and hair-splitting, but here again it was for the sake of ensuring a
perfectly sound foundation of our chief principles that I undertook it.
Very often, indeed, the question has been raised by the defenders of a
mechanistic theory of life, Why then did the organisms not reject all
poisons from the very beginning? We now may reply to that only--how
*could* they do so? How could they “know” what is a poison and what is
not, unless they had experienced it?--if we are allowed for a moment to
use very anthropomorphistic language.
We repeat, therefore, that the functional conditions of the organism
must have been actually changed in order that an adaptation may occur.
Nothing is more essential to a clear understanding of our problems than
to keep fully in mind the exact sense of this definition.
ON CERTAIN GROUPS OF PRIMARY PHYSIOLOGICAL ADAPTATIONS
*General Remarks on Irritability.*--Turning now to more special groups
of problems concerning physiological adaptations, let us begin with the
primary class of them, and let us first say a few words on a subject
which occasionally has been regarded as the basis of physiological
regulation in general. I refer to a most important fact in the general
physiology of irritability. Irritability of any kind is known to be
re-established, after it has been disturbed by the process of reacting
to the stimulus, and in certain cases, in which two different--or rather
two opposite--kinds of reactions are possible on the same substratum,
which increase with regard to one process whilst decreasing at the same
time with regard to the other. The irritability of the muscle or of the
leaves of *Mimosa* is a very good instance of the first case, whilst the
second more complicated one cannot be illustrated better than by what
all experience has taught us about the irritability of the retina. The
retina is more irritable by green rays and less by red ones the more
it has been stimulated by the latter, and more sensitive to light in
general the more it has been exposed to darkness; and something very
similar is true, for instance, as regards phototactic irritability in
plants, all these phenomena being in relation to the so-called law of
Weber.[91]
[91] I only mention here that certain modern psychologists have assigned
the true law of Weber to the sphere of judgment and not of sensation. If
applied to objective reactions only, in their dependence on objective
stimuli, it, of course, becomes less ambiguous, and may, in a certain
sense, be said to measure “acclimatisation” with regard to the stimulus
in question. The mathematical analogy of the law of Weber to the most
fundamental law of chemical dynamics seems very important.
As to “acclimatisation” in the more usual meaning of the word, with
regard to a change of the general faculty of resisting certain agents
of the medium, “immunity” proper is to form a special paragraph of what
follows, and to “acclimatisation” towards different degrees of salinity
(in algae or fishes) some special remarks will also be devoted on a
proper occasion. There remains only “acclimatisation” to different
temperatures; but on this topic not much more than the fact is known
(see Davenport, *Arch. f. Entw. Mech.* 2, p. 227). “Acclimatisation”
does not allow of a sharp general definition; it may be the result of
very *different* kinds of adaptations in our sense of the word.
It seems to me that there would be little difficulty in harmonising the
phenomenon of the inversion of irritability with the so-called principle
of the “action of masses” and with the laws of certain “reversible”
processes well known in chemistry. As to the simple fact of the
re-establishment of irritability after stimulation has occurred, or,
in certain other cases, the fact that in spite of permanent stimulation
irritability seems to exist permanently also, physical analogies or even
explanations might very well be found.[92]
[92] I should think that the problem of the re-establishment of
irritability, in principle at least, arises even when there is not a
trace of so-called “fatigue” or of a “refractory period.” The process
of restoring may be so rapid as not to be noticeable, nevertheless some
sort of restoring is to be postulated. We may say the “irritability” of
an elastic ball is re-established by its elasticity. A certain analogy
to this case may perhaps be found in the muscle. But the irritability
of nerves with respect to nervous conduction, and of glands with
respect to secretion, or of the articulations of *Mimosa* may be well
understood, hypothetically at least, if we assume that the ordinary
course of metabolic events is apt in itself to lead to a certain state
or condition of the organs in question upon which their irritability
is based. Certain general conditions of functioning, as for instance
the presence of oxygen for the contraction of the muscle, would better
be looked upon as necessary “means” of functioning than as being part
of irritability as such. “Fatigue,” of course, may also be due to
the absence of such “means” or to abnormal conditions originated by
functioning itself.
If now we ask whether there is anything like an adaptation appearing in
the general characteristics of irritation and irritability, it seems to
me that we may answer the question in an affirmative manner, as far as
primary regulation comes into account. We, certainly, have not studied
any abnormal regulatory lines of general functioning, we only have
studied general functioning itself; but, indeed, there was a certain
sort of regulation *in* functioning. Of course, by showing that one
of the most general features of all functioning is primary-regulatory
in itself, we do not deny the possibility of many specific functions
in which real secondary regulations actually do exist. Nothing indeed
is asserted about the *specific* character of functioning in its
different types, by proving that one of the *general* features of *all*
functioning may comparatively easily be understood. It seems to me that
this important logical point has not always received the attention it
deserved.
*The Regulation of Heat Production.*[93]--Having finished our
introductory remarks we now turn to the proper study of special
physiological functioning with regard to its adaptive side, and begin
with the most simple cases.
[93] Rubner, *Die Gesetze des Energieverbrauches bei der Ernährung*,
Leipzig u. Wein, 1902.
The so-called “regulation of heat” in warm-blooded vertebrates is an
instance of a special function which can be said to be regulatory in
itself. There exists a normal blood heat for each species, which is
maintained no matter whether the temperature of the medium rise or fall.
It might seem at first as if in this case there were a little more
of an adaptive regulation than only its well-known primary type; no
reversion, one might say, of the direction of one and the same process
occurs in the regulation of heat production, but one kind of process
is called into action if it is necessary to raise the temperature, and
another whenever it is necessary to lower it. Even in the dilatation
and constriction of capillary vessels there are different nerves
serving for each operation respectively, and far more important are the
increasing of transpiration for cooling, the increasing of combustion
for heating--two radically different processes. But, nevertheless, there
is a certain unity in these processes, in so far as a specific locality
of the brain has been proved to be the “centre” of them all; it is to
this centre of course that the analysis of heat production considered as
a kind of regulation or adaptation must be directed. Such an ultimate
analysis, it seems to me, would have to classify heat regulation under
the primary type of adaptations in physiology without any restriction.
The centre acts in one sense or in the other, if stimulated by any
temperature beyond a very limited range, and it is in the action of the
centre that the “regulation” of heat consists.[94]
[94] The phenomenon of fever we leave out of account here; it is
regarded by some as regulation, by others as a disturbance of heat
regulation. Of course, if the first view should ever prove to be the
right one, fever might be classified among the real regulations of the
secondary type.
*Primary Regulations in the Transport of Materials and Certain Phenomena
of Osmotic Pressure.*--Very similar phenomena of regulation are present
in many processes concerned in the whole of metabolism. Let us consider
for a moment the migration of materials in plants. Whenever any compound
is used at a certain place, a permanent afflux of this compound to
that place sets in from all possible directions. No doubt this is a
“regulation,” but it is also the function itself, and besides that,
a very simple function based almost entirely on well-known laws of
physical chemistry. And in other cases, as in the ascent of water to
the highest tops of our trees, which purely physical forces are said to
be insufficient to explain, we can appeal to the unknown organisation
of many cells, and there is nothing to prevent our attributing to these
cells certain functions which are, if you like to say so, regulatory
in themselves. Among other facts of so-called regulations there is the
stopping of metabolic processes by an accumulation of their products:
as, for instance, the transformation of starch into sugar is stopped,
if the sugar is not carried away. Of course that is a regulation, but
it again is an intrinsic one, and it is one of the characteristics of
reversible chemical processes to be stopped in that way. I know very
well that in this particular case a certain complication is added by
the fact that it is a so-called ferment, the diastase, which promotes
the transformation of starch into cane-sugar, and that this ferment is
actively produced by the organism: but even its production would not
prove that any real kind of secondary regulation exists here, if nothing
more were known about such an active production than this single case.
In a special series of experiments almost all carried out in Wilhelm
Pfeffer’s botanical laboratory at Leipzig, an attempt has been made
to discover in what manner the cells of plants are able to withstand
very high abnormalities of the osmotic pressure of the medium--that is
to say, very great changes in the amount of its salinity. That many,
particularly the lower plants, are able to stand such changes had been
ascertained already by the careful examinations of Eschenhagen; but
recent years have given us a more profound insight into what happens.
Von Mayenburg[95] has found that sundry of the species of *Aspergillus*,
the common mould, are able to live in very highly concentrated solutions
of several salts (KNO_3 and Na_2SO_4). They were found to regulate
their osmotic pressure not by taking in the salts themselves, but by
raising the osmotic pressure of their own cell sap, producing a certain
amount of osmotically active substances, probably carbohydrates. If
in this case it were possible to assume that the osmotic pressure of
the medium were the real stimulus for the production of the osmotic
substances in the cell, stimulus and production both corresponding
in their degree, we should be entitled to speak of a primary though
physiological[96] regulation only; and it seems to me that despite the
discoveries of Nathansohn that certain algae and cells of higher plants
are able to change the permeability of their surfaces in a way which
regulates the distribution of single salts or ions in the sap of their
cells without any regard to pure osmotic equilibrium, such a simple
explanation might be possible.[97]
[95] *Jahrb. wiss. Bot.* 36, 1901.
