Laws of form revisited

Michael J.Denton and the Platonic-Aristotelian conception of nature

The article by the biochemist Michael J. Denton, which we bring here in the original version followed by the Italian translation, was published recently in the prestigious English scientific weekly Nature. We thought it very useful to make it known to a wider public given its very interesting subject matter, so that it could be appreciated not only by experts in biology, but also by all those who follow the contemporary debate on the mechanisms that direct the process of the "evolution" in the world of life. In fact, the author, basing himself on incontrovertible scientific data, sketches a picture of nature where some formal rules exist, physically analyzable as the fold in the space of the polypeptide chains constituting proteins, rules that seem to direct many types of evolutionary phenomena. They could be parts of those laws, of a Platonic-Aristotelian type, however to be explained yet, that guide and organize the development of the biological world. Such a position, reducing the role of random mutations and natural selection, is clearly anti-Darwinist, even while remaining in the channel of orthodox scientific research. On the other hand, some ideas of Denton bring to mind the studies, classical up to this point, of the great cytogeneticist Antonio Lima-de-Faria, whose powerful publication Evolution without Selection (Elsevier, 1988) we soon hope to see in Italian, recently translated by Stefano Serafini, under the supervision of the geneticist Giuseppe Sermonti. If the contents of the article are worthy of recommendation, under another aspect there is all the more the very fact of its being published in a journal that up to now has always defended the Darwinian conception of evolution. In fact, Nature in past decades has many times attacked the "alternative" studies of some biologists and naturalists less inclined to follow the majority opinion. The same Denton in the 80s was strongly criticized in the pages of that journal for his book Evolution, a Theory in Crisis (Burnett, London 1985): Mark Ridley in fact charged it with scant competence in its argument and of having revived old outmoded criticisms against Darwin, tantamount to saying his book could not be considered within the ambit of "serious" research on evolution (Nature, 318, 1985, pp.124-5). Well then, after about 15 years Nature features an article from the "reprobate" Denton in the page dedicated to innovative concepts in biology, and that without the author even bringing the least modification to the essential lines of his anti-Darwinist thought. Quite the opposite ...

But who is Michael J. Denton? Let us see a brief profile, based on the information that he himself supplied to me. He studied medicine in the 60s at the University of Bristol, obtaining the title of Medical Doctor in 1968. Along with his scientific interests, he cultivated others, of a humanistic character, studying Semitic languages and history of the Mid-east at the University of Jerusalem. At the end of the sixties he entered the Department of Biochemistry at Kings College in London. There the scientific atmosphere was very exciting, creativity was the norm: one could converse very easily, even in the teahouse, with scholars of high level, like Maurice Wilkins, famous for his researches on the structure of the nucleic acids (DNA and RNA), enlarging thusly, still in an informal way, his own knowledge, according to a style unfortunately unknown in the Italian baronial universities. But -as for the negative side- Denton remembers that the reigning scientific paradigm at King's College was mechanistic and DNA-centric: in other words it held that is was ascertained that all biological forms are specified by a program in the genes which would be assembled bit by bit by natural selection in the course of evolution. Faced with this reductionist concept Denton already harbored some strong uncertainties, derived also from his studies on the development of the form of erythrocytes, or red blood cells. To make every thing arise from DNA seemed to him unrealistic and inconsistent with the experimental data. To reinforce his doubts on the presumed central role of the genes in determining all the forms was his acquaintance in the early seventies with the neutralist theories of the Japanese biologist Kimura, much discussed at King's College. According to this theory, many mutations (changes in the structure of the gene and therefore in its phenotypical manifestation) are "neutral", that is neither useful nor harmful for the organism carrying it, while for classical Neodarwinism, every mutation should have a selective value, positive or negative. Other authors on this path, potentially "heretical" to the "normal" science of Kuhnian memory, then were Brian Goodwin, with his concept of biological forms as natural species (cfr. B.C.Goodwin e G.C.Webster, Form and Transformation, Cambridge University Press, 1996) and Stuart Kaufmann, advocate of the theory of the "self-organization" of matter (see Stuart Kauffmann, At Home in the Universe, Oxford Univ Press, 1996). In the next decade, up to around the middle of the eighties, Denton increased his specialization in the medical field, focusing his attention on the genetics of the diseases of man, with particular reference to the degenerative pathologies of the retina, conducting with success many cutting-edge studies to map genes responsible for serious diseases. He began a period of studies and fertile research at the Prince of Wales Hospital in Sydney, Australia, then ended up at the University of Otago in New Zealand, where he now works. His excellent scientific qualifications had allowed him to write for journals of highest levels, like Nature, Genetics, American Journal of Human Genetics, PNAS, etc. Meanwhile in 1985 there appeared the first edition of the already cited Evolution, a Theory in Crisis (Burnett, London), published also in the USA a year later (Adler & Adler, Bethesda), and finally translated into French, Japanese and Korean. In it Denton, who had never abandoned his studies on the origin of living forms, criticized with an abundance of data the Neodarwinist claim to reduce the complexity of biological change to the simplistic interplay of random mutations and natural selection. It would be a success notwithstanding that is was an antidarwinist book, with a strong Platonic-Aristotelian connotation �the most qualified that appeared in the eighties� but it didn't support any creationist theory: that didn't stop the followers of Darwin from denigrating it as antiscientific insofar as creationist (Nature did its part, as already said!), while the true creationists misappropriated from it in a totally illegitimate way.

