the relation between functional regulation and form-regulation

THE RELATION BETWEEN FUNCTIONAL REGU- LATION AND FORM-REGULATION

BY

C. M. CHILD

The phenomena of regulation in the organic world have received much attention in recent years and it has become more and more evident that a consideration of these phenomena involves some of the most fundamental problems of biology. It is perhaps not going too far to say that the solution of the problems of regulation will constitute a solution of most of the other problems which underlie physiological biology. Moreover, we have, in the possi- bility of analyzing and modifying regulatory processes by experimental conditions, a means of attacking the problems involved, which is more exact and has already proven more fruitful than other efforts directed toward the same end.

Inorganic life structure and form are to the observer perhaps the most salient features and so constitute the most available criterion for distinction and recognition not only of the component parts of theorganism but of differentorganisms. Any method of procedure which permits the control, analysis, and modification of the processes which give rise to structure and form is, therefore, of the greatest importance, since it affords an insight into some of the phenomena most characteristic of and peculiar to organic life. The experimental method as applied in the field of form-regulation is of this character, and it has already demonstrated thar: many of the formative processes are dependent upon conditions which can be altered experimentally. Thus we are able in many cases to modify and alter the form and structure very widely. We are at present only on the threshold of this field of investiga- tion but the outlook for the future is most promising. As our methods improve and as we come to comprehend more clearly the character of the phenomena with which we are dealing the THE JOI'RYAL O F E X P F R I M E V T A C Z o b L O G l ' YOL. 111. V O . 4.

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field within which these methods are applicable will extend and the value of the results obtained will increase.

Certain workers in the field of form-regulation have, it is true, reached somewhat disappointing conclusions. Some maintain that the data are as yet insufficient to permit any interpretation, others that the phenomena of regulation belong to a totally different category from those of the inorganic world and that, therefore, we cannot hope to interpret them in terms of physics and chemis- try. T h e reason for these conclusions is, the writer believes, to be found in the fact that these authorities assume the formative processes to be a special series or complex of processes in the organism differing in nature from other so-called functional processes. T h e organism is regarded as possessing two groups or complexes of activities, the one giving rise to structure, the other concerned with the dynamic activities in the structure. Any such distinction seems to the writer entirely artificial and without basis in fact. Numerous examples of the dependence of structure for its existence upon dynamic or functional conditions are before us, and the only reason why the data are not still mort: abundant is that those already obtained have failed to attract due attention.

It becomes increasingly evident that the organism is primarily a dynamic or functional complex and the structure and form are merely visible expressions, of the dynamic conditions. T h e writer has attempted in various papers during the last three years ('02-'06a) to develop this idea and apply it to specific casesof form-regulation but it seems worth while to present in more general form some of the conclusions reached, together with some of the facts on which they are based, and to show how the ideas involved may be applied to other cases.

T h e process of form-regulation is commonlyregarded as consisting essentially in the replacement of a lost part-hence the term regeneration is used by some authors as synonymous with form- regulation. But form-regulation includes not onlythe replacement of lost parts : it may also involve hypertrophy or atrophy of parts remaining, the substitution of one part for another, the development of a part widely different from that lost, partial replace-,

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ment or no replacement a t all. The recognition of the fact that these various phenomena, some of which are widely different from regeneration in the original sense are fundamentally similar justi- fies the use of a term which has not the disadvantage of possessing another and different meaning. Moreover, the term regulation serves or should serve to call attention to the fact that there is something similar in these processes to what has long been known as regulation in functional processes.

In the following paragraphs some of the writer's conclusions are presented, perhaps often in somewhat positive fashion, but the positive form of statement has its value in the presentation of hypotheses.

The Initial Factor in Replacement of a Lost Part

Driesch ('01) maintains that the initial factor in regulation is a disturbance in function or in constitution. While the writer cannot agree with Driesch in regard to the sharp distinction which he makes between function and constitution, it is sufficiently obvious that the initial factor in the process of replacement consistsin some change in that part of the dynamic system which remains.

Have we any data which afford a clue as to the character of this change and the regions involved? In this connection certain experiments on flatworms may be mentioned first. In Stenostoma (Child, ' 02 ) or Cestoplana (Child ,'05b) after removal of the posterior end of the body at any levels except immediately posterior to the cephalic ganglia the posterior portion of the remaining part is used by the animal in much the same manner as the posterior portion of the part removed. The functional activities of this region which are involved in locomotion are readily observable since it forms the chief region of attachment and is employed almost constantly during progression. These forms possess means of adhesion along practically the whole length of the ventral surface but under normal conditions the posterior end is most used and the organs of adhesion are most highly developed there. This functional substitution is often very imperfect at first, but rapidly becomes more perfect and after a few hours

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the posterior end of the piece is employed in much the same manner as the original posterior end, though adhesion is apparently not as firm.