[96] Carbohydrates cannot be ionised, and therefore there is no doubt
that in von Mayenburg’s experiments the organism itself is actively
at work. As to compounds liable to ionisation, it has been noticed by
Maillard that a certain regulatory character is contained simply in the
physical fact that the degree of ionisation changes with concentration:
decrease of concentration for instance would be followed by an increase
of ionisation, and so the osmotic pressure may be preserved (*C. rend.
Soc. Biol.* 53, 1901, p. 880).
[97] In the different experiments of Nathansohn (*Jahrb. wiss. Bot.*
38, 1902, and 39, 1903) the salinity of the medium was changed in such
a way that there was in each case either an abnormal increase or an
abnormal decrease in the concentration of one single ion necessary
for metabolism. The cell was found to stand these abnormal changes in
such a way that in the case of the increase of the concentration of
the medium it did not allow more than a certain amount of the ion in
question to come in, and that in the case of the decrease it did not
allow more than a certain quantity of the ion to go out. It thus seems
as if the permeability of the surface were adjusted to a certain minimum
and to a certain maximum of every single ion or salt, the permeability
being stopped from within to without, whenever the minimum, and from
without to within, whenever the maximum is reached in the cell sap; both
irrespective of proper physical osmotic equilibrium (“Physiologisches
Gleichgewicht”). Thus, in fact, there only would be a case of primary
regulation, nothing more. It would all appear rather similar to what
occurs in the kidney. Of course we do not assert that our explanation is
right, but it is possible and is at the same time the most simple, and
it is our general practice always to prefer the most simple hypotheses.
There are many regulation phenomena connected with osmotic pressure
and permeability in animal physiology also, though at present they are
not worked out as fully as possible. The works of Frédéricq, J. Loeb,
Overton and Sumner[98] would have to be taken into account by any
one who wished to enter more deeply into these problems. We can only
mention here that permeability to water itself also plays its part, and
that, according to Overton’s experiments, it is a kind of solubility
of the media in the very substance of the cell surface on which all
permeability and its regulation depend.
[98] Many fishes are able to withstand great changes in the osmotic
pressure of sea-water; the osmotic pressure of their body fluids, though
never in a real physical equilibrium with the pressure of the medium,
nevertheless may vary whenever the abnormal conditions of the latter
exceed certain limits.
*Chromatic Regulations in Algae.*--The phenomena of osmotic pressure and
its regulation may be said to be the preliminaries of metabolism proper,
conditions necessary for it to take place. Now there is another branch
of such preliminaries to metabolism, in which the most interesting
regulation phenomena have been lately discovered. It is well known that
what is called assimilation in plants, that is, the formation of organic
compounds out of carbon dioxide (CO_2) and water, occurs only in
the light by means of certain pigments. This pigment is in all higher
plants and in many others the green chlorophyll, but it may be different
in certain species of algae, and can generally be said[99] to be of
the colour complementary to the colour of those rays which especially
are to be absorbed and to be used for assimilation. But here we have
“adaptedness,” not adaptation. It was in some species of primitive
algae, the *Oscillariae*, that Gaidukow[100] found a very interesting
instance of an active regulation in the formation of pigments. These
algae always assume a colour which corresponds to the accidental colour
of the rays of the medium and is complementary to it; they become green
in red light, yellow in blue light, and so on--that is, they always
actively take that sort of colouring which is the most suitable to
the actual case.[101] There indeed occurs a sort of complementary
photography in these algae; but, though adaptive, it could hardly be
said to exceed the limits of “primary phenomena.”
[99] See Stahl, *Naturw. Wochenschrift*, N. F. 5, 1906, No. 19.
[100] *Arch. Anat. Phys.*, Phys. Abt. Suppl., 1902.
[101] The adaptive phenomena discovered by Gaidukow depend upon a real
alteration in the formation of pigments. In the (primary) chromatic
adaptation of pupae of Lepidoptera with respect to the colour of
the ground they live upon, we only have the variable effects of
pre-established chromatophores (Poulton, *Phil. Trans. London*, 178 B,
1888; Merrifield, *Trans. Ent. Soc. London*, 1898). The same holds for
chromatic adaptations in crabs (Gamble and Keeble, *Quart. Journ. Micr.
Sci.* 43, 1900; Minkiewicz, *Arch. Zool. exp. et gén.* sér. 4, 7, notes,
1907).
*Metabolic Regulations.*--And now we enter the field of regulations in
metabolism itself. There are two kinds of outside factors of fundamental
importance for all metabolic processes: food is one, and oxygen is the
other. And metabolism as a whole is of two different aspects also:
it both serves for assimilation proper--that is, building up--and it
supplies the energy for driving the functional machine. It is clear
that food alone--together of course with the assimilating means of the
organism, can account for the first type of metabolism, while both food
and oxygen, or some sort of substitute for the latter, as in certain
bacteria, supply functional energy. Of course we are not entitled to say
that the importance of so-called oxidation or respiration is exhausted
by its energetic rôle: it certainly is not, for if it were, the organism
would only be stopped in its functions if deprived of oxygen but
would not die. It seems that certain substances always arise in the
metabolism, in the processes of decomposition, which have to be burnt up
in order not to become poisonous. But we shall return to the phenomena
of organic oxidation in another chapter of the book, and shall deal with
them from a more general point of view.[102]
[102] The theory of oxidation we have shortly sketched here was
developed in chapter B. 5, of my *Organische Regulationen*. Recent
discoveries of Winterstein’s (*Zeitschr. allg. Physiol.* 6, 1907)
have given the strongest support to my hypothetic statements, and, in
fact, can be said to have brought the doctrine of organic oxidation
to a critical point. There can be no doubt that oxygen not only plays
the “antipoisonous” rôle I had assigned to it, but that it is not
even of such great importance for the supply of functional energy as
former times had assumed. No doubt it serves to drive the functional
machine, but decomposition of certain chemical constituents of the
organism serves this purpose even more. The latter does so in the most
fundamental and original manner, so to speak, whilst oxidation only
burns up its products. Almost all elemental functions, in nerve-tissue
at least, go on very well in the absence of oxygen, provided that
certain “poisonous” substances, resulting from this anaërobic
metabolism, are constantly removed. In normal conditions that is
done by oxygen, and in doing so oxygen certainly assists the supply
of energy, but it does not furnish the whole of it. The difference
between so-called “aërobic” and “anaërobic” life almost completely
disappears under such a view, and many so-called “regulations,” of
course, disappear at the same time; there is no more “intramolecular
respiration.”
Let us now try to take a short survey of all the regulations discovered
relating to the substitution of one kind of food for another. We have
said that food serves in the first place as building material, in the
second place as fuel. It only deserves brief mention that, as all recent
investigations have shown, fats, carbohydrates, and albumen are equally
well able to serve as fuel.[103]
[103] But nevertheless albumen is not to be replaced altogether in
vertebrates by fat or carbohydrate; it probably serves some special
function besides combustion, even in the adult.
It is in the state of fasting, *i.e.* in the case of a real absence of
*all* nourishing materials, that the organism has proved to be capable
of regulations of the most marked nature, with regard to the combustion
of its own materials. Respiration, we know, must go on if death is to
be avoided, and now indeed it has been found that this process attacks
the different tissues of the organism subjected to fasting in such an
order that, after the combustion of the reserves, the most unimportant
tissues with regard to life in general are destroyed first, the most
important ones last. Thus in vertebrates the nerve cells and the heart
are preserved as long as possible; in infusoria it is the nucleus; in
flatworms, as the very careful studies of E. Schultz[104] have lately
shown, it is the nerve cells and the sexual cells which longest resist
destruction, whilst almost all the rest of the organisation of these
animals may disappear. I should not say that we can do very much with
these facts at present in our theoretical discussion, but they are
certainly witness of very astonishing adaptive powers.[105]
[104] *Arch. Entw. Mech.* 18, 1904.
[105] To a physiological friend of mine I owe the suggestion that it is
the permanently functioning tissues which stand hunger better than the
others, at least if the sexual cells might be regarded as capable of
a *sécrétion interne* in all cases. Then the adaptations in the state
of hunger might be said to be reduced in some degree to “functional
adaptation.” But it must remain an open question, it seems to me,
whether such a view may indeed hold in the face of the facts observed in
*Planaria* and infusorians.
We now turn to study the cases of a compensation of nourishments
serving for the real building up of the organism. Albumen, we know, is
absolutely indispensable for animals, even for adults, though nothing is
known about the purpose it serves in the latter; its place can be taken
of course by those less complicated compounds which result from its
first decomposition, effected by pepsin and trypsin, but nothing else
will do. The salts of sea-water, according to Herbst’s experiments, may
only vary to a very small degree if the development of marine animals
is to go on well; potassium may be replaced by caesium or rubidium,
and that is all. Much the same is true of the salts necessary to
plants. It will not surprise us very much to hear that algae can also
be successfully fed with the potassium salts of organic compounds, and
higher plants with acid amides or glucoses instead of carbonic acid, as
those products are normal steps in their assimilation; and it may also
be fairly easily understood that nitrogen can be offered in organic form
instead of as a nitrate.