At the end of the nineties Denton published his second book on the theme of evolution: Nature's Destiny: How the Laws of Biology Reveal Purpose in the Universe (Free Press 1998), where he held that the forms of life are intrinsically characteristic of the order of nature and not the fruit of extrinsic processes. Moreover, he affirmed that the laws of nature appeared structured and directed in a way specific for the self-manifestation of forms of life characterized by "rationality" such as Homo Sapiens. It is the theory of "Intelligent Design". The centrality of our species to the interior of the natural world is thus revived. Also, this book has been translated into other languages (French and Portuguese) a testimony of the rather widespread interest in Denton's theories (marginal notation: how has no Italian editor thought of publishing Evolution, a Theory in Crisis and Nature's Destiny? Inattention or conspiracy of silence imposed by the barons of homegrown Neodarwinism? A disarming sign of provincialism).

Currently Denton is writing a third book, titled The Nature of Biological Form, where he develops some concepts already mentioned above and taken up again in part in the article published by Nature. The core of his antimechanist discourse is that biological forms derive from the action of natural laws on the constituent material of life, while DNA is limited to influencing the form, but not in determining it. Into this framework he inserts the subject of the three-dimensional structure of proteins, the topic of the article first cited. It appears to me these ideas and intuitions constitute a stimulant and in many ways solid "working hypotheses", from their strong Platonic-Aristotelian tonality, hypotheses that soon could become an alternative theory to the simplistic Neodarwinist concepts.

Giovanni Monastra
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translated from Italian by Chuck Salvo

The text of the article:

Laws of form revisited

«Protein folds found in nature represent a finite set of built-in, platonic forms. Protein functions are secondary adaptations of this set of primary, immutable, natural forms».

