use of colloids in health and disease by alfred b. searl

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N HEALTH ANDDISEASE


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THE USE OF COLLOIDSIN

HEALTH AND DISEASE


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THE CHADWICK LIBRARY

THEUSE OF COLLOIDS INHEALTH AND DISEASEBY

ALFRED B. SEARLE

WITH FOREWORDBY

SIR MALCOLM MORRIS

LONDONCONSTABLE & COMPANY LTD

10 ORANGE STREET, LEICESTER SQUARE, W.C1920


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All rights reserved

Printed in Great Britain


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FOREWORDBY SIR MALCOLM MORRIS, K.C.V.O.

THE subject with which this book is concerned is oneof vast extent and enormous importance. It coverswide tracts of territory in physiology and medicine. All life processes, as Prof. Wolfgang Ostwald hassummarily said, take place in a colloidal system,and that is true both of the normal fluids and secretionsof the organism and of the bacterial toxins, as well as,in large measure, of the reactions which confer im-munity. If this is so, it would seem to be an obviousdesideratum that the drugs employed to combat diseaseshould be in the colloidal state, i.e. in a form in whichthey may be isomorphic and isotonic with the elementsof the body. Only so can they be expected to exerttheir full potency. The task of thus bringing theirremedial virtue to its highest point is not an easyone, for colloidal substances, unless prepared withconsummate skill and meticulous care, lack stability,and are prone to precipitation when brought intocontact with the electrolytes normally present in thebody tissues and fluids. That it is not beyond theresources of scientific chemistry is clearly shown inthis book. A measure of success has, in fact, beenachieved which leaves no doubt of the brilliant futurewhich lies before drugs in the colloidal form.To the study of colloids, both in health and disease,


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vi AUTHOR'S NOTEsome of the world's greatest investigators have devotedand are devoting their genius for research. Much thatwas mystery has already been elucidated. A veryconsiderable body of literature has accumulated, andthe time is ripe for such lucid expositions of ascer-tained results as will be found in these pages, writtenby an acknowledged master of the subject.

AUTHOR'S NOTETHE present volume is based on a lecture delivered atthe request of the Chadwick Trustees, under the chair-manship of Sir William Collins, K.C.V.O., and forms oneof a series of works published under their auspices.Some of the information also appears in the author'scontribution to the British Association Report onColloids, viz. The Administration of Colloids in Disease,published by the Department of Scientific and Indus-trial Research, and obtainable from H.M. StationeryOffice.

A. B. SEARLE.THE WHITE BUILDING,

SHKFFIKLD,November, 1919.


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CONTENTSFOREWORD .........AUTHOR'S NOTE ........

I. NATURE AND PROPERTIES OF COLLOIDS AGGLUTINA-TION ACTION OF RADIATIONS ON SOLS COLOUROF COLLOIDS .......

II. ANIMAL AND VEGETABLE FLUIDS ....III. THE HYGIENIC USES OF COLLOIDS PURIFICATION OF

WATER SOAPS ......IV. MICRO-ORGANISMS AND DISEASE TOXINS AND ANTI-

TOXINSV. POISONING DIGESTION AND COLLOIDS .VI. USE OF COLLOIDS IN MEDICINE ....

VII. PREPARATION OF COLLOIDAL SOLS ASSAYING COL-LOIDAL SOLS THE ULTRA-MICROSCOPE THE TYN-DALL PHENOMENON GOLD NUMBER STABILITYNUMBER . .

VIII. COLLOIDS AS GERMICIDES AND DISINFECTANTSIX. TYPICAL COLLOIDAL REMEDIES AND THEIR USES

GOLD SILVER MERCURY IRON ANTIMONYMANGANESE COPPER PLATINUM PALLADIUMOXIDE PALLADIUM NICKEL IODINE SULPHURARSENIC OXIDES QUININE COCAINE COM-

PLEX COLLOIDS ......X. CONCLUSION .......

INDEX .

PACKVvi

I

21

29

364245

5367

761083


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THE USE OF COLLOIDS INHEALTH AND DISEASECHAPTER I

NATURE AND PROPERTIES OF COLLOIDSTHE difference between a healthy and a diseasedorganism is so important, and the necessity for im-proving the health of the nation is so urgent, that anyapplication of knowledge to this end is worth very seriousconsideration. Consequently it is necessary that anypossible use of discoveries in branches of science,other than medicine, should be brought to the atten-tion of all concerned with the least possible delay.This application of knowledge gained in various fieldsof investigation to the improvement of health and thereduction of disease was one of the foundation prin-ciples of Sir Edwin Chadwick, whose generosity madethe present publication possible.The study of hygiene and of many diseases has been

enormously facilitated by the discovery that many ofthe ills that flesh is heir to, and many others which itis unnecessary to suffer, are due to the influence ofbacteria and their products. There is, however, astill wider cause of disease, of which bacteria formonly a part, which is due to the peculiar structure ofthe essential organs of all animals and vegetables a.


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2 USE OF COLLOIDS IN HEALTH & DISEASEstructure which has long been recognised in certainways, though some of its properties have only beenrealised within the last decade or two.We are all aware that living organisms are com-posed of a number of cells consisting of an externalenvelope, or membrane, and an enclosed fluid. Eventhe most complex animal structure can be shown toconsist of a vast number of such cells, differing enor-mously in their shape and functions, but all possessingcertain well-defined characteristics. The membranesor envelopes of these cells possess the peculiar propertyof allowing certain substances to pass through themquite readily whilst others cannot do so, and on thisproperty depend many of the most complex functionsof the whole organism. The processes of digestion andassimilation and the oxygenation of the blood arewell-known examples of the selective passage of certainsubstances through the membranes concerned. Someinvestigators, including Moore and Roaf, 1 do notaccept the idea of membranes of selective permeability,but consider the phenomena usually attributed tothem as being due to selective absorption. Thisappears to be specially applicable to living cells, asseveral colloids behave differently in these from whatthey do in synthetic, or dead, membranes.

It is well known that if a mixture of sand, gelatin,salt, and water were to be filtered through cotton wool,paper, or other recognised filtering medium, the sandwould remain on the filter, but the salt and gelatinwould pass through in solution in the water. It is not

1 Hober, Arch. ges. Physiol., 1913, 150, 15 ; Moore and Roaf,Roll. Zeits., 1913, 13, 133,


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NATURE AND PROPERTIES OF COLLOIDS 3so well known that if such a solution of salt andgelatin is placed in a parchment or collodion cup, andthe latter partially immersed in a vessel of water, thesalt will pass into the water, but the gelatin willremain behind in the cup. By repeatedly changingthe water in the outer vessel the whole of the salt maybe removed from the gelatin solution. This distinctiveproperty of salt and gelatin was investigated byThomas Graham, who found that all those substanceswhich pass readily through a filter, but not through amembrane, had certain other resemblances. He alsofound that some substances could exist in such a statethat they would pass either through a membrane ornot, according to their method of preparation. Fara-day extended this investigation, prepared a numberof substances in this state, and found that they hadproperties quite different from those ordinarily pos-sessed by them. Thus, metallic gold, which is peculiarlyinsoluble and resistant, could be obtained in so fine astate of suspension that it passed readily through allordinary filters and behaved as a solution. At thesame time its colour was entirely different from thatcharacteristic of the metal, being red or blue insteadof yellow, and its other properties were changed to acorrespondingly great extent.When Thomas Graham, in 1861, found that certainsolutions would pass through a membrane, whilstothers did not do so, he little realised how great adiscovery he had made. He had, in fact, found, andwas able to describe, a state of matter of which littleor nothing was realised at the time, though manyindustries, and indeed life itself, were and are dependent


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4 USE OF COLLOIDS IN HEALTH & DISEASEon it. Graham's chief discovery in this connectionwas that substances may enter into solution in sucha manner that they exhibit characteristics which arequite different from those of a true solution. To thisintermediate state he applied the term colloidal (from Kolla=g\ue), as glue, gelatin, and allied sub-stances were most readily recognised by him as beingin the colloidal state. Since Graham's time it has beenfound that most substances can be obtained in thecolloidal state, their occurrence being sometimes dueto reactions which are specially characteristic ofanimal or vegetable organisms and sometimes topurely inorganic changes.The colloidal state may be defined as a physical

condition of matter consisting of at least two parts orphases, one of which is the active substance and theother the one in which it is distributed. The formeris termed the disperse phase ; it is the active agent andmay consist of either solid or liquid particles which areso minute that they remain for an indefinitely longperiod in suspension. The second phase is either aliquid or an otherwise homogeneous complex material ;it is known as the dispersion medium. Such a definitiondoes not, however, give any clue to the peculiar pro-perties of substances when in the colloidal state, andit might be applied with accuracy to any turbid fluid.In a colloidal solution which not being a true solutionis preferably termed a sol the dispersed substance isable to react in a manner quite different from whatwould ordinarily be anticipated. The dispersed orsuspended particles are not merely so minute tHat theeffect of gravity on them is counterbalanced by other


