Advice I Cannot Possibly Follow

Doctor X, a scientist who has been aware of my work for several years, has emailed some “friendly,” but unsolicited, advice about this blog. He suggests that I “tone down” my rhetoric. He claims my proposal is merely a modest extension of conventional evolutionary theory; it may add to our understanding of cancer but that’s all it does. The citations it has received appear primarily in journals devoted to cancer not evolution and, according to him, that is as it should be; my claim to have developed an alternative to conventional evolutionary theory is wrong.

Oh, dear me!

Where shall I begin?

What if I review, not this blog’s language or what I wrote in my 1992 book Cancer Selection, but the exact wording of the two Letters published in the Journal of Theoretical Biology?  That’s it. Let’s see if I managed to surreptitiously sneak past the JTB reviewers some wild and crazy “rhetoric.”

Before quoting the Letters I think it worthwhile to briefly review my dealings with the JTB.

In my initial cover letter I made clear, as I had in prior submissions to other journals, that I had no scientific credentials, that I was a rank amateur. In due course I received a response enclosing JTB’s reviewer’s evaluation of my proposed full-length paper: he deemed it unsuitable for publication. Somewhat cheekily, I then telephoned the late Doctor James F. Danielli, Editor of JTB, and asked if it were possible to receive a second opinion. He agreed, telling me it would be reviewed by him and by a member of the journal’s Editorial Board. A few weeks later I was told they would consider publication providing I shortened my manuscript and submitted it as a Letter. I accepted their decision and a Letter was published in April 1983. Unfortunately, in reducing the text I had deleted an essential part of my theory. In an attempt to correct the omission I wrote a second Letter which was accepted and published in JTB in March, 1984. 

Following the first Letter’s appearance Nicholas Rothwell, a journalist for The Australian wrote:

Mr. Graham’s appearance in the journal is itself rather bizarre since this scientific publication is not normally given to printing theories by New York businessmen who happen to be amateur evolutionary theorists.

Indeed. I think it probable that because of my complete lack of scientific background and the nature of my idea, as well as the initial reviewer’s negative opinion, those two senior scientists at that respected journal (which had, and continues to have, a policy of not publishing speculation) gave my proposal an exceptionally careful reading.

So what did Dr. Danielli and his colleague agree was worthy of appearance in their journal? A proposed modest extension of conventional theory that might explain something or other about cancer’s evolutionary history? Or did they approve a far more radical idea? Let’s peek at those Letters and see what they in fact approved for publication.

Starting with the opening sentence in the first paragraph of the 1983 Letter I made clear that mine was not a modest proposal: “Cancer…played a major role in the origin and evolution of the Bilateria…” And in the final sentence of that opening paragraph I make the point that is essential to the core of my theory “all selected defenses against cancer would have enhanced the ability of the [Bilaterian] genomes to create organisms in which the genetic program is expressed with great fidelity in all somatic cells.”  [Emphasis added.]

As for my amplifying 1984 Letter, I not only confirmed my fundamental position—“Because the process leading to [lethal juvenile cancer in Bilaterians] is believed to begin with imprecise replication of the genetic program in a single cell, I conclude that all anti-oncogenes also function as enhancers of precise replication” [emphasis in the original]—but even asserted that “Those [Bilaterian] germ lines that created the most complex animals endured the most genetic losses to cancer and vice versa.”

To summarize, my published theory not only says that cancer defenses enabled precise cell replication during development—precision absolutely essential to the existence of all Bilaterians—but that those Bilaterian lineages that “benefited” from higher historical rates of lethal juvenile cancer were—as a result—able to produce animals of greater complexity.

Any truncation and distortion of my theory that excludes those two conclusions might render it more acceptable to Doctor X and others but if it does they are embracing a theoretical proposal they created, not me.  

