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March 12, 2014

Did a Carcinogenic Crucible Produce the Human Brain?



In writing my 1992 book Cancer Selection I had several objectives. I wanted to introduce to a wider audience the essential core of my peer-reviewed theory—that defenses against lethal juvenile cancer enabled precise construction of complex animals. My theory says that if cancer did not exist the Bilaterians would not exist. I also wanted to argue vigorously in favor of its acceptance as a major amendment to evolutionary theory, hoping for its adoption. Finally, I wanted to extend the theory, explain why I thought certain phenomena no one else associates with cancer actually originated as defenses against it. I wrote that sleep, animal senescence and the human brain originated largely because they defend against lethal juvenile cancer.

Regarding sleep, I wrote in the book that any future discoveries of increased immune activity during sleep, which is when somatic cells divide, would support my idea. Subsequent research seems to have done that. 

Although I am not aware of any published research supporting my proposal that animal senescence originated as an anti-cancer mechanism, an American scientist has informed The New York Times that he had reached the same conclusion. 

In the remainder of this posting I will concentrate on my third proposal, that cancer played a major role in the origin of the human brain. Much of what follows is an adaptation of material appearing in Chapter Nine.

I wrote in that chapter about the evolution of the land animals, the terrestrial Bilaterians, pointing out common physical features that appear to support my view that all Bilaterian lineages produced animals possessing defenses against cancer, prominently including the shielding of dividing cells from UV and other environmental radiation. For example, in humans and other vertebrates blood cells are produced inside large bones where they are protected from radiation. Another example: in four-legged animals most soft-bodied organs, which consist mainly of cells that divide, are shielded by reptilian shells, by mammalian fur and by pigmented skin. 

They are also shielded by musculature. Adult muscle cells are permanently post-mitotic; they are incapable of division and thus cannot be the site of cancer initiation. 

Besides muscles, there’s another group of somatic cells in Bilaterians that, once formed, are permanently post-mitotic: neurons, the cells of the nervous system. Let’s consider how that fact could have played a role in the origin of the human brain. 

When and where did our brain originate?

It was established, with the 1974 discovery in Ethiopia of the hominid fossil "Lucy," that our ancestors became bipedal about 3.5 million years ago and that they stood up before they acquired their large brains. The big brainsthey more than doubled in size from Lucy'sdid not appear until about 2 million years ago. That sudden appearanceand in evolution 1.5 million years is a short timeis not disputed. So quickly did the enormous brain appear that biologist Anthony Smith estimated that it grew at an average rate of 90,000 cells per generation (1).

The locale where our ancestors were thought to be living when the big brains suddenly appeared is highly significant. It was in or near the Great Rift Valley, which runs from North to South, dividing central Africa in half. West of the valley the land is covered with heavy foliage; it is mostly deep, dark jungle. To the east it's savanna; open land bombarded by fierce tropical sunlight. The valley itself, where the Lucy fossil was found, is one of the hottest places on earth. Suddenly spending entire days with the blazing African sun beating down on the top of their heads (thanks to their recent adaptation of bipedalism), I think early humans suffered significant losses of juveniles to lethal brain cancer initiated by solar (and, possibly, cosmic) radiation. Butand this is essentialmost modern brain tumors do not start in functioning brain cells, not in neurons. They begin in glial cells, dividing non-nerve cells that circulate inside the cranial vault.

If glial-cell brain cancer killed many proto-human and human children, I am convinced that selection pressure would have favored the acquisition of additional neuronsfunctioning brain cellson top of the smaller brain we inherited from Lucy and other ancestors. Newly acquired masses of non-dividing cells, placed above dividing cells could have blocked carcinogenic radiation and prevented juvenile death from brain cancer.   

Modern juvenile cancers support this idea.

In developing my theory I was quickly satisfied with the logic of the idea that cancer originated as a de facto quality control mechanism that worked by killing juveniles in which the development program was not expressed with utmost precision in all somatic cells. Over evolutionary time, natural selection would have collected defenses against juvenile cancer, including any that postponed death to the post-reproductive years. That is consistent with the actual experience of modern humans; it usually kills older people. But I had a problem, one that demanded solution. Some modern children die of cancer. How could that be? If lethal juvenile cancer originated >500 million years ago and natural selection accumulated defenses against it ever since, it shouldn’t be killing any of today’s young Bilaterians.

My solution to that problem (published in my second JTB Letter and amplified in Chapter Three of my book) was that as modifications to animals’ bodies were introduced the gene pools had to “learn” to construct precisely the newly-revised parts. In accord with common sense (and the near-perfect analogy of the "learning curve” phenomenon in manufacturing) mistakes made immediately following the new revisions’ introduction wouldover timebe reduced in frequency as lethal juvenile cancer eliminated the genomes of the individual animals that failed to express correctly the new modification, leaving only “perfect” animals to reach breeding age.

Modern pediatric cancer experience suggests that the learning curve is still functioning for humans: the sites where most childhood cancers originate were all subject to relatively recent modification. Because our immune systems are under constant pressure to cope with evolving pathogens it should not surprise us that leukemia is the leading cause of cancer death in American children. The second leading cause is brain cancer (2).

Once the human brain formation is completed (which occurs in about three years) the neurons are permanently post-mitotic and if post-mitotic cells shield dividing cells from carcinogenic radiation then the greater number of such cells acquired, the less likely juveniles succumbed to brain cancer.  

“Reverse-engineering” with the learning curve.

My idea that the relative recentness of their modification explains why certain sites are the initiation point for present-day pediatric cancers has received published support here and here. Although it is impossible to quantify and plot a learning curve for the human experience with pediatric brain cancer over millions of years we can imagine the outline of such a curve, with its lowest point (of lethal juvenile cancer frequency) at the present and the highest point in the years following the adoption of bipedalism. Although it is of course impossible to answer with any precision the question “How prevalent was lethal juvenile brain cancer in those early years?” My unquantifiable but useful response is, “High enough to explain the sudden appearance of our extravagantly large brains.”     

