of one of many experiments that he made on it, is as follows:--

"Finding but little satisfaction in what had been attempted on
this subject by Borellus and others, I endeavoured, about
twenty-five years since, by proper experiments, to find what was
the real force of the blood in the crural arteries of dogs, and
about six years afterwards I repeated the like experiments on
two horses, and a fallow doe; but did not then pursue the matter
any further, being discouraged by the disagreeableness of
anatomical dissections. But having of late years found by
experience the advantage of making use of the statical way of
investigation, not only in our researches into the nature of
vegetables, but also in the chymical analysis of the air, I was
induced to hope for some success, if the same method of enquiry
were applied to animal bodies....

"Having laid open the left crural artery (of a mare), I inserted
into it a brass pipe whose bore was 1/6 of an inch in diameter;
and to that, by means of another brass pipe which was fitly
adapted to it, I fixed a glass tube of nearly the same diameter,
which was 9 feet in length; then, untying the ligature on the
artery, the blood rose in the tube 8 feet 3 inches perpendicular
above the level of the left ventricle of the heart, but it did
not attain to its full height at once: it rushed up gradually
at each pulse 12, 8, 6, 4, 2, and sometimes 1 inch. When it was
at its full height, it would rise and fall at and after each
pulse 2, 3, or 4 inches, and sometimes it would fall 12 or 14
inches, and have there for a time the same vibrations up and
down, at and after each pulse, as it had when it was at its full
height, to which it would rise again, after forty or fifty
pulses."

3. _The Collateral Circulation_

After Hales, came John Hunter, who was five years old when the _Statical Essays_ were published. His experiments on the blood were mostly concerned with its properties, not with its course; but one great experiment must be noted here that puts him in line with Harvey, Malpighi, and Hales. He got from it his knowledge of the collateral circulation; he learned how the obstruction of an artery is followed by enlargement of the vessels in its neighbourhood, so that the parts beyond the obstruction do not suffer from want of blood: and the facts of collateral circulation were fresh in his mind when, a few months later, he conceived and performed his operation for aneurysm (December 1785). The "old operation" gave him no help here; and "Anel's operation" was but a single instance, and no sure guide for Hunter, because Anel's patient had a different sort of aneurysm. Hunter knew that the collateral circulation could be trusted to nourish the limb, if the femoral artery were ligatured in "Hunter's canal" for the cure of popliteal aneurysm; and he got this knowledge from the experiment that he had made on one of the deer in Richmond Park, to see the influence of ligature of the carotid artery on the growth of the antler. The following account of this experiment was given by Sir Richard Owen, who had it from Mr. Clift, Hunter's devoted pupil and friend:--

"In the month of July, when the bucks' antlers were half-grown,
he caused one of them to be caught and thrown; and, knowing the
arterial supply to the hot 'velvet,' as the keepers call it,
Hunter cut down upon and tied the external carotid; upon which,
laying his hand upon the antler, he found that the pulsations of
the arterial channels stopped, and the surface soon grew cold.
The buck was released, and Hunter speculated on the
result--whether the antler, arrested at mid-growth, would be
shed like the full-grown one, or be longer retained. A week or
so afterward he drove down again to the park, and caused the
buck to be caught and thrown. The wound was healed about the
ligature; but on laying his hand on the antler, he found to his
surprise that the warmth had returned, and the channels of
supply to the velvety formative covering were again pulsating.
His first impression was that his operation had been defective.
To test this, he had the buck killed and sent to Leicester
Square. The arterial system was injected. Hunter found that the
external carotid had been duly tied. But certain small branches,
coming off on the proximal or heart's side of the ligature, had
enlarged; and, tracing-on these, he found that they had
anastomosed with other small branches from the distal
continuation of the carotid, and these new channels had restored
the supply to the growing antler.... Here was a consequence of
his experiment he had not at all foreseen or expected. A new
property of the living arteries was unfolded to him."