In short, the animal has altered its behavior and in response to the new conditions has "learned" to use this part in place of the part removed. This altered function involves not merely the portion immediately adjoining the cut surface, but other parts for a greater or less distance anterior to this (Child, '05b). I n other words, a portion of the piece becomes functionally posterior even though its original position may have been far from the posterior end. If we follow the process of form-regulation which succeeds this change in function we.find that this part becomes in the course of time by a process of redifferentiation structurally as well as functionally a posterior end. I n Stenostoma the process of formation of the new posterior end is very rapid, and if we prevent the piece from attaching itself in the characteristic manner form-regulation is delayed (Child, '03a). I n this latter case then we have demonstrative evidence that the functional conditions connected with the use of the part in a certain manner are important factors in form-regulation. Moreover, facts which cannot be cited here lead us to the same conclusion in regard to Cestoplana.

In some of the flatworms, e . g., Planaria maculata (Morgan, '98, etc., and others) a new head region can be formed at any level of the body, in others, like Dendrocoelum, only in the more anterior regions (Lillie, 'or), and in still others, Leptoplana (Child, ' O ~ C ) , Cestoplana (Child, 'osb), etc., only from levels immediately posterior to, through, or anterior to the cephalic ganglia. Lillie was first to note that the pieces of Dendrocoelum capable of producing a new head react much more like the normal animal than those incapable of such regulation. T h e writer has observed the same difference in reaction in Leptoplana, Cesto- plana, and many other Turbellaria. Undoubtedly in these cases the character of the reactions is dependent in large measure on the physiological character of those portions of the nervous system which are present. I n all of these pieces where formation of a new head is possible the anterior end of the piece behaves in some degree, often very slightly it is true, like a head. We find, more-


over, that this “head-likeness” increases as time goes on and long before the new head is fully formed the behavior of the growing parts is very distinctly head-like. I n this case the piece is “learn- ing” to use the region as a head and the morphological development of the head follows.

I n these cases as well as in many others the behavior of the pieces and the use of the parts affords us valuable evidence as to what is really taking place. It must not be supposed that the movements themselves are the only or most important factors involved. They may and undoubtedly do play a part in many cases where particular regions are subjected to particular mechan- ical or other conditions in consequence of characteristic movements (Child, ’02, ’o3a, ’04a, ’oqb, ’ o ~ c , ’oga, ’osb), but their chief value is that they serve as a n index to internal conditions and changes.

These cases are perhaps sufficient to illustrate the point of view and to afford a certain basis in fact for it. Other facts which bear upon the same point have been cited and discussed in the papers above referred to. According to this point of view the first step in the process of form-regulation is functional regulation, an alteration in internal dynamic conditions in consequence of the disturbance of what we may call the physiological equilibrium of the system. T h e process of functional regulation is not, however, fundamentally a process of “trial and error” (see pp. 578, 579), for its nature is in large measure predetermined by the dominant reactive capacities of the system.

But can we bring such cases as the regeneration of an arm in the starfish, a leg in the crayfish, o r the amphibian, into the same category ? Is there any functional regulation in the direction of substitution of a part remaining for a part removed.

I n such cases as these the first visible change is the closure of the wound either by a mass of coagulated blood, leucocytes, etc., o r by cellular material and in all cases sooner or later by a mass of tissue composed of cells capable of division and growth. This process of wound-closure, while regulatory in nature in that it is the result of reactions in response to new conditions is not directly connected with the replacement of the lost part, but is primarily

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the result of purely local conditions. As is well-known, it occurs not only where replacement takes place later but also in those cases where there is no approach toward replacement. It is evident then that the closure of the wound is not, strictly speaking, the j r s t step in replacement of the lost part , although it m a y be the j r s t morphological step in regulation This distinction is important, for, as was pointed out above, regulation and even form-regulation involves much more than the replacement of lost parts.

But the small mass of growing, physiologically plastic tissue which closes the wound may stand, as soon as it forms, or strictly speaking as soon as it begins to form, in a relation to the whole system or organism more or less similar to that in which the part removed or some portion of it originally stood. This region must be subjected to many conditions-internal and sometimes external-similar in greater or less degree to those to which the part removed or some portion of it was subjected. The nerves which formerly led to the part or some of them now lead to this region and the regeneration of the nerves begins very early. It stands in the same or somewhat similar relations to other parts of the body as the part removed and must, as it forms, use a certain amount of energy which is derived from other regions in much the same manner as the part removed derived its energy. In short, this region may by virtue of its relations to the whole become the physiological representative in greater or less degree of the part removed. In case this physiological substitution takes place up to a certain degree further regulation occurs and the region begins to develop into the part removed. In case the substitution does not occur or is insufficient in degree to bring about further growth no replacement of the lost part occurs. As growth pro- ceeds the dynamic conditions are more and more modified so that the substitution becomes more and more complete until the missing part is fully formed.

