The Act of Creation (58 page)

 

 

 

Structure and Function

 

 

I shall take as my starting point two complementary aspects of the
evolutionary process: differentiation of structure and integration
of function. Regardless of what causal theory one adopts to account
for the evolution of higher forms of life, the
means
by which
progress is achieved is the development of more complex and specialized
bodily structures and of more elaborate ways of coordinating their
function. These are two
aspects
of a unitary process, not
two processes. In fact both terms, 'structure' and 'function', are
abstractions derived from imaginary cross-sections along the spatial or
temporal axis of indivisible spatio-temporal events.

 

 

Structure is a static concept of a process frozen in the specious present.
'Anatomy abstracts from time. It studies the organism conceived "at an
instant".' [1] A kidney, or a single kidney cell, which has stopped
functioning no longer has the same spatial structure as before; and while
it is still functioning its structure is changing at every moment. All
living matter continuously alters its shape and composition; it can be
said to preserve its identity only if both structure and function are
taken into consideration. Vice versa, function detached from structure
is the grin detached from the cat. Physiological processes, unlike
mechanical automata, are 'open systems'; Ostwald compared them to the
flame of a gas-burner. The flame is a relatively stable phenomenon;
but how is one to distinguish between its structure and function,
between combustible and combustion?

 

 

Most of the time it is both convenient and necessary for the biologist
and physician to forget that when he is speaking of 'structure' and
'function' he is using 'dirty concepts' -- otherwise his work would come
to a standstill. However, we shall soon come across problems where the
tacit implications of both terms will become relevant.

 

 

A second catch is the semantic ambiguity of the word 'function'. It can
either mean the role or part which my liver
ought
to play to keep
me in good health, or it can refer with heartless matter-of-factness to
what is in fact
happening
in my liver, i.e. not to its function
in the first sense but to its actual 'functioning'. In the first case,
the organ is considered as
part
of the organism; in the second
case it is treated, prima facie, as an independent whole. Whenever a
distinction is indicated, I shall use the word 'function' in the first
sense, and 'functioning' in the second.

 

 

 

The complementary aspects of structural differentiation and functional
integration are reflected at every step in the process of morphogenesis.

 

 

The giant molecules of DNA (dioxyribonucleic acid) in the chromosomes
of the fertilized egg are said to represent the blue-print of the
future organism. Let us consider for a moment this first code which
we meet at the base of the hierarchy. It is a 'code' in the twofold
meaning in which I have used that term: a canon of rules for making
an organism, represented in a 'coded', compressed language. The way in
which the coding is done deserves some attention. Each DNA molecule is
supposed to be capable of storing something of the order of 10^10 bits of
information. [2] According to the Watson-Crick model, the molecule has
the shape of a ladder twisted into a double helix. The two sides of the
ladder consist of uniform, linear chains of sugar groups alternating with
phosphate links. The rungs of the ladder are pairs of nitrogenous bases
attached on each side to the sugar groups in the double helix. There
are four of these bases: adenine, guanine, cytosine, and thymine, or
A, G, C, T for short. A is always paired with T, and G always with C,
so that the two sides of the ladder are complementary. The sequence of
bases as read down along one side of the ladder is the genetic code,
written in the four-letter alphabet, 'A', 'G', 'C', 'T'. Here, then,
floating in the nuclear sap, is the code which governs the skill of
creating a six-foot drum major with a slight squint and dimpled cheeks,
out of an egg with a diameter of a few microns.

 

 