All the anatomists had overlooked this physiological change in the living body, brought about by disease. And the surgeons, since anatomy could not help them, had been driven by the mortality of the "old operation" to the practice of amputation.

4. _The Mercurial Manometer_

Hale's experiments on the blood-pressure were admirable in their time; but neither he nor his successors could take into account all the physiological and mathematical facts of the case. But a great advance was made in 1828, when Poiseuille published his thesis, _Sur la Force du Coeur Aortique_, with a description of the mercurial manometer. Poiseuille had begun with the received idea that the blood-pressure in the arteries would vary according to the distance from the heart, but he found by experiment that this doctrine was wrong:--

"At my first experiments, wishing to make sure whether the
opinions, given _à priori_, were true, I observed to my great
astonishment that two tubes, applied at the same time to two
arteries at different distances from the heart, gave columns of
exactly the same height, and not, as I had expected, of
different heights. This made the work very much simpler,
because, to whatever artery I applied the instrument, I obtained
the same results that I should have got by placing it on the
ascending aorta itself."

He found also, by experiments, that the coagulation of the blood in the tube could be prevented by filling one part of the tube with a saturated solution of sodium carbonate. The tube, thus prepared, was connected with the artery by a fine cannula, exactly fitting the artery. With this instrument, Poiseuille was able to obtain results far more accurate than those of Hales, and to observe the diverse influences of the respiratory movements on the blood-pressure. He sums up his results in these words:--

"I come to this irrevocable conclusion, that the force with
which a molecule of blood moves, whether in the carotid, or in
the aorta, etc., is exactly equal to the force which moves a
molecule in the smallest arterial branch; or, in other words,
that a molecule of blood moves with the same force over the
whole course of the arterial system--which, _à priori_, with all
the physiologists, I was far from thinking."

And he adds, in a footnote:--

"When I say that this force is the same over the whole course of
the arterial system, I do not mean to deny that it must needs be
modified at certain points of this system, which present a
special arrangement, such as the anastomosing arches of the
mesentery, the arterial circle of Willis, etc."

Later, in 1835, he published a very valuable memoir on the movement of the blood in the capillaries under different conditions of heat, cold, and atmospheric pressure.

5. _The Registration of the Blood-pressure_

Poiseuille's work, in its turn, was left behind as physiology went forward: especially, the discovery of the vaso-motor nerves compelled physiologists to reconsider the whole subject of the blood-pressure. If Poiseuille's thesis (1828) be compared with Marey's book (1863), _Physiologie Médicale de la Circulation du Sang_, it will be evident at once how much wider and deeper the problem had become. Poiseuille's thesis is chiefly concerned with mathematics and hydrostatics; it suggests no method of immediate permanent registration of the pulse, and is of no great value to practical medicine: Marey's book, by its very title, shows what a long advance had been made between 1828 and 1863--_Physiologie Médicale de la Circulation du Sang, basée sur l'étude graphique des mouvements du coeur et du pouls artériel, avec application aux maladies de l'appareil circulatoire_. Though the contrast is great between Hales' may-pole and Poiseuille's manometer, there is even a greater contrast between Poiseuille's mathematical calculations and Marey's practical use of the sphygmograph for the study of the blood-pressure in health and disease. Marey had the happiness of seeing medicine, physiology, and physics, all three of them working to one end:--

"La circulation du sang est un des sujets pour lesquels la
médecine a le plus besoin de s'éclairer de la physiologie, et où
celle-ci à son tour tire le plus de lumière des sciences
physiques. Ces dernières années sont marquées par deux grands
progrès qui ouvrent aux recherches à venir des horizons
nouveaux: en Allemagne, l'introduction des procédés graphiques
dans l'étude du mouvement du sang; en France, la démonstration
de l'influence du système nerveux sur la circulation
périphérique. Cette dernière découverte, que nous devons à M.
Cl. Bernard, et qui depuis dix ans a donné tant d'impulsion à la
science, montre mieux que toute autre combien la physiologie est
indispensable à la médecine, tandis que les travaux allemands
ont bien fait ressortir l'importance des connaissances physiques
dans les études médicales."

