We are indeed grateful, M r. Provost, for the warm welcome that you have accorded the newly created University Laboratory of Physical Chemistry Related to Medicine and Public Health on the occasion of its first theoretical seminar in the Harvard Yard. Your suggestion that it would be most appropriate for these seminars to be held in Harvard Hall inevitably brought to mind the state of knowledge about blood at the time that interest in natural philosophy wasemerging as a tradition in these halls.
Discovery in the Seventeenth Century o f the Capillaries, o f Erythrocytes, and o f Bodily Interactions with the Atmosphere (1656-1667)
Roofs o f the concept that the blood circulates
As early as 1660, the Quaestiones in Philosophia at Harvard College Commencement included a discussion b y Elischa Cooke, “An Motus Sanguinis Sit Circularis?”1 The question that was debated in the affirmative, at Harvard Commencement in 1660, had been given essentially its final form b y the English physician, William Harvey, whohad died only three years before, in 1657. It is not without interest that the most incisive valedictory upon William Harvey should have been written b y perhaps the most important, as well as the most articulate, of the next generation—the great generation—of English natural philoso- phers. In A Disquisition about the Final Causes of Natural Things Robert Boyle records his conscientious effort to under- stand the nature of the foundations on which he was building :
1 In the Catalogue of an exhibition at Widener Library, Cambridge, Massa- chusetts, April 20th to June ist, 1951, on “The Development of Knowledge of Blood Represented by Manuscripts, and by Selected Books Published from 1490 to the 19th Century,” (1) the broadside of this Harvard College Commencement is reproduced on p. 37.
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And I remember that when I asked our famous Harvey, in the only Discourse I had with him, (which was but a while be fore he dyed) What were the things that induc’d him to think of a Circulation of the Blood? He answer’d me, that when he took notice that the Valves in the Veins of so many several Parts of the Body, were so Plac’d that they gave free passage to the Blood Towards the Heart, but oppos’d the passage of the Venal Blood the Contrary way: He was invited to imagine, that so Provident a Cause as Nature had not so Plac’d so many Valveswithout Design : and no Design seem’d 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 through the Arteries, and Return through the Veins, whose Valves did not oppose its course that way. (i, p. 18)
In allprobability it wasLeonardo da Vinci, inquisitive about the structure of the body of man, who first affirmed the non- Galenic concept that both the veins and the arteries arise in the heart (i, p. 14). Michael Servetus, a Spanish physician, is thought to have had insight into the problem of the circulation of blood. T h e reputation of Servetus m a y well have been en- hanced, however, by the distinction that his theological views were distasteful both to the Inquisition and to Calvin. Hewas burned at Geneva b y Calvin in 1553. N o other significant con- tributor to knowledge about blood emerged in the centers of reaction or of reformation, in Spain or in Switzerland, for many centuries.
In Italy, especially in Northern Italy, however, science flour- ished in the sixteenth century. It was to Padua that William Harvey went in the last years of the sixteenth century to acquire the knowledge born of direct observation of the structure of the body, a practice which had been initiated by Vesaliusless than a century earlier. Andreas Vesalius, son of the Court apothecary of the Holy Roman Emperor, studied at Paris under J. Sylvius and Guinther, arrived in Venicein 1535 (2) and became professor of anatomy at Padua in 1537.There he built the first anatomical theater and began clinical instruction and the post-mortem examination of cadavers. Vesalius established the relation be- tween anatomy, medicine, and surgery and in 1543,when 29 years old, his great work, De Fabrica Corporis Humani, appeared. In that year, also, he left Padua. T h e tradition which he created was however continued b y his pupils, b y Fallopius, b y Realdo Columbus, and by their pupils, Caesalpinus and Fabricius of Aquapendente. “The repute of this school was so great that men came from everywhere to acquire both the accumulated
The Formed and Fluid Parts of Human Blood 5
learning and the methods for the acquisition of new learning that had been developed.”2 (3)
One cannot but reflect on the historical accident that at the very time that Harvey was in Padua studying with Fabricius, the professor of physics was Galileo. The great strength of the Faculty of Padua, during this period, depended, in part, upon the freedom from restraint in teaching, and upon the prosperity of the wealthy trading Republic of Venice. There is no evidence that I know of, however, which suggests that Harvey was aware of the contributions that a Galileo could make, by bringing to bear the tools of mathematics and mechanics, to the solution of anatomical and clinical problems. Nor is it certain what influence Harvey had upon another student, at Padua at the time, Ignatius Loyola. The investigational approach that Harvey brought back to England was that of the anatomical school of Padua. Concentrating his attention on the blood, he announced, in 1628, in a monumental treatise, De Motu Cordis, that blood circulated within the body in a closed system maintained by the heart, acting as a pump (3, p. 2).