In many cases the growth of the regenerating part may proceed at least for a time without actual exercise or use of the part, though complete differentiation apparently does not occur without some degree of use. The regenerating arthropod appendage


is coiled beneath the closed end of the stump until the first moult following the operation. It is clear, therefore, that the conditions which determine the earlier stages of the growth and differentiation of the part are not identical with those to which the part is subjected later though they are just as truly functional. The growth of the new leg is not the result of the attempt to use the leg which is missing. The growing tissue begins to develop into a leg because its relations to the other parts of the system are in some degree similar to those of the leg removed. As it grows, the conditions approach more and more nearly those to which the normal leg is subjected, 1'. e., there is a gradual return of the functional conditions to the normal.

This condition, functional substitution in the tissue closing the wound, constitutes the one extreme as regards the process of replacement and results in the formation of the lost part wholly by the outgrowth of new tissue. At the other extreme are the cases similar to those first mentioned where the functional substitution involves a considerable portion of the piece and the process of replacement is one of redifferentiation of this region without the outgrowth of new tissue except that closing the wound. Between these extremes are found the various intermediate forms of form-regulation.

The Common Methods of Form-Regulation

If the functional substitution for the part removed is accomplished within the part remaining, the region involved undergoes a process of "redifferentiation " (Child, 'o6a) and the conditions determining the growth of new tissue from the cut surface may be largely or wholly absent except so far as closure of the wound is concerned. This is the case in Stenostoma (Child, ' 0 2 ) and in posterior regulation in Cestoplana (Child '05b). If, on the other hand, the substitution is confined to the region immediately adjoining the cut surface or to the tissue closing the wound form- regulation is almost wholly or wholly a process of regeneration. The substitution in the old part may, however, be incomplete and the distal portion of the part removed may be formed by the

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growth of new tissue, i. e., regeneration, while its basal portion is formed by redifferentiation as in Planaria maculata (Morgan, '98, etc.; Child, 'o6b). Again the substitution in the old part may be more complete a t one level than a t another and the relative amounts of regeneration and redifferentiation will vary at different levels. This is to some extent the case in Planaria maculata, for example, where the regenerated anterior region is shorter and the redifferentiated region is longer in pieces from levels near the head, while the reverse is true in pieces from the middle regions (Child, 'o6b). T h e difference is still more marked in Polychx- rus where the writer has found' that the new posterior end is formed almost wholly by regeneration in pieces from levels near the head and almost wholly by redifferentiation in pieces from levels near the posterior end, and the relative amounts of redifferentiation and regeneration show all intermediate conditions in pieces between these two extremes. And finally in some cases form-regulation at the posterior end may be largely or wholly a process of redifferentiation and at the anterior end a process of regeneration as is the case in Cestoplana (Child, 'osb). I n all these cases of "mixed "form-regulation the redifferentiation occurs in the region which is physiologically similar to the part removed to such a degree that substitution occurs readily and with relative completeness, while regeneration occurs where the substitution is confined to the tissue closing the wound or to regions immediately adjoining the cut surface.

I n short, the greater the physiological similarity between the old part or a given region of it and the new, the greater the amount of redifferentiation and the less the amount of regeneration. The reverse is also true up to a certain point. When the part remaining is so widely different from the part removed that no substitution is possible in any region not even regeneration occurs except in closure of the wound, and the missing part is not replaced. All intermediate stages between complete regeneration and mere wound-closure may occur in a single individual a t different levels. This is well illustrated in Leptoplana (Child, '04c) and in Cesto-

1 Not yet published.

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plana (Child, ’osb), whire the regeneration of the head is complete from levels anterior to or through the cephalic ganglia and in Cestoplana also from levels immediately posterior to the ganglia, and becomes increasingly incomplete with increasing distance from the ganglia, until in pieces from the posterior regions scarcely more than wound-closure occurs. The absence of regeneration beyond wound-closure in many higher forms is doubtless due largely to the fact that the physiological specification of the tissues is so great that no appreciable substitution occurs in any region after removal of a part.

But form-regulation may occur, nevertheless, even in such cases and may be represented by hypertrophy of other parts. A good illustration of this is the hypertrophy of one kidney following the removal of the other.

A process of destruction often occurs during form-regulation. This is commonly the case in redifferentiation where the structures formed and maintained by a given complex of conditions cannot persist under the altered conditions and so degenerate or atrophy. In a piece of Cestoplana from the prepharyngeal region, for example, the new pharynx appears a considerable distance from the posterior end of the piece and all the intestinal branches posterior to the new pharynx disintegrate and are replaced by others formed anew. It is probable that the movement of intestinal contents during contraction and extension plays an important part in this rather remarkable change. The data in this case are as yet un- published.