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NATURE AND PROPERTIES OF COLLOIDS 5forces which keep them in suspension (though theyare often only one-thousandth part of the size ofaverage bacteria), but they are in a state of unorderedoscillation which gives rise to the well-known Brownianmovement. They behave in a liquid in a manner very

a. Hydrogen molecules. b. Chloroform molecules.c. Haemoglobin molecules. d?> ,/,' Partides of colloidal gold.h (large circle). Particles which precipitate from gold suspensions.FIG. i. RELATIVE SIZES OF COLLOIDAL PARTICLES AND

MOLECULES(Scale i : 1,000,000)

similar to the molecules and atoms of a gas, and are inconstant movement, travelling at a high velocity andrepeatedly colliding with each other. There is nogroup of substances which are invariably colloids.Thus soaps dissolve in alcohol and behave as true


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6 USE OF COLLOIDS IN HEALTH & DISEASEcrystalloids ; in water they behave equally character-istically

as colloids. Common salt, on the contrary,behaves as a colloid in relation to benzole, but as acrystalloid when dissolved in water. Von Weimarnand others have shown that so many substances canbe obtained in the form of colloidal solutions that it isprobably correct to regard colloids as substances whichare in a particular state rather than as forming adistinct group of substances. Colloids are readilydivisible into two fairly well-defined groups to whichvarious names have been given by different investi-gators, the most generally accepted being emulsoid(fluid particles) and suspensoid (solid particles), assuggested by Wo. Ostwald. The colloids in the firstgroup have many of the properties of gelatin or glue ;they swell when immersed in a suitable fluid (water),absorbing a large quantity of it, and gradually becomeso dispersed as to possess many of the properties of asolution. The apparently solid particles have many ofthe properties of a liquid, and for this reason the termemulsoid is very aptly applied to them. The behaviourof emulsoids towards electrolytes is so complex thattheir classification on an adequate, yet simple, scaleis, at present, impossible. The second group ofcolloids contains substances which are much moresensitive to small traces of added substances, and theelectric charge acquired by them is much greater.They appear to consist of extremely minute particlesof solid matter, though this adjective must not beapplied too rigidly in this connection.There are many well-known organic substances

which occupy an intermediate position between


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NATURE AND PROPERTIES OF COLLOIDS 7colloids and crystalloids, and are conveniently termedsemi-colloids. Casein, soap, many degradation pro-ducts of albumen, peptones, and other constituents ofanimal organisms, and several dyes belong to thisclass. Thus albumen is a true emulsoid, but the pro-talbic and lysalbic acids derived from it diffuse throughthe parchment and behave in other ways as crystal-loids, whilst at the same time having several properties(such as opalescence, viscosity, and protectiveaction ) which are characteristics of colloids. Semi-colloids, such as soaps, may not be colloids underordinary conditions, but form colloidal sols when incontact with certain liquids ; they are sometimestermed colloidogens. Other semi-colloids are clearlyelectrolytes, but their boiling points and vapour pres-sures are approximately the same as those of water ;these and other properties are so abnormal that suchsubstances must be classed among the semi-colloids.Each colloidal particle also carries a characteristic

definite charge of electricity, some colloids beingelectro-positive and others electro-negative. Usually,when any given substance is in the colloidal state ithas the same electric sign, but by adopting specialmethods of preparation it is possible to produce somesubstances in a colloidal form in which the particlesmay have either a positive or a negative electriccharge. The electrification of colloidal particles maybe compared with that of a piece of glass suspended bya thin silk thread and rubbed with a piece of amal-gamated silk. If a second piece of glass similarlyelectrified by rubbing is brought near to the first therewill be a mutual repulsion. On the other hand, a


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8 USE OF COLLOIDS IN HEALTH & DISEASEpiece of ebonite which has been rubbed with fur willattract the glass because it carries an electric chargeof the opposite sign. The electric charge is not thetotal amount of electricity which the body possesses,but only the excess or deficit of that which it carriescompared with the neutral electrical condition.

It is important to note also that the chemical com-position, and often the physical appearance of a sub-stance, gives no indication of the electric charge whichit has acquired, so that unless the charge is definitelyinvestigated its existence may be overlooked. This hasto a large extent been the case in the study of manydrugs and other remedies.

Substances such as glass and ebonite are most easilycharged electrically as the result of friction, but thisis by no means the only or even the most importantcause of excitation. If two different metals aremoistened and brought into contact, a feeble but observ-able electrification is produced. This is easily shownby holding a silver and copper coin edgewise on thetongue. So long as the coins are separate no electrifica-tion results, but directly they touch each other at somepoint away from the tongue the taste produced by theelectrification becomes apparent. If two dissimilarmetals are partially immersed in a liquid which canchemically react on one of them, a simple voltaic cellor battery unit is formed, the electric current pro-duced depending on the sizes of the pieces of metaland on the nature of the fluid used. Chemical actionand electric phenomena are, indeed, so closely relatedthat in many instances one cannot occur without theother. In fact, many phenomena which are generally


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NATURE AND PROPERTIES OF COLLOIDS 9regarded as chemical are largely electrical in character,or at least may be helpfully considered as such.For example, the dissociation of a compound into

its elements or into two distinct groups of ions isfrequently accompanied by the assumption of definiteelectric charges by each of the groups. Thus, when asolution of common salt in water is made sufficientlydilute, the salt is dissociated into positively chargedsodium and negatively charged chlorine particles, orions. Sulphuric acid a more complex substance

is dissociated into positive hydrogen ions andnegative SO 4 ions. Even a partial dissociation of thefluid in which the substance is dissolved or suspendedmay cause the colloid to acquire an electric charge.Thus, water (H+-OH~) can form two classes of colloidsthe particles of which are respectively positively andnegatively charged, and it is suggested that in manycases there is a chemical combination with the liquid

aPt+H+-OH- = (Pt.H+)+OH-,or aPb+H+'OH- = (Pb,OH-)+H+ .The charge on a sol is very much less than on an

equivalent amount of the corresponding ion, and,therefore, a larger amount of sol will be required whenit is used as a reagent.Burton has estimated a charge for a single particle

of gold and silver sols on the assumption that theamount of Al in aluminium salts which just precipi-tates the gold or silver has acquired the same amountof positive electricity as that amount of negativeelectricity acquired by the precipitated particles.The volume of a particle is 2Xio~ 4 cc., so that


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io USE OF COLLOIDS IN HEALTH & DISEASE100 cc. of a sol with 6-5 mgms. silver contains 3 x io10particles. This volume of sol required 3-oxio~

5

and 2-6xio~ 5 gms. of A1 2(SO 4) 3 for precipitation,from which the charge on a particle is 2-8xio~ 2electrostatic units, and the charge on one gram-equiva-lent of silver in a sol is 4 per cent of the charge on onegram-equivalent of silver ion. This dissociation onsolution with the assumption of an electric charge iswell known to chemists, though it is not so obviousto others on account of the minuteness of the particlesand of the charges which they carry. There is ageneral agreement among those who have studied thesubject that colloidal sol particles are enclosed by adouble electric layer, as suggested by Quincke andHelmholtz ; when a particle is negatively chargedthere is a negatively electrified layer on its surface,whilst in the liquid immediately surrounding theparticle is a corresponding layer which is chargedpositively. Burton has shown that there is a layer ofhydroxide, or hydride, on the colloidal metals whichmay affect the external change on these sols. It isnot definitely known how this double layer is formed,and for most purposes it is sufficient to regard theparticles as positively or negatively charged, theeffect of the double layer being neglected.Any substance which conducts an electric current,

and is decomposed thereby into separate groups ofions, is known as an electrolyte. The terminals, orplates, by which the current is passed through a liquidare known as electrodes, the one by which the currentis supposed to enter being termed the positive (-J-)electrode, or anode, and the other, the negative ( )


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NATURE AND PROPERTIES OF COLLOIDS nelectrode, or kathode. When a current of electricityis passed through the solution the positively andnegatively charged groups tend to collect at theopposite ends of the solution, i.e. they tend to travelto each electrode respectively, and are in this wayseparated from each other, though they lose theircharacteristic charge as soon as they come into con-tact with the electrode. Thus, if a current of electricityis passed through water containing sufficient acid torender it a conductor, the oxygen atoms will pass tothe anode and the hydrogen to the kathode, eachescaping from the solution in the form of a gas withoutany electric charge. Between the electrodes, however,the oxygen ions have their distinctive charges and areable thereby to act very differently from the electricallyneutral gases bearing the same names. When a liquidis contained in a porous vessel or membrane, which ispartially immersed in a second liquid, and a currentis passed from one liquid to the other, the membraneplays an important part. It prevents the liquids frommixing rapidly, whilst it allows them to come intocontact with each other, so that by arranging theelectric current to pass in a suitable direction one sub-stance may be passed through the membrane and thusseparated more rapidly than by the slow process ofunaided dialysis or diffusion, whilst its separation fromother substances in solution is effected more easilyand with less general disturbance than if purelychemical methods are used. The chief investigationsof the movements of colloidal particles under the in-fluence of an electric current are based on the work of


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12 USE OF COLLOIDS IN HEALTH & DISEASELinder and Picton, 1 who with other observers havefound that the substances mentioned in Table Imove to either the positive or the negative electrode,as shown, when suspended in pure water. In dilutesolutions of salts, alkalies, or acids, entirely differentcharacteristics may be observed with the same colloidalparticles.