Roofs of microscopy and of biomechanics in Italy
Harvey died in 1657. This year saw reaction in Rome and the temporary eclipse of the first scientific society, the Accademia dei Lincei, of which Galileo had been an active member and for which he built a compound microscope. The year 1657 is also memorable as the year in which the Accademia del Cimento was founded by the Medici Grand Dukes, Ferdinand II and Leopold, who had been students of Galileo, in which “nine scientists, supplied with the means of scientific research, gave ten years of united effort to the elaboration of instruments, the acquisition of experimental skill, and the determination of fundamental truths ; so completely were their efforts welded together that their work was sent into the world like that of a single individual ; . . .M (4)
The enduring reputation of the Cimento rests upon the con- tributions of a single individual, Giovanni Borelli, who in the preceding year, 1656, succeeded Galileo in the Chair of Mathe- matics in Pisa. Borelli largely concerned himself with air pressure, with the mechanics of breathing and later with the motions of animals and attempted “to apply mechanics to the
1 In order to avoid a copious bibliography, reference has been made to (1), or to an earlier study: “Research in the Medical Sciences.” (3)
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study of animate beings as Galileo had applied it to the study of inanimate objects. He knew of work on atmospheric pressure done byTorricelliandBoyle:from this andfrom a knowledgeof muscular contraction he obtained a clear understanding of the mechanics of breathing. His quantitative work on the force exerted by the heart was in error by several orders of magnitude, but it nevertheless emphasized the essentially mechanical nature ofthecirculation.” (i,p.30)Thefounder ofBiomechanicswrote in his De Motu Animalium:
As is generally done in other physical-mathematical sciences, we shall endeavour, with phenomena as our foundation, to expound this science of the movements of animals; and seeing that muscles are the principal organs of animal motion, we must first examine their structure, parts, and visible action. (3, p. 3)
The extraordinarily brief but pregnant period which saw the rise of microscopy a n d biomechanical science—of Borelli a n d Malpighi in Italy, of Leeuwenhoek, Huygens, and Swammerdam in Holland; of Boyle, Hooke, and Mayow in England—concerned itself, within the limits of the techniques available at the time, with the properties and functions of the blood. A s a consequence of this preoccupation, Richard Lower in England and Jean Baptiste Denis in France in 1667 even attempted the transfusion of blood. The circulation of the blood, postulated by Harvey earlier in the seventeenth century, on the basis of the anatomical observations of the great Paduan school at which he had studied, and from which he brought back to England the flame of a great tradition, could b y then b e assumed.
Four years after Harvey died, the concept of the circulation of the blood w a s proved b y a professor of medicine a t Messina, Malpighi, whowasborn the year in which the De Motu Cordis of Harvey waspublished. Theprofessor ofmedicine at Messina had previously spent some years with Borelli in Pisa. Malpighi ”approached clinical and anatomical problems from the point of view of physics. His work became known not only throughout Italy, but in England. Indeed, the newly formed Royal Society bore the expense of publishing the greater part of Malpighi’s work. T h e dissemination of scientific knowledge through the intellectual intercourse of investigators, wherever they m a y b e working, is the proved method of stimulating scientific research. Intercourse may be established by a voyage, such as that of
The Formed and Fluid Parts o f Human Blood 7
Harvey to Padua or of Malpighi to Pisa, or b y correspondence and publications as between Malpighi and his British contempo- raries.” (3, p . 3)
Thus Malpighi wrote of his great discovery of the capillaries, in tw o letters to Borelli that were published in 1661. In 1661 also, Robert Boyle published The Sceptical Chymist: or Chymico- Physteal Doubts & Paradoxes in which he ” . . . emphasizes the value of the study of chemistry for its own sake exclusive of its aid to medicine and alchemy.” (1, p. 29)
Roofs o f biochemistry and o f microscopy in England and America
The influence of Boyle, Hooke, and the natural philosophers who founded the Royal Society was first brought to Americaand to Harvard b y Charles Morton. Charles Morton’s concern with natural philosophy presumably began a t Oxford. * ‘ On September 7, 1649, he was admitted a scholar at Wadham College, of which John Wilkins was the ‘intruded’ warden. . . . In 1652 he took his M . A . in course. . . . If Morton’s tastes were not scientific before he came to Oxford, he had come into the very milieu to turn them in that direction. For Oxford in the middle of the seventeenth century wasmuch more friendly to experimental science—the ‘New Philosophy’—than Cambridge; and Wadham College was the scientific center of Oxford.”