Marey's sphygmograph was not the first instrument of its kind. There had been, before it, Hérisson's sphygmometer, Ludwig's kymographion, and the sphygmographs of Volckmann, King, and Vierordt. But, if one compares a Vierordt tracing with a Marey tracing, it will be plain that Marey's results were far advanced beyond the useless "oscillations isochrones" recorded by Vierordt's instrument.

Beside this improved sphygmograph, Chauveau and Marey also invented the cardiograph, for the observation of the blood-pressure within the cavities of the heart. Their cardiograph was a set of very delicate elastic tambours, resting on the heart, or passed through fine tubes into the cavities of the heart,[1] and communicating impulses to levers with writing-points. These writing-points, touching a revolving cylinder, recorded the variations of the endocardial pressure, and the duration of the auricular and ventricular contractions.

[1] "On peut s'assurer de l'innocuité de ce premier temps de
l'expérience en examinant l'animal, qui n'est nullement troublé,
qui marche et mange comme de coutume. En comptant le chiffre du
pouls, on trouve quelquefois une légère accéleration, surtout dans
les premiers instants; mais les mouvements du coeur sont toujours
réguliers, et donnent, à l'auscultation, des bruits d'un caractère
normal." (Marey, _loc. cit._ p. 63.)

* * * * *

It is impossible here to describe the subsequent study of those more abstruse problems that the older physiologists had not so much as thought of: the minutest variations of the blood-pressure, the multiple influences of the nervous system on the heart and blood-vessels, the relations between blood-pressure and secretion, the automatism of the heart-beat, the influence of gravitation, and other finer and more complex issues of physiology. But, even if one stops at Marey's book, now more than forty years old, there is an abundant record of good work, from the discovery of the circulation to the invention of the sphygmograph.

II

THE LACTEALS

Asellius, in his account of his discovery of the lacteal vessels (1622), is of opinion that certain of "the ancients" had seen these vessels, but had not recognised them. He has a great reverence for authority: Hippocrates, Plato, Aristotle, the Stoics, Herophilus, Galen, Pollux, Rhases, and a host of other names, he quotes them all, and all with profound respect; and comes to this conclusion: "It did not escape the ancients, that certain vessels must needs be concerned with containing and carrying the chyle, and certain other vessels with the blood: but the true and very vessels of the chyle, that is, my 'veins,' though they were seen by some of the ancients, yet they were recognised by none of them." He can forgive them all, except Galen, _qui videtur nosse omnino debuisse_--"but, as for Galen, I know not at all what I am to think. For he, who made more than six hundred sections of living animals, as he boasts himself, and so often opened many animals when they were lately fed, are we to think it possible that these veins never showed themselves to him, that he never had them under his eyes, that he never investigated them--he to whom Erasistratus had given so great cause for searching out the whole matter?" Probably, the milk-white threads had been taken for nerves by those who had seen them: and those who had never seen them, but believed in their existence, rested their belief on a general idea that the chyle must, somehow, have vessels of its own apart from the blood-vessels. What Galen and Erasistratus must have seen, Asellius and Pecquet discovered: and Harvey gives a careful review of the discovery in his letters to Nardi (May 1652) and to Morison (November 1653). He does not accept it; but the point is that he recognises it as a new thing altogether.

A year or two after he had made the discovery, Asellius died; and his work was published in 1627 by two Milanese physicians, and was dedicated by them to the senate of the Academy of Milan, where Asellius had been professor of anatomy. The full title of his book is, _De Lactibus sive Lacteis Venis, quarto Vasorum Mesaraicorum genere novo invento, Gasparis Asellii Cremonensis, Anatomici Ticinensis, Dissertatio. Quâ sententiæ anatomicæ multæ vel perperam receptæ convelluntur vel partim perceptæ illustrantur._ He gives the following account of the discovery, in the chapter entitled _Historia primæ vasorum istorum inventionis cum fide narrata_. On 23rd July 1622, demonstrating the movement of the diaphragm in a dog, he observed suddenly, "as it were, many threads, very thin and very white, dispersed through the whole mesentery and through the intestines, with ramifications almost endless"--_plurimos, eosque tenuissimos candido-sissimosque ceu funiculos per omne mesenterium et per intestina infinitis propemodum propaginibus dispersos_:--

