Krafft Spirazines ATypeOfStructureBearingUponTheConstitutionOfProteinsAndTheCauseOfLife

7/28/2019 Krafft Spirazines ATypeOfStructureBearingUponTheConstitutionOfProteinsAndTheCauseOfLife

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** A,

^'i'--^^^^-r"^.^-'


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SPIRAZINESA Type of Chemical Structure Bearing Upon

the Constitution of Proteins and theCause of Life

ByCARL F. KRAFFT

Washington, D. C.


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Copyright 1930 byCarl F. Krafft

THE SCIENCE PRESS PRINTING COMPANYLANCASTER, PA.


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itlBR ARYJWFOEEAVOED

The ultimate cause and nature of life processesis a subject so intensely interesting that no fur-ther argument should be necessary to justify thepresentation of this booklet to the public. Whenit is considered that there is not only a dearth,but a total absence in scientific literature of spe-cific suggestions as to how such processes asgrowth and reproduction might be explained, itappears that any suggestion which is at all rea-sonable ought to be welcome. Nevertheless, whenthe spirazine hypothesis was first tendered to theeditors of scientific magazines in the summer of1926, it was condemned as being unscientific andcontrary to known facts, and was characterized asbeing only one out of a thousand other equallygood guesses, although the author has not yetreceived from the critics thereof a single sugges-tion as to what some of those other equally goodguesses might be.

Finally after the prospects of obtaining publi-cation through the usual channels seemed hope-less, a number of mimeographed pamphlets wereprepared and distributed among those who wereknown to be interested. An abstract notice ofthem was recorded in Chemical Abstracts, 22,2584 (July 20, 1928).


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4 Spieazines

In order to guard against the publication of apossible fallacy, two more years were then al-lowed to elapse so that a critical study might bemade of every phase of this hypothesis. Duringthis time it was submitted to numerous chemistsand biologists and their adverse criticisms wereearnestly solicited, but until the present time nota single valid criticism has been received. Sincethe hypothesis seems to be consistent with knownfacts, and has been found to explain a host ofphenomena which have not heretofore been ex-plained, it is believed that it should not be with-held from the public merely because it is not inaccordance with the personal views of certaineditors.


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SPIRAZINESINTRODUCTION

The various forms of life which are encoun-tered in nature exhibit such a variety of appear-ances and such a profusion of details that thecasual observer is often too bewildered by thecomplexity of his surroundings to gain a clearconception of life processes in their entirety andto distinguish what is fundamental and indis-pensible from what is superficial and unessential.The presence of life is usually recognized bycharacteristic bodily form, spontaneous mobility,and responsiveness to external stimuli, but theseproperties can all be closely imitated artificiallyand in the lower forms of life are often entirelyabsent, so that they must be regarded as secon-dary characteristics which have developed in thecourse of evolution and not as primary attributesof life itself.Every living organism is unique in that it con-

stitutes a self-contained entity having its ownlaws of action, and which is capable, under favor-able conditions, of producing others like itself.The phenomenon of self-perpetuation or repro-duction is exhibited by every living organismregardless of its rank in the plant or animal

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6 Spieazines

kingdom and establishes in nature a sharp line ofdemarcation between living and non-living things.Keproduction in its broadest aspect amounts tonothing more than self-duplication, but is funda-mentally different from any of the other processesheretofore known to science. It involves morethan mere dispersion or subdivision in that theprogeny retain not only the chemical compositionand physical state, but also, either actually orpotentially, the specific physical structure of theparent. Neither can it be regarded as merely aform of dissociation because the progeny arestructurally similar to the parent, whereas theions which result from dissociation of moleculesare always dissimilar from the undissociatedmolecules. All living organisms, notwithstand-ing their diversity of form and appearance, musttherefore possess something in common whichgives rise to that peculiar characteristic called"Me.''

Self-duplication cannot be due, primarily, tospecific configurations of tissues or membranesbecause there are innumerable species of bacteriawhich exhibit no internal heterogeneity whatever,even under the most powerful magnification. Thereal cause of life, whether it be a certain sub-stance or a specific detail of physical struc-ture, must exist on a scale smaller than about


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Spirazines 7

1/25,000 cm= 4,000 Angstrom units, and in thatregion we come dangerously close to the detailsof molecular structure.That the phenomenon of self-duplication must

be due, either wholly or partly, to specific chem-ical processes is generally admitted, but there isa prevailing opinion that the molecular structureswhich are necessary for this purpose must be ex-tremely complex. The failure of all previousefforts to devise some type of molecular structurewhich is capable of duplicating itself does notprove, however, that the solution of the problemmust lie in the direction of extreme complexity.The complex molecular structures which make upthe tissues of the higher plants and animals havedeveloped gradually in the course of evolution,and the fact that they are necessary for theproper physiological functioning of the particularorganisms in which they now occur does not provethat they were also the original cause of the fun-damental life processes in the more primitiveorganisms from which these higher plants andanimals have developed.With the exception of certain plasmodia andsyncytia which have no definite cell-walls, thebodies of all higher plants and animals consist ofaggregates of separate living cells, all of whichare formed according to the same general plan in


