The Axillae of San Stefano

I have only ever attended two scientific meetings, both of them annual conferences of AAAS, The American Association for the Advancement of Science. The first meeting was in 1982 and it was held in Washington DC. 

 

The reason I traveled from Manhattan to attend that conference stemmed from the discovery of oncogenes which had recently been reported in several newspapers. I had begun writing in 1978 my theory about lethal juvenile cancer’s role in the origin and evolution of complex animals and by 1982 I had written seven or eight versions. In all of those drafts I postulated the existence of cancer triggers in all Bilaterians’ normal somatic cells and after reading that some cancer theorists (but no evolution theorists) had also postulated the existence of such triggers, I started to call them by the scientific term, oncogenes.  

Pleased to learn that my hypothesized genes had actually been identified, I sent a copy of my latest draft to the reporter at New York’s Newsday who had written one of the earliest reports. My hope was that he might publish something about my idea. A few days later I telephoned him and after saying he did not understand my theory he made a suggestion. He told me about the annual conference of AAAS which included something called a “poster session.” He explained that the standards for acceptance in poster sessions were not very high and that I could probably have no difficulty “posting” my theory which could then be read by conference attendees. It was too late for me to post my paper at the 1982 meeting, but he suggested I  visit it anyhow with a view of submitting something for the 1983 meeting. I took his advice and arranged to attend for a single day to find out what a “poster session” was all about. I picked a day on which several prominent evolutionary biologists would be giving presentations in commemoration of the centennial of Charles Darwin’s death.

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.

Evaluating The Reviewer (Part Three)

In my last post I summarized the difference between me and the reviewer when it came to the question “Can jellyfish get cancer?” In this posting I will explain why that question is critically important, not to cancer researchers or to jellyfish enthusiasts, but to everyone who believes evolutionary theory ought to do what it now fails to accomplish: offer a reasoned mechanistic explanation for ~550 million years of Bilaterian evolution.

In the first paragraph of my peer-reviewed 1983 Letter “Cancer and Evolution: Synthesis” I made crystal clear what this reviewer completely ignores: the nucleus of my theory, its logical core. Here, with emphasis added, are the concluding sentences in that paragraph: 

“Although the precise cellular mechanisms involved in carcinogenesis are not considered here, it is assumed that within a target pre-mitotic cell the following sequence takes place: (a) the mutagen causes a mutational event and (b) oncogenes (Bishop, 1982) initiate transformation to the cancerous state following mitosis. It follows from this sequence that virtually all selected defenses against cancer would have enhanced the ability of the genomes to create organisms in which the genetic program is expressed with great fidelity in all somatic cells.” (1)

Evaluating the Reviewer (Part Two)

In “Cancer and Evolution: Amplification” my 1984 Letter in Journal of Theoretical Biology I make clear my conviction that cancer did not occur in every multicell lineage:

"[Oncogenes have] the potential for killing the organism in whose genetic program they are present, such deaths being initiated by the occurrence of a mutational event in a single somatic cell.  This theory states that oncogenes, thus defined, have been present in every cell of every specimen of every species of the Bilateria that ever existed, and that they have existed nowhere else in nature. " (Emphasis added)

The journal's Reviewer Number One takes a completely different view. As I wrote in my emailed letter to the journal’s editor:

“Reviewer #1 is clearly convinced that cancer can in principle occur in any multicell, that the initiation of the process does not require a specific triggering mechanism. He ignores the work of Varmus and Bishop (which earned a Nobel in 1985) and others in identifying cellular oncogenes, cancer-triggering mechanisms. I have already commented on the problems those discoveries create for conventional evolution theory.”

“Number One also suggests that if only they were examined more closely Cnidarians like jellyfish might exhibit cancer. My contrasting conclusion, inferred from their 500 million years of naked sun-bathing, is that death from carcinogenic UV radiation never threatened the jellyfish lineage. His preference for observational science and his rejection of inferential logic reminds me of the dozy bint I encountered who insisted that a certain 19th Century naturalist erred in concluding that direct observation was not a sufficient means of gaining insights into the history of extant animals.”

To summarize the critical distinction between me and the reviewer as to how the question “Was the jellyfish lineage influenced by cancer selection?” ought to be addressed:

James Graham: Using inferential logic, their ~500 million year history of unshielded exposure to carcinogenic UV radiation is sufficient to conclude that their evolution was unaffected by cancer.

Reviewer Number One: Ignore evolutionary history and do not use inferential logic. Simply observe enough extant jellyfish specimens long enough and cancer might be detected.

I have read enough of the writings of professionals in the biological sciences to know that many are convinced that there is only one scientific method; they seldom employ inferential logic and rely solely on laboratory investigation or direct observation in nature. But why would a scientist holding such narrow views undertake review of a paper submitted to a journal devoted to the historical science of evolution, a paper written by someone whose peer-reviewed published theory is the result of the same methodology he employs in the submitted manuscript?

