Introduction to "The Curious Disconnect"

This is the first of a series of postings by a guest blogger, Arlin Stoltzfus. Arlin has some important ideas about modern evolutionary theory and I'm happy to give him a chance to put them on Sandwalk.

Arlin Stoltzfus is a computational biologist with a background in bacterial population genetics and molecular evolution. He is a Research Biologist at the National Institute of Standards and Technology (NIST), and a Fellow of the Center for Advanced Research in Biotechnology. Much of his current work focuses on software and databases for evolutionary analysis, in collaboration with an international group of peers interested in improving interoperability. He also does basic research on evolution, and has contributed to our understanding of the history of introns, the origins of complexity, and the role of mutation in evolution. When he isn't doing science or spending time with family, his favorite diversions are playing the piano, bicycling, and martial arts.

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Introduction to The Curious Disconnect
Arlin Stoltzfus, ©2010
This is a longish introduction to a series of postings that will be released over the next 6 months or so. A version of this document with corrections and updated links will be maintained at http://www.molevol.org/files/cdblog/intro.html.

Striking a chord

The title of this series—The Curious Disconnect—comes from a 2002 article by eminent evolutionary geneticist Allen Orr (Orr 2002), who had broken new ground by developing predictive models of adaptation, and was reflecting on why such models weren't developed long ago, referring to "a curious disconnect between the verbal theory that sits at the heart of neo-Darwinism and the mathematical content of most evolutionary genetics".

That struck a chord with me. Since the 1990s, I had struggled with a "disconnect" that emerged while I was digesting a think-piece by paleontologists Elisabeth Vrba and Niles Eldredge (Vrba and Eldredge 1984). Among other things, Vrba & Eldredge made the startling suggestion that a key theme of "evo-devo" was that "bias in the introduction of phenotypic variation may be more important to directional phenotypic evolution than sorting by selection". By 1999 when Constructive Neutral Evolution appeared (Stoltfus 1999), my thinking had shifted noticeably toward emphasizing 1) the mechanistic distinction between the process of introducing variants and the (separate, subsequent) process of reproductive sorting (selection and drift), and 2) a research program of accounting for non-randomness (in evolution) by invoking both bias in the introduction process, and bias in the sorting process.

This way of thinking suggested that mutational-developmental bias in the introduction of variation was a general cause of evolutionary bias or direction. That contradicted two things I knew about evolutionary thinking. First, I knew that the notion of "internal" variational causes of direction, called "orthogenesis", had been rejected as a heresy. Second, I knew that, among contemporary researchers, mutation bias was not seen as a general bias on the course of evolution, but as a special aspect of neutral evolution, incompatible with selection.

I was confident that Vrba & Eldredge were headed in the right direction, but when I surveyed the theoretical literature, I could not find proof. Instead, Fisher, Haldane and Wright—the canonical founders of theoretical population genetics—all argued against a causal link between mutation and the direction of evolution, on the grounds that "mutation pressure" would be overcome by opposing "selection pressure", as in their mutation-selection balance models. Later, when "neutral" thinking became popular, this "opposing pressures" schema was interpreted to mean that mutation-biased evolution is possible, but only when selection "pressure" is absent. This was the conventional wisdom, but I knew it was wrong.

Thus, a few years later, when Lev Yampolsky and I (2001) used computer simulations to demonstrate that bias (mutational or developmental) in the introduction of variation is a possible cause of direction in neutral or adaptive evolution, we were showing a causal link that is both 1) a basic principle of population genetics, and 2) a heresy at odds with the professed views of the founders of population genetics.

What a "disconnect"! Indeed, the first premise of this blog series is that the "disconnects" in evolutionary biology are not just curiosities, but important challenges.

Deeper into the "disconnect"

Eventually I came to see these two "disconnects" as parts of the same syndrome. The retarded development of what Orr sees as predictive models of "Darwinian adaptation" is due mainly to the fact that the models are not properly Darwinian. These models (like many used in molecular evolution) treat evolutionary change as a recurring origin-fixation process in which new mutant alleles are introduced, and then individually face acceptance or rejection according to a probability function representing the effect of reproductive sorting.¹ Our Darwinian ancestors rejected this kind of "lucky mutant" or "mutationist" framework as anti-Darwinian.

Instead, they were committed to a view in which adaptation takes place at many loci simultaneously on the basis of infinitesimal variation so abundant that the process does not depend on the rate of new mutations. Given such a view, "evolution" can be reduced to shifting the frequencies of alleles already in the "gene pool". When evolution is redefined in this way, the introduction process disappears and its effects become inaccessible. This explains the retarded development of the Yampolsky-Stoltzfus model.

Notice that this is not just a matter of "verbal theory" versus "mathematical content". Vrba & Eldredge had a verbal theory that suggested a way to combine causes, and Yampolsky & Stoltzfus demonstrated its implications formally with computer simulations; Wright, Haldane and Fisher had a verbal theory of combining causes that drew on mathematical treatments of mutation-selection balance. These two conceptions of evolution lead to two different predictions on a major issue.

This suggests that there are different theories about the role of variation in evolution, and indeed, there are.

Having different theories is not a bad thing. In a healthy scientific discipline, one expects different theories to compete with each other for success in prediction and explanation.

The problem is that this healthy sorting-out process isn't happening. The disconnects mentioned above go back generations. The problem is not that we haven't solved them already, but that we are not consciously and openly engaged in solving them. Rather than having a rigorous and decisive debate to resolve these and other troubling issues, we are bogged down in confusion.

The Wrong Turn

How did things get so muddled? I have a possible explanation. I don't expect you to believe my explanation just yet, because it depends on a lot of arguments that I have not presented yet. However, I need to present this historical hypothesis anyway to provide a context.

The main reason, in my opinion, that the process of science has gone so badly off track in evolutionary biology is the success of the Modern Synthesis.The main reason, in my opinion, that the process of science has gone so badly off track in evolutionary biology is the success of the Modern Synthesis. The Modern Synthesis was simultaneously both a reactionary theory of evolution- lets call it "Darwinism 2.0"- and a progressive socio-political campaign to establish Evolutionary Biology as a discipline with a unifying "modernist" narrative (a claim to subsume all relevant phenomena).

As a scientific theory, the Modern Synthesis replaced Darwin's fictional process of "fluctuating variation" with a verbal theory of the "gene pool". Like software engineers trying to re-design a popular application for a new operating system, the architects of the Modern Synthesis re-engineered the mechanistic "back end" of Darwinism to fit Mendelian genetics, but they left the "front end" the same, in order to preserve the familiar "look and feel" of Darwinism 1.0.²

The mechanistic secret to Darwinism 1.0 was variation on demand: "altered conditions of life" automatically turn on the flow of variation, producing abundant infinitesimal hereditary fluctuations precisely when (due to the "altered conditions of life") they would be leveraged by selection to build adaptation. Genetics refuted Darwin's theory of fluctuation (along with Lamarck's theory). The "gene pool" theory in Darwinism 2.0 held that Mendelian populations act as dynamic buffers of genetic diversity, so that abundant infinitesimal Mendelian variation is "soaked up like a sponge" and even "maintained", ensuring its constant availability. Thus, in Darwinism 2.0, the evolutionary engine comes with a tank full of fuel that automagically keeps itself full; in Darwinism 1.0, there is no storage tank, but fluctuating variation supplies fuel on demand, directly to the engine. Either way, the abundance of formless infinitesimal "raw materials" ensures that selection may spring into action to build anything, anywhere, anytime.