Thus, some colloids such as globulin and silicic acidare negatively charged in alkaline solutions and posi-tively charged in acid solutions.

TABLE IANIONIC CATHONIC

(negatively charged and mov-ing to the positive pole)Antimony sulphideArsenic sulphideCadmium sulphidePlatinum solSilver solGold solMercury solSilver chlorideSilver bromideSilver iodideVanadic oxideTin oxideSilicaAniline blueIndigoMolybdene blueSoluble Prussian blueEosin

(positively charged and mov-ing to the negative pole)Hydroxides of

Iron, ChromiumCopper, AluminiumZirconium, CeriumThoriumBredig sols of

Bismuth, LeadIron, CopperHoffmann violetMagdalene redMethyl violetRosaniline hydrochlorideBismarck brownMethylene blueAlbumenHaemoglobinAgarTitanic oxide

1 Journ. Chem. Soc., 61, 148 ; 87, 63 ; 71, 568 ; 87, 1906.


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NATURE AND PROPERTIES OF COLLOIDS 13ANIONIC CATHONIC

(negatively charged and mov- (positively charged and mov-ing to the positive pole) ing to the negative pole)Fuchsine DiatomsIodine Unicellular algaeSulphur Vegetable organismsSeleniumShellacResinStarchMasticCaramelLecithinChloroformOil emulsionsAmoeba? and animal

organismsThe electric charges on gelatin, agar, and silicic acid are

very small and difficult to observe.

The rate of movement of a particle in an electricfield is independent of the size of the particle, but isaffected by the viscosity of the fluid and the potentialof the current.The employment of electricity remedially for effect-

ing the movement of the colloidal substances in theliving cells is, however, extremely limited, especiallywith regard to animal organisms, as a separate elec-trode would require to be introduced into each indi-vidual cell a hopelessly impracticable condition.The result of applying an electric current to a largearea is entirely different from that which occurs duringthe electrolysis of a single cell. When two sols of thesame sign are mixed they not only do not precipitate


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14 USE OF COLLOIDS IN HEALTH & DISEASEeach other, but the mixed sol acquires the stability ofthe more stable component. No adequate explanationof this fact has yet been published, though the factitself is indisputable. When two particles of oppositesign come within a suitable distance of each other theyare mutually attracted and, if sufficiently free, willeventually touch and discharge each other. Theproduct will then be electrically neutral unless one ofthe particles carries a larger charge than the other,when the product will carry the balance of the chargeor will decompose, forming an electrically neutralsubstance which settles more or less rapidly and anegatively charged product.

Substances in the colloidal sol state have correspond-ing electric charges and therein bear a very closeresemblance to substances which become ionised insolution. They attract particles of opposite sign andrepel those of like sign which come within the sphereof their influence, and when two colloidal sol particlesof opposite sign come into contact with each otherthey are mutually discharged, and the combined pro-duct settles more or less rapidly. Thus, the effect ofdischarging two colloidal sol particles is to removethem from the active colloidal state and to form aprecipitate or even a coagulum. This may, under someconditions, retain a certain amount of chemicalactivity, and being then in an intermediate statebetween a sol and a precipitate is conveniently knownas a gel. Gels are usually obtained when emulsoid solsare cooled or evaporated ; they may be regarded ascomposed of two liquid phases, whereas a sol bears acloser resemblance to a solid phase dispersed in a liquid


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NATURE AND PROPERTIES OF COLLOIDS 15one. Gels have characteristic optical properties, suchas double refraction.

Agglutination, or the precipitation of colloids of likesign, occurs in some cases, e.g. with toxins and bacteriasols. Though extensively used by some pathologistsas the basis of treatment of diseases due to toxins,bacteria, etc., the precise nature of the phenomenawhich produce agglutination are by no means wellunderstood. Lottermoser, in 1901, found that when apositive sol precipitates a negative one, the precipitatecontains both colloids.The amount of one sol required to precipitate

another varies with the nature of the sols, and theprecipitate contains both colloids, though, owing tothe difficulty of nitration without adsorption, theliability of the excess of colloid in the sol to precipitate,and the slowness of the reaction, it is often difficultto determine the amount of each colloid in a precipitate.The equivalent amount of sols required to cause

precipitation is not a chemical equivalent, but anelectrical one ; usually the maximum precipitationoccurs when the positive charge on one cell exactlyequals the negative charge on the other, but thenumber of particles, their size, and the rate of mixingaffect the results.

Substances in colloidal solution behave quite differ-ently from those which are merely in suspension.Thus, coarse suspensions are not affected by electro-lytes and they do not usually bear a definite electriccharge, whereas colloidal sols unless protected arevery sensitive even to traces of electrolytes, andreadily migrate towards one pole when an electric


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16 USE OF COLLOIDS IN HEALTH & DISEASEcurrent is passed through them. It is a mistake toregard them merely as fine suspensions, as the proper-ties of a substance undergo considerable change whenit is converted into the sol state. They do not behaveprecisely the same as either suspensions or solutions,but occupy an intermediate position for which theterm sol is preferable. It was at one time thoughtthat colloidal substances could be defined as thosewhich appeared to be in suspension but do not passthrough a parchment or collodion membrane into anexternal volume of water. This is by no means alwaysthe case, as Graham soon found, and since his timemore anomalies have been discovered. It is scarcelypossible, therefore, in simple terms to say preciselywhich substances are colloidal and which are not,though for most practical purposes the distinction isreadily appreciated. Like life/' we may have a fairlyclear concept, but cannot express it in mere words.The difficulty of finding a clear line of demarcation

between colloidal and other substances is greatlyintensified when living organisms are studied, asreactions take place in these which do not occur in thedead organism. For example, the peptones are aclass of nutritive substances which are in manyrespects typically colloidal, and in the laboratorytheir solutions do not pass through animal or vegetablemembranes. In the living organism, on the contrary,peptone solutions pass readily through certain mem-branes and owe their nutritive power to this property.Haematin, on the other hand, is a typical crystalloidsubstance which might be expected to pass readilythrough the blood vessels, yet it does not do so as


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NATURE AND PROPERTIES OF COLLOIDS 17long as the organism is alive. Here are two typicalsubstances, both acting precisely contrary to thegeneral behaviour of the groups to which they belong,whilst in the living organism, but behaving normallywhen removed from the organism and studied in vitro.This difference in behaviour impels all investigatorswho are aware of it to pause ere they draw conclusionsfrom laboratory experiments and apply them to theliving subject. Even in so apparently simple aphenomenon as the passage of a substance through amembrane, the effect of life may be to upset allprognostications from the tests on dead or syntheticmaterials. This fact needs specially to be borne inmind when dealing with the introduction of drugs andother substances into the living subject, or seriouslyerroneous conclusions may be drawn.Turning again to the characteristics of colloidal

substances, it should be observed that they are mostremarkably active, an apparently minute proportionof a suitable colloid frequently effecting the precipita-tion of many times its weight of another substancefrom solution. In this respect, many colloids re-semble enzymes, or so-called vegetable ferments, andbacteria, though they do not reproduce themselveslike living organisms. They owe their activity totheir minuteness and to the fact that substances whenin the colloidal state have an enormous surface areaas compared with their volume or weight, and aschemical reactions depend on the amount of contactbetween two or more particles these reactions willproceed the more rapidly and completely when thesubstances have a large surface area and are in a state

c


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i8 USE OF COLLOIDS IN HEALTH & DISEASEof oscillation. It is well known that chemical reactionscan only occur when two or more substances are indirect contact, and as the completeness of the reactiondepends on the amount of contact, colloidal substancesare very powerful because of the enormous area theypossess.On the other hand, mass plays an important partin all chemical reactions and largely regulates theirintensity. The mass of colloidal sol particles is sominute that the objectionable effect of intense reactionson the human subject are largely avoided, whilst theadvantages of rapid and complete reaction are secured.For this reason, certain medicines administered in thecolloidal form are not merely more active and possessgreater penetrating power, but they are free from thepoisonous effect of the same substances when given inthe form of tincture or solution. The difference inbehaviour of a solution of iodine in alcohol or aqueouspotassium iodide, when compared with that of colloidalsol iodine, is most impressive. The forms of iodineusually employed induce pain and other symptoms ofiodism, whereas large doses of colloidal sol iodine (ifthe preparation has been properly prepared) are quitefree from this risk. A colloidal preparation of iodinein petroleum or other mineral oil can be rubbed intothe skin without leaving any stain, the iodine beingabsorbed more readily than the oil. A solution ofcommercial iodine in alcohol or in potassium iodideleaves a characteristic stain when applied to theskin.The precise reason for this rapid absorption and