Before Darwin, most biologists adhered to a platonic model of nature. This implied that the biological realm consisted of a finite set of essentially immutable natural forms that, like inorganic forms such a atoms or crystals, are an intrinsic part of the eternal order of the world. Just as, today, we account for the form of atoms and crystals by a set of physical laws or "constructional rules", so the pre-darwinian biologists sought to account for the origin of biological forms in terms of a set of generative physical laws often referred to as the "laws of form". For many biologists today, platonic biology is an anacronism irretrievably laid to test, and the idea that biological forms might be intrinsic features of nature generated by physical laws is treated with incredulity. However, recent advances in protein chemistry suggest that at least one set of biological forms -the basic protein folds- is determined by physical laws similar to those giving rise to crystals and atoms. They give every appearance of being invariant platonic forms of precisely the type that the pre-darwinian biologists were seeking. Protein folds, the basic constructional units of proteins, each consist of a folded chain of between 80 and 200 amino acids. Some proteins consist of a single fold, but most are a combination of favo or more. During the 1970s, as the three-dimensional structure of an increasing number of folds was determined, it became apparent that the folds could be classified into a finite number of distinct structural families containing a number of closely related forms. The fact that protein folds could be classified in this manner provided the first line of evidence that the folds might be natural forms. Further evidence that the folds do indeed represent a finite set of natural forms is provided by detailed structural studies carried out over the past two decades which have revealed that the structure of the folds can be accounted for by what amounts to a set of "constructional rules" governing the way that the various secondary structural motifs, such as a-helices and b-sheets, can be combined and packed into compact three-dimensional structures. One is inevitably reminded of the atom-building rules governing the assembly of subatomic particles into the 92 atoms of the periodic table. Consideration of these "constructional laws" suggests that the total number of permissible folds is bound to be restricted to a very small number -about 4,000, according to one estimate. Confirmation that this is probably so is provided by a different type of estimate, based on the discovery rate of new folds. Using this method, Cyrus Chothia of Britain's Medical Research Council estimated that the total number of folds utilized by living organisms may not be more than 1,000. Subsequent estimates have given figures of between 500 and 1,000.

Whatever the final figure, the fact that the total number of folds represents a tiny stable fraction of all possible polypeptide conformations, determined by the laws of physics, reinforces the notion that the folds, like atoms, represent a finite set of built-in natural forms. The robustness of the folds offers another clue. The fact that the folds can retain their native conformations in the face of multiple different sorts of short-term deformations caused by the molecular turbulence of the cell, and in the face of extensive, long-term evolutionary changes in their amino-acid sequences, is precisely what would be expected if they are natural forms, specified by physical law. Again, the fact that the same fold can be specified by many different, apparently unrelated amino-acid sequences, suggesting multiple separate discoveries during the course of evolution, is further evidence that the folds are intrinsic features of the order of nature. Finally, the fact that in many cases the same fold is adapted to very different biochemical functions is precisely what would be expected if protein functions are secondary adaptations of a set of primary, immutable, natural forms. If forms as complex as the protein folds are intrinsic features of nature, might some of the higher architecture of life also be determined by physical law? The robustness of certain cytoplasmic forms, for example the spindle apparatus and the cell form of ciliate protozoans such as Stentor, suggests that these forms may also represent uniquely stable and energetically favoured structures specified by physical law. If it does turn out that a substantial amount of higher biological form is natural, then the implications will be radical and far-reaching. It will mean that physical laws must have had a far greater role in the evolution of biological form than is generally assumed. And it will mean a return to the pre-darwinian conception that underlying all the diversity of the life is a finite set of natural forms that will recur over and over again anywhere in the cosmos where there is carbon-based life.

Notes

1- Michael Denton and Craig Marshall are in the Department of Biochemistry, University of Otago, PO Box 56, Dunedin 9001, New Zealand. back to text ^

Further reading

• Chothia, C. One thousand families for the molecular biologist. Nature 357, 543-544 (1992).
• Chothia, C. & Finkelstein, A. V. The classification and origins of protein folding patterns. Ann. Rev. Biochem. 59, 1007-1039 (1990).
• Lindgard, P. & Bohr, H. How many protein fold classes are to be found? in Protein Folds (eds Bohr, H. & Brunak, S.) 98-102 (CRC Press, New York,1996).
• Kirschner, M., Gerhart, J. & Michison,T. Molecular "Vitalism". Cell 100, 79-88 (2000).
• Orengo, C. A., Jones, D. T. & Thornton, J. Protein superfamilies and domain superfolds. Nature 372, 631-634 (1994).

Michael Denton and Craig Marshall

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Articolo inserito in data: martedì 25 settembre 2001.

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