"Thinking at first sight that they were nerves, I did not
greatly heed them. But soon I saw that I was wrong, for I
bethought me that the nerves, which belong to the intestines,
are distinct from these threads, and very different from them,
and have a separate course. Wherefore, struck by the newness of
the matter, I stopped for a time silent, while one way and
another there came to my mind the controversies that occupy
anatomists, as to the mesenteric veins and their use; which
controversies are as full of quarrels as of words. When I had
pulled myself together, to make experiment, taking a very sharp
scalpel, I pierce one of the larger threads. Scarcely had I hit
it off, when I see a white fluid running out, like milk or
cream. At which sight, when I could not hold my joy, turning to
those who were there, first to Alexander Tadinus and Senator
Septalius, both of them members of the most honourable College
of Physicians, and, at the time of this writing, officers of the
public health, '_I have found it_,' I say like Archimedes; and
therewith invite them to the so pleasant sight of a thing so
unwonted; they being agitated, like myself, by the newness of
it."

He then describes the collapse and disappearance of the vessels at death, and the many experiments which he made for further study of them; and the failure, when he tried to find them in animals not lately fed. He did not trace them beyond the mesentery, and believed that they emptied themselves into the liver. The discovery of their connection with the receptaculum chyli and the thoracic duct was made by Jehan Pecquet of Dieppe, Madame de Sévigné's doctor, her "good little Pecquet." The full title of his book (2nd ed., 1654) is, _Expérimenta Nova Anatomica, quibus incognitum hactenus Receptaculum, et ab eo per Thoracem in ramos usque subclavios Vasa Lactea deteguntur_. He has not the academical learning of Asellius, nor his obsequious regard for the ancients; and the discovery of the thoracic duct came, as it were by chance, out of an experiment that was of itself wholly useless. He had killed an animal by removing its heart, and then saw a small quantity of milky fluid coming from the cut end of the vena cava--_Albicantem subinde Lactei liquoris, nec certe parum fluidi scaturiginem, intra Venæ Cavæ fistulam, circ[=a] dextri sedem Ventriculi, miror effluere_--and found that this fluid was identical with the chyle in the lacteals. In another experiment, he succeeded in finding the thoracic duct--"At last, by careful examination deep down along the sides of the dorsal vertebræ, a sort of whiteness, as of a lacteal vessel, catches my eyes. It lay in a sinuous course, close up against the spine. I was in doubt, for all my scrutiny, whether I had to do with a nerve or with a vessel. Therefore, I put a ligature a little below the clavicular veins; and then the flaccidity above the ligature, and the swelling of the distended duct below the ligature, broke down my doubt--_Ergo subducto paulo infra Claviculas vinculo, cum a ligaturâ sursum flaccesceret, superstite deorsum turgentis alveoli tumore, dubium meum penitus enervavit.... Laxatis vinculis, lacteus utrinque rivulus in Cavam affatim Chylum profudit._"

It is to be noted that Asellius and Pecquet, both of them, made their discoveries as it were by chance. Unless digestion were going on, the lacteals would be empty and invisible; and, on the dead body, lacteals, receptaculum, and thoracic duct would all be empty. For these reasons, it cost a vast number of experiments to prove the existence, and to discover the course, of these vessels. Once found in living animals, they could be injected and dissected in the dead body; but they had been overlooked by Vesalius and the men of his time.

From the discovery of the lacteals came the discovery of the whole lymphatic system. Daremberg, in his _Histoire des Sciences Médicales_ (Paris, 1870), after an account of Pecquet's work, says:--

"Up to this point, we have seen English, Italians, and French
working together, with more or less success and genius, to trace
the true ways of blood and chyle: there is yet one field of work
to open up, the lymphatics of the body. The chief honour here
belongs, without doubt, to the Swede Rudbeck, though the Dane
Bartholin has disputed it with him, with equal acrimony and
injustice."