non-staining action has not been definitely ascertained,


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NATURE AND PROPERTIES OF COLLOIDS 19but it has been repeatedly demonstrated in a varietyof cases.The action of radiations on sols. The y-rays of

radium and the X-rays have no action on colloidalsols. The positively charged a-rays of radium havenot sufficient penetrating power for any action theymay have to be important. The /3-rays of radium,which are negatively charged, hasten the coagulationof the positively charged particles and increase thestability of the negatively charged ones. A sample ofhaemoglobin was coagulated by the rays in severalhours by Hewin and Mayen. 1 Some albumen solswhen exposed to the ultra-violet light are rapidlycoagulated. These reactions partially explain some ofthe remedial effects of various radiations on the humansystem. It is clear that such effects are limited by thepermeability of the skin, and that for deep-seatedaffections better results may be anticipated from theintroduction of suitably charged particles (colloidalsols) into the blood stream.

The colour of colloids. The colour of the colloidsdepends chiefly on the size of the particles, and onlyto a small extent on their composition. Thus, thesmallest particles of colloidal gold, when seen bytransmitted light, are red and the larger ones are blue. 2The colour is, in each case, dependent chiefly on thescattering effect of the particles on the light trans-mitted through the liquid. In accordance withRayleigh's & Thompson's calculations, the intensity

1 CR., 138, 1904, 521 ; CR. Soc. de Biol, 57, 1904, 33.* Mee found the relation of the size to colour reversed in some

cases.


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20 USE OF COLLOIDS IN HEALTH & DISEASEof the scattered light varies directly as the sixth powerof the diameter of the particles and inversely as thefourth power of the wave-length. Hence, the intensityof the scattered light and the absorption are bothgreatest with the smallest particles. Stebbing foundthat very little light leaves a colloidal liquid, most ofit being absorbed. Svedberg found that colloidal solsare often more highly coloured than a true solution ofthe same element at the same concentration, but thatthe absorption spectra of the colloidal sols and solu-tions do not differ essentially. W. Ostwald l hasenunciated the law that with decreasing size of theparticles the absorption band of any colloidal solutionmoves to the shorter wave-lengths.

Mayer, Schaffer, and Terroine 2 have shown thattraces of alkali increase the size of the particles if thecolloid is positive, and reduce it if the colloid is negative.Traces of acid produce the reverse effect. The changein the dispersion thus effected varies with the colour ofthe sols. Zsigmondy 3 and Gutbier and Resenschack 4found that, on adding coagulating reagents, the colour ofgold sols changes consecutively from red to purple-red,red-violet, blue-violet, and deep blue, the colloideventually separating as flakes of powder or gel.

1 Roll. Chem. Beiheft., 2, 1910 ; n, 409.2 Comptes rendues, 1907, 145, 918.3 Zier, Erkentniss der Koll.4 Z.f. anorg. Chem., 1904, 39, 112.


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CHAPTER IIANIMAL AND VEGETABLE FLUIDS

THAT animal and vegetable fluids are largely colloidalin character is a fact which is now unquestioned, butlittle is known as to their precise nature. Thus, theparticles in cow's milk can be demonstrated under theultra-microscope, but those in human milk are toominute. This suggests that in adapting cow's milkfor feeding infants, it is not sufficient to endeavour tomatch the ordinary chemical analysis of human milk,but that cow's milk should be treated in such a mannerthat the product is in a similar colloidal state to thatof the human milk. The valuable superiority forinfant use of milk to which barley water, gruel, orother starchy solution has been added has long beenknown, but few have, as yet, realised that it is due tothe protective action (in a colloidal sense) of the addedsubstance. Gelatin, gum-arabic, or preferably gum-acacia, have an even stronger protective action, andthey possess the further advantages of being easier toprepare and of altering the composition of the milk toa less extent, whilst making it physically much morelike human milk.

In human milk the protective colloid is lact-albumen,which is present to the extent of 1-3 per cent (i.e. equalto the casein present), whilst cow's milk contains only0-5 per cent of lact-albumen and over 3 per cent of

21


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22 USE OF COLLOIDS IN HEALTH & DISEASEcasein. Of all the domestic animals, asses' milk bearsthe closest resemblance to human milk, both inchemical and colloidal properties.The coarse particles of curd which are formed when

cow's milk is coagulated by acids or rennet may bereplaced by finer, more flaky, and more porous curdsby diluting the milk with water, by adding lime-water(though this tends to prevent the coagulation altogetherand so may unduly delay its digestion or even cause itto be passed out of the body of an infant in the un-digested state), and by the use of one of the protectivecolloids previously mentioned.

Bearing in mind its colloidal nature, human milkcan best be imitated by using cow's milk as the basisand adding the following : (a) cream sufficient toraise the total fat present to 3-8 per cent (about 3 percent of the final mixture being required usually) ;(b) milk sugar to raise the total sugar content to6-2 per cent (about 3 per cent of the total mixturebeing usually required) ; (c) about I per cent of lact-albumen, or 2 per cent of gelatin, or a considerablylarger percentage of starch in the form of barley water,etc., as the protective colloid ; and (d) sufficientwater to effect the solution of the protective colloidand the sugar. If there is any risk of the cow's milknot being quite fresh, part of the added water maywisely be replaced by a tablespoonful of lime-water,which will neutralise any trace of acidity in the milkand will therefore increase its keeping power.

In the same way chemical analysis alone does notdetermine the value of even the essential propertiesof a foodstuff ; its physical condition particularly


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ANIMAL AND VEGETABLE FLUIDS 23if it is a colloidal substance is of at least equal andsometimes greater importance. Thus, cheese cannotbe digested by some people as it is too densely coagu-lated to be readily converted into a colloidal fluid.By preparing it under conditions which will facilitateits resuspension, its high value as a food material maybe utilised. The various preparations of casein whichare at present so popular as recuperatives dependlargely on the fact that they are colloidal substances,which can be resuspended or converted into colloidalfluids more easily than ordinary cheese or dried milk.Indeed, the chief test of such a preparation mayusefully consist in an examination of its propertieswhen mixed with water or other suitable fluid.The cell-structure of animal and vegetable organisms

closely resembles the cellular structure of the syntheticcells. The walls of such cell-structures are reallyemulsoid gels, the cell-fluid being an emulsoid sol.The gels which form the cell-walls and membranes ofthe body contain albumen- and gelatin-like substanceswhich swell in water and to a varying degree in solu-tions of acids, alkalies, and salts. In other words,living protoplasm is essentially a complex liquid ; thepresence of a network, observed in protoplasm whichhas been killed or fixed by various reagents, isnot apparently seen in the living material. The so-called cell-wall of the protoplasm of some low formsof life appears to have both the properties of a solidand of a liquid substance, and in this respect resemblesthe film of a soap bubble. For example, Chambers hasrecently (1917) found that a needle can be repeatedlypassed into living protoplasm without injuring it


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24 USE OF COLLOIDS IN HEALTH & DISEASEin any way and without leaving any trace of its track.Bacteria, etc., penetrate the cell-wall in a similarmanner without damaging it, just as well as through asoap-bubble. The outer layer of protoplasm is not,however, identical with the membrane to which thecells owe their semi-permeable properties.When a cell dies it passes from an emulsoid sol intoan emulsoid gel state and thereby changes its characterand reactions, one of the most remarkable differencesbeing that the liquid of the dead cell freely mixes withthe surrounding watery solution, whilst the contentsof the living cell do not escape in this manner. Undernormal conditions living cells are non-conductors andare largely impermeable, but under the influence ofcertain ions they become permeable and allow electri-cally charged particles to pass freely through them.When certain cells are immersed in a saline solutionthe sodium ions present increase their permeability ;the addition of calcium ions restores them to theirnormal condition. Hence simple solutions of salts donot form an efficient substitute for the blood or forthe sea-water in which marine creatures live ; a smallbut significant proportion of calcium salts is essentialunless a colloid, such as gelatin or gum-acacia, is addedin sufficient proportion to give the saline solution anosmotic pressure as high as that of the blood. Theselective permeability of living cells is very remarkable.Acids which are soluble in the cell or in the analogousliquid bodies readily penetrate the cells, but otheracids and strong bases do not. Weak bases (includingammonia and the amines) penetrate the cells withoutdifficulty.