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8 Spirazines

that they consist of an outer cytoplasm containingcentral bodies, asters, fibrillae, plastids, chon-driosomes, Golgi-bodies, etc., and an inner nucleuscontaining chromosomes, linin network, etc. Nu-cleated cells like those which form the bodies ofthe higher plants and animals have a definitelower limit of size, being never smaller than sev-eral (approximately five) microns in diameter.Since the diameter of the benzene ring, as mea-sured between the centers of the atoms, is aboutthree Angstrom units (3 X 10"^ cm), in diameter,it would take about seventeen thousand benzenerings arranged side by side to form an objectas large as the smallest living cell, or about2,500,000,000,000 to fill the volume thereof. It isprobably safe to say that a structure of such com-plexity could never have sprung into existencespontaneously from inorganic substances. Theconclusion is therefore inevitable that the typicalnucleated cell does not represent the most primi-tive form of life, but is probably the final resultof a long process of evolution.A much more primitive form of life is exhibitedby the bacteria which carry on the same processesof metabolism and pass through the same cyclesof growth and cell division as their nucleatedrelatives, so that they must be regarded as trueliving organisms. These differ from nucleatedcells in that they are definitely smaller in size, are


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Spirazines 9

usually formed according to some simple geo-metric figure, do not contain chromosomes, centro-somes, or other self-perpetuating bodies, andnever conjugate.The existence of a definite gap in size betweenthe smallest nucleated cells and the largest bac-teria indicates that bacteria represent a distinctlydifferent form of life from nucleated cells, andwhen we consider the extreme simplicity of theirforms and the homogeneity of their internal struc-tures we feel inclined to believe that they consti-tute the most primitive class of living organisms.Even the largest of them are not far above thelimit of microscopic vision, and there is everyreason to believe that there are innumerable spe-cies, similar in form and constitution to theirlarger representatives, which are too small for themicroscope to reveal.

In order to avoid a confusion of issues at theoutset, we shall for the present confine our atten-tion as much as possible to the bacteria, becausethese exhibit life processes in their simplest form.The problem of explaining life does not requirethat we should explain the entire process of evo-lution, but only those processes and character-istics which are common to all forms of life andwhich must have been exhibited by the most primi-tive form of living matter as it first appeared onthis earth.


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THE CHEMICAL BASIS OF LIFEThere being no evidence to justify us in assum-

ing that life is due, primarily, either to specificdetails of physical structure or to extreme com-plications of molecular structure, we find our-selves driven to the conclusion that life must bedue to some comparatively simple principle ofchemistry which has not yet been discovered. Tofind a clue to this we must investigate the molecu-lar structure of proteins, because these appear toconstitute the basis of all life processes. Fatsand carbohydrates, although formed during pro-tein metabolism, are evidently nothing more thanby-products which may be useful at times forfuel or skeletal support but do not enter into themolecular structure of living matter in such amanner as to exert any directing influence there-upon.

Protein substances, upon hydrolytic decomposi-tion, always yield as their principal cleavageproduct a mixture of amino acids or their diketo-piperazine derivatives, which may be representedgenerally as follows :

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Spikazines 11COOH


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12


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Spirazines 13Monobasic diamino acids:

Ornitliine

Arginine

Lysine

NH, COOH\ /CH2CH2CHoCH\NH2NH\NH COOH/ \ /NH2 CH2CH,CH2CH

NH2NH, COOH\ /CH.CH,CH2CH2CH\NH2

Hydroxy- and Thio-amino acids:Serine

Hydroxyglutamic acid

Cysteine

COOH/HOCH2CH\NH,H COOHO /CH.CHCH/ \HOOC NH,

COOH/HSCH,CH\NH,Cystine NH. COOH\ /HCCH,SSCH2CH/ \HOOC NH,


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14 SpieazinesGlutathione (Y-glutamyleysteylglycine)/COOH/HOOC CHzK ,C0 NH\\ V CHCH2SHOHCH2CHj/ ^]^jj CO^^NH,

Seterocyclic amino acids:Proline

Oxyproline

Histidine


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Spirazines 15Anhydrides :

Leucine anhydrideCH3\ CONHCHCH2CHCH3 NHCO

CH,/CHCH2CH\CH3Because of their frequent occurrence in living

tissues the formulas of creatine, uric acid, plantand animal nucleic acid, and lecithin should ac-company the above list:

Creatine COOH/HCH\N C==:NH/ ICH3 NH,

Uric acid

Plant nucleic acid

NHOC\\

-CO

PhosphoricI acid\ /4Animal nucleic acid

(Phosphoricacid /4

d-Ribose

Desoxy-Ribose

CNH^CONHCNH

GuanineAdenineCytosineUracyl

GuanineAdenineCytosineThymine


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16 SpirazinesLecithin

CH2OCOECHOCOE'CH3 CH3 CHoOPOH\l /\NCH2CHoO O/\CH3 OH

By suitable chemical treatment the above men-tioned amino acids may be condensed, with theelimination of water, to form either chain struc-tures known as polypeptides, or ring structuresknown as diketopiperazines :3 NH.CHE^COOH =NH2CHECONHCHECONHCHE^COOH +

2 H2O,2 NH2CHECOOH = CHECO/ \HN NH + 2 H.,0.\ /COCHE(E. Fischer, Untersuchungen liber Aminosauren, Polypeptide, und

Proteine, 1899-1906.)Since proteins constitute the principal struc-

ture-building food for animals, and upon diges-tion are decomposed into amino acids, in whichform they are assimilated by the tissues, it isgenerally thought that growth involves condensa-tion processes of a similar character, and thatamino acids exist in living tissues either as long


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Spieazines 17

polypeptide chains or as diketopiperazine rings.Such a theory, however, offers only an imperfectexplanation for the phenomenon of growth, andfails to otfer any explanation whatever for repro-duction with the transmission of inheritablecharacteristics to the progeny or for the infallibleprecision with which a single germ cell will trans-mit its own specific pattern throughout all thecells of the organism and on to the next genera-tion. The persistence with which living organ-isms will devour every bit of food material withinreach and invade the entire earth's surface withtheir progeny shows that they must possess in themolecular structures of their tissues some con-trivance which is definitely superior to ordinarychemical forces and which can function in a man-ner unknown to chemical science. What is neededfor this purpose is not some new form of moleculebut some new type of molecular structure; notsome new arrangement, but some new principle.