Rudbeck's work (1651-54) coincides exactly, in point of time, with the first and second editions, 1651 and 1654, of Pecquet's _De Lactibus_. It may be said, therefore, that the whole doctrine of the lymphatic system was roughed out half-way through the seventeenth century.

III

THE GASTRIC JUICE

From many causes, the experimental study of the digestive processes came later than the study of the circulation. As an object of speculative thought, digestion was a lower phase of life, the work of crass spirits, less noble than the blood; from the point of view of science, it could not be studied ahead of organic chemistry, and got no help from any other sort of knowledge; and, from the medical point of view, it was the final result of many unknown internal forces that could not be observed or estimated either in life or after death. It did not, like the circulation, centre itself round one problem; it could not be focussed by the work of one man. For these reasons, and especially because of its absolute dependence on chemistry for the interpretation of its facts, it had to bide its time; and Réaumur's experiments are separated from the publication of Harvey's _De Motu Cordis et Sanguinis_ by a hundred and thirty years.

The following account of the first experiments on digestion is taken from Claude Bernard's _Physiologie Opératoire_, 1879:--

"The true experimental study of digestion is of comparatively
recent date; the ancients were content to find comparisons, more
or less happy, with common facts. Thus, for Hippocrates,
digestion was a 'coction': for Galen, a 'fermentation,' as of
wine in a vat. In later times, van Helmont started this
comparison again: for him, digestion was a fermentation like
that of bread: as the baker, having kneaded the bread, keeps a
little of the dough to leaven the next lot kneaded, so, said van
Helmont, the intestinal canal never completely empties itself,
and the residue that it keeps after each digestion becomes the
leaven that shall serve for the next digestion.

"The first experimental studies on the digestion date from the
end of the seventeenth century, when the Academy of Florence was
the scene of a famous and long controversy between Borelli and
Valisnieri. The former saw nothing more in digestion than a
purely mechanical act, a work of attrition whereby the ingesta
were finely divided and as it were pulverised: and in support of
this opinion Borelli invoked the facts that he had observed
relating to the gizzard of birds. We know that this sac, with
its very thick muscular walls, can exercise on its contents
pressure enough to break the hardest bodies. Identifying the
human stomach with the bird's gizzard, Borelli was led to
attribute to the walls of the stomach an enormous force,
estimated at more than a thousand pounds; whose action, he said,
was the very essence of digestion. Valisnieri, on the contrary,
having had occasion to open the stomach of an ostrich, had found
there a fluid which seemed to act on bodies immersed in it; this
fluid, he said, was the active agent of digestion, a kind of
_aqua fortis_ that dissolved food.

"These two opposed views, resulting rather from observations
than from regularly instituted experiments, were the
starting-point of the experimental researches undertaken by
Réaumur in 1752. To resolve the problem set by Borelli and
Valisnieri, Réaumur made birds swallow food enclosed in
fenestrated tubes, so that the food, protected from the
mechanical action of the walls of the stomach, was yet exposed
to the action of the gastric fluid. The first tubes used
(glass, tin, etc.) were crushed, bent, or flattened by the
action of the walls of the gizzard; and Réaumur failed to oppose
to this force a sufficient resistance, till he employed leaden
tubes thick enough not to be flattened by a pressure of 484
pounds: which was, in fact, the force exercised by the
contractile walls of the gizzard in turkeys, ducks, and fowls
under observation. These leaden tubes--filled with ordinary
grain, and closed only by a netting that let pass the gastric
juices--these tubes, after a long stay in the stomach, still
enclosed grain wholly intact, unless it had been crushed before
the experiment. When they were filled with meat, it was found
changed, but not digested. Réaumur was thus led at first to
consider digestion, in the gallinaceæ, as pure and simple
trituration. But, repeating these experiments on birds of prey,
he observed that digestion in them consists essentially in
dissolution, without any especial mechanical action, and that it
is the same with the digestion of meat in all animals with
membranous stomachs. To procure this dissolving fluid, Réaumur
made the birds swallow sponges with threads attached:
withdrawing these sponges after a definite period, he squeezed
the fluid into a glass, and tested its action on meat. That was
the first attempt at artificial digestion _in vitro_. He did not
carry these last investigations very far, and did not obtain
very decisive results; nevertheless he must be considered as the
discoverer of artificial digestion."