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ANIMAL AND VEGETABLE FLUIDS 25Although sodium hydroxide does not enter the

living cells it greatly increases the rate of oxidationprocesses in the cells. This is due to the fact that thecell-wall is really a concentration of the componentsof the protoplasm of the cell, and in the presence ofsodium hydroxide the normal equilibrium is upset,and this produces marked changes in the cell, not-withstanding the fact that the sodium hydroxidedoes not penetrate into it.The cell materials, whilst being typical emulsoids,

behave in a far more complex manner than the syn-thetic emulsoid gels or the natural or synthetic sus-pension sols. Thus, albumen is electrically neutral andis precipitated by basic emulsoids (as histone) andbasic sols, which are positive sols. It is also precipitatedby acid emulsoids, such as silica sol and acid dyes,which are negative sols. Tannin and gallic acid behavesimilarly. Perrin l has suggested that primary cellgrowth and cell division are essentially colloidal innature, an idea which is, to some extent, supported bygalvanotropism in microscopic animals. 2 If this is thecase and there is much evidence in support of it astudy of the changes in the viscosity of the body fluidsunder certain circumstances, 3 the influence of certainsalts on the properties and action of the blood, 4 andthe laws regulating the permeability of the cell-wallsfor salts and colloids in the human body are bound to

1 Journ. Chim. Phys., 1904, II, 607.8 Miller, Journ. of Physiol., 1907, 215. Buxton and Rahe, Zs. /,

D. Ges., Bischam, XI, n to 12, p. 479.8 Rachlmann, Bert. kin. Wochensch, 1904, Heft. 8 ; DeutscheMed. Wochensch, 1904, Heft. 29.* Nanes, Chem. Beih. Physiol., 1910, 40, 327.


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ANIMAL AND VEGETABLE FLUIDS 27they can be removed by diffusion into an isotonicsugar solution, after which blood-corpuscles are muchless susceptible to precipitation by sols.

Blood-corpuscles which have been soaked in solu-tions of salts especially chlorides and sulphates aremade more easily precipitable by sols, especially ferrichydroxide sol.The fact that the blood is a typical complex

colloidal fluid is now accepted, and this is the basisof the treatment of numerous diseases, though manyphysicians have scarcely recognised it. The colour-ing matter hczmoglobin is definitely colloidal, andhence it is not surprising that the colouring matterobtained from different animals differs both in itscomposition and properties. In red corpuscles fromthe human subject, the haemoglobin is associated witha complex of various substances, some colloidal andothers crystalloidal, and with a liquid which is isotonicwith a solution of nine parts of common salt in amillion parts of water. If the red corpuscles areimmersed in a more dilute solution than this theyswell, and haemoglobin gradually passes from them tothe external solution (hczmolysis). The importanceof this phenomena which is characteristic of colloidalgels will be appreciated when considering the effectof colloidal substances in diseased conditions of thehuman subject.The characteristic behaviour of some of the waste

products of the human organism is also due to theircolloidal character. Thus, urine contains colloidalsubstances which normally prevent the uric acid fromseparating. This colloid may be removed by dialysis


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28 USE OF COLLOIDS IN HEALTH & DISEASEor precipitated by alcohol ; it appears to be a deriva-tive of nucleinic acid. Urines which are deficient inthis protective colloid may be prevented from deposit-ing uric acid on cooling by adding to them a suitablecolloid. Unfortunately, those colloids, such as gelatin,which are most successful in vitro, are absorbed by thealimentary tract and therefore do not reach thebladder in sufficient quantity to admit of their beingused in certain urinary diseases. Experiments withother colloids are now being made. In this connection,it should be noted that alcohol reduces the rate ofdiffusion of salts in gels, whilst urea, chlorides, andiodides increase it.


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CHAPTER IIITHE HYGIENIC USES OF COLLOIDS

THE important part played by colloidal sols and gelsin the maintenance of hygienic conditions is seldomrealised by those whose attention has not been calledto this aspect of the subject. The removal of harmfulimpurities in water, the disposal of sewage in an in-nocuous manner, and the effective disposal of dirt are all largely dependent on some colloidal properties,the precise nature of which is by no means well recog-nised by many of those engaged in the purification ofwater, or sewage, or who are habitual users of soap andother detergents.The study of colloids in relation to these subjects is

comparatively new, and much has yet to be learned.On the other hand, it is interesting to note how muchof the best modern practice and use of colloidal pro-perties has been reached by persistent investigationon the lines which had little or no bearing on therecognition of the real nature of colloids. Now thatthe importance of the colloidal state has been recog-nised in other branches of industry and science, it issurely not too much to hope that it will lead to equallystriking improvements in the sphere of hygiene. Afew words on each of the important subjects of sewage,water, and soaps must, however, suffice.

Sewage. Sewage consists essentially of water con-39


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30 USE OF COLLOIDS IN HEALTH & DISEASElaminated with excrement, kitchen- and other domesticrefuse, and matter washed from roads ; in some areasit may be further contaminated with other wasteproducts from factories, or other industries. Thiscontaminated matter is in three forms : (a) in sus-pension, as silt, sand, paper, rags, faeces, vegetable andanimal matter, etc. ; (b) colloidal matter in solutionor pseudo-solution ; and (c) in true solution. Inpurifying sewage the chief purpose is to separate thematter in suspension and to render harmless that incolloidal and in true solution. The chief difficulty indealing with sewage is that the matter in colloidalsolution prevents the effective removal of the coarsematerial in suspension, as well as assisting in keepingit in suspension in larger proportions than wouldotherwise be the case. Hence, if the colloidal mattercan be precipitated in a suitable form the most seriousdifficulty in sewage treatment is overcome.The complex nature of sewage is such that it is

impossible to treat each of its constituents separately,and this adds to the difficulty of purification. It is,however, recognised that the most difficult constituentsare the colloidal sols, and these can be precipitatedin accordance with the recognised methods for pre-cipitating other colloids. The most successful chemicalmethods of treatment depend on a recognition of thiscolloidal character and on the coagulation of thecolloidal sol by the addition of some other substancecarrying an electric charge of the opposite sign. Ferricand aluminium hydroxides have been largely used forthis purpose, and they are quite efficient. Their greatdrawback is the cost of treating such enormous volumes


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THE HYGIENIC USES OF COLLOIDS 31of liquid by any process of sedimentation and filtrationto remove the precipitated colloid and the difficultyhitherto experienced in converting this colloid into auseful material. The method which appears mostlikely to prove of value consists in utilising the factthat water which has been violently agitated with, orhas fallen through, air may become positively charged,and these electrically positive particles then effect thecoagulation of the negatively charged colloids in thesewage. Hence, by agitating the sewage with air,under suitable conditions, a complete coagulation ofits colloidal content is rapidly effected at a low cost,and the precipitate is one which settles with extra-ordinary rapidity. In the well-known activatedsludge process, air is blown through the sewage, theinventors of this process having apparently failed torealise that the electric charge of the water particlesis at least equally as important as the oxidising powerof the air. A modification of this process, in whichthe water is charged positively by agitating it super-ficially with air, offers still greater prospects of success,as it avoids the use of chemicals and the costlysupply of large quantities of air. In this connection itis interesting to note that beneficial action of the airat the seaside is probably due more to the particles init which have been positively charged by the violentbeating of the waves on the -shore, than to the ozoneto which this action is usually attributed. Thesepositively charged particles, reacting with the nega-tively charged bacterial and other undesirable colloids,precipitate them and render them harmless.The purification of sewage is complicated by the fact


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THE HYGIENIC USES OF COLLOIDS 33without alkali), is added to the water, and causes aprecipitation of the positively charged alumina, orferric oxide, which reacts with the negatively chargedbacteria, clay, etc., and precipitates them. Simultane-ously, the positively charged colouring matter is pre-cipitated by the negatively charged SO 4 ions, whilstany true colouring matter is adsorbed by the precipi-tated hydroxides. Any excess of alumina, or ferricoxide, is precipitated by agitation.Sometimes it is best to add the alkali first ; some-

times only after the aluminium or ferric sulphate.The latter is preferable when there is much colouringmatter to be removed.The natural purification of muddy water is largely

dependent on its colloidal character. Thus Skey lhas shown that suspended mud is precipitated byelectrolytes, including those in sea water. Hence,when a muddy river flows into the sea the proportionof mud which settles out, owing to the slower currentin the mixed water, is insignificant compared withthat which is precipitated by the electrolytes in thesalt water. Schloesing 2 has shown that deltas arechiefly due to this cause.