The code's remarkably complex activities are set off by a relatively
simple signal: the impact of the fertilizing agent. The principle involved
must indeed be relatively simple, because in virtually all main groups
of animals, including rabbits and sheep, normal development of the egg
can be induced by stimulation with non-specific, physical, or chemical
agents: heat or cold, salinity, ultra-violet rays, galvanic currents, or
puncture with a fine needle. Though it may be hurtful to the male's pride,
his seed seems to be a dispensable commodity. Its primary function is
to trigger off the egg; but -- with frogs at least -- a platinum needle
will do just as well.*
The main task of the growing cell is the manufacture of proteins which
constitute the basic stuffs of the body, and of protein-enzymes, which
control all its biochemical activities. The growing cell is primarily
a protein-producing factory, or rather a group of specialized plants,
each engaged in synthesizing one variety at a time among the thousands of
different types of protein-molecules. The order and quantity in which each
substance is produced is regulated by the genetic code. The key-substances
are the enzymes, which can be regarded as structural embodiments of
the genetic instructions coded in the DNA chains. Each discrete set of
instructions -- a code-word composed of several hundred code-letters --
contains the recipe, as it were, for a specific enzyme. It is usual to
call these sets of instructions 'genes' (although the meaning of this
traditional term has become somewhat blurred and some geneticists prefer
more non-committal words). Each code-word is composed of sub-wholes:
three-letter syllables like CTA, AAG, etc. Each of these sub-units in the
code-sequence is capable of 'recognizing' and transporting one particular
kind of sub-unit which goes into the making of proteins. These sub-units
or 'building-blocks' are the amino adds; there are twenty common varieties
of them. A protein usually contains all or most of the twenty varieties
of amino-acid units, strung together into a chain of two hundred or more
in a specific sequence. The number of permutations of twenty units in a
sequence of several hundred links is of course enormous, and accounts for
the impressive variety of proteins and protein-enzymes which go into the
making of our all-too-solid flesh. Thus the main process in morphogenesis
seems to consist in transcribing the implicit, 'functional' four-letter
alphabet of the code into the explicit 'structural' twenty-letter alphabet
of proteins.
The details of the process are only beginning to be known at the time
of writing; and progress has become so accelerated in this particular
field that by the time these pages appear in print much in them will
be outdated. Broadly speaking, we know at present of two kinds of
instruction-carriers between the genes and the protein-plants of the
cell. The first is 'messenger RNA'. The chemical structure of RNA --
ribonuclcic acid -- is closely related to that of DNA. The DNA chain
apparently manufactures 'messenger RNA' chains by the same process of
base-paring by which it replicates itself. Each messenger is supposed
to contain the 'recipe' of one specific enzyme, and to carry it to the
protein-plant, the ribosome. A second type of messenger is 'transfer
RNA'. Each variety of it is a much shorter chain, supposed to represent
a triplet of code-letters corresponding to a particular variety of amino
adds. When a transfer RNA unit meets an amino unit of the proper type in
the proper condition, it will attach itself to the unit like a sort of
locomotive, drag it to the ribosome plant, and shunt it into its proper
place in the nascent protein chain, according to the instructions of
its bigger colleague, the 'messenger RNA'.
This, in broad outlines, is the picture to date -- in the year after
the Crick-Watson-Wilkins team received the Nobel prize for 'breaking the
genetic code'. It is to a large extent derived from work on the genetics
of micro-organisms such as the colon bacillus, and there are reasons
to believe that something essential is still missing from the picture.*
But we need not be concerned with these niceties. What matters is that
we find, literally
ab ovo
, fixed, invariant codes in control of the
variable cell matrix. The order in which the various sub-codes -- the
genes -- become active and engage in producing their specific varieties
of messenger RNA is supposed to depend on the pre-set activities of
'operators' and 'repressors' in the chromosomes, and perhaps on some
additional biological clocks. But it must also depend to some extent on
feedback signals from the cytoplasm, including signals from neighbouring
tissues which reach the cell through its sensitive membranes. Finally,
recent experiments by Hyden [2a] have shown that in the nerve-cells of
the mature organism experiences retained in learning lead to more or
less lasting alterations in the chemical composition of the cell's RNA
content: a fact of great significance for the problem of memory.
The Cell-Matrix
The growing cell illustrates the relativity, or complementary nature,
of such terms as part and whole, or structure and function. 'What are
called structures are slow processes of long duration, functions are
quick processes of short duration. If we say that a function such as
the contraction of a muscle is performed by a structure, it means that
a quick and short process-wave is superimposed on a long-lasting and
slowly running wave' (Bertalanffy). [3]
