Mind and Knowledge

Chapter 4

Biological Complexity


Complex Hierarchical Constraint is simply a term that refers to any mechanism that gives rise to the hierarchical order through which anything that we can say exists has emerged into existence.  In every case the constraint is adapted to meet the requirements of the emergence even if it means that the constraint itself is complex. Clifford Grobstein, discussing the structure of living systems, began with a general equation developed from Simon's analogy of Chinese boxes.

S=(A,B,C,..,N)R 0

In the above equation, S is a set and A,B,C, through to N are also encompassing sets. R  is whatever defines the set as a level in hierarchical order. In a simple aggregate the properties of A are not changed by the relationship R. This is not true of living systems. Living systems do not form aggregates; they form collectives. He listed two kinds of collectives, The first he called facultative (reversible) collectives where the properties of the elements are changed by being part of the collective, but removed from the collective they revert to their individual status. He used as an example, colonies of bacteria whose members are altered in association but can be dispersed to return to individuals that may form another identical colony.

The second kind of collectives he mentioned were obligate collectives.  These, once formed, may not be dispersed. In a complex multi-cellular organism, special conditions are required to maintain individual cells or individual organs outside the collective relationship. If we examine the emergence of inorganic things we find that it is outside conditions that force the emergence itself.  If we gather the right combinations of subatomic particles in a location with the proper energetic relationships, an atom of a particular element will emerge.  Which element is completely predictable from the properties of the energetic relationships.  Organic compounds represent a higher level of hierarchical constraints, allowing for a greater variety of compounds than inorganic but again the determination of their structure is developed by the natural forces outside the objects. With living organisms the determination of the outcome of any change is formed inside the organism itself.  Grobstein said, "The history of organisms and the history of the whole biotic mass has been one of successive production of higher and higher forms of obligate collectives."   Organic molecules are formed as part of a living organism, and their continued existence depends on progressive replication.  An organism that does not continuously change is not static, it is dead. "Biological order," Grobstein explained, "exists as a number of levels in the living world, but fundamentally it is replicated at molecular levels followed by re-establishment of higher orders through successive transformation of information into collectives at a higher level."

The question that has eluded science since the Greeks is how order is re-established each new generation. In Grobstein's words, "As you know we are now thoroughly convinced that properties of successive generations are continuous, and that each generation begins with some amount of information which needs to be extensively processed before giving rise again to the maximum order of the fully formed adult."

As an example of the mechanisms whereby higher orders are generated out of lower orders, he described the action of protein to enzyme transformation. A protein molecule is a linear array of amino acids on a polypeptide backbone. In water solution, some side groups are hydrophobic and tend to move into the interior while others are hydrophilic and tend to remain on the surface. This causes a three-dimensional folding of the linear molecule according to the information programmed into it by its genetic sequence. This folding creates associations of sulfhydryl groups determined by the three-dimensional folding.  "In each instance of neogenesis," Grobstein said, " the properties that appear during the origin of the new set are not the simple sum of the properties of the components that make up the set." The properties which characterize the set may depend on new relationships that might be established within the set, or with the context in which it functions. Essential to the understanding of neogenesis is an appreciation of the concept of emergence that we have been discussing. "Hierarchical organization in biological systems", Grobstein stated, "thus is characterized by an exquisite array of delicately and intricately interlocked order. Steadily increasing in level and complexity and thereby giving rise neogenetically to emergent properties."

The translation of a two-dimensional linear sequence into an active three-dimensional matrix is essentially a mechanism for decoding specific chunks of genetic memory in terms of the immediate environment. The step from transformation to development, from the decoding of a specific protein molecule to the construction of a multi-cellular organism is a step from transformation to programming. One of the most important discoveries in modern cell theory is that in any given organism, regardless of how complex, a complete set of instructions for creating that particular organism is contained in the nucleus of each and every cell.  A sequence of nucleic acids will specify a particular protein, the sequence of such protein specifications is a program for the development and maintenance of that specific organism. That program itself is a complex system. James Bonner discussed how such a program operates.