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THE SPIRAZINE STRUCTUREGrowth and reproduction being the two indis-

pensible processes without which life is incon-ceivable, the molecular structure of living matterfrom which such life processes originate mustpossess the two following characteristics:

(1) It must be of such a nature that the processof growth by assimilation of amino acid moleculescan take place continuously without producingany sudden variation in its molecular configura-tion or chemical behavior; and(2) It must be capable of division into a plu-rality of portions each of which retains, eitheractually or potentially, all the essential character-istics of the original structure.Of the various geometric forms which molecu-lar structures might exhibit, the helical spiralappears to be about the only one which possessescharacteristics similar to those mentioned above,and it appears that the helical spiral is also theonly configuration, besides rings and chains,which the polypeptide molecule can be madeto assume. The ease with which diketopiperazinerings are formed from dipeptides, and the diffi-culty with which such rings are broken up, seemsto indicate that the valencies of the successive

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Spieazines 19

r/.g. iof.

N

H-NH-N

rig, ih .


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20 Spirazines

Fig. IC.

/c rig, id.


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Spieazines 21

carbon and nitrogen atoms in dipeptides are atsuch angles to one another as to give them a nat-ural tendency to form six-atom rings; and ifdipeptides tend to form six-atom rings, then poly-peptides would tend to form spirals with six-atom convolutions, which may be referred to,briefly, as ^^spirazines." Since the configurationof such structures in three dimensions of space isdifficult to visualize, several different viewsthereof are given in the accompanying diagrams.

It will be noticed that one of the valencies of thealpha carbon atom in these amino acids is alwaysoccupied by hydrogen. Chemically it would bepossible to attach more complex groups in thisposition, but it will be found upon experimenta-tion with atomic models that the presence of morecomplex groups in this position would render thespiral structure impossible, and it will be ob-served that complex groups never occur in thisposition in the decomposition products of naturalproteins.The two ends of such a spiral will be differentin that one end will be formed of a negative car-boxyl group whereas the other end will be formedof a positive amino group. When the dissimilar-ity of molecular structure at the two ends istaken into consideration, it seems highly improb-able that the ability to grow by assimilation of


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22 Spirazines

amino acid molecules could be possessed by bothends alike. The fact that the physiological effectsof different substances when injected into theblood stream are due almost entirely to the posi-tive kations seems to indicate that assimilationtakes place at the acid carboxyl ends, although theacid character of the chemically active portions ofliving matter may also be due to phosphoric acidradicles clinging to the positive amino groups ateither end of the spiral, and acting catalyticallyas intermediaries to facilitate the assimilation ofamino acid molecules, just like sulphuric acid actscatalytically to facilitate the combination of alco-hols with organic acids to form esters. The factthat phosphorus occurs principally in the nuclearmaterials where such assimilation is known totake place, and even there only in comparativelysmall amounts, seems to indicate that it does notenter permanently into the molecular structure ofproteins but is associated only Avith the activelygrowing portions thereof.The successive nitrogen atoms along each sideof the spiral will increase the basicity of the ter-minal nitrogen atom, just like the two nitrogenatoms in diazo compounds increase the basicity ofeach other. Similarly the carbonyl groups alongeach side of the spiral will increase the acidity ofthe terminal carbonyl group. We thus have a


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Spirazines 23

strongly basic group held firmly in close proxim-ity to a strongly acid group but yet not permittedto neutralize the latter, which appears to accountfor the remarkable ability of living matter or itsenzymes to digest all sorts of complex food mate-rials and to appropriate the resulting substancesspontaneously and continuously for the buildingup of its own molecular structures, for no matterhow many additional amino acid molecules areassimilated the configuration at the end of thespirazine remains the same.The similarity in form and appearance of apolypeptide spiral to a bacillus, a spirillum, or aconnective tissue or nerve fiber will be apparent.It should be capable of growing endwise by as-similation of additional amino acid molecules, andas long as the spiral form is maintained it willpossess a certain definite and characteristic mor-phology. It must remain permanently right-handed or left-handed which will account for theoptical activity always exhibited by substancesobtained from living tissues, and if transversefission occurs, each half should retain the right-handedness or the left-handedness and the cross-sectional pattern of the original structure, so asto exhibit in a very simple manner the process ofreproduction with the inheritance of parentalcharacteristics.