It was in the group of fungi that really important adaptations with
regard to the proper form-producing alimentation were first discovered,
and these are of a very complicated kind indeed. Fungi are known to
be satisfied with one single organic compound instead of the group of
three--fat, carbohydrate and albumen--necessary for animals. Now Pfeffer
showed that the most different and indeed very abnormal compounds were
able to bring his subjects to a perfect growth and morphogenesis; and,
moreover, he found that, if several kinds of such food were offered
together, they were consumed quite indifferently as to their chemical
constitution, but only with regard to their nutritive value: that sort
of food which had produced a better growth than another when both
were offered separately was found to save the latter from consumption
whenever both were offered together.
Here we are faced by one of the most typical cases of regulations in
metabolic physiology: the organism is able to decompose compounds of
the most different constitution, which have never been offered to it
before; but nevertheless, it must remain an open question whether real
“secondary” regulation has occurred, as nothing is known in detail about
the single steps of metabolism in these fungi. There *might* be some
ferments equally able to destroy different classes of compounds,[106]
and that the most nutritive compound is used up first *may* be a
question of physico-chemical equilibrium.
[106] In all cases where fungi of the same species are able to live on
different hosts, that is, to penetrate membranes of a different chemical
character, a similar objection as to the “secondary” type of such a
regulation may be made.
That is almost all[107] that is actually known of adaptation with regard
to the use of an abnormal food supply. Though important, it cannot be
said to be very much. But could we expect very numerous regulations
here at all after what we laid down in a former paragraph about the
possibilities of adaptive regulation in general? The functional state
must have been altered in order that such regulations may occur. Now
there is no doubt that this state may be really altered only if an
abnormal food has first been taken in altogether by the cell-protoplasm
of the body-surfaces, but never if it has only entered the cavity of the
intestine, which, strictly speaking, is a part of the exterior medium.
Fungi indeed not only take in the abnormal food, but also know what
to do with it, but all animals are obliged to treat first with their
chemical secretions what happens to be present in their intestine, in
order that it may be taken up by their living cells, and one hardly
can wonder that these secretions are only formed in correspondence to
a limited number of outside stimuli. In fact, as soon as we look upon
what adaptive or regulatory work happens in metabolism *inside* the body
interior, we meet, even in animals, regulations of a far more developed
type.
[107] The discovery of Weinland that adult dogs are able to produce
“lactase” in their pancreas, whenever they are fed, quite abnormally,
with milk-sugar, has recently been said to be vitiated by an analytical
mistake.
Discoveries of the last few years have taught us that almost all
metabolic processes in the organism, including oxidation, are carried
out by the aid of special materials, the so-called enzymes or
ferments. These are known to exist in the most different forms even in
the inorganic world. They are simply chemical compounds, of specific
types, that bring about chemical reactions between two other chemical
materials, which in their absence would either not go on at all or would
go on very slowly. We cannot enter here into the much disputed chemical
theory of what is called “catalysis”: we can only say that there is no
objection to our regarding almost all metabolic processes inside the
organism as due to the intervention of ferments or catalytic materials,
and that the only difference between inorganic and organic ferments is
the very complicated character of the latter and the very high degree of
their specification.
Such a statement, of course, does not say that all metabolism has proved
to be of a chemical nature: the *action* of the ferment when produced
is chemical, but we do not know at all *how* the ferment is produced;
we only know that a high degree of active regulation is shown in this
production. In fact, it has been proved in some cases, and probably will
be proved in a great many more in the near future, that all metabolic
ferments, whether they promote oxidation or assimilation proper or
chemical decomposition, are produced in a regulatory manner with regard
to the specific compound to be dissociated or to be built up. In this
way the whole field of metabolism is really covered by “regulations.”
Are they real “secondary” ones? Of course the regulatory correspondence
applies to the process of *secretion* in the *first* place, not to the
actual formation of the ferment inside the cell. The correspondence as
to secretion, no doubt, is of the primary type; is there any secondary
regulation with regard to the real *production* of the ferment? I am
sorry that I cannot answer this question affirmatively. Nothing is
*known* at present, even here, that really proves the existence of
adaptation of the secondary type: there *might* be a sort of statical
“harmony” at the base of it all, established before all functioning
*for* functioning.[108]
[108] Compare the excellent review of the subject by Bayliss and
Starling in the *Ergebnisse der Physiologie*, 5, 1906, p. 664. The
reader who misses here an analysis of the brilliant discoveries
of Pawlow and his followers, relating to so-called “psychical and
associative secretion,” will find these facts dealt with in another
section of the book. These facts, indeed, would prove vitalism, it seems
to me.
The only facts of secondary metabolic regulations which are known at
present have been found in combination with phenomena of restitution
after real disturbances of organisation, where, indeed, numbers and
numbers of regulatory changes of metabolism, both in animals and plants,
have also been recorded. But there is not one case of a secondary
regulation really known to affect pure metabolism alone.[109] This is a
new indicium of the primacy of *form* in the organism.
[109] It would be a true secondary metabolic regulation, if after the
extirpation of one gland another different one were to assume its
function. Nothing is known in this respect except a few rather doubtful
observations about the interchange of functions between thymus and
thyroid, except also the fact that the so-called lymph-glands increase
in size after the extirpation of the spleen. Even here, of course, a
sort of “restitution” would be included in adaptation proper.
IMMUNITY THE ONLY TYPE OF A SECONDARY PHYSIOLOGICAL ADAPTATION
There is only one class of physiological processes in which the type
of the real secondary regulation occurs. The discoveries of the last
twenty years have proved beyond all doubt, and future discoveries will
probably prove even more conclusively, that the so-called *immunity*
against diseases is but one case out of numerous biological phenomena
in which there is an adaptive correspondence between abnormal chemical
stimuli and active chemical reactions on the part of the organism and in
its interior, exceeding by far everything that was formerly supposed to
be possible in organic regulation.
The adaptive faculty of the organism against inorganic poisonous
substances[110] is but small comparatively, and is almost always due not
to a real process of active regulation but to the action of substances
pre-existing in the organism--that is, to a sort of adaptiveness but
not adaptation. Metallic poisons, for instance, may be transformed into
harmless compounds by being combined with albumen or sulphuric acid
and thus becoming insoluble, or free acids may be neutralised, and so
on; but all these processes go on to a certain extent only, and, as
was mentioned already, are almost always the result of reactions with
pre-existing materials. Only in a few cases is there any sort of true
adaptation to metallic substances, such as sublimate and, in a very
small degree, arsenic, comparable in some respects with the adaptation
to abnormally high temperatures. The organism which has been accustomed
to receive at first very small amounts, say, of sublimate, and then
receives greater and greater amounts of this substance by degrees, will
at the end of this treatment be able to stand a quantity of the poison
that would have been instantly fatal if administered at the first
dose.[111] But the explanation of this adaptation is not known in any
case; there seems to be some similarity between it and the so-called
histogenetic immunity against organic poisons.
[110] A good review is given by E. Fromm, *Die chemischen Schutzmittel
des Tierkörpers bei Vergiftungen*, Strassburg, 1903.
[111] Davenport, *Arch. Entw. Mech.* 2, 1895-1896, and Hausmann,
*Pflüger’s Arch.* 113, 1906.
It is in the fight against animal and vegetable poisons, such as those
produced by bacteria, by some plants and by poisonous snakes, that the
true adaptation of the organism reaches its most astonishing degree.
The production of so-called “anti-bodies” in the body fluids is not the
only means applied against noxious chemical substances of this kind: the
existence of so-called histogenetic immunity is beyond all doubt, and
Metschnikoff[112] certainly was also right in stating that the cells
of the organism themselves repel the attack of living bacteria. Cells
of the connective tissue and the white blood cells, being attracted by
them as well as by many other foreign bodies, take them in and kill
them. This process, called “phagocytosis” is of special frequency among
lower animals, but it also contributes to what is called inflammation
in higher ones.[113] And there are still other kinds of defence against
parasites, as for instance the horny or calcareous membranes, employed
to isolate trichinae and some kinds of bacteria. But all this is of
almost secondary importance as compared with the adaptive faculties of
the warm-blooded vertebrates, which produce anti-poisonous substances in
their lymph and blood.
[112] *Leçons sur la pathologie comparée de l’inflammation*, Paris, 1902.
[113] The other steps or phases in the process of inflammation have also
been regarded as adaptive: the increased quantity of body fluid for
instance is said to serve to dilute poisonous substances.
It is impossible to say here[114] more than a few words about the
phenomena and the theory of immunity proper, which have attained the
dimensions of a separate science. Let me only mark those general points
which are of the greatest theoretical interest. Discoveries of the most
recent years have shown not only that against the “toxins” of bacteria,
snakes, and some plants, the organism is able actively to produce
so-called “anti-toxins”--that is, soluble substances which react with
the toxins and destroy their poisonous character--whenever required,
but that against any foreign body of the albumen group a specific
reaction may occur, resulting in the coagulation of that body. But the
destruction of the noxious substance or foreign albumen actually present
is not all that is accomplished by the organism. “Acquired immunity”
proper, that is, security against the noxious material for a more or
less extensive period of the *future*, depends on something more. Not
only is there produced as much of the so-called “anti-body” as is
necessary to combine with the noxious, or at least foreign substances
which are present, but *more* is produced than is necessary in the
actual case. On this over-production depends all active immunity,
whether natural or, as in some kinds of vaccination, artificial; and
so-called “passive” immunity, obtained by the transfusion of the serum
of an actively immune organism into another also depends upon this
feature.[115]
[114] See Jacoby, *Immunität und Disposition*, Wiesbaden, 1906.
