The shape of things to come

Reader Wayne Fair kindly sent me a link to this overview article on morphogenetic fields, which has nothing (directly, at least) to do with Rupert Sheldrake or telepathy, but which does address an important and under-investigated subject. The author of this review article, Michael Levin, is particularly interested in the highly practical goal of organ regeneration after trauma or surgery, and the theoretical basis of form is closely tied into equally important medical issues such as the causes of cancer.

The wonders of genomic research (and, dare I say it, the huge emphasis on understanding evolution as genetics) tends to divert us from the deep mystery of form, which genetics does very little to address, and which seems, therefore, to be seldom considered in public discussion. As the abstract says:

Molecular cell biology and genetics have made great strides in understanding the mechanisms that regulate cell function. However, generalized rational control of shape is still largely beyond our current capabilities. Significant instructive signals function at long range to provide positional information and other cues to regulate organism-wide systems properties like anatomical polarity and size control. Is complex morphogenesis best understood as the emergent property of local cell interactions, or as the outcome of a computational process that is guided by a physically-encoded map or template of the final goal state?

The background to this is the truth that genes do not make new organisms – cells do, or perhaps, even organisms do – and they contain not only genes but a host of other processes and codes that are involved in form. In classic Evo-Devo, as Levin points out, the role of chemical gradients leading to differential genetic expression gives a crude understanding of how, for example, vertebrate segments develop, or limbs differentiate into digits. To get a basic idea of this, Sean B Carroll’s celebrated Endless Forms Most Beautiful is essential reading, though the book somewhat gives the impression that the processes are done and dusted, whereas even now, thirteen years after that book, they are “seen through a glass, darkly.”

What I find most fascinating about this fairly long, and detailed, paper is how it deals head on with some anomalous aspects of this mysterious business of development. The classic Evo-Devo approach is based, essentially, round emergent phenomena. Hence in the example of chemical gradients above, one would not predict in advance that simple local variations in chemical concentrations would have the ability to dictate form.

Emergent phenomena, then, are unpredictable local effects, in which relatively simple laws produce results you wouldn’t anticipate at larger scales. One familiar emergent phenomenon is the way atoms of metals come to “pool” their electrons to give metals their characteristic properties. In biology, another is the way that a few simple reflexes in individual animals will result in the global organisation of a murmuration of starlings, a swarm of bees or a shoal of herring.

Such emergent processes might be hard to understand (and perhaps in themselves indicative of inscrutable divine wisdom), but generally accord with methodological naturalism’s essentially bottom-up approach. But early in the paper, Levin drops a hint that such mechanisms may be far from adequate as explanations of form:

During later life, multicellular creatures must maintain their pattern – an active process of morphostasis that works to maintain the whole while individual tissues age or are removed by traumatic injury.

An extreme, well-known, example of this is the ability of salamanders to regenerate considerable portions of their anatomy: “eyes, limbs, lower jaws, hearts, and portions of the brain.” Incidentally, from another source:

…a recent study shows that two closely related species [of salamander] use different molecular strategies to regenerate their lost limbs.

Think, for a moment, about what that last fact implies about the evolution of the ability. It’s one thing to envisage a multi-potential zygote, as it reproduces, developing chemical gradients to which individual genes respond differentially, in some kind of evolutionarily programmed manufacturing flow-path, so that, presto changeo, it becomes a frog rather than a ball of undifferentiated zygotic cells.

But the situation is entirely different if your complete, differentiated, animal is capabable of reassigning cells to different cell lines and governing their reproduction and migration to the extent that, starting from a damaged state, the organism can regain its original shape and function. The same kind of plasticity is shown in brain damage, where regions of the brain are reassigned to new functions in order to restore as far as possible a mysterious universal called “normality.” The practical significance of this is huge:

A true understanding of the signals underlying this process would enable rational control of growth and form, giving rise to regenerative medicine applications that correct damage done by birth defects, degenerative disease, cancer, traumatic injury, and even aging. Similarly, a mature understanding of the origin and regulation of shape, including its genetic and epigenetic aspects, would deepen our understanding of evolvability…

Because it implies the local development of complexity, the concept of “emergent properties,” whilst nebulous enough to appear to cover a multitude of sins, cannot be the explanation for phenomena like these. They require, instead, some process of “target morphology.”

A “target morphology” is the shape, defined on multiple scales of size and levels of organization, which a biological system acquires during development, and maintains against cellular turnover (aging), stresses of life (remodeling and wound healing), and major injury (regeneration). Models involving the target morphology require a perspective, focused on information processing in cells and tissues, which emphasizes mechanisms common to the system-level patterning events that occur during embryonic development and regeneration, or fail to occur during neoplastic growth (more on this below). Target morphology models are eschewed in biology today, mainly because of a fear of teleology …. However, there are data that suggest that prepattern models should be considered.