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THE LINKING OF SPIRAZINESSince a single polypeptide spiral, being of

about the same diameter as the benzine ring,measures only about five Angstrom units (5 x 10'^cm. ) in diameter, it is evident that even the small-est bacteria, and all other fibrous forms of livingmatter which are visible under the microscope,must consist of aggregates of large numbers ofsuch spirals. The fact that about three-fourthsof the weight of living tissues is water seems toindicate that the polypeptide spirals of such tis-sues are not arranged in closely packed formationlike the molecules of a crystal, but rather in somesort of open or spaced-apart formation.Chemical union between adjacent spirals may

take place through either the amino, the carbonyl,or the alpha carbon groups. Three differentthings, taken two at a time, can produce six dif-ferent combinations. Some of these can be elimi-nated immediately as representing reactionsw^hich do not take place chemically. For example,two amino groups will not unite directly with eachother, nor will two carbonyl groups be very likelyto unite with each other permanently. The aminohydrogen from one spiral may, however, unitewith the carbonyl oxygen of an adjacent spiral so

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Spieazines 25as to form water molecules and leave the carbonylcarbon connected directly to the amino nitrogen.

,1 1A triple Junction of thegamma-gamtna-gamma tj^pe.

If the connection is formed through the sidechains attached to the alpha carbon atoms, then itappears that only a limited number of intermedi-ate atoms can be involved, because at any pointbeyond the third or gamraa carbon atom themovements of the side chains would be too muchat random to form the connecting complexesspontaneously.The branched hydrocarbon side chains con-nected to the alpha carbon atoms of valine, leu-


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26 Spirazines

cine, and isolencine are evidently the fragmentsof the complexes which connected adjacent spiralsin the original mass, because if the particularspirals which carried these branched side chainshad been connected by means of their amino andcarbonyl groups, then it is unlikely that theywould have produced the alpha amino acid groupsagain upon hydrolysis. In valine and isoleucinethe triple junction occurs at the beta carbon atom,whereas in leucine it occurs at the gaimna carbonatom. Phenylalanine and tyrosine also exhibit asimilar branching at the gamma carbon atom.No amino acid has ever been obtained from nat-ural proteins in which such a junction occurs atany point beyond the gamma carbon atom, norwould we expect to find such structures because atmore remote points the side chains would have toomuch freedom of movement to produce the triplejunction spontaneously. Aspartic acid appearsto have come from two spirals which were con-nected directly by means of their alpha carbonatoms without the presence of any intermediateatoms. Glutamic acid differs from aspartic acidin that it has one more CH2 group, which evi-dently formed the connecting link between twoadjacent spirals, although it may also haveformed a triple junction between three adjacentspirals.


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Spieazines 27It appears that a triple junction between three

adjacent spirals is the arrangement which occursmost frequently in nature, because a large num-ber of spirals connected in this manner will col-lectively form a cluster of hexagonal compart-ments as shown in Fig. 3, and a hexagon is one

Fig. 3. Hexagonalcompartments.of the few figures which when duplicated willcompletely cover a certain area, like the cross-sectional area of a bacillus or a connective tissuefiber. The only other possibilities are quadrilat-eral or triangular compartments, but the exis-tence of these, except at the free surfaces,appears very improbable because they would re-quire the connection of four and six adjacentspirals respectively. It does not appear that


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28 Spieazines

complexes for connecting six adjacent spiralsdirectly with one another can be formed sponta-neously under any conditions, although complexesfor connecting four adjacent spirals may beformed occasionally as follows:

\ /CH~CH/ \

The elementary composition of a protein willalso indicate to some extent the probable natureof the connecting complexes. For example, if thetriple junctions are entirely of the gamma-gamma-gamma type, then we may take as a rep-resentative portion thereof one-half of each ofthree adjacent spirals as illustrated in Fig. 2.This will have the following empirical formula:

C10H13N3O3,

and will have the following percentage composi-tion:

Carbon Hydrogen Nitrogen Oxygen53.9 5.8 18.8 21.5

This differs only slightly from the percentagecomposition found experimentally for crystallineegg-albumin, which is as follows:

Carbon Hydrogen Nitrogen Oxygen Sulphur51.48 6.76 18.14 22.66 0.96(Perkin & Kipping, Organic Chemistry, p. 577, 1922.)


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Spirazines 29The percentages of carbon and nitrogen in our

theoretical formula are slightly higher than thoseobtained experimentally, whereas the percentagesof hydrogen and oxygen are slightly lower. Thelow percentage of hydrogen can be accounted foron the theory that the individual particles ofalbumin are very small so that many additionalhydrogen atoms or hydroxyl groups would berequired to occupy those valencies which, in ourcontinuous three-dimensional hypothetical struc-ture would be used for connecting different por-tions thereof to one another. If, for example, weassume that there is a break in one of the hydro-carbon chains at every triple junction, and thata hydrogen atom occupies each of the unusedvalencies, then our theoretical formula wouldbecome :

C10H15N3O3,

which will give the following percentage compo-sition :

Carbon Hydrogen Nitrogen Oxygen53.4 6.7 18.6 21.3

The percentage of carbon is still slightly high,but that can be accounted for by the presence inalbumin of a few junctions of the beta type, theexistence of which is evidenced by the glutamic


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30 Spirazinesacid and arginine obtained therefrom uponhydrolysis.Sulphur occurs in the molecular structures of

nearly all proteins, but is seldom present inamounts greater than two or three percent. Al-though several different sulphur compounds havebeen obtained from proteins upon hydrolysis, yetthey all have their sulphur in chemical combina-tion with the beta carbon atoms of alpha aminoacids and appear to be merely ditferent cleavageproducts of the same original structures. Theprincipal sulphur-containing cleavage product iscystine, which contains a pair of sulphur atomsbetween two alpha amino acid groups. If weassume that all alpha amino acid groups werederived from spirazines, then we shall have toconclude that sulphur takes the place of thegamma carbon atoms at double junctions for con-necting two adjacent spirazines. It probablyoccurs only at the surfaces and not generallythroughout the interior molecular structures be-cause the interior structures would require triplerather than double junctions, and furthermorethe amount of sulphur in proteins is not sufficientfor general distribution.