Evaluating the Reviewer (Part One)

Although the disadvantages of my status as outsider heavily outweigh the advantages, occasionally a situation arises that gives me an opportunity to do something that would probably cause serious difficulties if I were on the faculty of a university or a member of an institutional research team. Perhaps the song "Freedom's just another word for nothing left to lose" exaggerates, but there are situations where the risk involved in reacting strongly to the incompetence of others is minimal and one is compelled to respond with frankness and vigor.

My idea—that lethal juvenile cancer played an essential role in the origin and evolution of complex animals—has gained some notice in journals; my two Journal of Theoretical Biology Letters and my amplifying book have been cited. But those citations appear in works devoted, not to Bilaterian evolution, which is the subject of my work, but to cancer. In an attempt draw the attention of the evolutionary community to my theory I recently submitted a manuscript to an evolution journal. Unfortunately, after review the journal rejected it. I then emailed the editor, telling him I accepted the finality of his decision, but that I found his reviewers' comments of poor quality. I went on to identify the principal reviewer's failings. My email to him was rather lengthy but I will summarize its major points in this and in subsequent postings.

Prior to sending my manuscript out for review the editor disclosed that he had contacted a few scientists about it, including “Doctor X,” who had previously offered me unsolicited (and unwelcome) advice which was the subject of this posting. In my letter to the editor I quoted  dismissive comments about me and my idea made by “X” in an interview with a journalist and in an email to a third party. I also told the editor that I believe his Reviewer #1 was actually “X” himself or his “intellectual, psychological and ethical clone.” I reached that conclusion because the reviewer’s comments reeked of the smugness “X” adopted in communicating with me.

What is most important in understanding what the reviewer did is that my manuscript contained nothing new; I made no original proposals. It is a concise, fact-based argument for the theory already published in the Journal of Theoretical Biology and in my Nature-reviewed book. By telling the editor that mine is a “dubious global theory” and taking the position that an argument in its favor doesn’t deserve publication in an evolution journal, “X” is implying that the following were wrong: the late James F. Danielli, FRS, founding editor of JTB and his co-reviewing member of that journal’s Editorial Board, Nature’s book reviewer and the Nature editor(s?) who decided, first, that my book was worthy of review and then approved publication of the (generally favorable) review. According to this single individual those biologists were all wrong to publish my ideas and he urged the editor not to allow the readers of his evolution journal to even learn of my theory’s existence.

To give some sense of the principal reviewer’s inaccuracies here’s a quote from my letter to the editor:

"Like [X], the reviewer is weirdly obsessed with “diversity.” In his relatively brief comments he mentions “diversity” or “diverse” thirteen times, giving the erroneous impression that my theory is all about (and only about) the number of extant species in Bilaterians versus the other multicells.

"He ignores what I emphasize: fundamental characteristics of Bilaterians…that distinguish them from cell colonies. To cite just one example, there is the matter of phenotypic uniformity in Bilaterians (to the point of eutely in nematodes and some insects). That widespread uniformity reflects a level of control over the precise construction of the entire soma, a degree of control not found in cell colonies. I think fundamental and obvious differences among multicells require solid theoretical explanation and in the historical science of evolution that means identifying explanatory events that occurred in the past. Reviewer #1 obviously does not. He is content with a theory that is silent on such important distinctions."        

This reviewer has read my book (as did “X”) so he knows that in addition to phenotypic uniformity I offer evolutionarily-effective mechanistic explanations (attributed to cancer selection’s postulated occurrence only in Bilaterians) for other fundamental differences between the Bilaterians and the cell colonies including the following:

UV radiation avoidance. The earliest Bilaterians burrowed in the sea bottom and their nearest descendants crawled on the bottom. The crawlers all possessed non-cellular external coverings and their marine descendants lived (for more than 300 million years) in the sea which itself affords environmental shielding from radiation. Of the terrestrial Bilaterians the only ones to shed external protection against radiation were vertebrates equipped with adaptive immune systems capable of killing cancer cells. Terrestrial invertebrate Bilaterians, which do not possess adaptive immune systems, all seem to have retained external non-cellular radiation shields.  In contrast, some cell colonies, notably jellyfish were not even provided external pigmentation which, like non-cellular shielding, would protect from the effects of mutagenic/carcinogenic radiation.

Flamboyant regeneration. With few exceptions (some annelids, echinoderms, salamanders) Bilaterians do not display the spectacular feats of regeneration found in other multicells.

Programmed senescence.  All Bilaterians display genetically-controlled senescence which I claim (on pages 82 and 83 of my book) is an anti-cancer mechanism. Not incidentally, an American biologist has reached an identical conclusion.

The reviewer does not even mention any of these four fundamental differences, all of which I identified in the peer-reviewed Letters and amplified in the Nature-reviewed book. He simply goes on and on (and on and on) about “diversity,” giving the editor the erroneous impression that because there are thousands of non-Bilaterian multicell species my theory is wrong.

Any student who submitted a paper containing such an egregious error would receive a failing grade. But this reviewer convinced the editor not to inform his readers of my published theory.

© 2013 by James Graham