“Sir Christopher Wren, scientist a n d architect, entered Wadham College in 1649, the same year with Morton” and “Robert Boyle settled a t Oxford in 1654.” (5, p p . x-xiii) T h e Oxford PhilosophicalSocietywasformallyorganizedin1651,and was “composed in large part of London virtuosi who h a d gone to Oxford during the Commonwealth period and who later were to return to London and be among the founders of the Royal Society. Sprat characterizes the weekly meetings of the group as follows :
‘Their proceedings were rather by action than discourse, chiefly attending some particular trials in Chymistry or Mechanicks; they had no rules nor method fixed. Their intention was more to communicate to each other their discoveries which they could make in so narrow a compass, than united, con- stant and regular disquisitions.’ ” (1, p. 25)
The year 1660, in which Elischa Cooke affirmed the question in philosophy of the Circulation of the Blood at Harvard Com- mencement was also the year of the restoration of Charles II to the English Throne.
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The formative period of the Royal Society, between 1660 and 1662, found a group meeting “to consult and debate concerning the promoting of experi- mental learning.,, . . . The number of members was restricted but included fellows of the Royal College of Physicians and professors of mathematics, physics, and natural philosophy. A royal charter was granted in 1662.Although the Royal Society has influenced science not only in England but throughout the world ever since, it was not created by government nor has it been dominated by government. It represented the spontaneous gathering of devotees of experi- mental science and reflected the need for intellectual intercourse of those con- cerned with promoting “experimental learning.” Its membership in the seven- teenth century included Boyle, Hooke, Newton, Leibnitz, Huygens, Malpighi, and Leeuwenhoek; the four last named were corresponding members who continued to work in other lands. Huygens, a mathematician, and Leeuwen- hoek, a lens grinder, were Dutchmen who, though affiliated with no university, devoted their whole lives to science, communicating their experimental results to the Royal Society, and through correspondence with the Royal Society maintaining contact with the scientific advances which were born of mathe- matics and physics and revolutionized biology and medicine.
Advances in medicine depend upon advances in our knowledge of bodily function. The study of function, which is physiology, depends in turn upon understanding of bodily structure. Although it is possible to some extent to observe the operation of a machine without understanding its structure, repair of the machine demands a more fundamental and intimate knowledge of its structure and of the interrelations between its parts. The study of gross bodily structure had, as we have seen, flourished in Padua in the sixteenth century, and knowledge of gross structure permitted Harvey to understand the func- tion of the heart in the circulation of the blood. The study of fine structure had to await the development of the microscope; this, in turn, depended on the theory of the nature of light, which is a branch of physics, and on the develop- ment of satisfactory lenses, which today would be called a branch of engineer- ing. The further development of both astronomy and biology depended upon these advances. . . .
The Royal Society furnished the medium for the exchange of information in this rapidly developing field. Hooke, a physicist and a microscopist, maintained intimate contact with astronomers and biologists, with Huygens, with Malpi- ghi, and with Leeuwenhoek. Leeuwenhoek more than anyone else used series of lenses in observing the fine structure of biological systems, and was the first to observe that the circulating fluid of the body, the blood, consists not only of a fluid part, which we now call plasma, but also of the cellular elements suspended in it which are responsible for its respiratory function.
Just as the development of biology and medicine is dependent upon the tools of physics, so the development of physics is dependent upon the tools of mathematics. Descartes, a French mathematician and philosopher, had devel- oped analytical geometry and methods for mathematical and graphical representation. The description of the movement of bodies in astronomy and in mechanics demanded still more powerful analytical tools, and the calculus was developed independently by a German philosopher, Leibnitz, and by Newton. By 1700, therefore, the mathematical tools which have sufficed almost to our
The Formed and Fluid Parts of Human Blood 9
own century were at hand, and the ground work had been laid for develop- ments in physics and in chemistry.