After Réaumur, the Abbé Spallanzani (1783) made similar observations on many other animals, including carnivora. He showed that even in the gallinaceæ there was dissolution of food, not mere trituration: and observed how after death the gastric fluid may under certain conditions act on the walls of the stomach itself.

"Henceforth the experimental method had cut the knot of the
question raised by the theories of Borelli and Valisnieri:
digestion could no longer be accounted anything but a
dissolution of food by the fluid of the stomach, the gastric
juice. But men had still to understand this gastric juice, and
to determine its nature and mode of action. Nothing could be
more contradictory than the views on this matter. Chaussier and
Dumas, of Montpellier, regarded the gastric juice as of very
variable composition, one time alkaline, another acid, according
to the food ingested. Side by side with these wholly theoretical
opinions, certain results of experiments had led to ideas just
as erroneous, for want of rigorous criticism of methods; it was
thus that Montègre denied the existence of the gastric juice as
a special fluid; what men took for gastric juice, he said, was
nothing but the saliva turned acid in the stomach. To prove his
point, he made the following experiment:--He masticated a bit of
bread, then put it out on a plate; it was at first alkaline,
then at the end of some time it became acid. In those days
(1813) this experiment was a real embarrassment to the men who
believed in the existence of a special gastric juice: we have
now no need to refute it.

"These few instances suffice to show how the physiologists were
unsettled as to the nature and properties of the gastric juice.
Then (1823) the Academy had the happy idea of proposing
digestion as a subject for a prize. Tiedemann and Gmelin in
Germany, Leuret and Lassaigne in France, submitted works of
equal merit, and the Academy divided the prize between them. The
work of Tiedemann and Gmelin is of especial interest to us on
account of the great number of their experiments, from which
came not only the absolute proof of the existence of the gastric
juice, but also the study of the transformation of starch into
glucose. Thus the theory of digestion entered a new phase: it
was finally recognised, at least for certain substances, that
digestion is not simply dissolution, but a true chemical
transformation." (Cl. Bernard, _loc. cit._)

In 1825 Dr. William Beaumont, a surgeon in the United States Army, began his famous experiments on Alexis St. Martin, a young Canadian travelling for the American Fur Company, who was shot in the abdomen on 6th June 1822, and recovered, but was left with a permanent opening in his stomach. Since the surgery of those days did not favour an operation to close this fistula, Dr. Beaumont took St. Martin into his service, and between 1825 and 1833 made a vast number of experiments on him. These he published,[2] and they were of great value. But it is to be noted that the ground had been cleared already, fifty years before, by Réaumur and Spallanzani:--

"_I make no claim to originality in my opinions_, as it respects
the existence and operation of the gastric juice. My experiments
confirm the doctrines (with some modifications) taught by
Spallanzani, and many of the most enlightened physiological
writers." (Preface to Dr. Beaumont's book.)

[2] _Experiments and Observations on the Gastric Juice, and the
Physiology of Digestion_, by William Beaumont, M.D.; Edinburgh,
1838.

Further, it is to be noted that Alexis St. Martin's case proves that a gastric fistula is not painful. Scores of experiments were made on him, off and on, for nine years:--

"During the whole of these periods, from the spring of 1824 to
the present time (1833), he has enjoyed general good health, and
perhaps suffered much less predisposition to disease than is
common to men of his age and circumstances in life. He has been
active, athletic, and vigorous; exercising, eating, and drinking
like other healthy and active people. For the last four months
he has been unusually plethoric and robust, though constantly
subjected to a continuous series of experiments on the interior
of the stomach; allowing to be introduced or taken out at the
aperture different kinds of food, drinks, elastic catheters,
thermometer tubes, gastric juice, chyme, etc., almost daily, and
sometimes hourly.