Soaps. Sir Edwin Chadwick was a firm believer inthe idea that the effectual preventative of all forms ofepidemic, endemic, and most other diseases, is theentire removal of all conditions of dirt, including foulair, defective drainage, and dirty surfaces of all kinds.He was most emphatic as to the necessity of personalcleanliness, and on one occasion he declared that if a

1 Ghent. News, 1868, 17, 160.2 Journ. Chem. Soc., 1874, 30, 37.


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34 USE OF COLLOIDS IN HEALTH & DISEASEgreat epidemic were to occur he would proclaim andenforce the active application of soap and water asthe chief preventative. In any consideration of thesubject of colloids in relation to health and disease,under the auspices of the Chadwick Trustees, it is,therefore, desirable to point out that the detergentaction of soap to which Chadwick and his colleaguesattached such importance is almost wholly due to itscolloidal character, by means of which it is able toreduce the surface tension between other solids( dirt ) and water, and to effect the removal of theformer by a process of colloidal solution. It is astriking fact that a i per cent solution of soap willreduce soot to so fine a state of subdivision that it willpass completely through any filter, and will remainsuspended indefinitely. In a 2 per cent solution ofsoap, on the contrary, the soot will be depositedalmost as rapidly from pure water In a similarmanner a solution of soap in water will disperse, orbring into colloidal solution, a sufficient proportionof dirt adherent to any cleansable surface to enablethe whole of the dirt to be removed in suspensionin the fluid. The addition of any abrasive or scouringmaterial such as finely ground sand or silica flourmay aid the cleansing process, but the chief feature ofit is, nevertheless, the production of a colloidal solutionof a sufficient proportion of the dirt to enable theremainder to be removed readily.The peculiar behaviour of soap has puzzled many

investigators, some of whom have doubted its colloidalcharacter yet have failed to find a complete explanationin a purely chemical conception. The true nature of


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THE HYGIENIC USES OF COLLOIDS 35soap is most probably shown by Bancroft, who hassuggested that undissociated soap appears to be almostwholly present in colloidal form, but in the presenceof water the sodium palmitate, or corresponding com-pound, is hydrolised, the OH ions being largelyadsorbed by the undissociated soap, the adsorbingsubstance then becoming an anion.


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CHAPTER IVMICRO-ORGANISMS AND DISEASE

THE microbic origin of many communicable diseasesis now generally recognised, and it is reasonable topresume a similar cause in many other diseases withwhich no specific micro-organism has been identified.Many of the disease-producing bacteria are sufficientlylarge to be readily visible under a powerful micro-scope, but others, such as those relating to yellowfever, foot-and-mouth disease, and tobacco disease,are too small to be directly visible. Their existencehas been discovered indirectly by means of theultra-microscope an instrument which is describedlater.

Whilst recognising the remarkable advances in thetreatment of many diseases which have resulted fromthe recognition of their bacterial or protozoal origin,the fact still remains that by far the most marvellouspreventatives of disease are contained within a normal,healthy body, in which, as Lister has clearly demon-strated, bacteria can only establish themselves whenconditions have arisen which create a state of un-healthiness.The period in which all zymotic diseases were

attributed solely to the introduction of bacteria, orprotozoa, into the otherwise healthy subject is,happily, passing away, and pathologists and others

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MICRO-ORGANISMS AND DISEASE 37are increasingly recognising as a fact the necessity forthe bodily conditions being suitable before the diseasegerms can multiply extensively in it. As a result ofthe wide recognition of this fact originally pointedout, though expressed in different terms, by Sir EdwinChadwick and his colleagues it is now seen thatattention should be concentrated on the state of thebody fluids and cells as well as on the invading micro-organisms. Now that the colloidal nature of the bodyfluids and cells has been recognised, it is possible tomake considerable progress in maintaining them in,or restoring them to, a suitable condition on purelychemical or physio-chemical lines. The subject is toovast to discuss in detail in the present volume, butbriefly it is now admitted that if the normal colloidalcondition of any of the more important body fluids, orcells, is disturbed by the advent of undesirable electro-lytes, salts, or colloids of the opposite sign, condi-tions are produced which provide a suitable nutrientmedium for many of the disease-producing germs whichare constantly coming into contact with the body. Ifthe altered body fluids or cells can be restored to theirnormal colloidal state without seriously damagingany other portion of the subject, the invading germswill soon perish and will be removed from the bodyby the normal processes of life. If this view of thematter is correct, it is of far greater importance torestore the disarranged colloidal state to its normalcondition than it is to endeavour to kill the invadinggerms without otherwise altering the state of thediseased or altered cells or body fluids. In the latterevent it will only be a question of time before the


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38 USE OF COLLOIDS IN HEALTH & DISEASEpatient is attacked by further organisms, and theseattacks will be continued until, by some means or other,the diseased organs regain their normal colloidal state,or until they are atrophied or have been removed bymeans of a surgical operation. If, on the contrary,the normal colloidal state of the diseased organ canbe restored, the body as a whole is well able to effecta complete recovery without any serious risk or delay.The importance of the influence of the soil uponthe seed, and the predisposition of the individualbody to attacks by germs, has been established bySir Wm. Collins in an essay published in 1884,dedicated to Herbert Spencer, who regarded it asopening the way to a considerable reform in pathology.If his theory (as to underestimated influence of evolu-tion on the specific disease-producing effects of or-ganisms whose cycle may be only a few hours or evenless than one hour, and whose rate of propagation isincalculable) is approximately correct the necessity ofmaintaining the body fluids in the correct colloidalstate must be obvious. The rational treatment ofzymotic disease must not depend solely on the destruc-tion of the germs by means of which the disease ispropagated ; the requisite attention must also bepaid to the soil, or medium, in which the germsexist in the body.This is readily understood when it is realised that

emulsions of bacteria may be regarded as suspensoidsprotected by an emulsoid sol. They are precipitatedby definite amounts of electrolytes, such as acids,heavy metal ions, and by aluminium and ferric ions,as are ordinary suspensions. Emulsions of bacteria


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MICRO-ORGANISMS AND DISEASE 39are not precipitated by alkalies and are not protectedfrom precipitation by other emulsoids, such as gelatin,as are many negative colloids. The addition of animmune serum to a bacteria sol greatly increasesthe sensitiveness of the latter to electrolytes, andapparently destroys the protecting part of the bacteriasol, which thus becomes a suspensoid sol.

Unfortunately, the colloidal characteristics of fluidscontaining bacteria are highly complex. Many of theirreactions appear to be partly of a colloidal and partlyof a chemical nature. Thus, the reaction betweenbacteria and agglutinins, including emulsin and gelatin,resembles an adsorption, but as sols of any one kind ofbacteria are affected only by the agglutinin produced inthe serum by the injection into the animal of the samekind of bacteria, this fact seems to imply the existenceof definite chemical properties. On the other handsome bacteria sols are definitely affected by inorganiccolloids in a manner which suggests both a colloidal anda chemical action.

Toxins and anti-toxins. Toxins are the products ofbacterial life, and are to some extent analogous to theexcreta of the higher organisms. They are decom-posed and rendered harmless by a number of sub-stances, of which special interest attaches to thoseother products of bacterial life (such as immune serum)known as anti-toxins. Thus, when a suitable immuneserum is added to the corresponding bacteria sol,the latter does not coagulate, even after dialysis, butit becomes so sensitive to electrolytes that the lattercoagulate it easily. This is explained by the suggestionthat the agglutinin in the serum destroys a protecting


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40 USE OF COLLOIDS IN HEALTH & DISEASEagent which is assumed to be present in the bacteriasol.A mixture of the corresponding agglutinin andbacteria sol is not precipitated by OH ions, butreadily so by acids and salts of the heavy metals.The addition of salts precipitates the colloids if thereis an equivalent of agglutinin to bacteria sol. If eithercolloid is greatly in excess of the other no precipitationoccurs.Both toxins and anti-toxins are colloidal, particu-

larly the latter. Thus, when a diphtheria toxin is treatedwith its anti-toxin, the reduction in toxicity depends onthe manner of administration. If the anti-toxin isadded in small quantities at long intervals much moreanti-toxin is needed.

Field and Teague 1 found that both toxin and anti-toxin migrate distinctly in an electric field. Theremay be a chemical compound between the toxin andthe anti-toxin, but more probably there is a mutualadsorption, the reaction being wholly colloidal. Adifficulty exists with both explanations, inasmuch asdiphtheric anti-toxin is the only one which will neu-tralise the diphtheria toxin, and, at present, boththese substances appear to possess both chemical andcolloidal properties.