Though the "gene pool" idea was ingenious, no such reconciliation of Darwinism and genetics was necessary. A century ago, upon the discovery of genetics, scientists began moving rapidly toward a fresh and credible framework combining Mendelian genetics with reproductive sorting. While Darwin had rejected a role for "sports" or mutants on the grounds that they violated his principle of natura non facit salta (nature does not make leaps), early geneticists had no such doctrinal allegiances. With minor exceptions, they were ready to follow the evidence wherever it seemed to be leading, happily embracing dramatic saltations, and just as happily embracing tiny increments of change, depending on where the evidence seemed to point. They did not need to reconcile genetics with Darwinism, only with evolution.

But that was not enough for some. And that is when we took The Wrong Turn.

Within a generation, the leaders of the new discipline of Evolutionary Biology were all marching under a flag of unification—and there was no turning back. In hitching itself to Darwinism 2.0, the newly minted discipline of Evolutionary Biology had mortgaged its future to purchase the theoretical analog of a baroque castle. The proud new owners of this castle were not about to knock down any walls, much less to sell the place for something brighter and more open.

Science seeks consilience, and gets . . . muck

Science is driven by ingenuity, but its also driven by our aversion to cognitive dissonance. Uncovering and addressing "disconnects" or contradictions or paradoxes results in consilience, e.g., consilience between our intuitive verbal thinking, our mathematical theories, and our experimental results.

Surprises and contradictions invariably emerge in any discipline, and so this process of seeking consilience did not stop just because we underwent a mass conversion to monotheorism. The process continues, not by rejecting inadequate conceptual structures and building new ones, but by treating every challenge as a superficial problem that can be patched up with formless globs of conceptual mud- think of feckless notions like "constraints" or "contingency" or "molecular evolution". "Contingency" is a clumsy attempt to adapt a teleological and deterministic world-view to fit dynamic indeterminism.

The notion of "constraints", likewise, is a kludge to adapt an idealized view in which selection chooses from among all that is possible, to fit more closely to the reality that the process of variation renders some possibilities more likely than others. Ideally, we would have a theory that treats variation not as a static precondition, but as a process with kinetics that impose biases on the process of evolution. What we have instead is a concept of "constraint" that, if interpreted literally, is inadequate to cover all but the most extreme cases of variational effects (which typically are not rigid restrictions, but mere quantitative preferences), and if interpreted vaguely enough, can cover anything. Recasting the role of variation in terms of dynamic processes would require major renovations to the baroque castle, and who has time for that? Rather than developing a new view, we have opted for the vagueness and flexibility of "constraints".

Likewise, under healthier conditions, "molecular evolution" would have brought down the castle. Remarkably, in the 1970's, the same clique of influential thinkers (Mayr, Simpson, Dobzhansky, et al) were both 1) congratulating each other for having unified biology—not just evolution, but all of biology—in the Modern Synthesis (Mayr and Provine 1980), and 2) waging a deliberate campaign to convince biologists that results from molecular comparisons that seemed to fly in the face of this Modern Synthesis were not a direct challenge, because "molecular" and "organismal" represented different "levels" of organization with different metaphysical leverages, one for addressing ultimate "why" questions, and the other for mechanistic "how" questions (Dietrich 1998). Darwinism 2.0 survived due to our willingness to embrace a vapid new catechism: molecular evolution is different (but we still have one theory).

The "curious disconnect" is like a major rift or canyon, but its so full of mud that some pandits survey the state of evolutionary biology, and see only solid ground:

Any criticism of the synthetic theory that turned out to have some substance was subsumed in a modified version of this theory. Instead of being a weakness, this ability to change is one of the chief strengths of the synthetic theory of evolution" (Hull, 2002)

This is the process of reconciliation at work, and as you can see, sometimes the result is a steaming pile of offal.

Thus, the second premise of The Curious Disconnect is that, in the absence of a rigorous reconciliation of "disconnects", what we got instead is just a muddled, non-rigorous reconciliation. As this process continued decade after decade, we got bogged down in the muck.

The last "Synthesis" we'll ever need, or want?

Importantly, when I refer above to The Wrong Turn, I do not mean merely that a weak theory emerged with enthusiastic support. That might have been easy to fix-- by simply discarding the theory later-- had it not been for a more subtle shift by which we came to believe that our discipline required a single formalism to encompass everything we do and to provide all the answers to The Big Questions of evolution. We decided that, in order to be legitimate, we had to have an "ism".

One indication that we feel this way is that every few years, one of my colleagues notices that we've outgrown our ism, leaving some embarrassing bits exposed, and proposes to remedy this by calling for a "Newer" or "Extended" Synthesis, or calling on us to "finish" The Unfinished Synthesis. Not only do these proposals imply that 1) we used to have a comprehensive synthesis, and 2) such a synthesis continues to be possible and desirable, they also tend to suggest 3) the next synthesis really is here already, and just needs to be acknowledged.

I disagree with all of this, for reasons that I'll explain in subsequent posts.

For now, I just want to note that this doctrine of monotheorism is an anchor weighing us down. It sets an unachievable standard. It leads us to be embarrassed about the "disconnects" that we have, and to imagine that one new "synthesis" paper is going to set things right again, as though we already have agreed on a new set of answers and all it takes is for someone to state them out loud.

Contradictions, conflicts and "disconnects" are inevitable. The healthy approach to them is not to pretend that they don't exist, or shouldn't exist, but to confront them, beginning with the process of developing deep awareness.

So, I'm not going to propose another "synthesis". My primary goal is to raise awareness of problems and to achieve intellectual clarity, not to propose solutions. Once we are aware of the problems, we might all agree on the answers, but I doubt that the answers will be so obvious.

Whats ahead

This posting is just an introduction. I've tried to make three points. The first point is that there are deep "disconnects" or problems in the structure of evolutionary thought that have persisted for decades. Some of these diconnects relate to the role of variation in evolution.

The second point is that decades of attempts to rationalize conflicts and rescue decrepit doctrines and prop up the reputations of dead authorities have left us bogged down in confusion. This is not because the scientific issues are necessarily hard (though in some cases they are). Its because of the baggage we are carrying.

The third point is that a key part of this baggage is the belief that at every point in time all our work has to be subsumed by one great theory that is central to our identity as a discipline. I hope to convince you to reject this way of thinking. The realization that there are major problems to be solved ought to be exhilarating, not embarrassing. In my view, we should be starting a dialog, not calling for a resolution as though the problems were known and the answers were obvious.