The Rate of Form-Regulation and the Limit of Size

The development of a part reproduced by regulation is often greatly accelerated as compared with normal ontogenetic development. This rapid development can be due to nothing but a dis- proportion between size and intensity of physiological conditions to which the part is subjected. It is a familiar fact that increase in intensity of functional conditions brings about increase in size or hypertrophy of the bart involved and decrease in intensity a decrease in size or atrophy. The new part in regeneration and often also in redifferentiation is at first much “too small, ” i. e., the

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intensity of the physiological conditions to which it is subjected corresponds to a region of much larger size and hence increase in size takes place very rapidly. During growth the relative intensity of the physiological conditions decreases and so continually approaches that existing in the original part before removal. Hence unless other factors prevent, the part will grow with decreas- ing rapidity until it attains approximately the size of the part removed.

In the flatworms where form-regulation will occur in starving pieces we find that the increase in size often ceases even before the new part has attained the proper proportions with respect to the old. In these cases the new part grows a t the expense of the old and may undergo absolute as well as relative increase in size while the old part is undergoing absolute decrease. In such cases an equilibrium between old and new parts different from that existing in the normal animal is attained. As the new part grows the conditions for further growth decrease in intensity and as the old part is reduced its demand for nutritive material becomes relatively more intense and a larger proportion of the material available is used up in its own activities. Therefore, growth in the new part must cease before it reaches normal proportions, even rn ith respect to the reduced size of the old part.

T h e Rela t ion between Ra te of Regula t ion and the Degree of Injury

Comparison of two series of pieces of Leptoplana, the one set consisting of the anterior one-fourth or one-fifth of the body, the other of the anterior four-fifths or three-fourths, both kept without food, shows that the pieces of the first series regenerate from their posterior ends very much more rapidly and a much larger amount of new tissue than the pieces of the second series (Child, 'o4b). Yet the pieces showing the greater and more rapid regeneration are only one-fourth as large as the others.

If we compare the behavior of the two sets of pieces during regulation, especially during the earlier stages after the regeneration has begun, we find that in the first series the new part is used to a much greater extent than in the second. Not only is this the case but the activity in the old parts also is much greater in the first series than


in the second or in the normal animal. The movements are more violent and the irritability appears to be greater. In short, to all appearances, marked modification in the dynamic conditions has resulted from the removal of the posterior four-fifths and a scarcely appreciable modification from the removal of the one-fifth.

When the new tissue has appeared it becomes in the first series the functional representative of the four-fifths removed, and in the second only of the one-fifth. The early stages of its growth are of approximately the same size in both cases but in the first series the intensity of dynamic conditions must be much greater in this region, since its role in the complex is much more extensive and important than in the second. It must demand and receive a much greater proportion of the energy of the complex. Conse- quently growth or hypertrophy is much more rapid and greater in amount. Moreover, if it is true that removal of the four-fifths has brought about an increase in the intensity of dynamic processes in the old part this will doubtless also tend to increase the rapidity of growth in the new part, especially during earlierstages, since it is involved in the various reactions. As the new part develops, the intensity of activity appears to decrease.

Here as in other similar cases it is not simply the degree of movements or exercise of the part that determines the rapidity and amount of growth, though this of course may constitute one factor. It is rather the conditions underlying the motor activity, the nerve stimuli, the metabolic conditions, etc., of which the motor activity is an index (Child, 'oqb, 'osb).

Zeleny has recently obtained somewhat similar results in several species of decapod crustacea and in a species of ophiurid (Zeleny, 'oga, 'o5b). In all of these cases the rate of regeneration increases with the degree of injury up to a certain point. These cases differ, however, from the case of Leptoplana in that here regeneration occurs from two or more different regions while there only one region is involved. Strictly speaking the case of Leptoplana is comparable to removal of larger or smaller parts of a single arm in the starfish or of a single leg in the crustacea. But if we remove three or four arms from the starfish or several legs from the crayfish each one of the newprimordia represents, when it appears, no larger

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portion of the complex than does the primordium of a single arm or leg cut off a t the same level, yet it regenerates more rapidly.

It was noted above that the short piece of Leptoplana showed much more intense activity than the long piece. It is perhaps not too much to say that this increased activity is a response or reaction to the absence of the four-fifths. O n receiving a stimulus the piece reacts but reaction in the normal manner is impossible and the result is (‘irradiation ” of the stimulus and the appearance of other more or less violent reactions. This fact of (‘irradiation” has long been recognized in nerve physiology and Jennings’ recent experiments on the modifiability of behavior show that it is an important factor in behavior.

Zeleny has been unable to observe any characteristic difference in activityconnected with the degreeof injury. But the reaction to the injury need not necessarily appear as actual motor activity; iT may take the form of increased rapidity of metabolism or other forms. I n those cases where increased motor activity is present it serves as an index to internal conditions but its absence does not necessarily indicate the absence of increased dynamic activity of other kinds.