We know, for example, that in humans we have two genes for making the two protein chains of hemoglobin, We know that those two genes are turned on for transcription of the messenger RNA's for making hemoglobin in certain body cells, those of the bone marrow, which gives rise to the reticulocytes and thence to the erythrocytes. Also, we know that those same genes do not make the messenger RNA for making hemoglobin in other cells of the adult organism. Clearly the genes for making hemoglobin are turned on in one kind of cell and make their appropriate messenger RNA, but in other kinds of body cells they are turned off and do not make their messenger RNA. We can think of many cases which show that particular elements of the genetic material are turned on only in particular places.

Hierarchical control programs, he said, must have the capability of turning on the right genetic specifiers at the right moment, in the right place, and in the proper sequence. By removing chromatin from a specific cell then transcribing it with RNA polymerase, researchers have determined that in any given cell between one and five percent of the DNA is available for transcribing. Ninety-five to ninety-nine percent is turned off. A class of proteins called histones which are found only in association with DNA of complex cells serve to turn off unwanted chromosomes. They are called repressor molecules. Bonner said that there is a limited number of such molecules and that they are essentially independent of the organism. 

Hormones are a special kind of messenger molecules that travel to specific cells and instruct those cells to turn on certain genes. " When cortisone," Bonner said, " which is a steroid, arrives in the liver, it behaves as though it were saying, 'Liver, turn on the following series of genes, so that the enzymes which those genes describe can be made,'  These are enzymes that have to do with particular metabolic responsibilities of the liver, and these genes become turned on."

There are many such molecules. They operate by turning on appropriate genes that were previously repressed. However, they do not accomplish this alone. When they arrive in a cell they bind with a protein that is capable of combining with only one kind of molecule, and it is this complex that turns on the gene. There are additional mechanisms that must be included in a development program. Consider, for example, that every cell in a multi-cellular organism is to some extent unique and occupies a unique position in the organism. In order for the cell to know just what it is supposed to be doing at any particular point in the lifetime of the organism it must perform tests.

Bonner went on to suggest that one way we can perform such a test is by having certain genes produce a volatile substance. Obviously the cell that is on the outside will have a low concentration of the volatile substance while one on the inside would have a high concentration. This low concentration might not turn on the genes for making the cell grow into a bud, while in a high concentration it could be the molecule that binds with the messenger RNA to turn on those genes that are responsible for the initiation of the bud pathway. As Bonner put it, "This is the concept we refer to as the development testthe hierarchical concept that a growing cell in a developing organism is continuously performing tests of its environment."

Every cell in every organism must have a set of tests that will tell it where it is in the organism, and at what stage of development or maturity the organism is. Even in a simple organism it is quite evident that this will require a complex program, and thus it will be hierarchical. In the development of an organism, first there must be a determination of which pathway is to be followed by the cell. "We do not know how many pathways there are. Bonner explained,"I sat down and tried to write them out for pea plants. I immediately wrote out about 30 different developmental pathways that must necessarily be involved in the development of a plant, and I presume that in the development of a higher animal such as ourselves, there must be even more pathways. So we turn on the set of genes which generates this pathway. That is hierarchical level number 1, or the highest development control level."  The second level in the hierarchy, Bonner said, is the turning on of genes that are responsible for sensing the concentrations of particular kinds of molecules in the environment, and the third is the turning on of genes that code for the appropriate enzymes according to the information contained in the environment. In other words, in order to have a development program capable of the creation of complex organisms it must be hierarchical.