[115] *Collected Studies on Immunity by Ehrlich and his Collaborators*,
translated by Ch. Bolduan, New York and London, 1906.
This phenomenon in particular--the production of *more* of the
antitoxin or the “precipitin” than is actually necessary--seems to
render almost impossible any merely chemical theory of these facts. The
reaction between toxin and antitoxin, albumen and precipitin is indeed
chemical; it may in fact be carried out in a test-tube; but whether the
production of the anti-body itself is also chemical or not could hardly
be ascertained without a careful and unbiassed analysis. There can be
no doubt that the well-known theory of Ehrlich,[116] the so-called
theory of side-chains (“Seitenkettentheorie”) has given a great impulse
to the progress of science; but even this theory, irrespective of its
admissibility in general, is not a real chemical one: the concept of a
regeneration of its so-called haptophore groups is a strictly biological
concept.[117]
[116] So-called genuine or innate immunity, in contrast to the immunity
which is acquired, is of course a case of adaptedness only and not of
adaptation. There also exists a high degree of specific adaptedness in
some animals with regard to their faculty of coagulating blood. (See Leo
Loeb, *Biol. Bull.* 9, 1905.)
[117] We cannot do more than barely mention here the problem of the
localisation of anti-body production. In general it seems to be true
that anti-bodies are produced by those cells which require to be
protected against toxins; that would agree with the general rule, that
all compensation of the change of any functional state proceeds from the
part changed in its function.
And, indeed, here if anywhere we have the biological phenomenon of
adaptation in its clearest form. There are very abnormal changes of the
functional state of the organism, and the organism is able to compensate
these changes in their minutest detail in almost any case. The problem
of the specification of the reactions leading to immunity seems to me,
as far as I can judge as an outsider, to stand at present in the very
forefront of the science. There cannot be the slightest doubt that
especially against all sorts of foreign albumens the reaction is as
strictly specific as possible; but there are some typical cases of
specificity in the production of antitoxins also. It is, of course,
the *fact* of specific correspondence between stimulus and reaction,
that gives to immunity its central position among all adaptations,
no matter whether the old hypothesis of the production of specific
anti-bodies proves tenable, or whether, as has been urged more recently
by some authors, the anti-body is always the same but reacts differently
according to the medium. In the latter case it would be the medium that
is regulated in some way by the organism in order to attain a specific
adaptedness.
NO GENERAL POSITIVE RESULT FROM THIS CHAPTER
But now let us look back to the sum of all the physiological reactions
studied, and let us see if we have gained a new proof of the autonomy of
life from our long chapter.
We freely admit we have not gained any really new *proof*, but we may
claim, I think, to have gained many indicia for the statement that
the organism is not of the type of a machine, in which every single
regulation is to be regarded as properly prepared and outlined.
It is precisely in the field of immunity that such a machine-like
preparation of the adaptive effects seems almost impossible to be
imagined. How indeed could there be a machine, the chemical constituents
of which were such as to correspond adaptively to almost every
requirement?--to say nothing of the fact that the production of *more*
of the protecting substance than is actually necessary could hardly be
said to be “chemical.”
In fact, we are well entitled to say that we have reached here the very
heart of life and of biology. If nevertheless we do not call the sum of
our facts a real proof of vitalism, it is only because we feel unable
to formulate the analysis of what happens in such a manner as to make
a machine as the basis of all reactions absolutely unimaginable and
unthinkable. There *might* be a true machine in the organism producing
immunity with all its adaptations. We cannot disprove such a doctrine by
demonstrating that it would lead to a real *absurdity*, as we did in our
analysis of differentiation of form; there is only a very high degree of
improbability in our present case. But an indirect *proof* must reduce
to *absurdity* all the possibilities except one, in order to be a proof.
Mechanistic explanations in all branches of functional physiology
proper, so much in vogue twenty years ago, can indeed be said to
have failed all along the line: the only advantage they have brought
to science is the clearer statement of problems to which we are now
accustomed. But we are not fully entitled to say[118] that there never
will be any mechanistic explanation of physiological functions in the
future. It may seem as improbable as anything can be; but we wish to
know not what is improbable but what is not possible.
[118] Here again I should like to except from this statement the
discoveries of Pawlow. See page 204, note 1.
Now of course you might answer me that after we have indeed
shown that the production of form, as occurring on the basis of
harmonious-equipotential systems, is a fact that proves vitalism,
the acts taking place on the basis of that form after its production
would have been proved to be vitalistic also, or at least to be in
some connection with vitalistic phenomena. Certainly they would, and
I myself personally should not hesitate to say so. But that is not
the question. We have to ask: Is any new proof, *independent of every
other*, to be obtained from the facts of physiological adaptation in
themselves? And there is really none. Mere regulatory correspondence
between stimuli and reactions, even if it be of the adaptive type and
occur in almost indefinite forms, never really disproves a machine as
its basis so long as the stimuli and reactions are *simple* and uniform.
Next summer, however, we shall see that vitalism may be proved by such a
correspondence if the two corresponding factors are not simple and not
uniform.
We most clearly see at this point what it really was in our analysis of
differentiation that allowed us to extract a real proof of vitalism from
it. Not the mere fact of regulability, but certain specific relations
of space, of locality, lay at the very foundation of our proof. These
relations, indeed, and only these relations, made it possible to
reduce *ad absurdum* any possible existence of a machine as the actual
basis of what we had studied. In our next chapter again it will be
space-relations, though analysed in a different manner, that will enable
us to add a second real proof of vitalism to our first one.
With this chapter we conclude the study of organic regulation in all its
forms, as far as morphogenesis and metabolism are in question.
But our analysis of these regulations would be incomplete and indeed
would be open to objections, if we did not devote at least a few words
to two merely negative topics, which will be taken more fully into
consideration later on.
A FEW REMARKS ON THE LIMITS OF REGULABILITY
There has never been found any sort of “experience” in regulations
about morphogenesis or in adaptations of the proper physiological
type. Nothing goes on “better” the second time than it did the first
time;[119] everything is either complete, whenever it occurs, or it does
not occur at all.
[119] The few cases of an “improvement” of morphogenetic acts in
hydroids described by myself are too isolated at present to be more
than mere problems (*Arch. Entw. Mech.* 5, 1897). The same is true, it
seems to me, with regard to certain recent discoveries made by R. Pearl
on *Ceratophyllum* (*Carnegie Inst. Wash. Publ.* No. 58, 1907); and by
Zeleny on a medusa (*Journ. exp. Zool.* 5, 1907). Pawlow’s discovery,
that the enzymotic composition of the pancreatic fluid in dogs becomes
more and more adapted to a specific composition of the food (either meat
or bread and milk) the longer such a specific composition is offered
to the individual animal, may probably be understood as a case of mere
functional adaptation of the cells of the digestive glands, if it stands
criticism at all (see Bayliss and Starling, *Ergeb. Physiol.* 5, 1906,
p. 682).
That is the first of our important negative statements about
regulations; the second relates to the phrase just used, “or it does
not occur at all.” There are indeed limits of regulability; adaptations
are not possible to every sort of change of the physiological state:
sickness and death could not exist if they were; nor is restitution
possible in all cases where it might be useful. It is a well-known fact,
that man is only able to heal wounds but is altogether destitute of the
faculty of regeneration proper. But even lower animals may be without
this faculty, as are the ctenophores and the nematodes for instance, and
there is no sort of correspondence between the faculty of restitution
and the place in the animal kingdom. It is not altogether impossible
that there may be found, some day, certain conditions under which every
organism is capable of restoring any missing part; but at present we
know absolutely nothing about such conditions.[120]
[120] Experiments carried out in the “Biologische Versuchsanstalt” at
Vienna indeed have shown that many animal types are capable of at least
a certain degree of restitution, although they had previously been
denied this faculty by zoologists.
But no amount of negative instances can disprove an existing
positive--which is what we have been studying. Our analysis based upon
the existence of regulations is as little disparaged by cases where no
regulability exists as optical studies are by the fact that they cannot
be undertaken in absolute darkness.
*D.* INHERITANCE: SECOND PROOF OF THE AUTONOMY OF LIFE
All organisms are endowed with the faculty of re-creating their own
initial form of existence.
In words similar to these Alexander Goette, it seems to me, has given
the shortest and the best expression of the fact of inheritance. Indeed,
if the initial form in all its essentials is re-created, it follows from
the principle of univocality, that, *ceteris paribus*, it will behave
again as it did when last it existed.
By the fact of inheritance life becomes a rhythmic phenomenon, that is
to say, a phenomenon, or better, a chain of phenomena, whose single
links reappear at constant intervals, if the outer conditions are not
changed.
THE MATERIAL CONTINUITY IN INHERITANCE
It was first stated by Gustav Jaeger and afterwards worked out into
a regular theory by Weismann, that there is a continuity of material
underlying inheritance. Taken in its literal meaning this statement is
obviously self-evident, though none the less important on that account.