There can be no doubt that a normal reaction normally carried out has a certain effect on the individual and that an attempt and failure to carry out the reaction has another and very different effect, viz: in the direction of altered character and increased intensity of reaction. T h e old experiments upon the reflexes of the decapitated frog are sufficient demonstration of the fact. T h e larger the number of arms or legs removed in the cases cited above, the more impossible is the accomplishment of the normal reactions and consequently the more intense the effect on the animal as regards other reactions. As the new tissue appears it becomes a more or less complete functional substitute for the parts removed-very incomplete a t first no doubt. I n the conditions of intensified activity resulting from the operation the functional conditions to which the regenerating structures are subjected must increase in intensity with the degree of injury. This increase will be all the greater because their presence is the first step in the approach to a normal method of reaction to which the system is, so

Func t iona l Regula t ion and Form- Regulation 571

to speak, “seeking. ” As regeneration goes on the functional substitution becomes more complete, and reactions take place more nearly in the normal manner, functional conditions become relatively less intense, and the rapidity of regeneration decreases.

Compensatory Hypertrophy

In a number of cases among the Crustacea (Przibram, ’01, ’02, ’05; Zeleny, ’oga), where an asymmetery of the chelae exists, removal of the more highly specialized chela is followed by a more or less complete transformation of the other into the more highly specialized type, and the regenerating chela develops into the less specialized form. Thus a reversal of asymmetry results. If the less specialized chela alone is removed no reversal occurs. Zeleny (’o5a) has obtained somewhat similar results with certain species of serpulids where two opercula, one large and functional, the other small and rudimentary, are present. Removal of the functional operculum results in a reversal of the asymmetry while no reversal occurs after removal of the rudimentary operculum. When the whole head region, including both opercula is removed both regenerate in the form of the functional structure. Wilson (’03) has found in Alpheus grounds for believing that when the nerve to the chela is cut the reversal does not occur, but further experiments along this line are needed.

A satisfactory interpretation of these cases on a functional basis appears possible. When the specialized chela or operculum is removed the disturbance of the system thus produced results in changes in reactions and it seems probable that the easiest and most natural change will be such that the less specialized or rudimentary organs will receive stimuli and be subjected to conditions which originally affected the specialized or functional structures. In fact, it is difficult to see how any other interpretation can be made to serve. Zeleny (’cga) postulates for the serpulids the existence of a “retardation stimulus” from the functional operculum which, so long as this is present, inhibits the development of the other. The nature of such a retardation stimulus is highly problematical, It seems to the writer much more probable that the failure of the rudimentary or less specialized part to develop

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beyond a certain point-under normal conditions is due rather to tlhe absence of adequate stimuli than to a positive inhibitory stirniulus. So long as the other more highly specialized part is present the animal reacts in a characteristic manner which involves the less specialized part only to a certain degree; and the structure of that part expresses the character of the conditions to which it has been subjected. Removal of the less specialized part does not alter the reactions to any such extent as removal of the other, hence the part removed regenerates in the same form. Removal of both places the new primordia on equal terms and both may produce the more highly specialized or the functional structure. Here, as elsewhere, the functional conditions involved are not primarily those connected with use or exercise of the part but the sum total of its dynamic relations to the whole system.

Polarity and Axial Heteromorphosis Physiological polarity in the developed organism may be defined

proi~isionally as a habit of reaction resulting from past or present relations. This polarity of the organism may be a consequence of the polarity of the egg and this in turn a consequence of the relations of the egg-cell to the body of the parent or of other conditions affecting the egg. At any rate there seems to be no good ground for believing that polarity is a permanent and fundamental property of the cell or of protoplasm, although certain authorities have urged this view.

Polarity may be rendered visible by structural differentiation along the axis or it may not, but in any case the structure is primarily a result not a cause. It may, however, become the determining condition in that it determines the character of the reactions.

T h e original polarity is commonly maintained in form-regulation simply because each of the parts reacts most readily in a manner approaching that in which it has reacted in the past. But this habit of reaction can be altered in certain cases. I n Tubu- laria, for example, pieces very commonly produck a hydranth at both ends, the oral hydranth, first the aboral later. The delay in the appearance of the aboral hydranth represents the time necessary to alter the character. of the reaction or in other words to

Functional Regulation and Form-Regulation 5 73

change the habit. Moreover, when the oral hydranth is pre- vented from forming, the aboral hydranth appears more quickly than when the oral hydranth is permitted to form. Here we have an example of the case discussed above in which failure to carry out a “normal” reaction or the reaction most readily performed results in increased intensity of other reactions. That the habit is really changed is shown by the fact that a second aboral hydranth develops more rapidly than the first. Undoubtedly structural changes in the various regions result from the changes in reaction but these are not visible in this form except in the structures produced at the cut surfaces.