In addition to the difficulty of treating such com-plex substances in accordance with general principles,there is the further disadvantage that, whilst bloodserum has normally a positive charge, most of the solsof the pathogenic bacteria are not coagulated by fluidswith such a charge. This remarkable behaviour may

1 Journ. Exp. Med., IX, 86.


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MICRO-ORGANISMS AND DISEASE /jibe due in part to the presence of a powerful protectingagent, but if this is correct it only transfers the diffi-culty without eliminating it. The value of a suitableimmune serum lies in its power of increasing thesensitiveness of the bacteria sols to electrolytes, andthus facilitating their precipitation. Much work isnow being done in the endeavour to ascertain thechemical or colloidal nature of the various agglutinins,and until the results of this work have been publishedjudgment on this matter must be deferred. The factthat so small a quantity of the agglutinins has suchfar-reaching effects is highly confirmatory of theiressentially colloidal character, and their peculiarspecificity may ultimately be found to be due to thesimultaneous production by the bacteria of a specificprotecting agent which, in its turn, may be decomposedby the elementary colloidal sols, though it resists theattack of compound sols. 1

1 Further information on the current views of the reactionsbetween agglutinins and bacteria will be found in :Immuno-chemistry, S. Arrhenius (Macmillan and Co.).Le mechanisms de V agglutination, J. Bordet. Annales de VInst,

Pasteur, 13, pp. 225 to 272. Mechanism of the Agglutination of Bacteria by Specific Sera,W. J. Tulloch, Biochem. Journ., 8, pp. 294-319.


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CHAPTER VPOISONING DIGESTION AND COLLOIDS

THE similarity between the poisoning of animals andthe stoppage of the reaction of certain metallic sols bysmall quantities of well-known poisons is very striking.Thus, the presence of a trace of prussic acid will reducethe speed of reaction of platinum sol on hydrogen per-oxide to half the normal rate, and a somewhat largerproportion will cause the reaction to cease. Enzymesand ferments are poisoned in a similar manner.

This great similarity between animal poisoningand a stoppage of a relatively simple chemical reactionis very important, as it suggests many other points ofpossible resemblance which are worth further studyand opens out large fields of chemical research inconnection with biological and physiological problems.Moreover, the relative ease with which the effect ofmetal and other sols on chemical reactions can bestudied and controlled, suggests that similar reactions

equally well controlled may be effected in thehuman subject with far-reaching results.Digestion and colloids. The reactions which occur

in normal digestion result in the production of sub-stances which are able to pass through the membraneof the alimentary canal into the blood stream. At thefirst glance, it may be supposed that such a passagewould exclude all colloidal sols, though precisely the

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POISONING DIGESTION AND COLLOIDS 43opposite is the case. It has been found that in thepresence of a crystalloid, such as common salt, thepassage of colloidal sols through the membranes isconsiderably increased, thus showing the importanceof the salt to the animal and human organism. Theadvisability of eating salt with so typical a colloidalgel as a boiled egg is thus seen to be based on a physi-ological requirement, and not merely on a matter oftaste.

It is important to observe that the products ofdigestion, and some other colloidal substances occur-ring in the animal organism, consist of much smallerparticles than artificially prepared colloids. Thushaemoglobin will pass through much less permeablemembranes than colloidal metals, and serum, albumen,and - protalbumoses are correspondingly finer in theorder given. This may partially account for theirability to pass through certain membranes. Donnanhas shown that the permeability of a membrane to asimple ion is greatly affected by the presence of a colloid.In some cases the colloid is hydrolised by some un-known means in the presence of an inert membraneand an electric potential is created. In both thesecases the difference between a living and a deadorganism must not be overlooked, though its import-ance should not be exaggerated.The nature of materials used for food is so varied

and the products of their digestion are so numerousthat for anyone who realises their essentially colloidalnature, it is easy to see that any change of state mayproduce a profound disturbance in the whole system,and that such a disturbance may appear to be quite


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44' USE OF COLLOIDS IN HEALTH & DISEASEout of proportion to the chemical activity of anycompound or element which may be present. For thisreason there can be no general cure for all forms ofindigestion, as each has its specific cause. If any suchgeneral remedy could exist it would be a substancewhich would effect the conversion of any food sub-stance into a colloidal sol of a nutritive and non-toxiccharacter.

Similarly, it is possible to see that improper food,unsuitably prepared, the absence of sufficient air, andthe neglect of sanitary and hygienic precautions mayeffect changes which are quite disproportionate to theactual weight of dirt or other objectionable matterpresent. The normal state of the body fluids is easilydisturbed, and whilst it is almost as easily restoredunder healthy conditions of life, restoration is madedifficult or even impossible if the conditions are un-suitable.


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CHAPTER VIUSE OF COLLOIDS IN MEDICINE

COLLOIDS have long been used more or less unwittinglyin medicine, the colloidal state being the only one inwhich certain medicaments can be administered, whilstothers exhibited as tinctures are converted intocolloids on dilution. Such crude forms are necessarilysubject to many disadvantages, and the true signifi-cance of their colloidal nature not having been recog-nised it is only natural that they should not be eitheras certain in action nor as free from objectionableproperties as colloids which have been specially pre-pared so as to secure the maximum colloidal efficiency.Thus, tincture of podophyllin and other resinous sub-stances are precipitated on diluting them sufficientlywith water, with the consequent formation of a smallproportion of colloidal sol. This sol is the most activetherapeutic constituent, and the remaining materialis only useful medicinally when it has been convertedby the action of the body fluids into an assimilableform. This conversion is accompanied by a seriousloss of material, both directly, by its conversion intoinert or undesirable substances, and indirectly by itstransport to portions of the organism where it cannotexercise the desired effect. Consequently, the acci-dental production of therapeutic agents in colloidal

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USE OF COLLOIDS IN MEDICINE 47activity of the latter are correspondingly greater thanthat of emulsions.The customary administration of any remedy

quite apart from the particular substance or drugwhich it may contain is primarily based on theassumption that such a remedy has a specific reactioneither with a substance in the body (such as the actionof pepsine on the undigested food) or an equally definite,but less understood, reaction whereby certain organsare stimulated to unusual effort, as in the administra-tion of emetics or purgatives. It is generally supposedthat the effect is roughly proportional to the doseadministered, though it is recognised that the optimumdose differs with different patients. In some casesparticularly in the administration of mercury com-pounds it is also realised that minute quantitiesadministered frequently have an effect which isentirely different from that of the same substanceadministered in a single and large dose. Still morestriking is the fact previously mentioned, that withsome remedies the changes are out of all proportionto the dose which may be administered. The greatchanges which occur in certain diseases are prevented,and the normal state is restored by quantities ofchemical agents which appear ridiculously small whenregarded as definite reagents. But such a conditionis a well-known characteristic of colloidal fluids, inwhich even a few drops of solution will effect a solidifica-tion of a large volume of material. The coagulation ofmilk by rennet or acid, and that of blood after a shortexposure to air, are typical illustrations of such achange. The extraordinarily rapid action of minute


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48 USE OF COLLOIDS IN HEALTH & DISEASEdoses of some poisons is probably a similar effect.Bearing in mind these great changes in conditionwhich result from the action of small amounts of activeagents, it is easy to see that a slight excess or deficiencyof some element present in minute proportions in theorganism may effect a profound change in the actionof that organism. The deficiency of phosphorus incertain nervous diseases is well recognised, and variousmethods of supplying it have met with encouragingresults. There is, however, a curious idea extant, thatan element in which there is a deficiency should beadministered in the same form as that in which itexists in the body. For instance, there is a popularidea that glycophosphates are superior to any otherphosphorus compounds, because the phosphorus inthe brain is chiefly found as a glycophosphate. Thisis quite a mistake, as will readily be seen if otheranalogous cases are considered. For instance, sugaris stored in the liver in the form of glycogen, but toadminister glycogen orally would be useless, as it isdestroyed in the stomach. It is essential that anymedicine should be administered in such a form thatits essential constituent will travel through the bodyuntil it reaches the part where it is required, and thatit shall arrive at that organ in such a state as to beused to the greatest advantage. To administer lecithinbecause lecithin has been isolated from the brainsubstance is to misunderstand the chemical changeswhich take place in assimilation, and to supply thesubject with a material in a form from which it has tobe converted to something more suitable. The factthat this conversion occurs merely shows how marvel-


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USE OF COLLOIDS IN MEDICINE 49lous an alchemist is the human organism ; it is noreason for the administration of chemical agents inunsuitable forms.The principle underlying the treatment of disease

by the administration of chemical compounds is muchmore easily understood when it is realised that thereactions deal largely with colloidal materials, andthat they may be effected most efficiently and with aminimum of disturbance to other organs by basingthe treatment on this principle.

This fact has been recognised in a half-hearted wayfor some years, but its implications were scarcelyrealised until a few years ago. This was due to anumber of causes, of which the two most importantwere the difficulty of studying the special properties ofsubstances in the colloidal state with the appliancesthen at hand, and the difficulty experienced in obtain-ing active colloidal fluids which were isotonic withand therefore stable in the body fluids to which theywere applied. The work of Ehrlich and others may,in certain respects, be regarded as attempting tosupply elements of a highly toxic character, such asarsenic, in such a form that they would affect thedisease-creating germs without harming the patientor host. Such methods suffer from obvious draw-backs, such as the caustic, irritant, or even toxic effectof the stabilising organic compound, and as the com-plexity of the compounds was increased, their essentiallycolloidal character gradually receded into the back-ground of the minds of the investigators until it waswholly overlooked.

