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April 20, 2015

Feedback Loops, One-Eyed Thinking and Turbo-Charged Selection

Put on your thinking caps!

That's an idiomatic expression used by American schoolteachers to encourage children to give careful consideration to a particular problem.

Feedback Loops 

The standard version of the Neo-Darwinian theory of Bilaterian evolution assertsimplicitly but emphaticallythat  during the ~550 million years of Bilaterian history there was no need for a  feedback loop connecting the smallest components of the developing animals—the individual somatic cells—to the entities controlling the production of those cells—the evolving gene pools. My proposed major additive amendment to that theory asserts, to the contrary, that because of the spectacular complexity found throughout the Bilateria and the exquisite precision of cellular construction evident during development of all individual specimens, a theory pretending to explain their existence demands it. I have concluded that such a feedback loop has existed since the origin of the Ur-Bilaterians and that it has played a critical, central role throughout evolutionary time. 

Feedback was initiated by lethal juvenile cancer, a process that began in a single somatic cell, a cell that had been imperfectly developed. We can assert that the pre-malignant cellat a point in time concurrent with (or immediately prior to) its transformation to the cancerous statewas always maldeveloped; carcinogens are mutagens and mutagens are carcinogens. (1) Cancer never begins in perfectly-formed cells.

Lethal cancer in developing animals caused the extraction from the gene pool of all their genetic material; the feedback process had begun. Events occurring in the smallest component of the developing animal had altered—qualitativelythe composition of the controlling gene pool.

But feedback loops function in two directions which prompts the question: How did lethal juvenile cancer effect the gene pool's control over construction of animals? I published an answer to that question in the final paragraph of my 1983 JTB Letter, where I wrote that the occurrence of lethal juvenile cancer (what I now call "cancer selection") imposed "the imperative that only those Bilaterian genotypes capable of extreme precision in the construction" of individual juvenile animals would survive to produce future generations; intense selection pressure—pressure to avoid death from cancer while a juveniledemanded that cells, the fundamental components, be replicated perfectly. That idea—which is the core of my theory has, as far as I know, received only a single passing mention in the literature: "[lethal juvenile cancer] may lead to positive-feedback cycles of oncogene evolution, leading to improved tumour suppression, greater developmental precision and complexity, and further adaptive changes ...  (Graham, 1992)." [Emphasis added.] (2)

One-Eyed Thinking
One of the more disappointing reactions to my theory was expressed orally by a prominent scientist who had been trained in evolutionary biology at a prestigious American university. He told me I was wrong to consider my theory "radical." His explanation? The occurrence of lethal juvenile cancer was nothing more than a form of "stabilizing selection."

I suspect that the term "stabilizing selection" was invented to convince students that they should dismiss as insignificant deaths of maldeveloped juvenile drosophila or mice that occur during laboratory experiments. Those experiments are completed in days or weeks and at their conclusion the subject populations remain composed of fruit flies or mice. But Bilaterian evolution occurred over ~550 million years and resulted in the production of the incredibly rich entire (except for the colonial cnidaria and porifera) Animal Kingdom. As I argue in How Did Bilaterian Evolution Happen?, in Chapter Five of my 1992 book Cancer Selection and in the manuscript TREE decided not to publish, the fact that every ancestor of every Bilaterian animal that ever existed survived to breeding age and the fact that every one of those innumerable ancestral animals consisted of precisely-constructed somatic cells, strongly imply the existence of a powerful selection-based mechanism linking somatic cells to gene pools, a mechanism that imposed an imperative of perfection. Labeling as "insignificant" the small number of deceased mal-formed juveniles misses the enormous theoretical problem presented by all those animals that reached maturity: what evolutionary mechanisms lie behind their perfection?

Treating cancer deaths of juveniles as evolutionarily insignificant is tantamount to proclaiming that the perfect expression of the genetic program in the somatic cells of every single Bilaterian that survived to breeding age in the last ~550 million years requires no explanation. Come to think of it, that's what the accepted theory implies as I was assured not long ago by a professor at an American university, the author of books on evolution.