If we assume a sulphur content of 2.5 percent,which is more than most proteins contain, thenthere would be about one cystine molecule or two


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Spikazines 31

sulphnr atoms for every eighteen spirazines,twelve triple junctions, or six polygonal compart-ments as seen in transverse section.

It will be observed that the molecular struc-tures of the various triple junctions are separateand distinct from one another, except for theirconnections to the intermediate spirazines. Sincethe spirazines themselves are all exactly alike,and since they can never be separated from oneanother by more than three or four intermediatecarbon atoms, it appears that there is a definitelimit to the molecular complexity of living mat-ter. We must not confuse manifoldness of struc-ture with intrinsic molecular complexity. Thenumber of variations that may be produced in thecross-sectional pattern of the simplest units ofliving matter by changing the connections of thespirazines with one another is enormous, andalterations of this sort in the nuclear material ofthe germ cells may result in all sorts of mutationsduring subsequent embryonic development, butthe complexity is in the biological significance ofthe pattern as a whole, and not in the chemicalbehavior of its component parts. Since the maxi-mum number of atoms in a triple junction is muchless than in many of the organic molecules whichhave been synthesized and studied by chemists,we may confidently expect that a satisfactory


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32 Spieazines

e>

a:


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Spirazines 33

Purine derivatives In situ.

a Flo. S'aNICY' \% ^h.


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34 Spikazineschemical explanation of all phases of vital activ-ity will soon be forthcoming.Evidence of direct connections between the

amino groups of one spiral and the carbonylgroups of an adjacent spiral is furnished by theurea and guanidine groups which occur in thepyrimidine and purine derivatives and in argi-nine and creatine respectively. When protoplas-mic structures are subjected to severe stresses, asmust occur in the nuclear material during celldivision, we would expect the hexagonal compart-ments to become flattened by lateral compressionin one direction or another so as to bring theamino groups of one spiral directly against thecarbonyl groups of another spiral, whereupon theamino hydrogen will combine with the carbonyloxygen to form water and leave the carbonyl car-bon atom of one spiral connected directly to oneor two nitrogen atoms of an adjacent spiral asillustrated in Figs. 4 and 5. Since the carbonylcarbon atom is already connected to the nitrogenatom immediately adjacent to it in the samespiral, we will have produced in this mannereither the urea or the guanidine complexes whichoccur so extensively in the products of both plantand animal metabolism. A connection betweenone carbon atom and two nitrogen atoms mayalso occur at the positive end of a single spiral


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Spirazines 35as illustrated in Figs. 4a and 5a. The formationof substances like arginine and uric acid may thusbe accounted for in several different ways asshown in the accompanying diagrams.

In the nucleated cells of plants and animalsthese urea and guanidine complexes occur princi-pally in the chromatin material of the chromo-somes. This chromatin material has a strongaffinity for dyes so that it stands out very promi-nently in stained preparations, but the fact thatit is conspicuous in appearance does not provethat it plays an important part in vital processes.If purine derivatives are formed in the mannersuggested in the preceding diagrams, then itappears that the chromatin material of thenucleus, which has generally been regarded as theseat of heredity, is actually nothing more than anaccumulation of waste material.

It is a significant fact that after cell division iscomplete, the chromatin material spreads outinto irregular patches over ths surface of thenucleus and is probably absorbed by the cyto-plasm while a new set of chromosomes developsin the interior of the nucleus. In order to ex-plain the supposed genetic continuity of thischromatin material it has usually been assumed,although not supported by a trace of experi-mental evidence, that at least a portion of it is


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36 Spieazinestransmitted to the new chromosomes that arebeing formed within the nucleus. The spirazinehypothesis, on the other hand, teaches that theseat of heredity must always consist of a coordi-nated system of spirazines, and that the urea andguanidine derivatives which may at times be lib-erated by certain configurations of spirazines inthe nucleus can serve only as chemical messengersor intracellular hormones by means of which thevarious configurations of spirazines in the nu-cleus can exert their specific influences upon theother portions of the cell. It appears from thespirazine hypothesis that heredity takes place intwo different ways. The inheritance of majorcharacteristics, such as the arrangements of thevarious tissues and organs by which the largergroups of plants and animals are distinguishedfrom one another, is probably determined directlyby the cross-sectional pattern of the nuclearspirazine structures and would not be subject toMendePs laws; whereas the inheritance of minoror modifying characteristics, such as the colorsor textures of tissues or organs already present,is probably determined by substances in a dis-persed or molecular state which have been liber-ated by the nuclear spirazine structures, and theinheritance of such minor characteristics wouldbe governed by Mendel's laws.


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Spirazines 37In the accompanying diagrams it has been pos-sible to represent the molecular structure of liv-

ing matter only in its statical aspect, but it shouldbe constantly borne in mind that the variousunits of living matter are not rigid crystallinestructures but are plastic molecular fabrics whichare almost continually in a state of metamorpho-sis and that it is the specific behavior of livingmatter and not its exact form or appearancewhich is carried on through successive genera-tions. It is impossible to represent adequately onpaper the various deformations of which thespirazine structure is capable, but it should benoted that besides mere flattening of the polygo-nal compartments in one direction or another asrepresented in Figs. 4 and 5, there is also the pos-sibility of longitudinal straightening out of thespirals themselves, which can take place withoutthe disruption of either the peptide linkings orthe connecting complexes at the triple junctions,so that almost every conceivable change of shapeis possible with these molecular structures with-out any mutilation of the pattern which is charac-teristic of the species.