For as all life is manifested on bodies, that is on matter, and as the
development of all offspring starts from parts of the parent bodies,
that is from the matter or material of the parents, it follows that in
some sense there is a sort of continuity of material as long as there is
life--at least in the forms we know of. The theory of the continuity of
“germ-plasm” therefore would be true, even if germ-cells were produced
by any and every part of the organism. That, as we know, is not actually
the case: germ-cells, at least in the higher animals and in plants, are
produced at certain specific localities of the organism only, and it is
with regard to this fact that the so-called theory of the “continuity of
germ-plasm” acquires its narrower and proper sense. There are distinct
and specific lines of cell-lineage in ontogenesis, so the theory states,
along which the continuity of germ-protoplasm is kept up, which, in
other words, lead from one egg to the other, whilst almost all other
lines of cell-lineage end in “somatic” cells, which are doomed to
death. What has been stated here is a fact in many cases of descriptive
embryology, though it can hardly be said to be more than that. We know
already, from our analytical and experimental study of morphogenesis,
that Weismann himself had to add a number of subsidiary hypotheses to
his original theory to account for the mere facts of regeneration proper
and the so-called vegetative reproduction in plants and in some animals,
and we have learned that newly discovered facts necessitate still more
appendixes to the original theory. In spite of that, I regard it as
very important that the fact of the continuity of some material as one
of the foundations of inheritance has clearly been stated, even if the
specialised form of the theory, as advocated by Weismann in the doctrine
of the “germ-lineages” (“Keimbahnen”) should prove unable to stand
against the facts.
The important problem now presents itself: What is the material, the
matter, which is handed down from generation to generation as the
basis of inheritance? Weismann, as we know, regarded it as a very
complicated structure, part of which by its disintegration became the
foundation of individual embryology. We have disproved, on the authority
of many facts, the latter part of this assumption; but of course the
first part of it may turn out to be true in spite of this. We have no
means at present to enable us to say *a priori* anything positive or
negative about the important question of the nature of that matter, the
continuity of which in inheritance is in some sense a self-evident fact,
and we therefore shall postpone the answer until a later point of our
analytical discussion.
ON CERTAIN THEORIES WHICH SEEK TO COMPARE INHERITANCE TO MEMORY
It will be advisable first to study some other theoretical views which
have been put forward with regard to inheritance. The physiologist
Hering, as early as 1876, compared all heredity to the well-known fact
of memory, assuming, so to say, a sort of remembrance of all that
has happened to the species in the continuity of its generations;
and several German authors, especially Semon, have lately made this
hypothesis the basis of more detailed speculation.
It is not clear, either from Hering’s paper[121] or from Semon’s
book,[122] what is really to be understood here by the word “memory,”
and, of course, there might be understood by it very different things,
according to the author’s psychological point of view. If he is a
“parallelist” with regard to so-called psychical phenomena, he would use
the word memory only as a sort of collective term to signify a resultant
effect of many single mechanical events, as far as the material world of
his parallel system comes into account, with which of course the problem
of inheritance alone deals; but if he maintains the theory of so-called
psycho-physical interaction, the psychical would be to him a primary
factor in nature, and so also would memory. As we have said, it is by no
means clear in what sense the word “memory” is used by our authors, and
therefore the *most* important point about the matter in question must
remain *in dubio*.
[121] *Ueber das Gedächtnis als eine allgemeine Function der organischen
Materie*, Wien, 1870. New edition in *Klassiker d. exakt. Wiss.*,
Leipzig, Engelmann.
[122] *Die Mneme*, Leipzig, 1904.
But another topic is even more clear in the theory of inheritance, as
stated in Hering’s and Semon’s writings. The hypothetical fact that
so-called “acquired characters” are inherited is undoubtedly the chief
assumption of that theory. Indeed, it would be difficult to understand
the advantage of the ambiguous word memory, had it not to call attention
to the hypothetic fact that the organism possesses the faculty of
“remembering” what once has happened to it or what it once has “done,”
so to speak, and profiting by this remembering in the next generation.
The zoologist Pauly indeed has stated this view of the matter in very
distinct and clear terms.
As we soon shall have another occasion to deal with the much-discussed
problem of the “inheritance of acquired characters,” we at present
need only say a few words about the “memory-theory” as a supposed
“explanation” of heredity. Undoubtedly this theory postulates, either
avowedly or by half-unconscious implication, that all the single
processes in individual morphogenesis are the outcome either of
adaptations of the morphological type, which happened to be necessary
in some former generation, or of so-called contingent “variations,” of
some sort or other, which also happened once in the ancestral line.
Such a postulate, of course, is identical with what is generally called
the theory of descent in any of its different forms. This theory is
to occupy us in the next lectures; at present we only analyse the
“memory-theory” as a theory of heredity in itself. In any case, to
regard memory as the leading point in inheritance, at least if it is to
signify what is called memory in any system of psychology, would be to
postulate that either adaptation or contingent “variation” has been the
origin of every morphogenetic process. Indeed, the American physiologist
Jennings did not hesitate to defend such a view most strongly, and many
others seem to be inclined to do the same.
But such an assumption most certainly cannot be true.
It cannot be true, because there are many phenomena in morphogenesis,
notably all the phenomena akin to restitution of form, which occur
in absolute perfection even the very first time they happen. These
processes, for the simple reason of their *primary perfection*, cannot
be due either to “learning” from a single adaptation, or to accidental
variation. We shall afterwards employ a similar kind of argument to
refute certain theories of evolution. It therefore may be of a certain
logical interest to notice that at present, combating the memory-theory
of inheritance, and hereafter, combating certain theories of descent,
we select not “adaptation” or “variation” as the central points to be
refuted, but the assumed *contingency* of both of them.
The word “memory,” therefore, may be applied to the phenomena of
inheritance only in a very figurative meaning, if at all. We do not
wholly deny the possibility of an inheritance of acquired characters, as
will be seen later on, and to such a fact there might perhaps be applied
such a term as “memory” in its real sense, but we simply *know* that
there *is* something in inheritance which has no similarity whatever
to what is called “memory” in any species of psychology. A primary
perfection of processes occurring quite abnormally proves that there is
a “knowing” of something--if we may say so--but does not prove at all
that there is a “remembering.”
THE COMPLEX-EQUIPOTENTIAL SYSTEM AND ITS RÔLE IN INHERITANCE[123]
[123] Driesch, *Organ. Regul.* 1901.
But we thus far have reached only negative results. Is the question
necessarily to remain at this point, which could hardly be said to be
very satisfying; or could we perhaps get better, that is, positive
results about inheritance by a change of our analytic methods? Let us
try to analyse the facts that occur in inheritance instead of beginning
with hypotheses which claim to be complete explanations. Perhaps we
shall gain, if but small, yet certainly fixed results by an analysis
which goes from the facts to the theory and not from the theory to the
facts.
Let the discussions that are to follow be placed upon a basis as broad
as possible.
Our studies of morphogenetic restitution have shown us that besides the
harmonious-equipotential systems another and widely different type of
morphogenetic “systems” (*i.e.* unities consisting of elements equal in
morphogenetic faculty) may also be the basis of restitution processes.
Whilst in the harmonious system the morphogenetic acts performed by
every single element in any actual case are single acts, the totality
of all the single acts together forming the harmonious whole, in the
other type of systems now to be examined, complex acts, that is, acts
which consist of a manifoldness in space and in time, can be performed
by each single element, and actually are performed by one or the other
of them. We therefore have given the title of “complex-equipotential
systems” to the systems in question, as all our denominations are based
on the concept of the prospective morphogenetic potency, that is of the
possible fate of the elements.
The cambium of the Phanerogams may be regarded as the very type of a
complex-equipotential system, promoting restitution of form. It runs
through the whole stem of our trees, in the form of a hollow tube,
placed between the inner and the outer cell-layers of the stem, and
either branch or root may originate from any single one of its cells,
just as circumstances require. We might call the cambium a system of the
“complex” type of course, even if every one of its constituents were
able to form only a root or only a branch by way of restitution. But in
fact one and the same element can form both of these complex-structures;
it depends only on its relative position in the actual part of the stem
isolated for the purposes of experiment, what will be accomplished in
every case. Here we have a state of affairs, which we shall encounter
again when studying regeneration in animals: every element of the system
may be said to contain potencies for the “ideal whole,” though this
ideal whole will never be realised in its proper wholeness.[124]
[124] The “ideal whole” is also proved to exist, if any *given*
“Anlage,” say of a branch, is forced to give origin to a root, as has
really been observed in certain plants. This case, like many other
less extreme cases of what might be called “compensatory heterotypy,”
are best to be understood by the aid of the concept of “prospective
potency.” It is very misleading to speak of a metamorphosis here. I
fully agree with Krašan about this question. See also page 112, note 1,
and my *Organ. Regul.* pp. 77, 78.
But there is no need to recur to the “ideal whole” in many other cases
of adventitious restitution in plants. On isolated leaves of the
well-known begonia, a whole plant, containing all the essential parts,
may arise from any single cell[125] of the epidermis, at least along the
veins, and in some liverworts it has been shown by Vöchting, that almost
every cell of the whole is able to reproduce the plant, as is also the
case in many algae.
[125] Winkler has discovered the important fact, that the adventitious
buds formed upon leaves may originate either from one single cell of
the epidermis or from several cells together; a result that is very
important with respect to the problem of the distribution of “potencies.”