In comparison, consider what I was told when I explained my theory in an informal conversation with a man who holds a doctorate in a medical-related field. How did he respond when I asserted that the accepted theory cannot explain the perfect construction of every cell in every ancestral Bilaterian? He simply pointed skyward and said "I am a believer." To give him and other "believers" credit, their "theory" does possess internal logic: if an all-powerful supernatural person has always been in charge of life on Earth no additional mechanistic explanation is needed. Unfortunately, biologists, most of whom scorn religionists' opinions on biological matters, are comfortable with a theory that says it was all done with jellyfish mechanisms, that no feedback loop between cells and gene pools was required. Their theory says that although Bilaterian gene pools, throughout all of evolution, were "blind" to lethal events occurring in individual cells, those gene pools nonetheless managed to produce with utmost precision and in unbroken chains the most complex things in the universe, every one of which was composed of such cells. 

Turbo-Charged Selection
Early in the development of my theory, when I sought helpful comments by sending copies of drafts to various biologists, one of them wrote back to tell me that I had an exaggerated view of the evolutionary significance of  juvenile deaths. He told me his conclusion was based on research he had personally conducted. I don't know what research that biologist performed, but I long ago concluded that he had not given the matter sufficient thought.

Thanks to the clear distinction between animals not yet capable of reproduction and those that can breedbetween juveniles and adultsthose of us who approach evolution as an historical science can reach, with certitude, certain significant conclusions: no animal that died as a juvenile had any descendants; all animals that ever existed descended from animals that had survived development. In the case of humans, a juvenile that died while a member (two or three million years ago?) of our emerging species does not have a single living descendant, but some earliest proto-humans that managed to breed now have seven billion descendants.

Natural selection working with life-or-death power on populations of juveniles had the potential for far greater import than did selection working through differential reproductive rates among populations of breeding adults.

A Hyper-Efficient System: Inferred, But Real

Although I appreciated the Crespi-Summers mention (2) of my idea, I think they were wrong to express it tentatively as in "may lead to," etc. If Bilaterians are indeed the most complex things known to exist then the mechanisms that produced them constituted the most efficient system for construction of complex objects that ever existed. None of the several hundred feedback loops whose illustrations were gathered by Google refer to a system of comparable efficiency, whether judged by the complexity of the components, the complexity of the end-products, the number of components comprising each end-product or the total number of such products produced since the system came to exist.

No industrial engineer would consider omitting feedback at the level of the smallest critical component in designing a system to manufacture complex end-products but, according to evolutionary biology textbooks, no such mechanism is needed to explain Nature's stupendously efficient system. (3)

[It has probably occurred to some readers that there must have been feedback loops connecting gene pools to somatic levels above that of individual cells. If, for example, the liver of a young mammal has been constructed of perfectly-formed cells but had been located inside the animal's stomach, that animal would die as a juvenile. Yes, of course there was feedback operating at the level of organs and organ systems, feedback that imposed an imperative of perfect construction, but if the gene pools had not acquired absolute control over formation of the cells, those organs could not exist.]


1. Ames BN, Durston WE, Yamasaki E, Lee FD. Carcinogens are mutagens: a simple test system combining liver homogenates for activation and bacteria for detection. Proc Natl Acad Sci U S A. 1973 Aug;70(8):2281–2285.

2. Crespi, B.J. & Summers, K., Positive selection in the evolution of cancer. Biol. Rev. Camb. Philos. Soc. (2006) 81:407-424.

3. As I noted in an earlier posting what is apparently the most popular textbook on evolution at American universities, Evolution by Douglas J. Futuyma, does not mention my idea even though the author is aware of its existence.

Comments and questions are welcomed here.

At this site you will find links to additional material including my original Letters to the Journal of Theoretical Biology and  the 1992 Nature review of my book.

Copyright © 2015 by James Graham

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