So, when we wade into the "curious disconnect", we are going to be up our ears in muck that has accumulated for generations. But, we are not going to get bogged down, because we understand the nature of the problem and we aren't going to solve it all at once. We got into this mess primarily by a kind of shallow historical conservatism, preserving old doctrines and old ideas at the expense of conceptual rigor. To get out of this mess, we have to believe that, in science, its better to be clear than to be right. Our rule is going to be "if in doubt, toss it out". For instance, I truly believe that evolutionary theory would be better off if we all stopped invoking "random" and "constraint", immediately, today. "Random" is a constant source of confusion due to evolutionary biologists who are wedded to the doctrine "mutation is random" but who aren't committed to using a standard meaning of "random", and who simply devise a special definition to rescue this doctrine.

If that sort of muck-raking sounds interesting to you, I hope that you will follow The Curious Disconnect as it unfolds. Below is a list of whats coming up (in no particular order, and subject to change):

• In a 4-part series, we'll explore The Mutationism Myth
  
• We'll see how a simple verbal ambiguity can cloud our thinking in theory(I) vs. theory(II)
  
• And we'll go further in this vein in Are there "mathematical" and "verbal" theories?
  
• In Render unto Selection we'll practice some ways to make causal attributions when multiple causes are at work
  
• Creativity and Gradualism will introduce the topic of Big Questions
  
• Then, in The Big Questions, we'll consider the scope and explanatory power of evolutionary theories (and be humbled by the results)
  
• In Mutation and Randomness (and other forms of domness), we'll learn how repeating a phrase will keep it alive even if no one knows what it means
  
• In What's your favorite popgen? we'll compare the 3 frameworks that have dominated theoretical evolutionary genetics
  
• I'll discuss Orr's particular "curious disconnect" in When "Darwinian" Adaptation Isn't
  
• We'll reject linguistic tyranny in Confronting Your Inner Fascist: what you "must" do
  
• You'll learn why I'm not yearning for another "synthesis" in The Last Synthesis We'll Ever Want
  
• We'll study ways to misinterpret evolutionary biology's simplest and most elegant theory in Misunderstanding the Neutral Theory
  
• In 4 Neutral Theories and 1 Big Misunderstanding we'll consider the neutral theories of biogeography, molecular evolution, paleontology and ecology
  
• So, you're saying its all just random? explains Constructive Neutral Evolution, and some curious responses to it
  
• In Scientific Creationism, we'll poke fun at the recurring phenomenon of scientific origin theories that push all the interesting stuff so far back in time that the theory has no useful implications

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1. This origin-fixation framework rose to prominence in the context of "molecular evolution" and the Neutral Theory, but can be traced back to the early work of geneticists such as TH Morgan. 2. For the sake of simplicity, I'm leaving out the theory originally known as "neo-Darwinism", which we could think of as "Darwinism 1.2". This view, championed by Wallace and Weismann, preceded the Modern Synthesis as well as many early discoveries of genetics, and it particularly emphasized the abundance and universality of infinitesimal variation. While Darwin's original view included acquired effects (a la Lamarck) and direct effects (a la Buffon), neo-Darwinism had only the mechanism of infinitesimal variation plus selection, which was the core of Darwin's theory and his most distinctive contribution. Dietrich, M. R. 1998. Paradox and persuasion: negotiating the place of molecular evolution within evolutionary biology. J Hist Biol 31:85-111. Hull, D. L. 2002. History of Evolutionary Thought. Pp. E7-E16 in M. Pagel, ed. Encyclopedia of Evolution. Oxford University Press, New York. Mayr, E., and W. B. Provine. 1980. The Evolutionary Synthesis: Perspectives on the Unification of Biology. Pp. 487. Harvard University Press, Cambridge, Mass. Orr, H. A. 2002. The population genetics of adaptation: the adaptation of DNA sequences. Evolution Int J Org Evolution 56:1317-1330. Stoltzfus, A. 1999. On the possibility of constructive neutral evolution. J Mol Evol 49:169-181. Vrba, E. S., and N. Eldredge. 1984. Individuals, hierarchies and processes: towards a more complete evolutionary theory. Paleobiology 10:146-171. Yampolsky, L. Y., and A. Stoltzfus. 2001. Bias in the introduction of variation as an orienting factor in evolution. Evol Dev 3:73-83.

Arlin Stoltzfus explains evolutionary theory

A few days ago, I asked the following questions, Is the "Modern Synthesis" effectively dead?, and What do they mean when they say they want to extend the Modern Synthesis?. The point I was trying to make was that there are many different views on evolutionary theory and it's often difficult to figure out which version of evolutionary theory someone is defending.

For example, which version of evolutionary theory is compatible with the "selfish gene" as a metaphor for evolution? Or for adaptation? Which version of the "Modern Synthesis" is being attacked in the book edited by Massimo Pigliucci and Gerd Müller? Is it the version defended by Ernst Mayr? Does it incorporate Neutral Theory and random genetic drift?

The "Mutationism" Myth I. The Monk's Lost Code and the Great Confusion

This is the second in a series of postings by a guest blogger, Arlin Stoltzfus. You can read the first part at: Introduction to "The Curious Disconnect". Arlin is challenging the status quo in modern evolutionary theory. He's not alone in this challenge but it's important to distinguish between kooks who don't know what they're talking about and serious thinkers who have something to say. Arlin is going to explain to you why everything you thought you knew about mutationism is wrong. I'm happy to give him a chance to post on Sandwalk.

This will be on the exam.

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The Curious Disconnect

The Curious Disconnect is the blog of evolutionary biologist Arlin Stoltzfus, available at www.molevol.org/cdblog. An updated version of the post below will be maintained at www.molevol.org/cdblog/mutationism_myth1 (Arlin Stoltzfus, ©2010)

The "Mutationism" Myth I. The Monk's Lost Code and the Great Confusion

The mutationism myth tells the story of how, just over a century ago, the scientific community responded to the discovery of Mendelian genetics by discarding Darwinism, and how Darwinism subsequently was restored.Our journey to explore The Curious Disconnect-- the gap between how we think about evolution and how we might think if we were freed from historical baggage-- begins with the Mutationism Myth. In this, the first of four parts, we are not going to confront any tough scientific or conceptual issues. Instead, we are just going to review an odd story about our intellectual history.

The Mutationism Story

While "myth" has the connotation of falsehood, the story that a myth tells isn't necessarily a false one. The mutationism myth, at least, is anchored in historical events.¹

The mutationism myth tells the story of how, just over a century ago, the scientific community responded to the discovery of Mendelian genetics by discarding Darwinism, and how Darwinism subsequently was restored. The villains of the story are the influential early geneticists or "Mendelians" who saw genetics as a refutation of Darwinism; the heroes are first, the founders of population genetics, theoreticians who sorted everything out in favor of Darwinism by about 1930, and second, the architects of the Modern Synthesis, activists who popularized and institutionalized what we're calling "Darwinism 2.0".

This story has been re-told in secondary sources for nearly 50 years, though I sense that the frequency is decreasing as this episode passes into ancient history. To find examples, try looking up "mutationism" (sometimes "Mendelism" or even "saltationism") in the index of a book about evolution.

I encourage you to consult whatever sources you have and to share the stories that you find. Note that you won't always be successful. A quick survey of several dozen contemporary books on my shelf reveals that most don't address this episode specifically (a notable absence, in some cases ²); some tell the mutationism myth with varying degrees of panache; and a few provide a historical account rather than a myth. The few historical accounts that I found were in Gould's 2002 The Structure of Evolutionary Theory, Strickberger's 1990 textbook Evolution, and the Wikipedia entry on "Mutationism".