The chemistry of the English school of natural philosophy related to medi- cine largely through the concern of Boyle, Hooke, and Newton with the nature of . . . the atmosphere. The need of air for life was recognized. Hooke noted that the movement of the lungs was merely a mechanical device for bringing air into the body ;he proved by experiment that an animal could be kept alive with- out any movement, of the lungs, provided airwas driven in by a bellows and per- mitted to escape by mechanical means. Thèse brilliant early experiments in arti- ficial respiration were supplemented by the observations of his contemporary, Mayow, “that animals exhaust the air of certain vital particles. . . . that some constituent of the air absolutely necessary to life enters the blood in the act of breathing.” . . . The vital constituent was, of course, oxygen. Mayow had thus noted the function in respiration of the oxygen in the air, Hooke the function of the lungs, Harvey of the heart, Malpighi of the capillaries, and Leeuwenhoek had discovered the red blood corpuscles in the blood stream. The anatomical and physical advances in Italy and in England had by 1700 thus made possible some understanding of the mechanical bases of bodily processes. (3, pp. 4-7)
By 1700, as has previously been pointed out, this body of scientific knowledge had been incorporated into our American academic tradition. Charles Morton, who died in 1698, came to America in 1686 and
. . . brought over a set of his manuscript outlines with him, and the Com- pendium Physicae seems to have been adopted at Harvard shortly after his arrival. The title page of one of the earliest copies contains the date 1687, and the theses physicae on the Harvard Commencement broadside that year prove that the Compendium had already affected the scientific outlook at Harvard for the better. (5)
The scientific background ofthe NewWorld and ofthe OldWorld has remained the same since 1680. That research continued to flourish in Europe for two centuries before comparable con- tributions to knowledge were made in America must depend therefore rather upon the scientific environmentthan upon the state of scientific knowledge.
Discovery in the Eighteenth Century of the Elementary Composition of the Atmosphere (1756-1774)
The incisive, direct observations of the English natural philosophers ; of the followers of Boyle, Hooke, and Mayow upon the role of the gases of the atmosphere in respiration ; of Christo- pher Wren upon the action of drugs when injected into the
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circulation, of Richard Lower upon the transfusion of blood in animals and of the Newtonian, Stephen Hales, on the rate of the circulation of blood in the body, were appraised and organized into a system of quantitative knowledge only in the eighteenth century. As so often happens “Where New apperance is before the Eyes, New Suppositions thereupon arise,” (6) and arise rapidly under the stimulus of the new observations. As a result the full advance that is possible on the basis of existing knowledge takes place in a few decades. Thereafter a long delay may follow until new knowledge born of observations, often in remote or even undiscovered fields, makes possible new advances in the area we are here considering—of blood and the circulation—as well as in other areas.
The new knowledge that was required in this area was, on the one hand, of the nature and properties of the gases; of the “airs” that passed through the lungs into the body; on the other, of the body fluids and tissues affected by the gases exchanged. A full century elapsed after the work of Boyle before the elementary chemistry of the gases was developed. Van Helmont, a Belgian contemporary of Galileo, had long since noted the gas, carbon dioxide, that accumulated during fermentation, but not until
1756 did Joseph Black, a Scottish investigator, prepare this gas from chalk. Ten years later, in 1766 Cavendish produced hydro- gen by the action of acids on certain metals; in 1772 Scheele distinguished the inert gas of the atmosphere, nitrogen; and in 1774 Priestley, by heating oxides, isolated oxygen. Within eight- een years, therefore, these gases of the atmosphere were isolated as chemical entities. The transformation of the nitrogen of the atmosphere into the nitrogen of which all plant and animal tissues are composed—the “fixation of nitrogen*’—was not to be understood for many years, or achieved as a chemical process until our own times.
The discoveries of these mid-eighteenth century chemists, who for the first time separated the elements of which the gases of the atmosphere are composed and could therefore investigate their properties as chemical substances, could now be integrated with the observations of the great seventeenth century generation of natural philosophers that combined experiment upon natural systems with reason ; were they physical, mechanical, biological, or chemical systems. Their philosophy and the new chemistry were thus the heritage of Lavoisier.
