Morphogenesis the mystery of pattern formation

Among the many scientific puzzles posed by living organisms, perhaps the toughest concerns the origin of form. Put simply, the problem is this. How is a disorganized collection of molecules assembled into a coherent whole that constitutes a living organism, with all the right bits in the right places? The creation of biological forms is known as morphogenesis, and despite decades of study it is a subject still shrouded in mystery.

The enigma is at its most striking in the seemingly miraculous development of the embryo from a single fertilized cell into a more or less independent living entity of fantastic complexity, in which many cells have become specialized to form parts of nerves, liver, bone, etc. It is a process that is somehow supervised to an astonishing level of detail and accuracy in both space and time.

In studying the development of the embryo it is hard to resist the impression that there exists somewhere a blueprint, or plan of assembly, carrying the instructions needed to achieve the finished form. In some as yet poorly understood way, the growth of the organism is tightly constrained to conform to this plan. There is thus a strong element of teleol ogy involved. It seems as if the growing organism is being directed towards its final state by some sort of global supervising agency. This sense of destiny has led biologists to use the term fate map to describe the seemingly planned unfolding of the developing embryo.

Morphogenesis is all the more remarkable for its robustness. The developing embryos of some species can be mutilated in their early stages without affecting the end product. The ability of embryos to rearrange their growth patterns to accommodate this mutilation is called regulation. Regulation can involve new cells replacing removed ones, or cells that have been repositioned finding their way back to their 'correct' locations. It was experiments of this sort that led Driesch to reject any hope of a mechanistic explanation and to opt instead for his vitalist theory.

Although mutilation of the developing organism is often irreversible after a certain stage of cell specialization, there are organisms that can repair damage even in their adult form. Flatworms, for example, when chopped up, develop into several complete worms. Salamanders can regenerate an entire new limb if one is removed. Most bizarre of all is the hydra, a simple creature consisting of a trunk crowned by tentacles. If a fully developed hydra is minced into pieces and left, it will reassemble itself in its entirety!

If there is a blueprint, the information must be stored somewhere, and the obvious place is in the DNA of the original fertilized egg, known to be the repository of genetic information. This implies that the 'plan' is molecular in nature. The problem is then to understand how the spatial arrangement of something many centimetres in size can be organized from the molecular level. Consider, for example, the phenomenon of cell differentiation. How do some cells 'know' they have to become blood cells, while others must become part of the gut, or backbone? Then there is the problem of spatial positioning. How does a given cell know where it is located in relation to other parts of the organism, so that it can 'turn into' the appropriate type of cell for the finished product?

Related to these difficulties is the fact that although different parts of the organism develop differently, they all contain the same DNA. If every molecule of DNA possesses the same global plan for the whole organism, how is it that different cells implement different parts of that plan? Is there, perhaps, a 'metaplan' to tell each cell which part of the plan to implement? If so, where is the metaplan located? In the DNA? But this is surely to fall into an infinite regress.

At present biologists are tackling these puzzles by concentrating their research on the theory of gene switching. The idea is that certain genes within the DNA strand are responsible for certain developmental tasks. Normally these genes lie dormant, but at the appropriate moment they are somehow 'switched on' and begin their regulatory functions. The sequencing of gene switching is therefore most important. When it goes wrong the organism may turn into a monster, with anatomical features appearing in the wrong places. Experiments with fruit flies have produced many such monstrosities. This research has led to the identification of a collection of master genes called the homeobox, which seems to be present in other organisms too, including man. Its ubiquity suggests it plays a key role in controlling other genes that regulate cell differentiation.

Exciting though these advances are, they really concern only the mechanism of morphogenesis. They fail to address the deeper mystery of how that mechanism is made to conform with a global plan. The real challenge is to demonstrate how localized interactions can exercise global control. It is very hard to see how this can ever be explained in mechanistic terms at the molecular level.

What help can we gain from studying other examples of the growth of form in nature?

In the previous sections we have seen how many physical and chemical systems involving local interactions can nevertheless display spontaneous self-organization, producing new and more complex forms and patterns of activity. It is tempting to believe that these processes provide the basis for biological morphogenesis. It is certainly true that, generally speaking, nonlinear feedback systems, open to their environment and driven far from equilibrium, will become unstable and undergo spontaneous transitions to states with long-range order, i.e. display global organization.