Sample stories

Lets look at a few examples of the mutationism story. Readers who want to check out a freely available online source from the scholarly literature may refer to Ayala and Fitch, 1997 (http://www.ncbi.nlm.nih.gov/pubmed/9223250?dopt=Citation). One example that really caught my eye is not from scientific literature, but from the 2005 obituary for Ernst Mayr in The Economist:

It was not that biologists had given up on evolution by the 1940s-quite the contrary. But they had got very confused about its mechanism. . . . The geneticists of the early 20th century did not help. They rediscovered the laws of inheritance first developed 40 years earlier by Gregor Mendel, an unsung Moravian monk. They also discovered the idea of genetic mutation. But instead of linking these things to natural selection, they came up with the idea of "saltation"-in other words, sudden mutational shifts from one well-adapted species to another. Nor, the geneticists complained, had there been enough time for natural selection to do its work, given what they had discovered about the rate at which mutations occur, and the fact that most mutations are deleterious. It was all a bit of a mess. . .Mr Mayr's advantage over the laboratory-bound biologists who had hijacked and diluted Darwin's legacy was that, like Darwin, he was a naturalist-and a good one. (anonymous, 2005)

Of course, this is a magazine article, written by anonymous staff writers-- typically one doesn't see such florid language in the scholarly literature. But did the staff writers of the Economist (representing elite opinion) really originate this story, based on their own personal recollections of the 1930's? Of course not. Mayr himself popularized the image of geneticists as laboratory-bound geeks lacking the organic insight of "naturalists". This disdain for the geneticists who "hijacked" Darwin's legacy is readily apparent when evolutionary writers depict geneticists as fools holding "beliefs" that have "obvious inadequacies", unable to understand or "grasp" their own scientific findings:

"It is hard for us to comprehend but, in the early years of this century when the phenomenon of mutation was first named, it was regarded not as a necessary part of Darwinian theory but as an alternative theory of evolution! There was a school of geneticists called the mutationists, which included such famous names as Hugo de Vries and William Bateson among the early rediscoverers of Mendel's principles of heredity, Wilhelm Johannsen the inventor of the word gene, and Thomas Hunt Morgan the father of the chromosome theory of heredity. . . Mendelian genetics was thought of, not as the central plank of Darwinism that it is today, but as antithetical to Darwinism. . . It is extremely hard for the modern mind to respond to this idea with anything but mirth" (Dawkins, 1987, p. 305)

"According to mutationism, random changes in the hereditary material are sufficient for adaptation without much, or any, selection at all. Mutations just somehow happen to be adaptive, the right changes simply manage to occur. The inadequacies of this view are obvious" (Cronin, 1991, p. 47).

"Darwin knew nothing of this [i.e., genetics] but as it turned out, his ignorance was sublimely irrelevant to the problem he was really interested in tackling: evolution. This point was not fully grasped by biologists. Many early geneticists at the dawn of the 20th century, thought their discoveries of the fundamental principles of genetics somehow cast doubt [on], or rendered obsolete, the concept of natural selection. It took several decades of experimentation and theoretical (including mathematical) analysis to show not only that there was no conflict inherent between the emerging results of genetics and the older Darwinian notion of natural selection, but that the two operate in different domains." (Eldredge, 2001, p. 67)

"Mendelian particulate inheritance (today, we call the "particles" genes) was originally identified with De Vries's "mutation theory", according to which new variations or species originated in large jumps, or macromutations, and evolution was exclusively explained by mutation pressure. Darwinian naturalists, believing that Mendelism was synonymous with mutation theory, held on to theories of soft inheritance, while they considered selection a weak force at best. They did not know of the new findings in genetics that would have supported Darwinism. (SegerstrŒle, 2002)

Notice how, in every version of the story above, the position taken by early geneticists just doesn't make sense. This isn't a story of theory versus theory, its a story of confusion ultimately yielding to reason.

If de Vries and the other geneticists are playing the role of the pied piper in this story, the "naturalists" are like the children lured away from their Darwinian home. Ultimately the innocents are returned, and order restored, by (oddly enough) mathematicians:

"Between 1918 and 1932 Fisher, Haldane, and Wright showed that Mendelian genetics is consistent with natural selection. Only then, more than 60 years after the publication of The Origin of Species, was the genetic objection to natural selection finally removed. Modern molecular and developmental genetics have confirmed in exquisite chemical detail the key aspects of genetics necessary for Darwin's ideas to work: that the genetic material is DNA, that DNA has a sequence, . . . mutates . . . contains information . . " (p. 16 of Stearns and Hoekstra, 2005)

Anatomy of a Myth

In a subsequent post, we will look at original sources to see what the "mutationists" actually believed, and why. And eventually we will integrate this into the bigger picture of how evolutionary theory developed. But for now, lets just summarize the pattern that is apparent in the literature.

First, the mutationism story is clearly a story or myth, and not an ordinary scientific truth claim. We can see this because the story-tellers are not using ordinary scientific conventions to convince us that the story is true. If you or I were making an ordinary scientific argument (for instance) for an effect of "translational selection" on codon usage, we would mention a correlation between codon frequencies and the abundance of corresponding tRNAs, citing the classic work of Ikemura (1981), and we might even repeat a figure showing this correlation, to impress this point upon the minds of readers (e.g., just as in Ch. 7 of Freeman & Herron, 1998).

When I see instances of the mutationism story, typically I don't find quotations illustrating what the mutationists believed, nor facts & figures to refute their views, but only vague attributions and generalized claims. Apropos, the following quotation from Ernst Mayr never fails to make me laugh:

The genetic work of the last four decades has refuted mutationism (saltationism) so thoroughly that it is not necessary to repeat once more all the genetic evidence against it. (Mayr, 1960)

And the puissant Dr. Mayr proceeds on, not boring the reader with any tiresome "genetic evidence", nor citing sources that might allow the reader to evaluate the truth of his statement. Its a story, after all.

By contrast, the 3 sources that I mentioned above as providing scientific history, rather than myth, all make reference to specific experimental and theoretical results, and reveal knowledge of specific historically important scientific works. For instance, Strickberger's reference list includes Johannsen, 1903, as well as the 1902 paper by Yule that reconciled Mendelian genetics with quantitative variation (in neo-Darwinian mythology, credit for Yule's work is given to little Ronny Fisher, who was 11 at the time).

Second, every story has a plot or "action", and the main action of the mutationism story is a turn of fate in which power is temporarily in the hands of the wrong people or ideas. In archetypal terms, its a story of usurpation and restoration: the throne is usurped, and the kingdom falls into darkness and confusion until the throne is restored to the king's rightful heirs. The mutationism episode didn't have to be told that way: it might have been presented as a period of reform (in which old ideas were abandoned) or discovery (when new territory was mapped out). Instead, its presented as a mistake, an interlude of confusion, a collective delusion.

Indeed, another way to look at the mythic action is that the Mendelians are wizards or false prophets who place the kingdom under a spell, leading folks astray and causing them to believe things that they just shouldn't have believed.