Colloidal fluids only retain their characteristic


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USE OF COLLOIDS IN MEDICINE 51not being isotonic with the physiological fluids in thediseased organs to which they were applied werecoagulated immediately after their administration tothe patient.Many attempts to secure stability by means of

organic compounds were made, and eventually themain difficulties were overcome especially with regardto certain colloidal elements. One of the chief causesof trouble was due to the fact that if a colloidal sub-stance is prepared in the purest possible state in adisperse medium (such as water) of great purity, theproduct will be highly unstable. Even a trace ofmaterial of the opposite electric sign will cause theprecipitation of the colloid. If, on the contrary, thesubstance is converted into the colloidal state in thepresence of certain other colloids and of certain salts,the desired colloid will not have its activity impairedin the least degree, but it will be quite stable and can bemixed with normal blood or other body fluids withoutbeing rendered inactive by them. The salts andadditional colloids exercise a protective action on thecolloid chiefly under consideration, and so enable it tobe used under circumstances which would otherwisebe impossible. The therapeutic action of the protec-tive agent must not be overlooked ; usually it appearsto be negligible, but occasionally it has been observedto be of considerable importance.

Failure to realise the necessity for stabilising theremedial colloids by rendering them isotonic with theblood serum, and protecting them against precipitationby undesirable agents, was thus one of the chief causesof failure of the earlier investigators, but it has been


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52 USE OF COLLOIDS IN HEALTH & DISEASEentirely overcome in the case of a large number ofcolloidal sols mentioned later, and these are quitestable and effective. Yet in consequence of the failurewhich resulted from such ignorance of the essentialproperties of all colloidal fluids, British medical menwere at first rightly averse to using colloidal pre-parations, and the subject remained in a parlousstate for some time. In fact, it so remained untilsuitable methods of preparing stable and isotoniccolloidal sols were discovered in 1910-1913 by thelate Henry Crookes a son of Sir Wm. Crookes andwere extended and improved by his colleagues andsuccessors, as well as by other investigators.


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CHAPTER VIIPREPARATION AND ASSAYING OF COLLOIDAL SOLS

ANY substance can be obtained in the colloidal stateif the conditions under which it is prepared are suit-able. All colloidal sols are prepared by either

(1) Dispersing or breaking down the larger particlesin the presence of a suitable fluid ; or

(2) By condensing particles in solution untilthey form larger suspensoid particles.The dispersion may be effected

(a) Mechanically, as by grinding the substanceand fluid together ; l(b) By dilution, as when a gum is dissolved in

alcohol solution and the solution poured into a largevolume of water ;

(c) By using electrodes of the substance to be dis-persed immersed in a suitable liquid and passing anelectric current through them ;

(d) By the addition of a suitable electrolyte (such1 Colloidal solutions must not be confounded with the sugges-

tions made by homcepathists with respect to prolonged triturationof a solid material or to the administration of small doses at regularintervals.No trituration, however prolonged, will convert some materialsinto a colloidal sol state, and even those which can be convertedare too much contaminated with non-colloidal material and aretoo unstable to be of much service. As regards dosage, it is awell-known characteristic of all colloidal reactions that if the wholeof the reagent is added rapidly its effect is much greater than if itis added in small quantities at a time.

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54 USE OF COLLOIDS IN HEALTH & DISEASEas an acid or alkali) to a colloidal gel. From theanalogy between this process and that of animaldigestion it is frequently termed peptisation.The condensation may be effected by chemical

reduction, oxidation, hydrolysis, or double decom-position. Thus, colloidal gold sol is readily obtainedby reducing a dilute solution of gold chloride, formicaldehyde, or phosphorus in the presence of potassiumcarbonate. Colloidal sulphur sol may be obtained byadding a solution of sodium hyposulphite drop bydrop to a dilute solution of sulphuric acid, heatingthe mixture to 80 C. for a short time, filtering offany insoluble sulphur and neutralising with sodiumcarbonate.Although many colloidal sols are made by hydrolysis

(i.e. by the action of water on them) this is seldomused as a method of preparation. The methods ofpreparation just indicated do not as a rule yieldcolloids which are stable in the presence of serum.For this purpose they must be modified so as to pro-duce a stable fluid. It is most important to observethat it is relatively easy to produce a colloidal sol oflow stability and containing a considerable proportionof impurities ; it is peculiarly difficult to prepare puresols which remain stable when mixed with the blood-serum and other physiological fluids. Yet the use ofimpure and unstable sols is so serious that no painsmust be spared in ensuring the purity and stabilityof the sols used for remedial purposes, and particu-larly those which are administered by intravenousor intramuscular injection. For these reasons, theremedial colloidal sols prepared by the amateur should


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PREPARATION OF COLLOIDAL SOLS 55not be used until exhaustive tests have proved theirefficacy and stability. The author is aware of a numberof severe cases of poisoning which were due solely tothe use of impure colloids with a very low degree ofstability. As many colloidal sols of high stability andsuitability for administration either orally or hypo-dermically can now be purchased, there is little or noadvantage to be gained by medical men preparingthese sols.The stabilising or protecting of a colloidal sol depends

on its being in a state of equilibrium between theforces tending to cause these small particles tocoalesce (surface tension) and those tending to causedispersion of the colloid throughout the medium.Stability appears to be due, in most cases, to a unionof the particles to be stabilised with those of the pro-tective colloid or with ions which have a stabilisingaction. Zsigmondy maintains that stability is whollydue to the equilibrium between the adsorption anddissociation of ions by colloidal particles. The in-stability which is most serious in colloidal sols used asmedicines is that which results in coagulation.

Stability is secured in a variety of ways, includingthe following :

(a) Preparing the sol in the presence of those sub-stances in which it is required to be stable, i.e. bysubstituting an appropriate fluid for water as a solventfor the various substances from which the colloid isproduced. Thus colloidal sulphur, prepared in asolution in which water is replaced by a physiologicalsalt solution, is much more stable after injection intothe blood than colloidal sulphur prepared in pure


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56 USE OF COLLOIDS IN HEALTH & DISEASEwater. On the other hand, the former is liable to setup undesirable reactions within the body unlessspecial precautions are taken to remove the undesir-able salts by a process of selective dialysis.

(b) Adding a protective agent such as gelatin or pro-talbinic acid prior to producing the sol.

(c) Preparing the sol so that all the dispersed par-ticles are of the same size and without any appreciablesurface tension in the dispersing fluid.

(d) The presence of chlorine or of other charac-teristic ions appears to be essential to the stabilityof positive sols. If these ions are removed the sols areunstable.

(e) Removing the greater part (but not the last traces)of electrolytes. This method is inapplicable to colloidsused for medical purposes.Assaying sols. It is of utmost importance to de-

termine the activity of a sol just prior to its use unlessit is definitely known that it is sufficiently stable forits activity to be relied on implicitly.The percentage of active colloid cannot be de-

termined by any of the ordinary chemical methods asthe colloidal state is physical rather than chemical incharacter. Thus, a colloidal solution of silver gives noprecipitate with a solution of a chloride, a colloidalsolution of iodine does not produce a blue colour withstarch solution. Hence, it sometimes happens that achemist may report that a certain solution does notcontain a particular element or compound if the latteris in a colloidal sol state. By appropriate treatmentusually by converting the substance into the crystalloidstate the ordinary methods may be applied, but they


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ASSAYING COLLOIDAL SOLS 57do not differentiate between the proportions of colloidaland crystalloidal substance when both are present.The chief methods of determining the activity andtherefore the value of the sol are :

(a) Observation of the movement of the particlesby means of an ultra-microscope.

(b) Observation of the intensity of the Tyndallphenomena.

(c) Determination of the gold number.(d) Observation of the time taken for a deposit

to form.(e) Observation of the effect of the addition of

the solution to serum or other characteristic physio-logical fluid.

A. Arc Lamp. B. Slit. C. Primary Lens. D. Secondary 'Lens.E. Condenser ( I in. objective). F. Cuvette. G. Microscope.

FIG. 2. DIAGRAM SHOWING ACTION OF ULTRA-MICROSCOPE

(a) The ultra-microsoope affords the simplest andmost rapid means of ascertaining the activity of thecolloidal particles in a sol. When properly prepared,colloidal sols are transparent or slightly opalescent,coloured or colourless, pass readily through a filterpaper, are apparently homogeneous in chemical be-haviour but under the ultra-microscope are seen tocontain minute particles in a state of rapid motion, theparticles being comparable in size to those of molecules


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58 USE OF COLLOIDS IN HEALTH & DISEASEin

use of colloids in health and disease by alfred b. searl

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