In the animal kingdom it is chiefly and almost solely the phenomena
of regeneration proper which offer typical instances of our systems,
since adventitious restitution, though occurring for instance in the
restitution of the lens of vertebrates from the iris, and though
connected also with the events in regeneration proper,[126] is of but
secondary importance in animal restitution, at least, if compared with
restitution in plants. If we study the regeneration of a leg in the
common newt, we find that it may take place from every section, the
point of amputation being quite at our choice. Without regarding here
the exact order of the regeneration phenomena, which is almost unknown
at present, we in any case can say without any doubt that the line
of consecutive possible cross-sections forms a complex-morphogenetic
system, as every one of them is able to give rise to a complex organ,
viz. the foot and part of the leg. It is an open question whether this
complex system is to be called “equipotential” or not. It indeed seems
to be inequipotential at the first glance, for each single section has
to form a different organogenetic totality, namely, always that specific
totality which had been cut off; but if we assume hypothetically that
the real “Anlage” which is produced immediately by the cells of the
wounded surface is the very same for all of them, and that it is the
actual state of organisation which determines to what result this
Anlage is to lead,[127] we may say that the series of consecutive
cross-sections of a newt’s leg does form a morphogenetic system of the
complex-equipotential type, promoting secondary regulations of form.
[126] The “regeneration” of the brain of annelids for instance is far
better regarded as an adventitious formation than as regeneration
proper: nothing indeed goes on here at the locality of the wound; a new
brain is formed out of the ectoderm at a certain distance from it.
[127] A full “analytical theory of regeneration” has been developed
elsewhere (*Organ. Regul.* p. 44, etc.). I can only mention here that
many different problems have to be studied by such a theory. The
formation of the “Anlage” out of the body and the differentiation of
it into the completely formed results of regeneration are two of them.
The former embraces the question about the potencies not only of the
regenerating body but of the elements of the Anlage also; the latter
has to deal with the specific order of the single acts of regenerative
processes.
Now all these difficulties vanish, if we consider the regeneration of
animals, such for instance as many worms of the annelid class or our
familiar ascidian *Clavellina*, in which regeneration in both directions
is possible. The wound at the posterior end of the one half which
results from the operation forms a posterior body half, the wound at
the anterior end of the other half forms an anterior one. Again, it is
the ideal whole which we meet here: each section of the body indeed may
be said to contain the potencies for the production of the totality,
though actually this totality is always realised by the addition of two
partial organisations. The title of complex-equipotential systems thus
seems to be fully justified as applied to the systems which are the
basis of regeneration: each section of the regenerating body may in fact
produce the same complex whole, or may, if we prefer to say so, at least
prepare the ground for that complex Anlage, out of which the complex
totality is actually to arise, in the same manner.
It often occurs in science, that in rather strange and abnormal
conditions something becomes apparent which might have been found
everywhere, which is lying before our eyes quite obviously. Are
we not in just such a condition at present? In order to study the
complex-equipotential systems, we turn to the phenomena of regeneration
and of restitution in general; we occasionally even introduce hypotheses
to render our materials more convenient for our purposes; and all the
time there is one sort of complex-equipotential system in the body of
every living being, which only needs to be mentioned in order to be
understood as such, and which indeed requires no kind of preliminary
discussion. The system of the propagation cells, in other words the
sexual organ, is the clearest type of a complex-equipotential system
which exists. Take the ovary of our sea-urchin for instance, and there
you have a morphogenetic system every element of which is equally
capable of performing the same complex morphogenetic course--the
production of the whole individual.
Further on we shall deal exclusively with this variety of our systems,
and in doing so we shall be brought back to our problem of heredity. But
it had its uses to place our concept of the complex-equipotential system
upon such a broad basis: we at once gave a large range of validity to
all that is to follow--which, indeed, does not apply to inheritance
alone, though its significance in a theory of heredity may be called its
most important consequence.
THE SECOND PROOF OF LIFE-AUTONOMY. ENTELECHY AT THE BOTTOM OF INHERITANCE
After we had established the concept of the harmonious-equipotential
system in a former chapter, we went on to study the phenomena of the
differentiation of it, and in particular the problem of the localisation
of all differentiations. Our new concept of the complex-equipotential
system is to lead us to an analysis of a different kind: we shall pay
special attention to the origin, to the *genesis* of our complex systems
that show equipotentiality.
If we review the process of ontogenesis, we are able to trace back every
complex system to a very small group of cells, and this small group of
cells again to one single cell. So in plants the cambium may be shown
to have originated in a sort of tissue-rudiment, established at a very
early period, and the ovary may be demonstrated to be the outcome of a
group of but a few cells, constituting the first visible “Anlage” of the
reproductive organs. At the end then, or from another point of view at
the beginning, a single cellular element represents the very primordial
egg-cell.
The whole cambium, there can be no doubt, must be regarded as the result
of a consecutive number of cell-divisions of the one cell from which it
originates. So must it be with the ovary. The primordial egg-cell has
undergone a long line of consecutive divisions; the single eggs are the
last result of them.
We now proceed to some considerations which have a certain
logical similarity to those which inaugurated our analysis of the
differentiation of the harmonious-equipotential systems, though the
facts in question are very different.
Viewed by itself without any kind of prepossessions, as it might
be by any one who faces a new problem with the single postulate of
introducing new natural entities--to use the scholastic phrase--as
little as possible, the development of the single egg might be regarded
as proceeding on the foundation of a very complicated sort of machine,
exhibiting a different kind of construction in the three chief
dimensions of space, as does also the organism which is to be its result.
But could such a theory--irrespective of all the experimental facts
which contradict it--could such a theory stand before the *one* fact,
that there occurs a *genesis* of that complex-equipotential system,
of which our one single egg forms a part? Can you imagine a very
complicated machine, differing in the three dimensions of space, to
be divided hundreds and hundreds of times and in spite of that to
remain always the same whole? You may reply that during the period
of cell-divisions there is still no machine, that the machine is
established only after all the divisions are complete. Good; but what
then constructs this machine in the definitive cells of our systems, say
in the eggs? Another sort of machine perhaps? That could hardly be said
to be of much use. Or that entelechy of which we have spoken? Then you
would recur to our first proof of vitalism and would burden entelechy
with a specific performance, that is with the construction of the
hypothetic machine which you are postulating in every single egg. But of
course you would break the bounds of physics and chemistry even then.
It seems to me that it is more simple, and so to say more natural, not
to recur to our first proof of life-autonomy in order to keep to the
“machine theory” in this new branch of inquiry, but to consider facts as
they offer themselves to analysis.
But then indeed we are entitled to draw an independent second proof of
the autonomy of life from our analysis of the genesis of systems of the
complex-equipotential type. We say it is a mere absurdity to assume that
a complicated machine, typically different in the three dimensions of
space, could be divided many many times, and in spite of that always
be the whole: therefore there cannot exist any sort of machine as the
starting-point and basis of development.
Let us again apply the name entelechy to that which lies at the very
beginning of all individual morphogenesis.
Entelechy thus proves to be also that which may be said to lie at
the very root of inheritance,[128] or at least of the outcome of
inheritance; the individual formation of the next generation is shown
not to be performed by a machine but by a natural agent *per se*.
[128] And, of course, at the root of every new starting of certain
parts of morphogenesis also, as in regeneration and in adventitious
budding; these processes, as we know, being also founded upon
“complex-equipotential systems,” which have had their “genesis.”
THE SIGNIFICANCE OF THE MATERIAL CONTINUITY IN INHERITANCE
But what about the material continuity appearing in inheritance, which
we have said to be almost self-evident, as life is only known to exist
on material bodies? Is there not, in fact, a serious contradiction
in admitting at the same time entelechy on the one side and a sort
of material condition on the other as the basis of all that leads to
and from inheritance? Next summer the relation between matter and our
autonomous agent of life will be studied more fully; at present it must
be enough to state in a more simple and realistic way, what we hold
this relation to be. There is no contradiction at all in stating that
material continuity is the basis of inheritance on the one side, and
entelechy on the other. It would be very inconvenient for us if there
were any: for the material continuity is a mere fact and our entelechy
we hope we have proved to exist also; if now there were any sort of
contradiction in assuming the existence of both of them, of course it
would be fatal to our proof.
Let us try to comprehend what is meant by the statement that entelechy
and something material are at work in inheritance at the same time.
Entelechy has ruled the individual morphogenesis of the generation which
is regarded as being the starting-point for inheritance, and will rule
also the morphogenesis of the generation which is to follow; entelechy
determines the egg to be what it is, and the morphogenesis starting from
this egg to be what it is also. Entelechy, at present, is not much more
for us than a mere word, to signify the autonomous, the irreducible of
all that happens in morphogenesis with respect to *order*, in the one
generation and in the next. But may not the material continuity which
exists in inheritance account perhaps for the material elements *which
are to be ordered*? In such a way, indeed, I hope we shall be able to
reconcile entelechy and the material basis of heredity. May it not be
that there exist some “means” for morphogenesis, which are handed down
from generation to generation, always controlled by entelechy, and which
constitute the real significance of the continuity of matter during
inheritance?