The Formed and Fluid Parts of Human Blood 11
The advances of Black, Cavendish, Priestley, Scheele, and others made it possible for Lavoisier to investigate changes occurring during breathing, burning, and other forms of com- bustion, and to show that both carbon dioxide and water— produced from hydrogen and oxygen—were products of normal respiration (3, p. 8). To early workers the inert gas, nitrogen, was considered “foul” since it remained in a closed system from which animals had exhausted the oxygen.
Understanding of the chemical nature of the natural gases which enter into bodily processes made possible their use, under controlled conditions, as tools for physiology and medicine. Firm scientific foundations had been laid for research in the chemistry of the natural products of the body which are constituted of carbon and nitrogen, as well as hydrogen and oxygen. Half a century after the death on the guillotine of Lavoisier, the tax collector, and just over a century before our times, Justus Liebig paid an understanding tribute to Lavoisier, the scientist :
By the application to Chemistry of the methods which had for centuries been followed by philosophers in ascertaining the causes of natural phenomena in physics—by the observation of weight and measure—Lavoisier laid the foundation of a new science, which, having been cultivated by a host of distinguished men, has, in a singularly short period, reached a high degree of perfection.
It was the investigation and determination of all the conditions which are essential to an observation or an experiment, and the discovery of the true principles of scientific research, that protected chemists from error, and con- ducted them, by a way equally simple and secure, to discoveries which have shed a brilliant light on those natural phenomena which were previously the most obscure and incomprehensible.
The most useful application to the arts, to industry, and to all branches of knowledge related to chemistry, sprung from the laws thus established; and this influence was not delayed till chemistry had attained its highest perfection, but came into action with each new observation. . . .
In earlier times, the attempt has been made, and often with great success, to apply to the objects of the medical art the views derived from an acquaint- ance with chemical observations. Indeed, the great physicians who lived towards the end of the seventeenth century were the founders of chemistry, and in those days the only philosophers acquainted with it. . . .
Physiology took no share in the advancement of chemistry, because, for a long period, she received from the latter science no assistance in her own devel- opment. This state of matters has been entirely changed within five and twenty years. . . .
Before the time of Lavoisier, Scheele, and Priestley, chemistry was not more closely related to physics than she is now to physiology. At the present day chemistry is so fused, as it were, into physics, that it would be a difficult
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matter to draw the line between them distinctly. The connexion between chemistry and physiology is the same, and in another half century it will be found impossible to separate them. . . .
My object in the present work has been to direct attention to the points of intersection of chemistry with physiology, and to point out those parts in which the sciences become, as it were, mixed up together. It contains a col- lection of problems, such as chemistry at present requires to be resolved; and a number of conclusions, drawn according to the rules of that science, from such observations as have been made, (i, p. 48)
Discovery in the Early Nineteenth Century of the Elementary Composition of Living Matter (1806-1842)
The century that intervened between the observations of Boyle, Hooke and Newton, and of Black, Cavendish, Scheele, Priestley and Lavoisier was followed by another century before the composition of the organic substances of which all living matter is composed could be effectively investigated. The Lucretian theory, that matter was constituted of atoms, com-
bined with each other in fixed proportions, was revived b y Dalton in his New System of Chemical Philosophy in 1808 (3, p. 9). In the same year Gay-Lussac developed the numerical relations be- tween the atoms in gases and Berzelius published his lectures on animal chemistry, in which organic chemistry was, for the first time, based on the atomic theory. Three years later, in 1811, Avogadro suggested that the “little masses” which exerted the pressures of gases were constituted of fixed combinations of atoms (3, p. 9). The elements of which the most complex organic molecules of the body, the proteins, are composed—carbon and nitrogen, oxygen and hydrogen—had by then been recognized and isolated.
The theory of the combination of the elements with each other, in multiple proportions, wasgenerally accepted within a thirdof a century. Just as Lavoisier could build upon the observations of Boyle and Hooke, and the chemistry of Black, Cavendish, Scheele, and Priestley, so Liebig could build on the observations of Lavoisierand the chemistry of Dalton, Gay-Lussac, Avogadro, and Berzelius.
In the century between Liebig and our times there were again chemical advances; this time in synthetic organic chemistry, electrochemistry, physical chemistry, and in the chemistry of eatural products; especially of proteins.
