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November 25, 2013

An Open Letter to Armand Marie Leroi

Dear Armand,

I’ve recently been persuaded that I should stop identifying you as “Doctor X” and as “Reviewer Number One” of the rejected manuscript. Hence this Open Letter.

This will of necessity include material you may have read in my post-rejection email to the editor of Trends in Ecology and Evolution (TREE) and, perhaps, in prior posts to this site. Sorry, but some duplication cannot be avoided. After all, the prime purpose of an “open” communication is to reach other people, not the nominal addressee.

Parts of this message will be disrespectful. Sorry about that, but you’ve earned it.

August 20, 2013

Do Naked Mole Rats Confirm That Senescence is a Cancer Defense?

On page 83 of my 1992 book Cancer Selection I wrote: My theory thus explains the origin and function of [Bilaterian] aging. The programmed shutdown of the cell-renewal process was one of several mechanisms selected to avoid cancer in the earliest [Bilaterians.]

Although The New York Times reported in 2006 that Dr. Norman E. Sharpless of the University of North Carolina reached a similar conclusion (“I don’t think aging is a random process—it’s a program, an anticancer program …”) I am not aware of any published research that would directly confirm or refute this particular part of my theory. But researchers working with naked mole rats may have recently given it some — indirect and tentative — support.

As noted here, here, here and elsewhere these rodents seem to be exceptionally long-lived, with one specimen reaching 28 years. They are exceptional rodents for another reason: they do not get cancer. As reported in 2009 by researchers at the University of Rochester, “a naked mole rat has never been found with tumors of any kind.” More recently (and potentially more significantly) those researchers reported that they have “discovered the chemical that makes naked mole rats cancer-proof.”

So naked mole rats distinguish themselves from other rodents in two ways: they live much longer and they experience zero cancer. In comparison mice live about two years and seem highly susceptible to cancer; a 1962 examination of tumors in randomly gathered wild mice found an incidence of “… 121 neoplasms in 98 animals of a total 225,” an occurrence in forty-four percent of specimens.  (See reference.)

What then is the connection, if any, between the long lives of naked mole rats and their freedom from cancer? A mere coincidence or something more significant?

In Chapter Nine of Cancer Selection I offered a cancer-centered explanation for many fundamental differences between terrestrial vertebrates and terrestrial invertebrates: the vertebrates possess adaptive immune systems capable of killing cancer cells and invertebrates do not. Equipped with that “fail-safe” defense the vertebrate gene pools could produce animals no longer equipped with many preventive defenses against cancer.  In many vertebrate lineages the animals grew larger and lived longer. Larger sizes and longer lifespans required increased mitosis and, given the presence of oncogenes, greater risk of cancer initiation, but, with the presence of the adaptive immune system, no probable long-term increased risk of cancer death. (1)

Not equipped with an adaptive immune system capable of destroying cancer cells, the terrestrial invertebrates depended completely on defenses against cancer initiation. They avoided exposing somatic cells to carcinogenic radiation and eschewed those hallmarks of many vertebrate lineages: increased body sizes and extended lifespans.

If Sharpless and I are correct and Bilaterian senescence is a cancer defense mechanism, did something similar happen with naked mole rats? Did the presence of hyaluronan (HMW-HA), the chemical discovered by the Rochester investigators, reduce the risk of death from cancer to such an extent that it permitted lowering another defense, programmed senescence? Might molecular biologists one day determine that the origin of hyaluronan preceded the mole rats’ extension of lifespan far beyond that of other rodents? (2)

                                                                       *   *   *

Reference: Dawes, Clyde J., “Phylogeny and Oncogeny” pp 1-39 in Neoplasms and Related Disorders of Invertebrates and Lower Vertebrate Animals, National Cancer Institute Monograph 31, July 1969 (Dawes, C.J. and Harshbarger, J.C., eds.)


1. A complete pdf of Chapter Nine is now available for downloading at

2.  I argue in Chapter Seven of my book that most Bilaterians do not regenerate damaged tissue as flamboyantly as non-Bilaterian multicells. After further thought, I now think that the exceptional regenerating capability of echinoderms may be related to their apparent immunity to cancer. See Starfish Secrets: Did Echinoderms Cure Cancer?

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 © 2013, 2014 by James Graham

This page was archived at The WayBack Machine on April 20, 2015.

April 15, 2013

Once in Galapagos a Lady ...

What follows is a re-posting of my initial (July 2009) entry to this blog. In it I suggest that perhaps scientists who fail to "see" cancer's role in Bilaterian evolution are emulating a woman who didn't approve of my airplane reading.  
This happened in the late 1970s or maybe in the early 1980s. I was returning to New York from a European business trip on a wide-body jet. As was my habit, I had a book with me and once we were airborne, I started to read it, a Penguin trade paperback entitled Evolution, its author, John Maynard Smith. 