    

So, how, if I were so inclined, could I possibly follow Doctor X’s advice? Shall I approach the current editors of JTB (with cap in hand and feet ashuffle) and humbly apologize for having foisted on their esteemed publication two Letters laden with irresponsible rhetoric? Should I beseech them to permit me— please?—to rewrite the Letters to reflect Doctor X’s view: that evolution may have managed to—well, to do something or other to the cancer mechanism—but that anti-cancer adaptations could not possibly have also enabled the Bilaterian gene pools to control with precision the production of somatic cells during development. Of course the complete avoidance of somatic mutations during all stages of development would have eliminated the possibility of lethal juvenile cancer while also (it is a tautological certainty) enabling precise replication of cells but … (I need to think of something to follow that “but”). As for my proposal that the most complex Bilaterians were products of higher levels of cancer selection than their simpler brethren, well I have no idea what I could have possibly been thinking when I wrote that. It is, of course, ridiculously wrong.

All kidding aside, Doctor X, it is not rhetoric. It’s logic.

As the recipient of unsolicited advice I will now return the favor and respectfully offer this suggestion to Doctor X: Give this matter further thought.

Perhaps on your next long flight you might contemplate what must have been involved in the manufacture of the airplane you’re seated in and in all the airplanes constructed in all the world’s factories over the past 100-plus years. You wouldn’t seriously consider it possible that the people in charge of those manufacturing facilities did not employ procedures to ensure, with high probability, that the individual working parts were fabricated with precision. The cumulative result of aviation history makes clear that as the planes became more complex and flew greater distances at higher altitudes and at greater speeds the rate of fatal quality-control failures—crashes caused not by poor design or extreme weather or pilot error but by a particular type of imperfect manufacture, the malformation of a specific individual part—became almost non-existent. Once you have an accurate appreciation of the essential role of quality control in the history of airplane manufacture turn your thoughts to the most precisely “manufactured” objects on the plane: the bodies of the humans on board, each of which is far more complex than any airplane and consists of many more working parts. A Boeing 747 consists of about five million parts. We humans have about ten trillion somatic cells and every adult (and every ancestor of every adult) was constructed of precisely-made individual cells. As I explain in recent posts to this site (here and here) the number of those “perfect” cells in all the Bilaterian breeders that ever existed was uncountably high (trillions of trillions?). Such perfection must, in my view, be explained by evolutionarily-effective mechanisms. As you intensify your thinking about those perfect cells keep in mind two facts about cancer that no evolutionist should ignore: (1) all Bilaterian somatic cells contain cancer triggers (oncogenes) and (2) lethal juvenile cancer is initiated by things that interfere with precise replication: mutagens are carcinogens. Wouldn’t even the earliest Bilaterian gene pools have quickly “discovered” that the simplest solution to the problem of lethal cancer during development was not to suppress non-existent tumors but to avoid completely the possibility of tumor formation? And how could they do that? By executing the development program with great precision.  If mutagens are carcinogens then the avoidance of the molecular events caused by mutagens avoids cancer; perfect cell replication is a perfect anti-cancer mechanism.

My theory says that anti-cancer selection pressure occurred in Bilaterian lineages from the time of their origin and that it occurred in no other multicells. To anyone who thinks my idea is a minor matter, another ho-hum revision of conventional theory, I quote from the final paragraph of the 1983 Letter where I assert that if my proposal were adopted evolutionary theory “would offer, as it does not now, a mechanistic explanation for a generally ignored, but nonetheless perplexing problem: why, if they had access to the same mechanisms as the Bilateria, did the germ lines of [cell colonies] not create multicells with complex vital organs? Or, conversely, if tissue-level multicells were sufficiently adapted to ensure the survival of their germ lines for hundreds of millions of years, why do organisms of so much greater complexity exist in such abundance in the Bilateria?” No rhetoric I’ve posted to this site or wrote in my book says more clearly and with greater emphasis that my proposal is radically different from conventional theory.