The Formed and Fluid Parts o f Human Blood 13
The more complex organic molecules of natural systems were studied by Berzelius and Liebig during the first part of the nineteenth century. Liebig was professor of chemistry at Giessen and later at Munich. His laboratory at Giessen became the center for the study of proteins, including the plasma proteins. The group working with him included his colleague Mulder, who made the first elementary analysisoftheproteins, estimated their molecular weights from the small amounts of sulfur and phosphorus they contained; a n d Bence Jones, a n Englishman, who investigated the proteins that appear in the urine of those with certain diseases of the bone marrow.
Just asMalpighireported hisobservationsofthecapillariesin letters to Borelli, so Prosper-Sylvain Denis, a French physician, reported his experiments to Liebig many years before his Mémoire sur le sang . . . suivi d’une notice sur Vapplication de la méthode d’expérimentation par les sels a V étude des substances albuminoïdes appeared in 1859 (7)· Denis noted the proteins of plasma that precipitated upon dilution a n d redissolved upon addition of salt, and are called globulins.
Observations upon the propenies of albumins
The far more soluble proteins of plasma had been called albumins because of their close resemblance to those of whiteof egg; a resemblance that h a d been investigated a century earlier by Hermann Boerhaave a n d Carolus Guillelmus Poerner in terms of the chemical reactions that were recognized in the eighteenth century.
It is not without interest that it was Boerhaave who, in 1737, posthumously published the Biblia Naturae of Swammerdam, in which is described the observations upon erythrocytes in
1658, of the Dutch physician who died in 1680.
. . . . In the blood I observed the serum, in which floated an enormous number of orbicular particles, rejoicing in a very regular shape, seen as an oval when viewed broadside. Moreover these particles themselves are seen to contain another humor within themselves and if I looked upon them from the side, they almost resembled crystalline rods, and a variety of figures; and no doubt in the same way they are rolled around in the serum of the blood. (1, p. 24)
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We owe to Boerhaave, therefore, the very accurate, and probably the earliest description of the red corpuscles in the blood, as well as one of the earliest and most complete studies upon t h e proteins of serum.
Observations upon the properties of fibrinogen
By the eighteenth century the microscope had become a com- mon tool. N e w observations have ever since continued t o b e made with its aid, often b y the same investigator who was con- tributing new observations based on the newer tools of an emergent chemistry. T h e English physician, William Hewson, who first described the white cells of the blood, noted in 1771, in An Experimental Inquiry into the Properties of the Blood, t h e influence of physical conditions and of chemical reagents upon the color of the red blood cell; as well as their influence upon the
serum of blood, he noted that the protein, which we now call fibrinogen, was essential for the clotting of blood, for ” b y agitating fresh blood with a stick, so as to collect this substance on the stick . . . the rest of the blood remains fluid.” (1, p.
The state of knowledge of the “composition of animals” just before the time of Liebig is “familiarly explained” in a volume entitled “Conversations on Chemistry” (8) published at Green- field, Massachusetts, in 1820:
On attending for the first time experimental lectures, the author found it almost impossible to derive any clear or satisfactory information from the rapid demonstrations which are usually, and perhaps necessarily, crowded into popular courses of this kind. But frequent opportunities having afterwards occurred of conversing with a friend on the subject of chemistry, and of repeating a variety of experiments, she became better acquainted with the principles of that science, and began to feel highly interested in the pursuit. It was then that she perceived, in attending the excellent lectures delivered at the Royal Institution, by the present Professor of Chemistry, the great advantage which her previous knowledge of the subject, slight as it was, gave her over others who had not enjoyed the same means of private instruction. Every fact or experiment attracted her attention, and served to explain some theory to which she was not a total stranger; and she had the gratification to find that the numerous and elegant illustrations, for which that school is so much distinguished, seldom failed to produce on her mind the effect for which they were intended.
Hence it was natural to infer, that familiar conversation was, in studies of this kind, a most useful auxiliary source of information; . . . and to record, in the form of dialogue, those ideas . . . first derived from conversation.
The Formed and Fluid Parts of Human Blood 15
A “Vocabulary of Chemical Terms” gives the following definitions :
Albumen. The modern name for coagulable lymph.
Fibrine. That white fibrous substance which is left after freely wasing the
coagulum of the blood, and which chiefly composes the muscular
Gelatine. A chemical term for animal jelly.
Gluten. A vegetable substance somewhat similar to animal gelatine.3
The final “conversation” between M rs. B . and her students is “On the Composition of Animals.”