What delusional spell did the Mendelians cast? In the story by Eldredge, or by Stearns & Hoekstra above, the spell is that Mendelian genetics is inconsistent with "the concept of natural selection" (Eldredge). In the story told by SegerstrŒle, Cronin, Mayr and The Economist, the delusional spell is a bit different: the principle of selection is irrelevant because mutational jumps alone explain evolution.

Third, the key to restoring Darwin's kingdom was to add the missing piece of genetics. Ultimately, after the period of darkness ended, the discovery of genetics "provided the missing link in Darwin's theory" (SegerstrŒle, 2002), or "The missing link in Darwin's argument was provided by Mendelian genetics" (Ayala & Fitch, 1997). Darwinism was restored, not by taking away the power of genetics, but by redirecting it to support Darwinism. Clearly, genetics is the key to ruling the kingdom, like the One Ring that Rules them All in Tolkien's world. The ones who have the ring have the power.

The story is made more fascinating by the fact that the key to power is literally a code of rules developed by a monk that remained lost for nearly half a century. The usurpers who discover The Monk's Code misinterpret it, and use it to overthrow the true king, establishing a reign of error. But when The Founders decipher the true meaning of the Monk's Code, The Architects campaign throughout the kingdom, spreading the news: the Monk's Code proves that Darwin is the true king. Darwin's rule is re-established, all opposition ceases, and the kingdom is unified.

Homework

If you would like to contribute a mutationism story, I would be happy to start a collection if you make it easy for me by providing a complete and well formed text item. Be sure to provide a quoted passage with a source, citing exact page numbers. If we get enough stories, lets try to recruit a sociologist or historian to study this further.

Summary

To summarize, the mutationism story is a myth that is retold in secondary sources. The basic story is simple: the discoverers of genetics misinterpreted their discovery, thinking it incompatible with Darwinism; Darwinism went into disfavor; population geneticists came along and showed that genetics was the missing key to Darwinism; Darwinism was restored and once again reigned supreme.

Next time on the The Curious Disconnect, we'll start pulling on some of the loose threads of this story.

For now, note how the writers quoted above are genuinely baffled by our scientific history. It just doesn't make sense to them. A century ago, most of an entire generation of scientists thought of genetics as a contradiction of Darwinism. This is a historical fact, and presumably it has an explanation that rational folks can understand by examining what scientists of the time wrote. But this historical fact mystifies Dawkins, Eldredge, Cronin, and others.

References

Anonymous. 2005. Ernst Mayr, evolutionary biologist, died on February 3rd, aged 100. The Economist, February.

Ayala, F. J., and W. M. Fitch. 1997. Genetics and the origin of species: an introduction. Proc Natl Acad Sci U S A 94:7691-7697.

Cronin, H. 1991. The Ant and the Peacock. Cambridge University Presss, Cambridge.

Dawkins, R. 1987. The Blind Watchmaker. W.W. Norton and Company, New York.

Eldredge, N. 2001. The Triumph of Evolution and the Failure of Creationism. W H Freeman & Co.

Freeman, S., and J. C. Herron. 1998. Evolutionary Analysis. Prentice-Hall, Upper Saddle River, New Jersey.

Gould, S. J. 2002. The Structure of Evolutionary Theory. Harvard University Press, Cambridge, Massachusetts.

Ikemura, T. 1981. Correlation between the abundance of Escherichia coli transfer RNAs and the occurrence of the respective codons in its protein genes: a proposal for a synonymous codon choice that is optimal for the E. coli translational system. J Mol Biol 151:389-409.

Mayr, E. 1960. The Emergence of Evolutionary Novelties. Pp. 349-380 in S. Tax, and C. Callender, eds. Evolution After Darwin: The University of Chicago Centennial. University of Chicago Press, Chicago.

SegerstrŒle, U. 2002. Neo-Darwinism. Pp. 807-810 inM. Pagel, ed. Encyclopedia of Evolution. Oxford University Press, New York.

Stearns, S. C., and R. F. Hoekstra. 2005. Evolution: an introduction. Oxford University Press, New York.

Strickberger, M.W. 1990. Evolution (1st edition).

Notes
¹ The defining characteristic of a myth is not that it isn't literally true, but that it isn't told for reason of being literally true, but for reason of being meaningful or poignant: a myth is a story with a cultural value, not necessarily a literal-truth value. The connection between myths and untruths, then, has to do with discoverability: when we find a pattern P = { X people are repeating story Y }, where X is a large number, this pattern by itself does not prove that Y is a myth because X people might have all discovered or verified Y independently; but if Y has diverse elements that are untrue (or unverifiable), then we can conclude that its repetition does not signify independent verification, suggesting that its a myth.



²The Oxford Encyclopedia of Evolution does not have an article on mutationism; the article on Morgan says nothing of his views on evolution; there is no article on Bateson; mutationism is only addressed peripherally in Hull's article on the history of evolutionary theory; it is mainly addressed in SegerstrŒle's article on neo-Darwinism.

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The Mutationism Myth, VI: Back to the Future

This is the eighth in a series of postings by guest blogger, Arlin Stoltzfus. You can read the introduction to the series at: Introduction to "The Curious Disconnect". The first part is at: The "Mutationism" Myth I. The Monk's Lost Code and the Great Confusion. The second installment is: Theory vs Theory. The third part is: The Mutationism Myth, II. Revolution. The fourth installment is: The Mutationism Myth: III Foundations of Evolutionary Genetics. Part five is The Mutationism Myth, IV: Mendelian Heterodoxies. The sixth installment was The Mutationism Myth, V: The response to Mendelian heterodoxies.

This is Arlin's last contribution. The entire series has been an excellent introduction to the history of evolutionary theory and the concept of mutationism. There are many ways in which the so-called "Modern" Synthesis has to be revised and extended. One of them is to reinstate the concept of mutationism which was purged from evolutionary theory in the 1940s. If you want to understand why this is important then these articles are the place to start.

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The Curious Disconnect

Today on The Curious Disconnect (credits), we wrap up our 6-part series on the Mutationism Myth, and set the stage for the future by locating the primary weakness of the 20th century neo-Darwinian consensus in its theory of variation.

I'd like to thank Larry Moran for hosting this series of posts on Sandwalk. If it still seems like a good idea later in the year, I will continue the Curious Disconnect on my own blog site (to be announced).

The Mutationism Myth, part 6. Back to the Future

The Mutationism Myth, a story about how the discovery of genetics affected evolutionary thought, continues to be part of modern neo-Darwinism's monologue with itself (e.g., Charlesworth and Charlesworth, 2009), being used even by leading thinkers calling for an "Extended" Synthesis (e.g., Pigliucci, 2010 ¹). Since April, we've been deconstructing the Mutationism Myth by exploring what the early Mendelians actually thought, and how their view was replaced by the Modern Synthesis (MS).

Today we'll take the opportunity to review what we've learned and start unpacking its relevance for the future of evolutionary biology.