In the case of the embryo, the initial collection of cells forms a homogeneous mass, but as the embryo develops this spatial symmetry is broken again and again, forming an incredibly intricate pattern. It is possible to imagine that each successive symmetry breaking is a bifurcation process, resulting from some sort of chemical instability of the sort discussed in Chapter 6. This approach has been developed in much detail by the French mathematician René Thom using his famous theory of catastrophes. (Catastrophe theory is a branch of topology which addresses discontinuous changes in natural phenomena, and classifies them into distinct types.)

There is, however, a deep problem of principle involved in comparing biological morphogenesis with the growth of structure in simple chemical systems. The global organization in, say, convection cells is of a fundamen tally different character from the biological case, because it is spontaneous. It happens in spite of the fact that there is no 'global plan' or 'fate map' for these systems. The convection cells do not form according to a blueprint encoded in the fluid molecules. In fact, the convective instability is unpredictable and uncontrollable in its detailed form. Moreover, such control as there may be has to be exercised through the manipulation of boundary conditions, i.e. it is irreducibly global and holistic in nature.

By contrast, the essential feature of biological organization is that the long-range order of an organism is far from being spontaneous and unpredictable. Given the structure of the DNA, the final form is determined to an astonishing level of detail and accuracy. And whereas a phenomenon such as convective instability is exceedingly sensitive to random microscopic fluctuations, biological morphogenesis is, as we have seen, surprisingly robust.

Somehow the microscopic one-dimensional strand of genetic information has to exercise a coordinating influence, both spatial and temporal, over the collective activity of billions of cells spread across what is, size for size, a vast region of three-dimensional space. Identifying physical processes, such as bifurcation instabilities, that allow physical structures to undergo large abrupt changes in form are undoubtedly relevant to the mechanism of morphogenesis. However, they leave open the problem of how such changes can be controlled by an arrangement of microscopic particles, especially as this control is of a non-local character involving boundary conditions. It is the relationship between the locally stored information and the global, holistic manipulation necessary to produce the relevant patterns which lies at the heart of the 'miracle' of morphogenesis.

In the face of these difficulties, some biologists have questioned whether the traditional mechanistic reductionist approach can ever be successful, based as it is on the particle concept, borrowed from physics. As remarked earlier, physicists no longer regard particles as primary objects anyway. This role is reserved for fields. So far the field concept has made little impact on biology. Nevertheless, the idea that fields of some sort might be at work in morphogenesis is taken seriously. These 'morpho-genetic fields' have been variously identified as chemical concentration fields, electric fields or even fields unknown to present physics.

The activity of fields could help explain biological forms because fields, unlike particles, are extended entities. They are thus better suited to accounting for long-range or global features. However, there still remains the central problem of how the genetic information containing the global plan, which supposedly resides in particle form in the DNA, communicates itself to the fields and manages to impose upon them the requisite pattern. In physics, field patterns are imposed by boundary conditions, i.e. global, holistic control.

There is a further problem about the field concept in morphogenesis. As each cell of a given organism contains the same DNA, it is hard to see how the coupling between a field and a DNA molecule differs from one molecule to another, as it must if they are to develop differently. If the fields tell the DNA molecules where they are located in the pattern, and the DNA molecules tell the fields what pattern to adopt, nothing is explained because the argument is circular.

A possible escape is to suppose that somehow the global plan is stored in the fields themselves, and that the DNA acts as a receiver rather than a source of genetic information. This radical possibility has been explored in detail by biologist Rupert Sheldrake, whose controversial ideas I shall touch upon at the end of Chapter 11.

A survey of morphogenesis thus reveals an unsatisfactory picture. There seem to be fundamental problems of principle in accounting for biological forms in terms of reductionistic physics. The scientist can clearly see organizing factors at work in, for example, the development of the embryo, but has little or no idea of how these organizing factors relate to known physics.

In many ways the development of the embryo embodies the central mystery of all biology, which is how totally new structures and qualities can emerge in the progression from inanimate to animate. The problem is present in the collective sense in the biosphere as a whole. This brings us to the subjects of evolution and the origin of life.

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