Such phenomena raise at least two problems for conventional biology, both of them implying “outlawed” Aristotelian concepts: formal causation, and final causation (or teleology). Some of the research Levin describes strongly suggests that, even at the one cell stage, but also right through to the multicellular adult stage, there is some global concept of what the whole organism is “supposed to be like,” a form towards which developing embryos, juveniles, or even damaged adults, all “aim” as a target.

Now, clearly neither Levin nor anyone else in this field is suggesting that such things are supernatural. They are, after all, investigating the mechanisms in the areas of chemistry, electrical fields and so on. But nevertheless those mechanisms require a new approach to the science, and the acceptance of possibilities often discounted: that the giraffe determines its parts at least as much as the parts determine the giraffe.

One small, but striking, example he gives of this is injury to red deer antlers – which are, as we know, shed entirely and regrown each year:

In some species of deer, injuries made to the antler at a given spot not only produce a small bump as the bone heals, but also recur as larger ectopic growths in the same location in subsequent years’ antler racks.

The injury, shed with the antlers, is reproduced, and actually increased into a new branch, with each subsequent annual growth. Broadly speaking, the injury to the temporary, peripheral structure seems to distort the “template” on which the antler rack is based each year. But how could that happen? Where is the template stored? It is clearly not simply a genetic developmental program, as another set of findings shows:

Importantly … large-scale morphostasis does not simply depend on recapitulating fixed developmental programs (cit.). For example, the tadpole face is quite different from that of a frog; during metamorphosis, a series of deformations must be executed and various organs and tissues displaced towards their appropriate locations. Remarkably, when developmental defects were induced in the tadpole (by manipulating the embryonic voltage gradients that guide craniofacial patterning), the process of metamorphosis was able to adjust accordingly (cit.). Most organs were still placed into the right final positions, using movements quite unlike the normal events of metamorphosis, showing that what is encoded is not a hardwired set of tissue movements but rather a flexible, dynamic program that is able to recognize deviations, perform appropriate actions to minimize those deviations, and stop rearranging at the right time.

The frog, therefore, is not the sum of arbitrarily evolved local developmental programs (even if we had a better understanding of what those are), but somehow it’s as if the frog-concept exists before, and apart from, those processes. How platonic is that? Although not mentioned in the article, such possibilities would account for the phenomenon I noticed even doing embryology in my school zoology in the 1960s: that the production of morphologically comparable vertebrates (fitting a neat evolutionary hierarchy) actually involves apparently arbitrarily different embryological processes.

The existence of entirely different regeneration processes in closely related salamanders, mentioned above, is another analogous instance of where the goal (a “normal” animal form) seems to have priority over the means.

Put teleologically, instead of evolution producing a development process which it tweaks to vary the morphological outcomes, the phenotype comes first, and (for reasons unknown) the manufacturing process is optional. Such thinking doesn’t come easily to developmental biologists: “Emergent models are preferred because of their parsimony.” But Levin points out that emergent processes are not empirically superior, and evidence like that already mentioned, and more, is not explicable by them. By contrast:

… the target morphology hypothesis predicts that one does not have to explicitly model low-level interactions in silico in order to predict what shape will result from a given patterning state at time t – that some measurable quantity exists now that is predictive and functionally determinative of the next patterning states.

Levin goes on to describe some of the science emerging from, and underlying, such studies – which will be better appreciated by your reading the article than by my trying to summarize it. But the implications for practical questions like wound healing are immense:

Suppose a structure needed to be changed in a biomedical setting – e.g., fixing a birth defect or inducing remodeling of a damaged organ. How do we know what signals must be provided? If the shape is truly emergent, this may be an impossible problem in the general case, requiring direct bioengineering (which is unlikely to be feasible in the case of complex organs such as limbs, eyes, etc.) because the relationship between cell-level rules and final patterning outcome is simply too complex for any tractable model to be able to reverse. On the other hand, if a mapping exists between a known set of physical parameters and the final pattern that will be built by new growth, then it is of the highest importance to understand the mechanisms of information storage and encoding, so that the information in this structure can be changed, and thus induce the organism to remodel accordingly.

So potentially you don’t have to model an exact “emergent” process in detail, which is practically impossible, but find instead how to tell the organism, “grow a new eye.” Magical thinking? No, because salamanders or planarians do it to order naturally. The processes are there, whether or not they fit our usual approach to science.