Axial heteromorphosis can be brought about in various ways in many of the lower forms. T h e isolation of very short pieces is perhaps the simplest method. I n these cases the piece is not large enough to represent the whole complexand the reaction in which the piece has been most intimately involved in the past becomes the chief or only possible reaction and similar structures are produced a t both ends. We find, therefore, that pieces of this kind often produce a t both ends the structures characteristic of the regions with which they have been most closely associated in the past. Sometimes other special factors modify this result, e.g., preparation for fission in Planaria maculata (Child, ’o6b), or as in Tubularia and some other hydroids the dominance of a particular reaction- complex throughout the individual. This latter case requires a word of comment : pieces of Tubularia from any part of the stem or from the stolons produce hydranths much more frequently than they do stolons when the ends are not in contact with a surface or solid. Polarity in this form is commonly indicated by the relative size and rapidity of formation of the hydranths from different ends and a t different levels of the piece rather than by the formation of typically different structures, though occasionally stolon-formation occurs a t the aboral end even without contact. It is possible, however, as the writer has found, to increase experimentally and without contact the intensity of the stolon-forming reaction to such an extent that almost every piece will give rise to stolons at the aboral end. Many of these stolons will after a considerable time produce hydranths a t their tips. T h e writer is inclined to believe

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thai: the hydranth-forming reactions may be interpreted as primarily a reaction to lack of nutriment. This reaction occurs most readily of course in those parts which have been most closely associated with it in the past.

I n a number of forms short pieces are not necessary for the occurrence of heteromorphosis. These include Tubularia and various other hydroids, some other ccelenterates, the earthworm and some other forms. In some of these as in Tubularia one form of reaction is dominant throughout, and in others, like the earthworm, this dominance is regional. I n the earthworm, for example, pieces from the posterior region commonly produce tails at both ends (Morgan, '02). T h e head-forming reactions can occur only in the more anterior regions. T h e very close relation between head-formation and the nervous system in this as well as in many other cases indicates that important factors in polarity are situated in the nervous system.

Heteromorphosis may also occur in various forms when a short piece is grafted in reverse position on a much longer piece. In suclh cases the short piece produces a t its free end the structures characteristic of the end of the longer piece with which it is united. These are undoubtedly simply cases of physiological dominance of the larger component. T h e greater intensity of its reactions alters the conditions in the small piece so that this becomes functionally a part of the other. This is doubtless accomplished by the passage of stimuli from the larger into the smaller piece and it may be by the actual growth of nerves in some cases.

T h e regulation of a piece into a complete individual with typical axial differentiation and maintenance of the original polarity depends upon the relative difference in reactive capacity in the difierent regions. I n all such cases the piece must possess the power to react in some degree like the whole. Its isolation brings into play potentialities not evident while normal relations were maintained, and the regions best fitted by past associations, for particular reactions perform them most readily and thus the original polarity persists.

Functional Regulation and Form-Regulation 5 75

The Relation Between the Nervous System and Form-Regulation

This relation which is very general, though of course not univer- sal, affords the strongest evidence in favor of the view that form- regulation is a functional process. No good ground has been dis- covered for assuming the existence of a peculiar trophic or formative influence originating in the nervous system. Goldstein, in a recent paper (’04), gives a most interesting discussion of the subject and concludes that the relation between the nervous system and growth and differentiation is essentially functional in character.

It must be remembered, however, that the nervous system adds nothing fundamentally new to the phenomena of life. The trans- ference of stimuli in definite directions and along more or less definite paths occurs where no visible nervous system exists. In- deed the development of the nervous system itself is probably in greater or less degree the result of such conditions. The problem of form-regulation is, therefore, not necessarily different in its fundamental features in those cases where no nervous system exists or where regulation occurs in the absence of visible nerves, as compared with those where visible nervous structures are present.

Conclusion

Regulation in general may be defined as a return to physiological equilibrium after such equilibrium has been altered by external conditions (Child, ’o6a). Holmes (’04) has recently given a very similar definition which he developed from the idea of symbiotic relations or “social pressure.” As the writer has attempted to show in a previous paper (’o6a) the idea of symbiotic relations does not afford a basis for the replacement in form-regulation of a part similar to that removed since removal of an element or a group of elements in the symbiotic complex must, according to Holmes’ assumption, alter the condition of the whole in such manner that the ‘‘social pressure ” upon the part which becomes the substitute for the part removed will be different from that originallyexerted upon this part, and something else rather than a duplicate of the part removed must be formed. But a characteristic feature of form-regulation is a return or approximation to the original con-