"Such have been this man's condition and circumstances for
several years past; and he now enjoys the most perfect health
and constitutional soundness, with every function of the system
in full force and vigour." (Dr. Beaumont, _loc. cit_. p. 20.)

In 1834 Eberlé published a series of observations on the extraction of gastric juice from the mucous membrane of the stomach after death; in 1842 Blondlot of Nancy studied the gastric juice of animals by the method of a fistula, such as Alexis St. Martin had offered for Dr. Beaumont's observation. After Blondlot, came experiments on the movements of the stomach, and on the manifold influences of the nervous system on digestion.

It has been said, times past number, that an animal with a fistula is in pain. It is not true. The case of St. Martin is but one out of a multitude of these cases: an artificial orifice of this kind is not painful.

IV

GLYCOGEN

Claude Bernard's discovery of glycogen in the liver had a profound influence both on physiology and on pathology. Take first its influence on pathology. Diabetes was known to Celsus, Aretæus, and Galen; Willis, in 1674, and Morton, in 1675, noted the distinctive sweetness of the urine; and their successors proved the presence of sugar in it. Rollo, in 1787, observed that vegetable food was bad for diabetic patients, and introduced the strict use of a meat diet. But Galen had believed that diabetes was a disease of the kidneys, and most men still followed him: nor did Rollo greatly advance pathology by following not Galen, but Aretæus. Later, with the development of organic chemistry, came the work of Chevreuil (1815), Tiedemann and Gmelin (1823), and other illustrious chemists: and the pathology of diabetes grew more and more difficult:--

"These observations gave rise to two theories: the one, that
sugar is formed with abnormal rapidity in the intestine,
absorbed into the blood, and excreted in the urine; the other,
that diabetes is due to imperfect destruction of the sugar,
either in the intestine or in the blood. Some held that it
underwent conversion into lactic acid as it was passing through
the intestinal walls, while others believed it to be destroyed
in the blood by means of the alkali therein contained."[3]

[3] _Reynolds' System of Medicine_, vol. v., art. "Diabetes
Mellitus."

Thus, before Claude Bernard (1813-1878), the pathology of diabetes was almost worthless. And, in physiology, his work was hardly less important than the work of Harvey. A full account of it, in all its bearings, is given in Sir Michael Foster's _Life of Claude Bernard_ (Fisher Unwin, 1899).

In Bernard's _Leçons sur le Diabète et la Glycogenèse Animale_ (Paris, 1877), there is a sentence that has been misquoted many times:--

_Sans doute, nos mains sont vides aujourd'hui, mais notre bouche peut être pleine de légitimes promesses pour l'avenir._

This sentence has been worked so hard that some of the words have got rubbed off it: and the statement generally made is of this kind:--

_Claude Bernard himself confessed that his hands were empty, but his mouth was full of promises._

Of course, he did not mean that he was wrong in his facts. But, in this particular lecture, he is speaking of the want of more science in practice, looking forward to a time when treatment should be based on science, not on tradition. Medicine, he says, is neither science nor art. Not science--_Trouverait-on aujourd'hui un seul médecin raisonnable et instruit osant dire qu'il prévoit d'une manière certaine la marche et l'issue d'une maladie ou l'effet d'une remède?_ Not art, because art has always something to show for its trouble: a statue, a picture, a poem--_Le médecin artiste ne crée rien, et ne laisse aucune oeuvre d'art, à moins d'appliquer ce titre à la guérison du malade. Mais quand le malade meurt, est-ce également son oeuvre? Et quand il guérit, peut-il distinguer sa part de celle de la nature?_