Another practical implication is in the field of cancer. Our models tend to focus on local genetic, or epigenetic problems, leading to uncontrolled cell-lines. But it is at least possible that a truer approach is the failure of a morphological region to retain its relationship to the whole organism, establishing its own, dysfunctional, “morphogenetic field” which results in the genetic changes observed:

On this view, tumors form when cells stop obeying the normal patterning cures of the body: “cancer as part of an inexorable process in which the organism falls behind in its ceaseless effort to maintain order” (cit.). This view, focusing on the role of the cells’ microenvironment, has been defended recently (cit.) as an alternative to the mainstream gene-centered paradigm that sees irrevocable changes in DNA sequence or gene expression profile as a fundamental change driving tumor stem cells (cit.).

But consider that, speculatively, a little further. If it is not the case that genetic or epigenetic errors govern tumour formation, but rather that morphogenetic errors are firstly to blame, then it would be the case that ultimately morphogenesis was the basis for the “evolution” of the tumour in its mutations and gene expression (an evolution described in Josh Swamidass’s published work in Nature Genetics). The tumour could then be viewed as seeking to achieve a pathological target form, its genetics being merely the means used by whatever global mechanisms determine that target form.

There are, of course, profound therapeutic implications to that. But given that tumour evolution is set forth, by Swamidass amongst others, as a model for biological evolution, any support for this “top-down” view of tumour formation would also tend to turn evolutionary theory on its head. For what if the primary occurrence was the variation, or mutation, of the global target morphology? What, in other words, if new forms are primary, and genetic changes are the result of the organism’s genome falling into line with the new design?

Planarian worms, Levin describes, can be fooled physiologically into regenerating an extra head, a patern which not only remains stable over repeated surgical divisions, but in normal reproduction:

The physiological network behavior becomes canalized into a long-term change of pattern, which is stable across the normal reproductive mode of this animal (fission + regeneration). Thus, a line of such 2-headed animals could be maintained, which would be identical in DNA sequence to the normal 1-headed worms and yet have radically different behavior and body-plan architecture. The evolutionary implications of this are apparent, and demonstrate that the biophysical, epigenetic aspects of patterning may play an important role in evolution, as selection operates on animal morphologies.

This is the long term inheritance of acquired characteristics completely independently of genetics. So far, so Lamarckian – but differing from Lamarck because the primary driver of such evolution is not function, but form.

This, of course, omits an account of the origins of the teleological global forms. Two-headed planarians are monsters not likely to survive natural selection for long, and evolution has to account instead for “endless forms most beautiful.” The arrival of the forms is, in that sense, no more mysterious than the genetic arrival of the fittest, in the conventional genetic view. It is less considered purely because biology’s main focus is reductionist: material efficient causes building up to the totality are the only permitted mechanisms, and genes fit that paradigm.

Teleology has been excluded for centuries, and formal causation is not even admitted to exist. As Arthur Jones once pointed out to me, our theory of evolution cannot be complete until we have a proper theory of development. In the context of Levin’s article, that means explaining how the observed top-down expressions of form actually work.

But since that would entail admitting outlawed concepts into science, it’s probably not surprising that most work keeps searching for the keys under the streetlight of chance genetic variations, the steps from those to hummingbirds, pitcher plants and mankind being so plausible and all.

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About Jon Garvey

Training in medicine (which was my career), social psychology and theology. Interests in most things, but especially the science-faith interface. The rest of my time, though, is spent writing, playing and recording music.
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2 Responses to The shape of things to come

  1. WayneFair says:

    Jon – honored by the attribution and thrilled to read your reflections on this. For me it inexorably leads to the immanent yet transcendent reality of the Divine Logos – and calls into question the ontological presuppositions of scientism and as well as the scholastic two-storey universe of Nature and Grace. “In Him we live and move and have our being” may be one of the profoundest statements in all of scripture (somewhat ironically taken from a “pagan” source – as a self-evident example of the revelation of the Logos within all creation at all times to all peoples). This Word is proclaimed incessantly without words, and yet that “voice is not heard” (Ps.19). Such deafness attests to the noetic effects of “sin” (our idolatrous demand for autonomy) – so that consequently we suppress the Truth, and, in turn, “worship” (ascribe ultimate value and creative power) to the creature over against the Creator.

    • Avatar photo Jon Garvey says:

      Glad you liked it, Wayne. As you see, the follow-on post is not unrelated.

      Strictly speaking, of course, teleology does not entail divine involvement – but it certainly points to a world in which care and purpose are the stuff of reality.

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