5 76 C. A4. Child

dition and any interpretation must recognize this fact. In the paper above referred to the writer has called attention to the fact that replacement of the missing part cannot occur unless that portion of the system remaining is capable of reacting in a manner essentially similar in some degree to the part removed. But mere capacity to react in this manner is not sufficient in most cases. This method of reaction must be the predominant or characteristic method, for if it is not, then a structure different from the part removed or nothing at all is replaced. This idea affords a basis for understanding why the ability to replace lost parts is limited in many cases. When by removal of a part the system is altered to such an extent that the previous method of reaction becomes impossible or is no longer the dominant method, replacement cannot occur. In such cases, however, provided the system is not altered to such a n extent that continued existence is impossible, some other form of regulation may occur and a new equilibrium may be established differing more or less widelyfrom the old. Thus when we remove the ganglia from Leptoplana and various other polyclads the processes characteristic of the head-region can no longer occur and the head is not replaced. In Planaria,on the other hand, removal of the ganglia does not alter the complex to such an extent as in Leptoplana since the nervous system is not as highly cephalized here and the headless piece or certain parts of it still retain the ability to react like a head in sufficient degree to initiate the process of head-formation. When this process is once started the ability to perform the characteristic reaction increases and the return to the original condition is gradually accomplished. The removal of the part brings into play various potentialities of reactions which exist in the remaining piece by virtue of its past relations to the whole and those processes which are predominant determine the character of form-regulation. But objection may be raised that a region in the middle of the body of Planaria, for example, has not been associated in the past with reactions or processes characteristic of the head and tail regions. If we observe the living animal, however, we find that the more intense motor reaction of either end may visibly involve the middle region in greater or less degree. They must also involve it in many ways not visible. It is

Functional Regulation and Form-Regulat ion 577

probably true that the middle region does not while still a part of the whole initiate such reactions, because whenever conditions which give rise to such reactions are present other parts of the body react much more readily than this. But when we sever its connection with other parts we find that it is visibly capable of initiating such reactions, though of .course very imperfectly and much less promptly than the original head and tail regions. T h e abilityto develop a new head and tail cannot arise from anything else than this ability. In this particular case-Planaria-this ability evi- dently depends in large measure upon the nervous system. This idea does not conflict in any way with that developed in the fore- going sections, viz: that a functional substitution of some degree must precede and initiate the process of replacement. It is evident that such functional substitution cannot occur unless the system retains the ability to react to some extent like the part removed. T h e substitution may alter the reaction of a larger or smaller part of the piece but the very fact of substitution depends on the occurrence in the system of reactions resembling in greater or less degree those of the part removed.

In connection with the views expressed above a recent paper by Jennings (’05), and also certain parts of his book (’06), are of inter- est. Jennings’ recent work has demonstrated the high degree of modifiability in the behavior even of the lower organisms and here he attempts to apply the conclusions reached to other fields. His views on the individucll adjustment or regulation of behavior are based on the following premises.

I Definite internal processes are occurring in organisms. 2 Interference with these processes causes a change of be-

hzvior and varied movements, subjecting the organism to many different conditions. ,

One of these conditions relieves the interference with the internal processes so that the changes in behavior cease and the relieving condition is thus retained. ”

T h e selection of the process or reaction which relieves the interference depends upon the fact of relief.

Jennings attempts to apply this “method of trial and error” in reaction to the phenomena of regulation in other fields, pointing

“

6 ‘

“3

578 C. M . Child

out the possibilitythat the selection of the apparently advantageous reaction is to be found in the fact that it relieves disturbing conditions.

It is perhaps sufficiently evident from what has been said above that Jennings’ views and the writer’s are somewhat similar in certain respects. The physiological equilibrium which forms the basis of Holmes’ and the writer’s definition of regulation corresponds to the condition postulated by Jennings in which the various physiological processes are occurring without interference : the alteration of equilibrium is brought about by some interference-in the cases under discussion in this paper usually by removal of a part. In consequence of this interference a more or less extensive rearrangement of dynamic processes occurs which becomes manifest in alteration of the localizatiou and perhaps also of the character of the reactions : because of the occurrence and continuation of certain of these processes a return to equlibrium occurs; but the writer does not believe with Jennings that the continuation of particular processes is necessarily due to the fact that they “relieve the interference;” their relation to relief may, however, bring about their intensification.