Review

In the Mutationism Myth (see part 1 for examples), the founders of genetics misinterpret their discovery, concluding that evolution takes place by large mutational jumps, without selection. The false gospel of these "mutationists" brings on a dark period of confusion and error that lasts until the 1930s, when theoretical population geneticists (Fisher, Haldane and Wright) prove that Mendelian genetics is not only compatible with selection, but provides the missing link that completes Darwin's theory and unites all the biological disciplines. The "Modern Synthesis" combining genetics and selection becomes the foundation for all subsequent evolutionary thought.

As we discovered, the Mutationism Myth isn't very accurate. Heredity is not missing from Darwin's theory; selection is not missing from the Mendelian view. Darwin had a theory of heredity both in the sense of a set of phenomenological laws, and in the sense of a mechanism to account for them (part 2). Both were wrong. The Mendelians synthesized genetics and selection, rejecting Darwin's "Natural Selection" theory due to its dependence on fluctuations or "indefinite variability" (defined by Darwin as the subtle variations that arise anew each generation in response to conditions of life). As we know today, such enrivonment-induced fluctuations are non-heritable.

In part 3, we found that the Mendelians laid the conceptual foundations of evolutionary genetics (later formalized mathematically), while part 4 addressed how their view diverged from Darwinian orthodoxy. The Mendelians assumed that new hereditary variants arise rarely and discretely, by mutations whose effects may be large or small. Each new mutation is likely to be rejected, but it may be accepted by chance, especially if it improves fitness. Because, in this view, change depends on discrete events of mutation, the Mendelians (part 4) considered the process of mutation to be a source of initiative, discontinuity, creativity and direction in evolution (Stoltzfus, 2006). This view expanded the role of variation well beyond the subordinate role of raw materials that Darwin had imagined.

The Mendelians were unable to convince naturalists (the majority of their biologist peers) to accept their new view of evolution, nor even a new view of inheritance. Many naturalists remained wedded to Lamarckian and Darwinian views of "soft inheritance".

As we found out in part 5, the "Modern Synthesis" (modern neo-Darwinism) claimed to reconcile Darwin's own view with genetics, though it quietly ignored Darwin's errors while depicting the Mendelians as foolish "saltationists", dismissing their "lucky mutant" view and their ideas about the role of mutation in evolution. In the MS view, each species has a "gene pool" that automatically soaks up and "maintains" hereditary variation, providing abundant "raw materials" for adaptation. The key innovations of this view were to define "evolution" as "shifting gene frequencies" in the "gene pool", to erase the link between "Darwinism" and Darwin's own theory of soft inheritance, and to develop a theory of causation in terms of population-genetic "forces", in which continuous shifts in allele frequencies are the common currency of causation. The new theory put mutation in a subordinate position of supplying infinitesimal "raw materials" for selection. As a result, the MS created a consensus where the Mendelians had failed: naturalists such as Ernst Mayr found that they could accept Mendelian genetics without giving up adaptationist preconceptions.

A bright line

The backdrop for this whole discussion (in case you missed it) is that the MS is strikingly wrong in its neo-Darwinian departures from the Mendelian view. I've implied this several times, and perhaps I've waved my hands and pointed vaguely to mountains of molecular evidence contradicting the MS, but I haven't made this point perfectly clear.

In a moment, I will do that, but first I want to make clear what is at stake.

The Mendelians allowed that evolutionary change could be initiated by an event of mutation, and they interpreted this to mean that mutation was (to an unknown degree) a source of initiative, discontinuity, creativity and direction in evolution. The MS represents a very deliberate rejection of this view, and proposes instead that evolution is a complex sorting out of available variation to achieve a new multi-locus equilibrium, literally by "shifting gene frequencies" in the "gene pool". The rate of evolution, in this view, does not depend on mutation, which merely supplies the "gene pool" with variation; evolution is not shaped by mutation, which is the "ultimate" source of variation, but not the proximate source.

When I made this distinction at a 2007 symposium in honor of W. Ford Doolittle, Joe Felsenstein was in the audience and pointed out that, while Fisher may have looked at things in this way, Wright's stochastic view took into account random events, like new mutations. It's true that Wright's "shifting balance" model assigns a prominent role to random genetic drift, while Fisher's view was deterministic. However, these are just two different flavors of the same "shifting gene frequencies" paradigm: neither view incorporates new mutations. The absence of new mutations from Wright's shifting balance process is apparent from the fact that Patrick Phillips (1996) extended it to include a new starting phase ("phase 0") of "waiting for a compensatory mutation".

The fact that contemporary evolutionary biologists, for the most part, don't understand this aspect of their intellectual heritage is not evidence of a cover-up. Scientists don't get much chance to learn history. The history that they absorb is mainly from stories that appear in scientific writings, like the Mutationism Myth and the Essentialism Story, stories that represent Synthesis Historiography (Amundsen, 2005), the discipline of telling history in ways that make things turn out right for the Modern Synthesis. Synthesis Historiography teaches us that "saltationism" (Mayr's pejorative term for the Mendelian view) and other alternatives to neo-Darwinism are nonsensical, "doomed rivals", supported only by "typologists", creationists, vitalists and other crazies. That is, Synthesis Historiography teaches the TINA doctrine: There Is No Alternative.

As contemporary research drifts away from the "gene pool" theory and the Darwinian doctrines of the MS, each evolutionary biologist remains confident that, due to the TINA doctrine, his own view must be "neo-Darwinian". In reality, alternatives are being explored with increasing vigor in molecular evolution, evo-devo, and evolutionary genetics.

A few folks today are in the reverse situation of being familiar with MS orthodoxy, but not with recent research. Dawkins (2007) stakes his critique of a book by "intelligent design" creationist Michael Behe entirely on his faith in the gene pool theory. Behe claims, in effect, that there was not sufficient time for all the mutations needed to account for evolution. Dawkins responds by attacking the premise that evolutionary rates depend on mutation rates:

"If correct, Behe's calculations would at a stroke confound generations of mathematical geneticists, who have repeatedly shown that evolutionary rates are not limited by mutation. Single-handedly, Behe is taking on Ronald Fisher, Sewall Wright, J.B.S. Haldane, Theodosius Dobzhansky, Richard Lewontin, John Maynard Smith and hundreds of their talented co-workers and intellectual descendants. Notwithstanding the inconvenient existence of dogs, cabbages and pouter pigeons, the entire corpus of mathematical genetics, from 1930 to today, is flat wrong. Michael Behe, the disowned biochemist of Lehigh University, is the only one who has done his sums right. You think? The best way to find out is for Behe to submit a mathematical paper to The Journal of Theoretical Biology, say, or The American Naturalist, whose editors would send it to qualified referees."

With his signature over-the-top rhetoric, Dawkins insists that "mathematical genetics" has proven that evolutionary rates are not limited by mutation. Allowing for some exaggeration, this is an accurate representation of MS orthodoxy ca. 1959, the approximate vintage of Dawkins's views. If Mayr had been alive, he might have said the same thing.