Although my theory is ignored in evolution textbooks and journals the idea that cancer defenses enhanced replicative efficiency and thus enabled complexity received some notice in Crespi and Summers’ 2006 review article Positive selection in the evolution of cancer where, in a paragraph beginning, “As first described by Graham (1992) in his book Cancer Selection,” the authors note that evolutionary changes may lead to increased cancer rates and “Such [cancers]…may lead to…greater developmental precision and complexity…” [Emphasis added.] The sequence Crespi and Summers describe actually appeared, in succinct form, in my 1984 Letter: “Selection of adaptive pro-oncogenes would have increased the pressure for more effective anti-oncogenes, which, because of their inherent replication enhancive properties, would have enabled the surviving gene pools to create the more complex (or larger or more exposed) animals whose development was by then imbedded in the genetic program.”

Finally, is it possible that although mine may indeed be a radical proposal it is simply wrong? That anti-cancer defenses were not necessary for the emergence and evolution of the Bilaterians? Might not evolutionary mechanisms, as is implicit in conventional theory, that produced jellyfish and other cell colonies have been entirely responsible for Bilaterian evolution? I invite anyone who thinks that to compose a plausible explanation of how that may have happened. Simply take pen (or pixels) in hand and describe how the mechanisms that enabled the jellyfish gene pools to produce nothing but jellyfish for more than 500 million years also managed to produce blue whales, butterflies—and thee and me.

REFERENCES

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

                

Graham, J. 1983. Cancer and Evolution: Synthesis.  J. theor.Biol. 101, 657.

Graham, J. 1984. Cancer and Evolution: Amplification. J. theor.Biol. 107, 341.

  

  Rothwell, N. 1983. Cancer sparked human evolution, claims researcher. The Australian. April 26.

Thompson, A. 2007. Oldest Known Jellyfish Fossils Found. Live Science.com. October 30. 

Copyright © 2012 by James Graham

How Did Bilaterian Evolution Happen? (Continued)

A FACT-BASED EXERCISE

PART TWO: A PROPOSED SOLUTION

POPULATIONAL THINKING

Although in Part One I used the legitimate analytical device of limiting to actual breeders my introductory examination of the historical evolution of Bilaterians, in reality throughout their long history of ~550 million years all Bilaterian gene pools were producing complete populations of animals, including those juveniles that did not survive development. And to understand how the actual breeders could have produced those unbroken chains of perfection we need to consider what mechanisms, operating on entire populations, could have favored that outcome. Before doing that I need to explain why I find certain terms favored by many biologists less than useful in this exercise.

I consider “negative selection” and “positive selection” unnecessary and misleading in considering, as I am, evolution over deep time. Yes, there were “victims” of selection (animals that died as juveniles) and “beneficiaries” of selection (the breeders) but they were all products of the same force: natural selection operating on the entire population. Juveniles afflicted with mal-formed vital organs died from those specific mal-developments and juveniles with perfectly formed organs (barring, of course, other causes of early death) passed their “genes for perfection” to offspring.

Some refer to the elimination of mal-formed juveniles as “stabilizing” selection. Again, I consider attempts to narrow the definition of selection by such gratuitous parsing not only unhelpful but profoundly misleading. If one thinks that lethal juvenile cancer was only an instrument of “stabilizing” selection because it eliminated imperfectly formed developing animals, it misses entirely the role played by selection pressure resulting from such deaths, pressure that enabled the affected gene pools to produce with great precision the most complex things known to exist in the universe. 

      

THE EERIE EFFICIENCY OF SELECTION

As I wrote in my August 27^th posting I was perplexed by the reaction of two scientists to my idea; they said I was probably correct but I was wrong to insist that my idea was a radical departure from Neo-Darwinism. Here’s where I think they may have erred: they applied short-term thinking to the problem I address which is the entire history of Bilaterian evolution. They were probably thinking that cancer-caused deaths of individual juveniles was just another form of “stabilizing selection” and that I was therefore wrong to insist that without those deaths Bilaterians would not exist.

How Did Bilaterian Evolution Happen?

A FACT-BASED EXERCISE

PART ONE: THE PROBLEM REDEFINED

My objective in this two part posting is to consider the fact of Bilaterian evolution in a new way, one that, in my opinion, both reveals the inadequacy of conventional theory and identifies its replacement.  Reading both parts will consume only a few minutes, but it is my hope that they will inspire others to give the problems I describe sufficient thought.