THE EXPERIMENTAL FACTS ABOUT INHERITANCE
Discoveries of the last few years do seem to show that such means
of a material character, though not the foundation of that order of
processes which is inherited, are nevertheless among the most necessary
conditions for the accomplishment of inheritance in general. It is
scarcely necessary to remind you that for very many years all concrete
research on heredity proper--that is, the actual comparison of the
various specific characters in the generations of the grandfather, the
father, and the child--was due to Galton. You may also be aware that in
spite of Galton’s inestimable services it was not till 1900 that one of
the active principles concerned in inheritance was found independently
by de Vries, Correns, and Tschermak, and that this principle happened
to be one that *had* been discovered already, stated with the utmost
clearness and precision by the Augustinian monk, Gregor Mendel,[129] as
early as 1865, though it had been completely forgotten ever since.
[129] New edition in the “Klassiker d. exakt. Wiss.” Leipzig, Engelmann;
see also Bateson, *Mendel’s Principles of Heredity*, Cambridge, 1902.
The so-called “rule of Mendel” is based upon experiments with hybrids,
that is, with the offspring of parents belonging to different species,
or, at least, varieties, but it relates not to the characters of the
generation resulting immediately from hybridisation, the “first”
generation of hybrids, as we shall call it, but to the characters of
that generation which is the result of crossing the hybrids with each
other, provided that this leads to any offspring at all. There are many
cases indeed, both amongst animals and plants, where the offspring of
the hybrids, or in other terms the “second” generation, is found to
consist of individuals of three different types--the mixed[130] type
of the hybrids themselves, and the two pure types of the grandparents.
Whenever the individuals of the “second” generation are separated into
these three different types, hybrids are said to “split.” It is the
fact of this splitting on the one hand, and on the other hand a certain
statement about the numbers of individuals in the three different types
of the “second” generation, that gives its real importance to Mendel’s
rule.
[130] For the sake of simplicity I shall not deal here with those
cases of hybridisation in which one quality is “recessive,” the other
“dominant,” but only allude to the cases, less numerous though they be,
where a real mixture of maternal and paternal qualities occurs.
Before discussing what may follow from Mendel’s discovery for the
theory of heredity, we must lay stress on the fact that there are many
exceptions to his rule. In quite a number of cases the hybrids are of
one or more types, which remain constant: there is no splitting at all
in the second generation. But that does not affect the rule of Mendel in
those cases where it is true. Where there is a “splitting” in the second
generation, there also are the numerical proportions stated by Mendel;
there never are other relations among the numbers of individuals of the
mixed and of the two pure types than those given by his rule. I regard
it as very important that this real meaning of Mendel’s principle should
be most clearly understood.
From the fact of the splitting of hybrids in the second generation most
important consequences may be drawn for the theory of inheritance; the
split individuals, if crossed with each other, always give an offspring
which remains pure; there is no further splitting and no other change
whatever. The germ-cells produced by the split individuals of the second
generation may therefore be said to be “pure,” as pure as were those of
the grandparents. But that is as much as to say that the pureness of
the germ-cells has been preserved in spite of their passing through the
“impure” generation of the hybrids, and from this fact it follows again
that the union of characters in the hybrids must have been such as to
permit pure separation: in fact, the germ-cells produced by Mendelian
hybrids may hypothetically be regarded as being pure themselves.[131]
[131] This hypothesis was first suggested by Sutton and is at present
held by orthodox Mendelians; but probably things are a little more
complicated in reality, as seems to be shown by some facts in the
behaviour of so-called “extracted recessives.” In Morgan’s *Experimental
Zoology*, New York, 1907, a full account of the whole matter is given.
We have not yet considered one feature of all experiments in
hybridisation, which indeed seems to be the most important of all for
the theory of inheritance, if taken together with the fact of the
pureness of the germs. The rule of Mendel always relates to one single
character of the species or varieties concerned in hybridisation, and
if it deals with more than one character, it regards every one of them
separately; indeed, the rule holds for every one of them irrespective
of the others. We cannot study here how this most important fact of
the independence of the single characters of a species with regard to
inheritance leads to the production of new races, by an abnormal mixture
of those characters. We only take advantage of the fact theoretically,
and in doing so, I believe, we can hardly escape the conclusion that
the independence of the single characters in inheritance, taken
together with the pureness of the germ-cells in the most simple form
of hybrids, proves that there occurs in inheritance a sort of handing
over of single and separate morphogenetic agents which relate to the
single morphogenetic characters of the adult. We may use Bateson’s
word “allelomorphs” for these agents, or units, as they may be called,
thereby giving expression to the fact that the single and separate
units, which are handed over in inheritance, correspond to each other in
nearly related species without being the same.
And so we have at least an inkling of what the material continuity of
inheritance is to mean, though, of course, our “single and separate
morphogenetic agents,” or “units” or “allelomorphs” are in themselves
not much more than unknown somethings described by a word; but even then
they are “somethings.”
Besides the researches relating to the rule of Mendel and its
exceptions, founded, that is, upon a study of the “second” generation of
hybrids, there is another important line of research lately inaugurated
by Herbst, which investigates the first generation in hybridisation.
The hybrids themselves are studied with the special purpose of finding
out whether the type of the single hybrid may change according to the
conditions of its development, both outer and inner. The discoveries
thus made may lead some day to a better understanding of the intimate
nature of the “units” concerned in heredity, and perhaps to some
knowledge of the arranging and ruling factor in morphogenesis also.
Starting from the discovery of Vernon, that the hybrids of sea-urchins
are of different types according to the season, Herbst[132] was able
to show that differences among the hybrids with regard to their being
more of the paternal or more of the maternal type, are in part certainly
due to differences in temperature. But there proved to be still another
factor at work, and Herbst has succeeded in discovering this factor by
changing the internal conditions of morphogenesis. Whenever he forced
the eggs of *Sphaerechinus* to enter into the first[133] phase of
artificial parthenogenesis and then fertilised them with the sperm of
*Echinus*, he was able to approximate the offspring almost completely
to the maternal type, whilst under ordinary conditions the hybrids in
question follow the paternal far more than the maternal organisation.
[132] *Arch. Entw. Mech.* 21, 22, and 24, 1906-7; see also Doncaster,
*Phil. Trans. Royal Soc.* London, B. 196, 1903. The influence of
different temperature upon the organisation of the hybrids is not
always quite pure, inasmuch as the paternal and the maternal forms may
themselves be changed by this agent. In spite of that there exists an
influence of the temperature upon the hybrid *as such*, at least with
regard to certain features of its organisation.
[133] Only the nucleus of the egg had entered its first stages of
activity.
What is shown, in the first place, by these discoveries is the
importance of an arranging and ruling factor in spite of all units. The
organism is always one *whole* whether the paternal properties prevail
or the more complicated maternal ones; in other words, all so-called
properties that consist in the *spatial relations of parts* have nothing
to do with “units” or “allelomorphs,” which indeed cannot be more
than necessary means or materials, requiring to be ordered. As to the
character of the morphogenetic single and separate units themselves
Herbst is inclined to regard them as specific chemical substances which
unite correspondingly during nuclear conjugation, forming a sort of
loose chemical compound. It would depend on the constitution of this
compound whether germ-cells of hybrids could become pure or not.
THE RÔLE OF THE NUCLEUS IN INHERITANCE
At the end of our studies on heredity we hardly can avoid saying a
few words about the problem of the localisation of the morphogenetic
units in the germ-cells themselves. Is it in the protoplasm or in the
nucleus that they are placed? You all know that this question was for
a long time regarded as more important than any other, and perhaps
you have already blamed me for not raising it until now. But in my
opinion results gained by the purely analytical method and carefully
established, are always superior to those which are of a merely
descriptive nature and doubtful besides. The famous problem of the part
played by the nucleus in inheritance is both descriptive and doubtful:
it is only, so to say, of factual, not of analytical importance, and
quite insoluble at present.
As for our second proof of vitalism, stating that no kind of machine
inside the germ-cells can possibly be the foundation of their
morphogenesis, it is clear that the protoplasm and the nucleus may both
come into account here on equal terms. If you prefer to say so, it is to
the nucleus and to its division in particular that the second proof of
autonomy relates, while the first, though not over-looking the presence
of nuclei,[134] deals “especially” with the protoplasmic nature of its
“systems.”
[134] The first proof of vitalism, indeed, rests upon the analysis of
the differentiation of an harmonious-equipotential system as a *whole*:
this *whole* cannot be a machine that would relate to differentiation as
a *whole*; the question whether there might be any machines distributed
*in* the whole, in the form of the nuclei is of no importance at all in
this argument. Moreover the pressure experiments (see page 63) prove the
unimportance of such “machines” for the specificity of differentiation,
and the second proof of vitalism shows that the nuclei cannot be
regarded as machines accounting for differentiation in *any* way.
What then can we say, on the basis of actual facts, about the part taken
by the protoplasm and by the nucleus in inheritance, now that we have
learnt from our analytical discussion that both of them cannot be any
kind of morphogenetic machine, but can only be means of morphogenesis?
Let us state our question in the following way: whereabouts in the
germ-cells are those “means” of morphogenesis localised, the existence
of which we infer from the material continuity in the course of
generations in general and from the facts discovered about hybridisation
in particular?
The first of the facts generally said to support the view that the
nucleus of the germ-cells exerts a specified influence upon the
processes of development and inheritance, relates to the proportion
between protoplasm and nuclear material in the egg and in the spermiae.