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38 Spirazines

Fi . 6. Transverse sectionshowing diaqrammcitically theprohahle moieculat structure ofthe simplest form of life*


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THE SIMPLEST FORM OF LIFEHypotheses concerning the origin and constitu-

tion of the simplest living organisms must neces-sarily be surrounded by a great deal of uncer-tainty, but any hypothesis, however speculative,is preferable to total darkness.Although life must have commenced by the

formation of single polypeptide spirals, yet itcould not have existed in any sort of a stable andself-perpetuating form until a number of suchspirals had clustered together into parallel for-mation and had become permanently joined toone another. It does not appear that a series ofpolypeptide spirals connected edge to edge toform a single polygonal compartment could con-stitute a permanent living organism because theexposed corners would render such a structureextremely vulnerable. Structures of this sortwere probably formed temporarily when life firstemerged from inorganic substances, but theymust have become reinforced inmaediately by theaddition of more spirals. If we assume that therewas first formed a single hexagonal compartment,and that an additional hexagonal compartmentwas then formed upon each of the sides of theoriginal one, there would have been produced acluster of seven compartments which would be

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40 Spieazines

considerably more stable than a single compart-ment because there would not be more than twoexposed corners on any one of the seven compart-ments. It is doubtful, however, whether even astructure of seven compartments could exist per-manently because the two exposed corners onevery peripheral hexagon would constitute re-gions of weakness, whereas if we would substitutepentagons for hexagons at the periphery thenthere would be too much straining of the triplejunctions.

If, however, this structure would become sur-rounded with another layer of hexagonal com-partments it would be rendered considerablymore stable because only the alternate compart-ments at the periphery would then have two ex-posed corners and the remaining compartmentsonly one, and if the compartments with two ex-posed corners be changed over into pentagonsthen none of them will have more than one ex-posed corner. Since each peripheral polygon nowoccupies only one-twelfth of the entire circumfer-ence, it appears that conditions at the peripherywill not be materially changed by the addition ofmore layers of compartments. A cluster of nine-teen polygonal compartments arranged as shownin Fig. 6 should therefore possess as much stabil-ity as any larger structure and probably repre-sents the simplest form of life.


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THE CAUSE OF CELL DIVISIONEvery living organism exhibits during some

period of its existence the phenomenon of celldivision, which may take place either by simplefission as in the case of bacteria, by budding as inthe case of yeasts, by direct amitotic division ofthe nucleus as in the case of pathological growthsor tissues of a transcient nature, or by mitoticdivision of the chromosomes either with or with-out the formation of centrosomes and asters as inthe case of nearly all higher plants and animals.The process is always entirely spontaneous, sothat it must be the result of internal and not ofexternal forces.

It has been suggested that cell division mightbe due to the fact that as an organism growslarger there will be a point reached where it willbecome physically unstable, due to the fact thatits mass, Avhich contributes to its instability, in-creases as the third power of its linear dimen-sions, whereas its surface, which by reason of itssurface tension contributes to its stability, in-creases only as the second power of its lineardimensions. Such an explanation is inadequatebecause the mere presence of a large mass orvolume would not cause an object to divide intofragments unless it be acted upon by external

41


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42 Spirazines

forces, and it has never been shown that physicaldisturbance is necessary for cell division.Cell division cannot be attributed to surface

tension because the eifect of surface tension isalways to hold a body together and never to sepa-rate it into fragments, but even if surface tensionwould act in the opposite direction from that inwhich it actually does act it would still be insuf-ficient to account for cell division because thecohesive strength of protoplasmic fibers is fargreater than any force that could possibly resultfrom surface tension.Another suggestion has been that cell division

might be due to the fact that as an organism be-comes larger its food requirements increase withthe third power of its linear dimensions whereasthe quantity of food within reach increases onlyas the first or second power. This explanation isalso inadequate because shortage of food wouldonly cause an organism to become under-nour-ished, which might retard its growth and eventu-ally result in its death, but would not cause it todivide. Attempts to explain cell division on thebasis of food economy have been due to a confu-sion of the principles of phylogeny with the prin-ciples of ontology.Numerous other hypotheses have been pro-posed, but they have all been found untenable for


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Spirazines 43

Mechahical U/usttatiohof Celt Division

Fig. 7c(^

r/ . 7^'


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44 Spikazinesone reason or another. A more complete accountof them will be found in E. B. Wilson's book on*^The Cell in Development and Heredity.''