Simon showed us how complex hierarchical structure increased the efficiency of a process of manufacturing watches, but two of the most important results of complex hierarchical structure are simplicity and freedom. Simplicity, for example, H. H. Pattee said, turns out to be very complex. "We really do not mean just 'simplicity,'" as he stated it, "The simplification that results from the hierarchical constraints of an organization must be balanced by how well it functions." In the analytical approach two basic problems must be overcome. Pattee explained first that hierarchical controls both limit and give more freedom at the same time. "The constraints of the genetic code on ordinary chemistry make possible the diversity of living forms. At the next level, the additional constraints of genetic repressors make possible the integrated development of functional organs and multicellular individuals. At the highest levels of control we know that legal constraints are necessary to establish a free society, and constraints of spelling and syntax are prerequisites for free expression of thought.

The second problem about constraints is that they always appear arbitrary to a large extent. As far as we can see, the same type of life could exist with a number of different genetic codesthat is, with different assignments of nucleic acid codons to amino acids. Molecules that perform the function of messengers, such as hormones or activator molecules, appear to have only arbitrary relation to what they control. Other hierarchical rules are more obviously conventions. We know we can drive on either the left or right side of the road as long as there is collective agreement, just as we know we can give the same instructions in many different languages using different alphabets. In other words, hierarchical constraints or rules are embodied in structures that are to some extent "frozen accidents."

Searching for a physical basis for the origin of hierarchical control programs is essentially a search for the origin of life, which Pattee calls, "...The origin of those control constraints that free living matter to evolve along innumerable pathways that non-living matter, following the same detailed laws of motion, cannot follow. In other words, although we recognize structural hierarchies in both living and non-living matter, it is the hierarchical control program that is the distinguishing characteristic of life."

Considering the origin and development of structural hierarchies, we have number hierarchiesthat is crystals made up of stable atoms, organisms made up of cells with high autonomous stability. We have hierarchies of dynamic time scales, short time associated with small structures and strong forces, and long times associated with large structures and weak forces. We can often write dynamical equations for any single level by approximating that one particle is typical of the collection, that fast motion on lower levels are averaged out and that slow motions on higher levels are constant.

This is what Simon called near-decomposability. However well this might operate in analyzing structural hierarchies, Pattee tells us that hierarchical control systems are not that simple:

In a control hierarchy the upper level exerts a specific, dynamic constraint on the details of the motion at lower level, so that the fast dynamics of the lower level cannot simply be averaged out. The collection of subunits that forms the upper level in a structural hierarchy now also acts as a constraint on the motion of selected individual subunits. This amounts to a feedback path between levels. Therefore the physical behavior of a control hierarchy must take into account at least two levels at a time, and what is worse, the one particle approximation fails because the constrained subunits are atypical.

As described by Bonner, cells do not simply aggregate as molecules do to form crystals. Chemical messages from the collection of cells constrain the action of the cell according to the genetic control program. In the same way, while we live according to certain patterns determined by our personal lifestyle, society constrains us to live according to some authority; however we define that authority. Another important point is that there is nothing special about the molecules, or, for that matter, the men who provide that constraint. Pattee also said that the major question is, "How do structures that have only common physical properties achieve special functions in a collection?"

Pattee saw that the problem of understanding hierarchical control arises to a great extent from our classical acceptance of the relationship between structure and function. In his words, "Therefore most biologists today hold strongly to the strategy of looking at the molecular structure for the answers to the question of 'How it works'." This, he said, is analogous to a mathematician trying to deduce the nature of computation from the ways computer hardware is wired together. "The problem," as he put it, "is precisely at the interface level between the detail of the structure and the abstraction of the function." It is at this point that he explained that function or control can only arise through "selective loss of detail."

To understand this, Pattee said that we require a clear realization of what he means when he uses the term "hierarchical control." For example, given a solution of saltwater, the sodium and chlorine atoms are free to move about in three dimensions, they have three translational degrees of freedom. After some time has passed, some may have gathered to form a crystal. Those ions that now land on the surface of that crystal have fewer degrees of freedom. It forms a collective constraint on the individual ions. This does not mean it is a hierarchical control program because the constraint leads to a fixed crystalline structure.