I here is one point in connection with form-regulation which Jennings has not discussed but which is of considerable importance in this connection and that is the frequency of return or approximation to the original condition. This is so characteristic of regulation that certain authors like Driesch (’01) have made it the basis of their definition. In the regulation of behavior and of chemical processes it cannot be supposed that only a single method of reaction exists whereby the interference can be removed or dimin- ished. In many cases, indeed, this is visibly not the case and the organism may attain in consequence of the interference an equilibrium widely different from the original. It seems probable, for example, that the formation of a new head at the posterior end and a tail at the anterior end or of these structures on the right and left side respectively of the piece in Planaria would remove or diminish the interference and so constitute a return to equilibrium, but this does not usuallyoccur. It is necessary to recognize the fact thatthe possi- bility of reaction is limited somewhat strictly by the past relations of the part or, in other words, by its reactive capacity. In short, the

rp

Functional Keplu t iorL and Form-Regulation 5 79

reaction leading to replacement of the lost part is usually the reaction which the piece can perform most readily, i.e., that for which it is best adapted. T h e endeavor has been made to direct attention to this fact in the preceding paragraphs. Hence the process of trial and error does not occur to any great extent in most cases and a very high degree of uniformity in the processes of form-regulation exists. Moreover, a particular reaction-complex must continue fairly constant for a considerable period of time before it becomes manifest in such extensive structural development as appears in form-regulation. If the characters of such reactions were not very strictly limited we should expect a much greater range of variation in the processes of form-regulation than occurs. That variation in the results does occur has been pointed out by various authors. T h e writer has called attention to the fact that in Leptoplana (Child, ’04c) some individuals are more capable than others of producing head-like structures in the absence of the ganglia, as well as to numerous other cases. I n a recent paper (Child, ’06b) a rather remarkable case of this kind has been noted: in certain species of Planaria very small pieces from the middle region of the body may produce any one of five different results, viz: single tail- less anterior regions, single headless posterior regions, double anterior regions, double posterior regions, or normal animals. This region is apparently “indifferent,” i.e., neither anterior nor posterior reactions are dominant in particular parts of the piece though both are possible in some degree, and the result depends apparently upon a “chance, ” i.e., upon certain internal conditions not a t present recognized. These contribute to determine what reactions shall become dominant in each piece.

But the variation in processes of form-regulation in general is not sufficiently great to indicate that “trial and error” plays any important rde. T h e reactions which bring about form-regulation do not continue because they “relieve the interference” but because they are dominant in the part in consequence of its past relations to other parts. I n the regulation of behavior there is doubtless often a greater range of possibilities, but even here it appears probable that the character of the regulatory reaction i s deter- mined, in many cases a t least, not by the fact that it “relieves the

580 C. M . Child

interference” but by the character of the ‘‘ apparatus ” or system under the existing coiiditions.

All the evidence points us to the conclusion that the phenomena of form-regulation are not essentially different from other dynamic phenomena in organisms and that they must be interpreted on a dynamic basis. As the writer has maintained in various papers the organism is primarily a dynamic complex and visible structural features are primarily incidents or by-products of the dynamic processes. Formative processes, so-called, do not differ fundamentally from processes of behavior.

Objection to such interpretation may be made on the ground that it is not really a n explanation but rather a step away from explanation in that it groups phenomena apparently relatively simple in the same category with the most complex phenomena of life. I n answer to this it may be said that the first step in true interpretation is the recognition of the nature of the problem. With increasing knowledge of vital phenomena it is becoming more and more evident that we cannot select a single group of these phenomena and “explain” them without reference to other groups. The organism is not a mosaic of independent complexes acting in different ways. There is not a particular group of dynamic processes concerned in building the machine and another in keeping it going. We shall find similar laws governing all whatever may be our final conception as to the nature of these laws. Semon (’04) has recently proceeded from a somewhat similar idea, in his exceed- ingly interesting attempt to interpret the phenomena of heredity, habit and memory on a common basis.

Recognition of the fact that the fundamental problems are the same in fields before regarded as distinct or only remotely related is always an advance and when different observers in these different fields recognize this fact independently of each other, the signific- ance of the conclusions is necessarily greater than it would be otherwise.

Hull Zoological Laboratory University of Chicago

May, 1906

Funrt ionnl Regulation and Form-Regulation 581

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Archiv fur Entwickelungsmech. Bd. xv,

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and Parts of Zooids in Stenostoma. mech., Bd. xvii, H. I, 1903.

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GOLDSTEIN, K., '04.-Kritische und Experimentelle Beitriige zur Frage nach dem Einfluss des Zentralnervensystems auf die embryonale Entwickel- ung und die Regeneration. Archiv fur Entwickelungsmech. Bd. xviii, H. I, 1904.

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Journ. of Exp. ZoOl., vol. ii, No. 4, 1905. '06.-Behavior of the Lower Organisms, New York, 1906.

MORGAN, T. H., '98.-Experimental Studies of the Regeneration of Planaria Macu- Archiv fur Entwickelungsmech. Bd. vii, H. 2 und 3, 1898.

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'og.-Die "Heterochelie" bei decapoden Crustaceen (zugleich: experimentelle Studien uber Regeneration. Dritte Mittheilung). Archiv fur Entwickelungsmech. Bd. xix, H. 2, 1905.

SEMON, R., '04.--Die Mneme als erhaltendes Prinzip im Wechsel des Organischen Geschehens. Leipzig, 1904.

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the relation between functional regulation and form-regulation

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