It appears that spontaneous cell division canbe explained only on the basis of a heterogeneousinternal structure, such as is postulated by thespirazine hypothesis. In order to convey as cleara conception as possible of the underlying princi-ples, a mechanical illustration will be used. InFig. 7a two clamps are applied to a rope and theirends forced apart by means of jack screws. Letus assmue that each screw is able to exert a forceof one gram, but that it takes three grams to tearthe rope. The structure in Fig. 7a will thereforenot divide of its own accord. Let us now add toeach end of this structure another rope clamp andanother pair of jack screws as shown in Fig. 7b,these additional parts being identical with thehomologous parts of the original structure. Eachtime when such additional units are added to theends of this structure the tension of the rope isincreased, so that eventually it will tear in two atthe center. If, now, Ave substitute a polypeptidespiral for the rope, and double or triple junctionsfor the clamps and jack screws, then we will haveconditions substantially as they exist in bacteriaor other simple forms of living matter. Growthby assimilation of additional amino acid mole-


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Spieazines 45cules will continue endwise, and if the connectingcomplexes are of the proper kind their mutualrepulsion will eventually become sufficient tooverpower the cohesive forces of the spirals them-selves so that after the organism becomes of acertain length it will spontaneously divide intotwo halves without the intervention of any exter-nal forces.

Cell division may also be attributed to a differ-ence in molecular structure between the outerportions and the interiors of the bacteria, chro-mosomes, or other elementary units of livingmatter. As has already been explained, the outerportions probably contain many double junctionswith pairs of sulphur atoms in the places of thegamma carbon atoms, whereas the interiors mustbe composed mostly of triple junctions. It ishighly improbable that two such radically differ-ent structures would occupy exactly equal vol-umes, and since the surface layers are incapableof shifting longitudinally upon the interior struc-tures there will be a gradual increase in tensionof the less voluminous structure as the organismgrows in length, so that eventually it will becometorn in two. This process is clearly illustrated bycell division of a bacillus. If the internal struc-tures are more voluminous than the surface struc-tures, cell division will begin by the formation of


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46 Spirazinesa circumferential groove and will result in theproduction of daughter cells with rounded ends.However, if the surface structures are the morevoluminous, then the interior portions will sepa-rate first and leave the daughter cells with con-cave ends.Although a heterogeneous internal structure is

always necessary for spontaneous cell division,yet the specific manner in which it is broughtabout need not always be the same. A single cellmay contain as many as three different kinds ofself-perpetuating bodies, namely the nuclearstructures (chromosomes), the central bodies(centrosomes and asters), and the plastids(leucoplasts and chloroplasts). These three areso different from one another in their structuresand behaviors that it would hardly seem possiblefor all of them to undergo cell division bythe same specific method. The nuclear structuresand the plastids probably divide as the result ofinternal stresses which may be produced in vari-ous ways as has already been explained, butdivision of the central bodies is probably due toentirely different causes.A central body consists of a radiating clusterof protoplasmic fibers called the aster, whichappears to grow from a tiny central region calledthe centrosome. Central bodies sometimes ap-


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Spirazines 47

pear to be formed de novo from cytoplasmicmaterial and usually occur in pairs, although fouror more may occur in a single cell. A constantcirculation of fluid is maintained inwardlythrough the astral rays and outwardly throughthe spaces between the rays, which is probablythe means employed for gathering food materialfor growth.The clustering of the astral rays about commoncenters may be due to conditions similar to thosewhich cause the molecules of a polar solute toarrange themselves with the same ends towardthe solution. As these astral rays grow longerand become more numerous they will becomemore crowded in the region of the centrosome, sothat the entire structure will eventually becomeunstable, will cave in, and two separate centro-somes will make their appearance. The raysfrom these two daughter centrosomes will tend tospread out in all directions and as a result oftheir mutual encounters will cause the two newasters to move away from each other and towardsthe opposite sides of the cell.

f^f^ -*^-^ f^^^t t B A R YJSGJ^.


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THE SELF-CONSCIOUS MINDA discussion of psychical matters in a treatiseon biochemistry may seem frivolous at first

glance, but when we consider what a close and in-separable relationship there exists between mindand living matter, and what a powerful governingaction the mind has over the body, then it wouldseem to be not only pertinent, but in fact neces-sary in a treatise of this character to give themental factor full consideration.The mind functions in three different ways. It

gives us sense perceptions, it forms the mediumfor thought and memory, and it enables us to actvoluntarily through the exercise of our free will.There is no satisfactory evidence to show thatmind is a separate entit}^ capable of existing in-dependently of living matter, or that it can reachout and act beyond those molecular structures inwhich it originates. It cannot be a substancebecause it does not possess any of the propertiesby which substances are recognized. Neither canit be a vibration, or, in fact, any form of energybecause it will produce no effect upon even themost delicate of physical instruments.Although many fantastic ideas prevail as to the

intrinsic nature of the mind, yet if we confine our-48


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Spirazines 49

selves strictly to the evidence presented by knownand demonstrable facts, then we must regardmind not as a self-sustaining entity, but rather asa property or attribute of living matter.Mind is synonymous with self-consciousnessbecause whatever can be said of the mind can alsobe said of the self-consciousness. Without mindor self-consciousness we can have neither sensa-tion, thought, memory, or volition.The individual self-consciousness is coexten-sive with the central nervous system. Most of thecells of our bodies form parts of us physiologi-cally but not mentally. In order for a cell to formpart of us physiologically it is only necessary forthe cell as a whole to be definitely coordinated inposition and specifically related in function to theother cells of the body, but in order to form partof us mentally it must be coordinated with thecells of the central nervous system on a molecularscale, that is, its individual spirazines must becoordinated with or joined to those of our centralnervous system in a specific manner, so that elec-tric impulses passing along a certain spiral orpolygonal compartment of on^ of these cells willbe transmitted to a certain spiral or polygonalcompartment of the other instead of being dissi-pated and lost in the surrounding protoplasm.