Although it may seem counter-intuitive, those of us who resolutely view evolutionary biology as an historical science have certain advantages over those who primarily employ tools of observational science. We cannot observe past events and we certainly cannot climb into a time machine and perform experiments in the pre-Cambrian, but because we accept Bilaterian evolution as fact we can reach certain useful conclusions, conclusions that demonstrate the gross inadequacy of conventional theory.

To begin this exercise, the most useful conclusion to be drawn from the fact of evolution is that not a single ancestor of any animal that ever existed died as a juvenile. It is a tautological certainty: because only adults breed we know that all the actual breeders survived pre-adult life. From that indisputable fact we can infer, with utmost confidence, that every breeder was the beneficiary of “perfect” development. (Convinced as I am that reproduction by significantly mal-developed animals was extremely rare in the past—as rare as it is in the present—I place “perfect” in quotes simply to deflect potential nitpicking.)

The fact of evolution permits me to state—also with certitude—that these links of perfect development—perfect animals begetting perfect animals—in all the chains that produced all extant Bilateria never once broke: all extant animals are products of uninterrupted chains of perfection.

THERE IS NO MODEL …

In a friendly email exchange I had not long ago with a research scientist who had read my book he asked if I had a model to support my theory. If he asked that question today I would say that he could find a suitable “model” in many biology textbooks; it’s the standard “tree of life” showing biologists’ best estimate of the various Bilaterian lineages’ relationship to one another and to the founding Ur-Bilaterians.  Included in this exercise are all chains of perfect construction of actual ancestors of all living animals in all extant species of Bilaterians: millions of lineages producing millions of trillions of breeders over ~550 million years.  

BUT THERE IS A CONTROL GROUP ...

According to my theory only the Bilaterians are products of cancer selection; except in cases like flowering plants which co-evolved with certain Bilaterians, I agree with the consensus that the evolution of all other multicells is adequately explained by Neo-Darwinism’s mechanism; cancer selection played no part in their history. 

As my control, to compare with the unbroken chains of breeding Bilaterians, I nominate the jellyfish. According to this report fossil evidence shows that more than 500 million years ago jellyfish “showed the same complexity as modern jellyfish.” In other words, in their lineages the unbroken chains of perfection might be summarized as “perfect jellyfish begetting perfect jellyfish without easily discernible morphological changes” for more than 500 million years.

No, It Is Not Neo-Darwinism, and, Yes, It Is Radical

The two most perplexing responses to my idea that lethal juvenile cancer played an essential role in the origin and evolution of all Bilaterians were from two respected scientists (one a biologist, the other, not) and were very similar in their conclusion. A fair summary of both views might read like this: “You are probably correct Mister Graham, but so what?”

Of course neither scientist used those words. The non-biologist said he thought I was correct but that my idea was simply another way of expressing Neo-Darwinism. The biologist, after stating no objection to my theory, said that I was wrong to consider it “radical.”

Perhaps the best place to begin considering whether or not my idea is radical is with the following sentence from my 1984 Letter to the Journal of Theoretical Biology:

“Those [Bilaterian] germ lines that created the most complex animals endured the most genetic losses to cancer and vice versa.”

I could have said the same thing less succinctly but more emphatically:

Those Bilaterian germ lines that “benefited” the most from intense selection pressure emanating from lethal juvenile cancer produced the most complex animals. We humans, as (arguably) the most complex of all Bilaterians, owe everything to this nightmarish disease; without the death in our lineage of uncountable millions of young animals we would not exist. Neither would civilization.