Another supporting fact.

Children have thick hair only on the top of their heads. Early humans lost their thick body hair, and biologists believe they shed it to survive in the heat of the savanna. But most of our body heat escapes through our heads. That's why people wear hats in cold weather. If we got rid of body hair to keep cool in the African heat, its retention by juveniles in the one place where it would most interfere with body-cooling suggests that something else was involved. I think children’s hair protected them against sunlight-caused cancer. Hair's ability to defend against cancer has been established in experiments; nude mice (they're shaved daily) exposed to ultraviolet radiation display increased tumor formation.

The inadequacy of the only other explanation.

Any attempt to attribute our brain’s sudden enlargement solely to the survival benefit of higher intelligence faces serious obstacles. Why did it happen so quickly? And what conceivable environmental changes could have possibly occurred in that pre-civilization era, changes that could have intensified selection pressure to the point where slightly smarter proto-humans out-bred those with slightly smaller brains? And if slightly improved intelligence was the key to survival why did selection continue to demand further accumulation of even larger brains, of additional billions of neurons?

Alfred Wallace was convinced that natural selection could not explain the human brain. He argued that natural selection would produce the sufficient, but not the supererogatory. Wallace was correct (3). Natural selection never anticipates; it solves only here-and-now problems, not those that might possibly arise millions of years in the future. There was no conceivable survival benefit on the African savanna for possession of the neuronal power that would eventually invent calculus, compose symphonies and conceptualize, design and execute rocket trips to the moon. Yet the human gene pool did amass those billions of additional non-dividing cells when it did and a comprehensive theory of evolution requires a plausible explanation. My proposal provides the missing here-and-now problem: lethal juvenile brain cancer originating in glial cells. 

Summary.

A theory must possess internal logic. It must be plausible. The concurrence of an event—the adoption of bipedalism—in one of the sunniest places on Earth, a carcinogenic crucible, followed by the quick amassment of neurons providing superfluous intelligence is consistent with my idea that the post-mitotic neurons shielded glial cells and prevented death of juveniles.

The speed of our brain’s enlargement can be explained by the effect of lethal juvenile cancer, what I call “cancer selection.” It is my impression that biologists tend to over-emphasize the significance of differential reproduction rates (possibly because they are observable and measurable) and underestimate the significance of juvenile deaths (because it cannot be measured.) Dead juveniles always left zero descendants and zero is, biologically, a very powerful number: in the unfolding of a lineage over evolutionary time the difference between “none” and “some” is enormous, much greater than observable differences in the descendant-counts of breeding adults. It is self-evident that there are no living descendants of juveniles that died two million years ago. It is also self-evident that all humans that now exist descended from children that lived a very long time ago and avoided lethal juvenile cancer. “None” remains “none” and for humans “some” is now seven billion (4).

A proposed experiment. 

Although the idea that cancer selection was the primary driver of our brains’ sudden growth may strike some as overly audacious, I suggest an experimental test of the underlying idea that post-mitotic cells provide effective UV shielding of dividing cells: 

Place nude mice in cages with the source of UV radiation located below the cages, shining up on the mice. This would be equivalent to turning the mice upside-down. Place a control group in cages with UV radiation shining down on them, in emulation of nature. If the “upside-down” mice display higher rates of tumor formation than the control group the idea that placement of post-mitotic cells reduces exposure of dividing cells to carcinogenic radiation has received some confirmation. 

Please note that this is a tentative suggestion, made by an amateur. Others might devise a more appropriate experiment, perhaps one that would test directly whether or not masses of living neuronal cells provide effective shielding to living glial cells.

Notes.

1. Smith, Anthony. The human pedigree: inheritance and the genetics of mankind, Allen and Unwin, 1975.

2. The leading cause of childhood deaths (ages 5-14) in the USA is accident. Cancer is the second leading cause.

3. He mistakenly required a supernatural explanation for products of the human brain: "At about the same time, he began to maintain that natural selection cannot account for mathematical, artistic, or musical genius, as well as metaphysical musings, and wit and humour. 

4. In my April 20, 2015 posting I iterate the neglected importance of selection that operated on populations of premature animals, introducing (in the hope that it might help overcome the failure to recognize its momentous significance) the phrase "Turbo-Charged Selection."   


A cautionary note.

I am not suggesting in this proposal that higher intelligence did not offer important beneficial advantages to the savanna primitives. After all, they, or their relatively close descendants, invented the first tools, adopted the use of fire, invented agriculture, tamed animals, created language and otherwise climbed the first and most critical steps toward the formation of civilization. None of that would have been possible without the increased intelligence provided by the larger brain.

Unfortunately, I need to make that as clear as possible because of past experience. One scientist, perhaps motivated by some hidden psychological problems of his own, has gone out of his way to portray me as his intellectual inferior. After reading my book he intimated to a journalist that I thought the sole function of snails’ shells was to protect against cancer, that I ignore the shells also protect against predation. He actually believes it possible that an amateur who, with no substantive assistance from anyone, achieved publication—twice—in a prominent peer-reviewed biology journal and whose biology book received a positive review in Nature is nonetheless capable of such stupidity. (Snails, by the way, are not even mentioned in my book.) Unfortunately, his asinine comment was published by the journalist.

So to be absolutely clear: yes, increased intelligence provided huge survival benefits to our distant ancestors. But intelligence would have been irrelevant if a sufficient number of children had not survived.

Comments and questions to the author 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 © 2014 by James Graham

This page was archived at the WayBack Machine on April  21, 2015.