In due course a meal was served and I placed the book in the pocket in front of me.

“I see you’re reading that book on evolution.”

It was the woman to my left. A fellow American, a dignified lady of a certain age who had the appearance and manner of someone who had the time (widow?) and money (life insurance proceeds?) to travel the world at her leisure and who spent her time and her money doing exactly that.

I glanced at her and saw from the unsmiling tightness of her mouth that this was not a pleasant query. Oh oh, I thought. Here it comes. 

“So, do you believe in it? In evolution?”

To have given a completeand completely honestanswer I would have replied, Yes, I’m absolutely convinced that evolution did happen but the accepted theory fails to explain the existence of complex animals. It has a fatal flaw, butnot to worryI’ve figured out how to fix it. Instead, I took the easy way out and, nodding my head and mumbling, let her know that I found it quite convincing but (the primary function of mumbling?) didn’t care to talk about it.

My fellow passenger then delivered what I am sure she considered the final word on the matter, a triumphant conclusion to our brief conversation.

January 29, 2013

Twenty-five Questions Not Solved by Conventional Evolutionary Theory

1. In all Bilaterian species individ­ual specimens are very similar to one another; they all have the same complex vital organs arranged in a virtually uniform manner. Some species of nema­todes and rotifers even exhibit eutely: each specimen consists of the identical number of cells arranged in precisely the same pattern. Such strict unifor­mity of entire phenotypes is not found in other multi­cel­ls (plants, Porifera and cnid­arians). In those phyla, plasticity reigns. How could the same mecha­nism, natural selection, possibly explain the emergence of both strict pheno­typic uniformity and wide­spread pheno­typic plasticity?

2. In cell colonies (plants, cnidarians, and Porifera) the most complex and highly organized tissues are those directly involved in sexual reproduc­tion. Natural selection ex­plains sex-organ complexity: if those organs had not functioned with exquisite precision the lineages would have perished. But Bilaterian complexity is different. In those animals vital organs located throughout the body perform func­tions not di­rectly involved in sexual repro­duction. How can the identical mechanism -- natural selection -- logically ac­count both for the existence of complex vital organs in ani­mals and their absence in cell colonies?

3. Among cnidarians, large organisms are found in sunny habitats; in the genus Cyanea some jellyfish grow to two meters in diameter. All jellyfish are comparatively simple organ­isms. However, among the later­ally symmetrical animals the combination of large size and exposure to sunny habi­tat is found only in the most transformed lineages, the terrestrial vertebrates. These animals are extremely complex. There seem to be no large, relatively simple animals (as simple, say, as annelids) living in sunny habitats. Why not?
4. Based on the fossil record the earliest Bilaterians all avoid­ed exposure to sunlight. Somatic cells were not directly exposed until about 400 mil­lion years after those ani­mals first appeared, and then only in lineages that produced animals with adaptive immune systems. In fact, most extant Bilaterians avoid expo­sing unprotected cells that divide. On the other hand, plants, Porif­era and most cnida­ria­ns do not avoid sun­light; many spend all their days bask­ing in it. What is the evolu­tion­ari­ly plausible expla­nation for this fundamental differ­ence in the life histo­ries and observed characteristics of the two groups of multicells?

5. Jellyfish fossils found in 2007 in Utah are estimated to be more than 500 million years old. According to University of Kansas investigators the ancient jellyfish were phenotypically very similar to present day jellyfish. It seems that, compared to Bilaterians, there has been little organismic transforma­tion in the cnidarians (and in the Porifera). What is the mechanistic expla­nation for such (what some might call) unpunct­uat­ed equilibrium? 

6. The theoretical problem of senescence, contrary to the opinion of some, has not been solved. Most plants, unlike all Bilaterians, do not exhibit programmed aging. An exception is found in certain bamboo species where all the individual plants live for a fixed number of years before they flower and reproduce. Then all the individual plants die. This is true aging -- the pro­grammed cessa­tion of mitosis following a fixed time period.

But programmed death dependent on cues from the environment which is exhibited by most plants (think of annual plants dying in the fall) is not aging; bring the geraniums inside before frost and they will survive to spring. Perhaps some annual plants do not survive indoors but with few exceptions plants do not undergo the temporal-sensitive slowdown in cell renewal that is the hallmark of aging in Bilaterians. Studies of Porifera and cnidarians indicate that they too do not age. 

All Bilaterians age and investigators have actually identified (in some species) genes "for" senescence.

How could the identical mechanism -- classic Darwinian selection -- possibly account for both the presence of such a fundamental character in all the Bilaterians and its absence in virtually all other multi­cells?