Let’s compare that statement to what the Index of the Second Edition of Evolution by Douglas J. Futuyma (apparently American universities’ most popular evolutionary biology textbook) says about “cancer selection”:  absolutely nothing.  Perhaps some reference to my idea is buried in the text but I don’t have access to Professor Futuyma’s book and with its listed retail price of $121.95 it will probably remain unread by me.  It is possible, of course, that because of the limited attention it has received, my idea could have escaped the notice of an author of an evolution textbook. Yes, that would be possible for other authors but I know it is not the case for Professor Futuyma who, while editor of the journal Evolution, read my manuscript proposing the theory and decided it was not worthy of publication. (I thank him, belatedly, for providing the amusing epigraph to Chapter Fourteen of Cancer Selection.)

COMPARING THE TWO THEORIES

In summary, here’s my comparison of the two theories as they relate to cancer and Bilaterian evolution:

Graham:  Lethal juvenile cancer (cancer selection) played an absolutely essential role in the origin and evolution of Bilaterians. If cancer did not exist and had not actually killed uncountable millions of developing animals none of the Bilaterians could have existed.

Neo-Darwinism:  Cancer did not play any role in Bilaterian evolution. If cancer never existed all animals could have come into existence in forms very similar to extant animals. They might not have acquired certain anti-cancer characteristics but, although such defenses might interest medically-oriented researchers, they are of no interest whatsoever to theorists attempting to understand Bilaterian evolution.

   

The theories summarized in those statements cannot both be correct. One of them must be wrong and I’m convinced it’s the widely-accepted conventional theory known as Neo-Darwinism. In my next posting I will propose a mental test that supports that view.

Speeding Neutrinos, Cold Fusion ... and Cancer Triggers?

Earlier this year I submitted a little essay to The New York Times for consideration by their Op-Ed editor. When The Times didn't accept it I sent it to the Science Editor of The Guardian who also declined. Although the matter of hyper-fast neutrinos was subsequently resolved (the neutrinos were disqualified) my point remains valid: the discovery of cellular oncogenes ought to have shocked the evolutionary biology community, compelling at least a few of them to take a hard look at their theory. 

The following is that essay. It's been slightly edited, mainly to include relevant links. 

The world’s physicists' community has been rocked by the report from Italy that researchers have clocked neutrinos traveling faster than the speed of light. Many physicists have expressed skepticism, but the researchers have rechecked their measurements and claim they are accurate. Time will tell if those findings are ultimately accepted. We intrigued bystanders can only wait for the ultimate outcome: either those observations were somehow flawed or basic physics theory needs tweaking, if not a major revision.

The speedy neutrinos remind me of another alleged finding that shocked physicists: the 1989 report that two American scientists (Martin Fleichmann and Stanley Pons) had produced nuclear fusion at room temperature.

As reported in The New York Times, announcement of that claim was followed by a "frenzy" of activity in "hundreds of laboratories." At Yale, graduate students labored night and day in an underground bunker placing five tons of lead bricks around sensitive detectors and tiny plastic bottles, in order to shield their experiment from stray radiation. Researchers at the University of Washington and at MIT also worked frantically to confirm the Fleichmann-Pons finding. One MIT theorist pulled an all-nighter, trying to develop a mathematical explanation for the discovery.

A Revealing Exchange of Emails

A couple of years ago I came across a comment made on line by an American university professor who teaches evolutionary biology that suggested he might be receptive to my idea linking cancer with the evolution of complex animals.

As has been my practice in recent years, I sent Professor X a complimentary copy of Cancer Selection. I don’t usually attempt further contact with recipients of my gift books, but in this case I did send him an email, a few months after I had sent him the book.

In response to something Professor X had posted on line I reminded Professor X that I had sent him a book and tried to elicit a positive response by including in the body of my email the argument I make in Chapter Five but using a slightly different approach. It is identical to the approach I later used in my 2011 talk to researchers at UCSF.

Here’s the argument I made in the email to Professor X: I claimed that there are certain “mega facts” regarding the history of Bilaterians, facts that all evolutionist would consider indisputable, facts that demand a mechanistic explanation, one not offered by accepted theory.

Fact 1. No Bilaterian animal that bred died as a juvenile. This is a tautological certainty: juveniles, by definition, cannot engage in the reproductive act, therefore all animals that engaged in reproduction lived long enough to reach adulthood.