Meanwhile, no one who has been active in evolutionary genetics research in the past 15 years would represent the current state of knowledge in this way. If you want to know what a contemporary researcher would say, take a look at the most recent issue of Evolution in which the article by Douglas Futuyma (famous for his evolution textbook) gives many examples of how evolutionists (including himself) repeated the doctrine that mutation does not "limit" evolution, but argues that we are no longer making this dubious assumption. Another example would be the piece by Ronny Woodruff and James Thompson (1998) that introduces their symposium volume on Mutation and Evolution.²

Yet the MS and its "gene pool" theory have left their mark on evolutionary biology, even if the MS itself has largely disappeared from the collective memory of researchers. One indelible mark is what Gillespie calls "The Great Obsession" of population genetics to understand the "maintenance of variation", but that's a story for another day.

Another indelible mark is the long absence of mutationist models of "adaptation", a topic that has blossomed just in the last dozen years. Allen Orr has achieved well deserved fame for his innovations in this area, and we'll discuss his work briefly in the next section. For now, let us note how other researchers have pointed out the absence of such models:

"Almost every theoretical model in population genetics can be classified into one of two major types. In one type of model, mutations with stipulated selective effects are assumed to be present in the population as an initial condition . . . The second major type of models does allow mutations to occur at random intervals of time, but the mutations are assumed to be selectively neutral or nearly neutral." (Hartl & Taubes, 1998)

"The process of adaptation occurs on two timescales. In the short term, natural selection merely sorts the variation already present in a population, whereas in the longer term genotypes quite different from any that were initially present evolve through the cumulation of new mutations. The first process is described by the mathematical theory of population genetics. However, this theory begins by defining a fixed set of genotypes and cannot provide a satisfactory analysis of the second process because it does not permit any genuinely new type to arise. " (Yedid and Bell, 2002)

These authors are not trying to make a point about history or about the Modern Synthesis: they are simply claiming the novelty of their own models of adaptation that incorporate new mutations. And what they are saying is that the paradigm of 20th-century population genetics is "shifting gene frequencies": overwhelmingly, it's a body of theory about what happens to the variation that is present in a population as an initial condition, not about a larger-scale process in which there are new beneficial mutations.³

One small step for a phage, one giant leap for evolutionary biology

The actual role of mutation in evolution is not what is theorized in the MS. Many arguments could be made to support this contention, but I'm going to make just one argument drawing on one source, namely Rokyta, et al., 2005. I choose this argument because it is particularly compelling and concise. My argument addresses the lucky mutant view of initiative or (to put it another way) dynamics.

Rokyta, et al. is a study of parallel evolution in an experimental population of the bacteriophage phiX174, published in Nature Genetics. It was hailed as "the first empirical test of an evolutionary theory" (Bull & Otto, 2005), where the theory in question is Orr's (2002) ingenious extension of Gillespie's (1984) "mutational landscape" model to take into account predictions of extreme value theory.⁴

In spite of the fancy name, the "mutational landscape" model of sequence evolution is simple. Rather than considering all conceivable evolutionary changes from a starting sequence, we simplify the problem by considering only changes that occur via 1-bp mutations. That set of possibilities, by definition, is the "mutational landscape" or (my preferred term) the "evolutionary horizon". Each change will shift the evolutionary horizon, but it's easy to recompute the horizon, because it's easy to enumerate (theoretically) all the alternative sequences.

We are going to make this a model of beneficial changes ("adaptation"). A beneficial mutation is introduced into the population of N individuals at some total rate Nu, and faces acceptance with a probability of 2s, based on the classic formula p = 2s for the probability of fixation of a new beneficial mutation.⁵ For beneficial substitution i with selection coefficient s_i, the probability⁶ is just Nu*2s_i. If we divide an individual Nu*2s_i by the sum of all such values on the horizon, we get a normalized probability: the probability that the next step in our evolving system is step i. The factor Nu*2 is the same for every step, so it cancels out: only the s_i values matter. To evolve our sequence, we just sample from this probability distribution of possible steps, then recompute the new evolutionary horizon in preparation for the next step. Easy! ⁷

From past experiments, Rokyta, et al. know which steps on the horizon are beneficial, and they even know the selection coefficients. They know that sometimes, the same evolutionary steps happen in parallel, in replicate phage populations. They can compare the observed pattern of parallel evolution with the pattern predicted from theory.

Now, the preceding description suggests something fascinating: the cutting edge of evolutionary genetics today, with papers that get published in Nature Genetics with commentaries, uses experimental systems to explore the "lucky mutant" view of parallel evolution.

But the story gets even better. Rokyta, et al actually reject Orr's model, in its original version. They find more parallel evolution than expected. Why? Because the model treats all mutation rates equally. Note above that we canceled out mutation rates on the grounds that they are all the same. But that's not realistic. Some mutations are more likely than others, and this will affect the rate at which they are introduced into the population and subjected to acceptance or rejection. The more heterogeneity in rates of mutation, the more parallel evolution. Rokyta, et al. found that if they revised the model to take into account transition:transversion bias (I think it's about 5-or 6-fold under the experimental conditions), then the predicted amount of parallelism matched the observed amount.

Just let that soak in for a moment. We have an experimental study and a precise model. Evolution in this model is characterized by origin-fixation dynamics, dependent on the rate of mutational introduction of new alleles, and on their probability of fixation. Both factors affect the outcome of evolution; both factors affect the chance of parallelism. The experimental study eliminates (statistically) a model that lacks mutational bias in the introduction of new alleles. Thus the study clearly illustrates the dual causation of evolutionary change, in regard to its dynamics.

Back to the future

The MS is wrong, and not in a small way: it's wrong because reality just looks too much like the antithesis of the MS, i.e., the mutationist view. For instance, as we found out in part 4, Vavilov (1922; see Stoltzfus, 2006) understood the dual causation of parallel evolution, including the role of parallel variation. By contrast, Mayr famously said that the search for homologous genes or homologous mutations was foolish.

This mistaken prediction is repeated ad nauseam in the evo-devo literature. If you have been following along, you now understand why Mayr would make such a prediction. The MS makes substantive claims about evolution, among which are the claim that, while mutation is ultimately necessary to keep the "gene pool" from drying up, selection doesn't need to wait for a new mutation, but draws together a multi-locus optimum from the abundance of raw materials in the gene pool; "evolution" is so far removed from the process of mutation, with so many complex dynamic processes interceding, that the outcome of evolution does not depend on specific events of mutation. If evolution really were like that, parallel mutation would be unimportant. That is, Mayr's prediction accurately reflects the logic of the MS. But as the Rokyta, et al study (and many others) show, the prediction is not fulfilled.

According to Dawkins, "the entire corpus of mathematical genetics" from 1930 to "today" (i.e., about 1959, for Dawkins) would be "flat wrong" if one accepts the premise that evolution depends on new mutations, or that it is limited by the mutation rate. While this view is not often defended, that isn't because it's Dawkins's own personal opinion. Dawkins is accurately characterizing a theory that makes substantive claims about the world, a theory that most of us have forgotten. One of these claims is that "evolution" can be represented mathematically as a process of shifting the frequencies of alleles already present in an initial population, without new mutation; sometimes this doctrine is invoked by saying that "macroevolution" can be extrapolated from "microevolution".