In the case of screw-dislocation, there are imperfections in the crystal growth. This constraint, while preserving its screw structure, speeds up the binding of ions by an enormous factor. Thus it provides a more active control process. Yet, eventually it still results in a fixed rigid structure. In order to arrive at a control system that approximates those found in living systems, we need a set of constraints that hold between certain degrees of freedom but do not result in rigid bodies. More than that, because a balloon constrains the gas inside it without freezing into a rigid body, it results in a boundary condition, not a hierarchical control.

What we need to find, then, is a clearer description of the degree of constraint that gives rise to a control hierarchy. We can state two conditions that must be satisfied. First, an effective control event cannot be simply a passive spatial constraint, but must actively change the rate of one particular event, reaction, or trajectory relative to the unconstrained rates. This condition is fulfilled by most devices that we normally associate with existing control systemsfor example, switches and catalysts. Second, the operation of the constraint must be repeatable without leading to the freezing up of the system. Another way to say this is that control constraints must limit the trajectories of the system in a regular way without a corresponding freezing out of its configurational degrees of freedom.

The term "constraint" normally means a forcible limitation of freedom. The force of gravity limits the freedom of a falling body but it leaves the body no freedom at all. We need a concept of constraint that acts to increase freedom. This is where the concept of a hierarchical constraint plays a significant part. The law of motion relates the detailed trajectory or state of the system to dynamical time. In a hierarchical constraint, the language is about a situation in which the dynamic detail has been purposely ignored.

One of the fundamentals of hierarchical control programs is selective neglect of certain details, In Bonner's description of neogenesis, he brought up the concept of the "development test." It is the purpose of these tests to turn on specific genes and ignore the rest. Here is the second point that Pattee makes: It is not just a selective loss of detail that gives rise to hierarchical control programs but the optimum loss of detail. This implies that if there is a point in the gradient of detail that will cause the system to operate more efficiently, then normal evolutionary forces will tend to move the system toward that point. Constraints that are too tight result in rigid bodies; constraints that are too loose result in boundary conditions that have no repeatable effect on the system. In his words, "Hierarchical controls arise from a degree of internal constraint that is independent of  selected details of' the dynamical behavior of its elements."

Hierarchical controls arise from a collection of elements but act on individuals of that collection. Pattee called this "statistical closure", or in his own words, "... a collection of elements that is established and that persists largely because of the rates of their combination." He also said that, "This in turn implies a population dynamics for the elements and therefore a real-time dependence. Furthermore, the rates of specific combinations of elements must be controlled by collections of the elements of the closed set."

"An example of statistical closure would be the well-known principle of evolution that natural selection does not operate deterministically on individuals, but statistically on the breeding population. The effect of natural selection, however, must be recorded in the hereditary memory of the individual organism. Therefore, selection is a collective restraint that limits the detailed structure of the individual elements of the collection and establishes a statistically closed set, which we call the breeding population."

We cannot understand the nature of biological hierarchies simply by a finer look at molecular structure, by the solution of detailed equations of motion, nor by the application of non-equilibrium statistical thermodynamics. A physical theory of hierarchic control would deal with the interface between levels. Bonner said,"It would explain how complex collections of interacting elements spontaneously separate out persistent and coherent descriptions and functions under the constraints that relate them. The origin of life is the lowest level of this process where genotypes (descriptions) and phenotypes (functions) are generated by the constraints of a genetic code. As yet, such a physical theory does not exist."

In our examination of complexity in living things we found a new level of complexity in Complex Hierarchical Constraint.  We also found hierarchical control programs.  These are organized out of the same physical laws that operate on simpler objects.  It is a higher level of complexity in the same way that the basic computer language is a higher level of complexity in computer programming from machine language.  Just as higher levels of computer languages make it possible for us to increase the variety of things we can do with computers, so this higher level of Complex Hierarchical Constraint allows nature to increase the variety of things in the universe.  These ideas have barely been studied and I would venture to say that the variety of higher level structures of constraint in the universe will turn out to exceed anything that we can imagine at this early stage.  However the next important step I would like to discuss is the stage we call "Man".