This proportion is very different in the two sexual products, as we
know, there being an enormous preponderance of the protoplasm in the
egg, of the nucleus in the spermatozoon. This seems to indicate that
the proportion between protoplasm and nucleus is fairly indifferent
for inheritance, as all the facts go to show that inheritance from
the father is as common as inheritance from the mother. It is in the
nucleus, and in the nucleus alone, that any similarity of organisation
exists between the two sexual products, so very different in all other
respects: therefore the nucleus should be the organ of inheritance. The
phenomena of nuclear division, of karyokinesis, which are quite equal in
both sexual cells, are certainly well fitted to support this hypothesis.
There seems indeed to be some truth in this reasoning, but nevertheless
it must remain hypothetical; and it must never be forgotten that
there may be very probably some sort of morphogenetic importance in
protoplasm also. Rauber and afterwards Boveri[135] have tried to prove
experimentally that it is on the nuclear chromatic substance only that
inheritance depends, but the first of these authors failed to get any
results at all, and the latter obtained only ambiguous ones. Godlewski,
on the contrary, has fertilised purely protoplasmic egg-fragments of
the sea-urchin with the sperm of quite another group of Echinoderms,
and obtained in spite of that a few stages of development of the
pure maternal type. This experiment seems to place the morphogenetic
importance of protoplasm beyond all doubt.
[135] Boveri tried to fertilise enucleated fragments of the egg of
*Sphaerechinus* with the sperm of *Echinus*. He failed to get any
results in isolated experiments, but found a few small larvae of the
pure *Echinus* type in large cultures consisting of shaken eggs. But
later experiments on hybridisation in sea-urchins have shown that a full
hybrid of *Echinus* and *Sphaerechinus* may be purely paternal also.
I should prefer not to make any definite statement about our problem at
present. Our actual knowledge of the organisation and metabolism of both
nucleus and protoplasm is so extremely small and may relate to such very
insignificant topics, that any definite decision is impossible. I myself
believe that the nucleus plays an important part in heredity, perhaps
even a greater one than protoplasm, but this is only my belief.[136]
[136] Surely the new results of Herbst, mentioned above, are another
indication of the importance of something in the nucleus. The first
stage in parthenogenesis, which he used in his experiments, is a nuclear
phenomenon.
The discovery of Gruber and others, that Protozoa are only capable of
restitution if they contain at least a fragment of the nucleus, has
also been used occasionally as a proof of the morphogenetic importance
of the nucleus. But might not this absence of restitution where nuclear
material is lacking be understood equally well on the hypothesis of Loeb
and R. S. Lillie that the nucleus is a centre of oxidation in the cell?
Remove the heart from a vertebrate and the animal will not digest any
more; but in spite of that the heart is not the organ of digestion.
And so we lay stress once more upon this point: that the experimental
results of hybridisation and the analytical results obtained by the
discussion of the complex-equipotential systems are of greater value
to the theory of heredity than all speculation about the importance or
unimportance of special constituents of the cell, of whose organisation,
chemistry, and physics, scarcely anything is known at present.[137]
[137] Boveri (*Ergebn. üb. d. Konstitution etc. des Zellkerns*, Jena,
1904; and “Zellen-Studien VI.” *Jen. Zeitschr.* 43, 1907) has made it
highly probable by experiments that the different chromosomes of the
nucleus of the sexual products play a different part in morphogenesis,
though not in the sense of different single representatives of
different single organs. This doctrine, of course, would not alter
the whole problem very much: the chromosomes would only be *means* of
morphogenesis and nothing else, no matter whether they were of equal or
of different formative value. It only is with regard to the problem of
the determination of sex (see page 107, note 3), that the morphogenetic
singularity of *one* certain specific chromosome can be said to be
proved.
VARIATION AND MUTATION
Heredity, it has been said, may be understood as resting upon the fact
that each organism forms its own initial stage again, and that this
initial stage always encounters conditions of the same kind.
If this statement were quite correct, all the individuals of a given
species would be absolutely alike everywhere and for ever. But they
are not alike; and that they are not alike everywhere and for ever is
not merely the only real foundation of the so-called theory of descent
we possess, but also forces us to change a little our definition of
heredity, which now proves to have been only a sort of approximation to
the truth, convenient for analytical discussion.
In the first place, the conditions which surround the initial stages
of morphogenesis are not quite equal in every respect: and indeed
the offspring of a given pair of parents, or better, to exclude all
complications resulting from sexual reproduction, or amphimixis, as
Weismann called it--the offspring of one given parthenogenetic female
are not all equal among themselves. The individuals of each generation
are well known to vary, and it is especially in this country that the
so-called individual or fluctuating variation has been most carefully
studied by statistical methods, Galton and Weldon being the well-known
pioneers in this field.[138] In fact, if we are allowed to assume that
this sort of variation is the outcome of a variation of conditions--in
the most general meaning of the word--we only follow the opinion
which has almost universally been adopted by the biologists[139] that
are working at this branch of the subject. Variation proper is now
generally allowed to be the consequence of variations in nutrition;
the contingencies of the latter result in contingencies of the former,
and the law of contingencies is the same for both, being the most
general law of probability. Of course under such an aspect fluctuating
variation could hardly be called an exception, but rather an addition to
inheritance.
[138] H. M. Vernon, *Variations in Animals and Plants*, London, 1903.
[139] De Vries, *Die Mutationstheorie*, i., 1901; and Klebs, *Jahrb.
wiss. Bot.* 42, 1905.
But there are other restrictions of our definition of heredity. The
initial stage which is formed again by an organism is not always quite
identical in itself with the initial stage of its own parent: Bateson
and de Vries were the first to study in a systematic way these real
exceptions[140] to true inheritance. As you know, de Vries has given
them the name of “mutations.” What is actually known on this subject is
not much at present, but nevertheless is of great theoretical value,
being the only real foundation of all theories of descent, as we shall
see in the next lectures. “Mutations” are known to exist at present only
among some domesticated animals and plants. Nothing of a more general
character can be said about their law or meaning.[141]
[140] They would not be “real exceptions” if Klebs (*Arch. Entw. Mech.*
24, 1907) were right in saying that both variations and mutations owe
their existence to external agents. What is really *proved* by Klebs
is the possibility of changing the *type* of a curve of variation and
of provoking certain discontinuous varieties by external means. See
also Blaringhem (*Comptes rend.* 1905-6, and *Soc. de Biol.* 59, 1905),
and MacDougal (*Rep. Depart. Bot. Res., 5th Year-book Carnegie Inst.*,
Washington, 129).
[141] H. de Vries, *Species and Varieties: their Origin by Mutation*,
London, 1905. A short review of the “mutation-theory” is given by Francé
in *Zeitschrift f. d. Ausbau d. Entwickelungslehre*, i. 1907. It is well
known that Gautier, and, in the first place, Korshinsky, advocated a
similar view previous to the authors named in the text.
CONCLUSIONS FROM THE FIRST MAIN PART OF THESE LECTURES
In finishing our chapter on inheritance, we at the same time have
finished the first main part of our lectures; that part of them which
has been devoted exclusively to the study of the morphogenesis of the
*individual*, including the functioning of the adult individual form.
We now turn to our second part, which is to deal with the problems of
the diversities of individual forms, with morphological systematics. The
end of our chapter on inheritance has already led us to the threshold of
this branch of biological science.
The chief result of the first main part of our lectures has been to
prove that an autonomy of life phenomena exists at least in some
departments of individual morphogenesis, and probably in all of them;
the real starting-point of all morphogenesis cannot be regarded as a
machine, nor can the real process of differentiation, in all cases where
it is based upon systems of the harmonious equipotential type. There
cannot be any sort of machine in the cell from which the individual
originates, because this cell, including both its protoplasm and its
nucleus, has undergone a long series of divisions, all resulting in
equal products, and because a machine cannot be divided and in spite of
that remain what it was. There cannot be, on the other hand, any sort
of machine as the real foundation of the whole of an harmonious system,
including many cells and many nuclei, because the development of this
system goes on normally, even if its parts are rearranged or partly
removed, and because a machine would never remain what it had been in
such cases.
If our analytical discussions have thus led us to establish a typical
kind of vitalism, it follows that we can by no means agree with Wilhelm
Roux in his denomination of the analytical science of the individual
form and form-production as “Entwickelungsmechanik,” “developmental
mechanics,” a title, which, of course, might easily be transformed
into that of “morphogenetic mechanics,” to embrace not only normal
development, but restitution and adaptation too. We feel unable to speak
of “mechanics” where just the contrary of mechanics, in the proper
meaning of the word, has been proved to exist.
Names of course are of comparatively small importance, but they
should never be allowed to be directly misleading, as indeed the term
“Entwickelungsmechanik” has already proved to be. Let us rather say,
therefore, that we have finished with this lecture that part of our
studies in biology which has had to deal with morphogenetic physiology
or physiological morphogenesis.
Once more we repeat, at this resting-point in our discussions, that both
of our proofs of life-autonomy have been based upon a careful analysis
of certain facts about the distribution of morphogenetic potencies in
two classes of morphogenetic systems, and upon nothing else. To recall
only one point, we have not said that regeneration, merely because it
is a kind of restitution of the disturbed whole, compels us to admit
that biological events happen in a specific and elemental manner, but,
indeed, regeneration *does* prove vitalism, because it is founded upon
the existence of certain complex-equipotential systems, the analysis of
the genesis of which leads to the understanding of life-autonomy. This
distinction, in fact, is of the greatest logical importance.