We are now come to the last branch of chemistry, which comprehends the most complicated order of compound beings. This is the animal creation, the history of which cannot but excite the highest degree of curiosity and interest, though we often fail in attempting to explain the laws by which it is governed.
[Student] But since all animals ultimately derive their nourishment from vegetables, the chemistry of this order of beings must consist merely in the conversion of vegetable into animal matter.
Mrs. B.: Very true; but the manner in which this is effected is, in a great measure, concealed from our observation. This process is called animalization, . . . A new principle abounds in the animal kingdom, which is but rarely and in very small quantities found in vegetables; this is nitrogen. . . .
[Student] Animal compounds contain, then four fundamental principles; oxygen, hydrogen, carbon, and nitrogen?
Mrs. B .: Y es; and these form the immediate materials of animals, which are gelatine, albumen, and fibrine. . . . These three kinds of animal matter, gela- tine, albumen, and fibrine, form the basis of all the various parts of the animal system; either solid, . . . or fluid, . . . Gelatine, or jelly, is the chief ingredient of skin, and of all the membranous parts of animals. . . .
The next animal substance we are to examine is albumen; . . . the white of egg, for instance, consists almost entirely of albumen; the substance that composes the nerves, the serum, or white part of the blood, and the curds of milk, are little else than albumen variously modified.
In its most simple state, albumen appears in the form of a transparent viscous fluid, possessed of no distinct taste or smell; it coagulates at the low temperature of 165 degrees, and, when once solidified, it will never return to its fluid state. . . .
8 In the previous Conversation “On the Nature and Composition of Vegetables,” Mrs. B. had discussed gluten: “The fecula of wheat contains also another vegetable substance which seems peculiar to that seed, or at least has not as yet been obtained from any other. This is gluten, which is of a sticky, ropy, elastic na- ture; and it is supposed to be owing to the viscous qualities of this substance, that wheat-flower forms a much better paste than any other.”
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We may now proceed to fibrine. This is an insipid and inodorous substance, having somewhat the appearance of fine white threads adhering together; it is the essential constituent of muscles or flesh, in which it is mixed with and softened by gelatine. It is insoluble both in water and alcohol, but sulphuric acid converts it into a substance very analogous to gelatine.
These are the essential and general ingredients of animal matter; . . .
The very word—protein—did not exist until the nineteenth century; until Liebig’s time. It was Mulder, who recognized that the elementary analysis of various vegetable and animal proteins were so nearly alike as to suggest their identity,4 who gave to this class of substances the name protein; meaning of the first importance. T h e core of proteins, which Mulder thought were identical, had been treated with acids and alkalies and were, of course, denatured. Moreover, as has so often happened in protein chemistry, improvement in methodics, soon demon- strated differences, as well as similarities, in the elementary composition of various proteins.
In Liebig’s time close intercourse among those working in the same field in distant lands was no longer maintained by cor- respondence alone. N e w journals were coming into existence in each field; Berzelius was publishing his annual reports and Liebig the Annalen de Chemie which brought the results of new investi- gations before an ever widening body of investigators. Liebig’s Animal Chemistry, or Organic Chemistry in its Application to Physiology and Pathology, published in 1842, and parts of which were eagerly learned of by the British Association for the Advancement of Science in 1840 and 1842, soon appeared in book form (1, p. 47). In it the extensive][analysis\ipon the elementary composition of various proteins were published and thus brought to the attention of the scientific world. An English edition was edited b y William Gregory of Aberdeen, and an American edi- tion, published in Cambridge, Massachusetts, in 1842, w a s edited by the Erving Professor of Chemistry and Mineralogy at Harvard, John W . Webster. Following the murder of his colleague, the Professor of Medicine, Webster ended on the gallows the opportunity of effectively expounding in the United States the insight into animal and vegetable life contributed by the new organic chemistry of natural products.
4 Results which were discussed in more detail in a Harvey Lecture given in 1939 (9).
The Formed and Fluid Parts of Human Blood 17
Meanwhile, synthetic organic chemistry had created a revolu- tion which temporarily distracted attention from the natural products and systems of which the body is composed. Another co-worker of Liebig’s: Wöhler, synthesized urea in 1828. Syn- thesis of many simple organic molecules followed, and the earlier organic chemistry—the chemistry of the materials of which the tissues of man, animal, and plants are constituted—was tem- porarily eclipsed by preoccupation with the synthesis and with the pharmacology of unnatural products.