To Claude Bernard, experiments on animals for the direct advancement of medicine seemed a new thing: new, at all events, in comparison with the methods of some men of his time. He was only saying what Sir John Burdon Sanderson said in 1875 to the Royal Commission:--

_It is my profound conviction that a future will come, it may be a somewhat distant future, in which the treatment of disease will be really guided by science. Just as completely as mechanical science has come to be the guide of the mechanical arts, do I believe, and I feel confident, that physiological science will eventually come to be the guide of medicine and surgery._

Anyhow, lecturing a quarter of a century ago on diabetes, his special subject, Claude Bernard spoke out his longing to compel men into the ways of science, to give them some immediate sign which they could not refuse to see:--

"At this present time, medicine is passing from one period to
another. The old traditions are losing ground, and scientific
medicine (_la médecine expérimentale_) has got hold of all our
younger men: every day it gains ground, and will establish
itself against all its critics, and in spite of the excesses of
those who are over-zealous for its honour.... And when men ask
us what are the results of scientific medicine, we are driven to
answer that it is scarcely born, that it is still in the making.
Those who care for nothing but an immediate practical
application must remember Franklin's words, _What is the use of
a new-born child, but to become a man?_ If you deliberately
reject scientific medicine, you fail to see the natural
development of man's mind in all the sciences. Without doubt,
our hands are empty to-day, but our mouth may well be filled
with legitimate promises for the future."

He died in 1878. The following account of the discovery of glycogen is taken from his _Nouvelle Fonction du Foie_ (Paris, 1853):--

"My first researches into the assimilation and destruction of
sugar in the living organism were made in 1843: and in my
inaugural thesis (Dec. 1843) I published my first experiments on
the subject. I succeeded in demonstrating a fact hitherto
unknown, that cane-sugar cannot be directly destroyed in the
blood. If you inject even a very small quantity of cane-sugar,
dissolved in water, into the blood or under the skin of a
rabbit, you find it again in the urine unchanged, with all its
chemical properties the same.... I had soon to give up my first
point of view, because this question of the existence of a
sugar-producing organ, that I had thought such a hard problem of
physiology, was really the first thing revealed to me, as it
were of itself, at once."

He kept two dogs on different diets, one with sugar, the other without it; then killed them during digestion, and tested the blood in the hepatic veins:--

"What was my surprise, when I found a considerable quantity of
sugar in the hepatic veins of the dog that had been fed on meat
only, and had been kept for eight days without sugar: just as I
found it in the other dog that had been fed for the same time on
food rich in sugar....

"Finally, after many attempts--_après beaucoup d'essais et
plusieurs illusions que je fus obligé de rectifier par des
tâtonnements_--I succeeded in showing, that in dogs fed on meat
the blood passing through the portal vein does not contain sugar
before it reaches the liver; but when it leaves the liver, and
comes by the hepatic veins into the inferior vena cava, this
same blood contains a considerable quantity of a sugary
substance (glucose)."

His further discovery, that this formation of sugar is increased by puncture of the floor of the fourth ventricle, was published in 1849. It is impossible to exaggerate the importance of Claude Bernard's single-handed work in this field of physiology and pathology:--

"As a mere contribution to the history of sugar within the
animal body, as a link in the chain of special problems
connected with digestion and nutrition, its value was very
great. Even greater, perhaps, was its effect as a contribution
to general views. The view that the animal body, in contrast to
the plant, could not construct, could only destroy, was, as we
have seen, already being shaken. But evidence, however strong,
offered in the form of numerical comparisons between income and
output, failed to produce anything like the conviction which was
brought home to every one by the demonstration that a substance
was actually formed within the animal body, and by the
exhibition of the substance so formed.

"No less revolutionary was the demonstration that the liver had
other things to do in the animal economy besides secreting bile.
This, at one blow, destroyed the then dominant conception that
the animal body was to be regarded as a bundle of organs, each
with its appropriate function, a conception which did much to
narrow inquiry, since when a suitable function had once been
assigned to an organ there seemed no need for further
investigations....