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50 Spirazines

Thought and memory may be explained on thetheory that a previous impulse from a sensorynerve has produced such a forceful coordinationof certain of the spirazines of the cerebral cortexthat the surrounding structures have become per-manently modified in such a manner that theywill retain the spirazines in their new positionsfor some time thereafter.Free will and volition are probably due to the

spontaneous activity of the spirazines in ourcerebral cortex and differ from memory only inthat the electric impulses which are produced bysuch activity have found an outlet through themotor nerves instead of being confined to themolecular structures of the cerebral cortex.Whether the exercise of free will involves any

violation of the laws of nature is a question onwhich there is much difference of opinion. Ac-cording to the laws of nature the behavior ofevery physico-chemical system is fixed and pre-determined, whereas the exercise of free will in-troduces an arbitrary and indeterminate factor.Since there cannot be two independent systems ofgoverning forces operating in the same place andat the same time, we must either regard free willas a delusion, or we must assume that living mat-ter does not come under the domain of those nat-ural laws which govern physico-chemical systems.


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Spieazines 51

The existence of free will is being made knownto us directly through our self-consciousness, andit would be very dogmatic and unscientific for usto reject the testimony of our self-consciousnessin so far as it furnishes us with a basis for ourbelief in free will, but yet to accept it in so far asit informs us of the operation of the laws ofnature.The classical principles of mechanics, electro-

dynamics, and thermodynamics, which seem tosignify predetermination to the exclusion of freewill, were derived from experiments upon iso-lated physico-chemical systems and deal onlywith the effects of simple elementary forces orwith the combined or average effects of largenumbers of atoms or molecules. There is no arti-ficial device known which will respond to thespecific behavior of a single selected atom. Eventhe streaks produced in supersaturated vapor bythe individual alpha and beta particles of radio-active substances constitute no exception to thisrule, for what is really being observed hereis only the presence of a particle and not the spe-cific behavior thereof.

It is only through the medium of living matterthat the individual behaviors of the variousatoms can make themselves known to us. In themolecular structure of living matter the variousatoms are coordinated and connected with one


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52 Spirazinesanother in a specific manner so that the relationof each atom to the structure as a whole is differ-ent from that of any other atom. In chemicallyorganized structures of this sort the specificeffect of each atom will be transmitted along thespirazines of the protoplasmic fibers to other partsof the cell, just like the specific effect of eachatom of a molecule is transmitted to other parts ofthe latter. An individual atom may therefore ex-cite a nerve or other protoplasmic fiber in such amanner as to produce a response of which we maybecome aware. Such responses may manifestthemselves either as thoughts, sensations, or voli-tions and will not conform to any of the laws ofnature by which the world about us is governedbut will appear to us as entirely arbitrary andwithout natural causation, although they mayactually have been predetermined by intra-atomicconditions which are beyond the reach of physico-chemical methods of exploration. Predetermina-tion by natural law ends where atomic structurebegins, because w^e cannot extend the laws ofnature by analogy into realms where conditionsare not the same as those under which such lawswere derived.The arbitrary behavior of living matter affects

primarily the second law of thermodynamics be-cause this law applies only to systems in whichthe variable components are capable of approach-


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Spirazines 53

ing a random state of distribution, whereas in themolecular structure of living matter the orderlyarrangement of the atoms along the sides of thepolygonal compartments will tend to sort outrather than mix up the molecules or ions withinthem. The passageways through these polygonalcompartments are only about ten Angstrom unitsin width, which is not sufficient to permit any freeflow of fluid therethrough. Since the spirazineswhich form the walls of these compartments arepolar structures, they will render the electric fieldswithin such compartments unsymmetrical so as tofacilitate the migration of molecules or ions in onedirection but retard them in the opposite direction.The direction of migration of molecules or ionsthrough these compartments may also be con-trolled by side chains extending inwardly fromthe walls thereof and functioning in a mannersimilar to check valves. These side chains maybe in the form of fat or carbohydrate moleculesin the process of formation which have not yetbecome detached. Since they consist of only sin-gle chains of atoms they will be sufficiently sensi-tive to respond to the approach of individualmolecules or ions, and like Maxwell's demons willclose or open the passageways through the polyg-onal compartments according to whether a certainion or molecule approaches from one direction orfrom the other.


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54 Spikazines

In either case the effect will be a sorting out ofdifferent kinds of molecules or ions from one an-other or an accumulation of molecules or ions ofthe same kind so as to build up osmotic or hydro-static pressures or electric potentials. Theseprocesses will take place in contravention to thesecond law of thermodynamics because the energywhich is thus rendered available will not havebeen obtained entirely from the oxidation of foodmaterial but partly from the heat of the sur-roundings.

Vital energy of this sort should not be con-fused with vital force, for the two have nothing incommon. The principle of vital energy is entirelyconsistent with the laws of nature and supple-ments rather than contradicts them, whereas thedoctrine of vital force assumes the existence ofsome mysterious power which is supposed to actin contravention to the laws of nature to controlsuch processes as metabolism, growth, and repro-duction. Vital energy is within the realm of thecomprehensible and the possible existence of sucha form of energy has been suggested by physicistslong before the conception of the spirazinehypothesis, whereas vital force is supposed to besomething which is incomprehensible to thehuman mind, and the existence of which would becontrary to all the principles of science.


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Krafft Spirazines ATypeOfStructureBearingUponTheConstitutionOfProteinsAndTheCauseOfLife