The same considerations apply to the relations between the genetic
code and the cell-matrix. The latter is of course a very complex
structure, equipped with an animal and a vegetal pole, with chemical and
morphogenetic gradients, and with a variety of organelles -- these, in
their ensemble, are the members of the matrix. Each member is a sub-whole
governed by its sub-code which can be turned on and off by orders 'from
above', but once triggered into action follows its autonomous functional
pattern. The
centrosomes
and
kinetosomes
, for instance,
are organelles of apparently similar structure but vastly different
functions. Both possess the privilege of self-replication when the cell
divides; both have a cylindrical shape and are made up, it seems, of
eleven fibres -- two in the centre, nine outside. But these deceptively
simple structures revealed by the electron-microscope are complete
biochemical machines in miniature. The kinetosomes are attached to the
cilia or flagella of motile cells and trigger off their activities. The
centrosomes provide the poles of the spindle apparatus, which effects
cell division; they establish connections with the chromosomes in the
distant nucleus, tear the pairs of duplicated chromosomes apart as it
were, and direct them towards their new locations in the centres of the
two nascent daughter cells.
To take another example, let us cast a quick glance at the most glorious
of organelles, the mitochondria. There are fifty to five thousand of
them according to the type of cell and (together with the chloroplasts
of green-leafed plant-cells) they are 'the power plants of all life
on earth'. As a physicist has said, waxing lyrical on a biological
peccadillo, they 'feed on negative entropy and drink orderliness from
the environment'. [4] The chloroplasts do it by photosynthesis,
the mitochondria by extracting a very special form of energy from
the chemical bonds in glucose, fat, and proteins. The end product is
ATP -- adenosine-triphosphate -- the universal carrier used by the
organism to supply the energy needed for the contraction of muscles,
the transmission of nerve impulses, the manufacture of proteins, and
so on. The synthesizing of ATP is carried out in three main stages
(glycolysis, Krebs cycle oxidation, and 'respiration'*) involving about
fifty different successive reactions, each of them catalyzed by a specific
enzyme system. A single mitochondrion may possess up to forty thousand
of such enzyme systems; their assemblies are arranged in the membrane
of the organelle in patterns which have been described as 'wiring
diagrams'. They represent the sub-codes which govern the operations of
the energy plant. It also has a complex feedback system: in the presence
of an excess of ATP, for instance, the organelle will contract.
Even this very sketchy outline indicates the hierarchic organization
of the living cell - -once considered the ultimate 'atom' of life. The
genetic code is blue-printed in the chromosomes; but the chromosomes
do not deal directly with the sub-matrices on lower levels of the
hierarchy. They do not interfere with the stepwise operations of breaking
down glucose into phosphoglycerate, into lactate, into pyruvate, into
citrate, and so forth; these operations, just as those of the spindle
apparatus of the centrosomes, are governed by their own sub-codes. Each
organelle is a highly integrated structure and enjoys a considerable
amount of functional autonomy. Its operations are switched on or off
by signals from the higher echelons; but these signals are addressed,
as it were, to the code which governs the action-pattern of the whole
organelle, and not to its subordinate parts. Generally speaking, we shall
see that
a matrix on any level of the hierarchy is represented on the
next-higher level by its code
. Or, to put it the other way round:
the members of a matrix are sub-matrices which respond as functional
units to signals activating their codes.
Nucleus and Cytoplasm
The fertilized egg contains the total pattern of the unborn individual.
This privileged position of a single cell representing the whole is of
short duration: after the first few cleavages, the daughter cells begin
to differentiate; they lose their potential capacity of reconstructing the
whole individual, and are reduced to being parts of the growing embryo.
The process involves both the nucleus and the cytoplasm, but in different
ways. The characteristics of different types of cells, tissues, organs,
are essentially the characteristics of their cytoplastic structure,
which vary from type to type. The nuclei which (jointly with the cell's
environment) determine that structure also differ according to cell-type,
but in a subtler, more 'functional' than 'structural' way. It is generally
assumed that each cell in the mature organism inherits a complete set of
the genetic blue-print in the DNA chains of its chromosomes; but only a
fraction of the set remains active -- i.e. those genes which govern the
cell's specialized functions; the remainder is permanently 'switched
off'. As mentioned before, the activity of the enzyme-producing genes
is supposed to be controlled by 'operators' and 'repressors' built
into the chromosomes; and these regulators in turn are controlled by
feedback from the cytoplastic environment. [5] Thus the changes in the
nucleus could be described as
functional specialization
: only
certain sub-codes -- fractions of the complete code -- remain operative;
whereas the changes in the cytoplasm of successive generations amount
to
structural individuation
.