If evolution actually worked like this, then evolutionary change would not exhibit a dependence on the rate of mutation, and Dawkins would be right in his criticism of Behe. But this is wrong. In fact, the dependence is so sensitive that effects of only a few-fold are noticeable, as the Rokyta, et al study (and many others) shows.

I'm not going to mince words. The MS is wrong, and not in a small way: reality looks too much like the mutationist view that we (the scientific community) rejected when we bought into the MS. We need another theory₁, perhaps several others.

The road less traveled

What's wrong about the MS, and what its replacement(s) must replace, is its theory of the role of variation in evolution. In future posts on the Curious Disconnect, I intend to focus on this issue. The Mutationism Myth suggests a lesson about how to develop (or rather, how not to develop) a theory of variation.

Darwin knew that hereditary variation played a vital role in evolution. He studied the subject intensely. He found that organisms vary in many different ways, and on many scales, but the evidence on heredity was bewildering and inconclusive. Lacking the means to derive a mechanism of evolution by reasoning upward from genetics, Darwin reasoned downwards from his premises that 1) organisms are exquisitely and pervasively adapted to their niches, 2) selection must have played some role in this, and 3) Mother Nature never makes a jump. Gould argues that Darwin's willingness to posit precise restrictions on variation was a stroke of genius.⁸ Darwin knew that discrete "sports" (mutants) could be heritable, but he discounted them: they could not make his theory work as desired. Instead, he staked his "natural selection" theory on the heritability of fluctuations, because they were infinitesimal, indefinite (unbiased), and "everywhere present", being induced in abundance whenever organisms encountered altered "conditions of life". Inferring the heritability of fluctuations completed his theory and made it work.

But it was wrong: the fluctuations that made Darwin's theory work are non-heritable, as the Mendelians discovered.

The architects of the MS tried again, with advantages unavailable to Darwin. Not only did they know genetics, they had some mathematical tools to work out unforeseeable implications of genetic concepts. However, they didn't have the knowledge to distinguish among different, genetically consistent modes of evolution. They had to fill in this gap somehow. Their downwards Darwinian reasoning and their upwards Mendelian reasoning met in the middle with the "gene pool": a theory of population genetics that would supply abundant, infinitesimal, "random" variations, in order to rationalize their commitment to the same premises Darwin accepted. That was the genius of the MS.

But again, it was wrong.

If we look at Darwinism in Popperian terms, as a theory₁ that takes risks and generates potentially falsifiable claims, then (counterintuitively) it is largely a theory of the role of variation in evolution. The claims that selection is "important", and that it has some inalienable role in adaptation, carry little risk and have been widely accepted for 150 years. By contrast, the restrictions that Darwinism places on variation, in order to make it a subordinate factor that supplies "raw material" to selection, are risky and controversial, e.g., the claim that variation is random with respect to the direction of evolution, or that the rate of evolution does not depend on the rate of mutation, or the "gradualist" claim that variation is not a source of discontinuity. The architects of the MS invested the "gene pool" with nearly magical properties in order to improve the prospects for adaptation. Problematic claims about the role of variation are, and have been for 150 years, the overwhelming basis for scientific criticism of Darwinism.

And this problematic view of variation is based on reasoning from the premise that organisms are exquisitely and pervasively adapted to their niches, to the conclusion that variation must play just the right role of supplying abundant raw materials to make this possible. I believe that there is something fundamentally wrong with this mode of reasoning. Perhaps it betrays a kind of subconscious Panglossian agenda. Every time I give a lecture on mutation-biased evolution, someone suggests that perhaps the mutation biases themselves are adaptive, as though this inference could restore one's faith that everything turns out for the best, and that "the ultimate source of explanation in biology is the principle of natural selection" (Ayala, 1970). Remarkably, the evo-devo-inspired view that seems destined for inclusion in the emerging "Extended Synthesis" is headed down much the same path, with a focus on the idea that the process of variation has been jiggered to make things turn out right for adaptation. What's revealing about this new view is how little attention its proponents have paid to understanding precisely, in terms of population-genetic causation, how the process of variation shapes evolution, before jumping ahead to the shadowy inference that the process of variation itself was shaped by selection for this very role.

We are not going to go down that same road here on the Curious Disconnect, which should make things all the more interesting.

References

Ayala, F. J. 1970. Teleological Explanations in Evolutionary Biology. Philosophy of Science 37:1-15.

Bull, J. J., and S. P. Otto. 2005. The first steps in adaptive evolution. Nat Genet 37:342-343.

Charlesworth, B., and D. Charlesworth. 2009. Darwin and genetics. Genetics 183:757-766.

Dawkins, R. 2007. Review: The Edge of Evolution. Pp. 2. International Herald Tribune, Paris.

Gould, S. J. 2002. The Structure of Evolutionary Theory. Harvard University Press, Cambridge, Massachusetts.

Hartl, D. L., and C. H. Taubes. 1998. Towards a theory of evolutionary adaptation. Genetica 103:525-533.

Medawar, P. B. 1967. The Art of the Soluble. Methuen and Co., London.

Nei, M. 2007. The new mutation theory of phenotypic evolution. Proc Natl Acad Sci U S A 104:12235-12242.

Orr, H. A. 2002. The population genetics of adaptation: the adaptation of DNA sequences. Evolution Int J Org Evolution 56:1317-1330.

Phillips, P.C. 1996. Waiting for a compensatory mutation: phase zero of the shifting-balance process. Genetical Research, Cambridge 67:271-283.

Rokyta, D. R., P. Joyce, S. B. Caudle, and H. A. Wichman. 2005. An empirical test of the mutational landscape model of adaptation using a single-stranded DNA virus. Nat Genet 37:441-444.

Woodruff, R. C., and J. D. Thompson. 1998. Preface in R. C. Woodruff, and J. D. Thompson, eds. Mutation and Evolution. Kluwer, Dordrecht, The Netherlands.

Yedid, G., and G. Bell. 2002. Macroevolution simulated with autonomously replicating computer programs. Nature 420:810-812.

Notes

¹ Pigliucci, along with Gerd Muller, edited a book on "the extended Synthesis" with papers from a select group of thinkers who were invited in July, 2008 to a special meeting in Altenberg, Austria. The book is now available in paperback: http://www.amazon.com/Evolution-Extended-Synthesis-Massimo-Pigliucci/dp/0262513676

² from p. 1 "Although mutation is a key parameter in the genetics of populations, the role of mutation as an evolutionary factor has been debated since the time of Darwin. Early geneticists, who held to the 'classical' view of the genome as being homogeneous with occasional mutant alleles, saw new mutation as a major determining force in adaptive change. When the classical view was replaced with the 'balance' view of the genome, i.e., highly heterogeneous, pre-existing variation became more important as the resource on which selection would act. Many, therefore, began to disregard new mutation as a significant force in evolution, since the level of genetic diversity is already so high that new mutants would generally be expected to add little to that resource . . . Mechanisms responsible for maintaining levels of genetic diversity became the focus of attention, and mutation pressure is now thought by many to have only minor significance, especially when compared to selection, recombination, gene flow, and similar factors. We think this position, like the classical view, is too extreme. While there can be little doubt that mutation per se is not the principle driving force it was once believed to be for phenotypic evolution, we see growing evidence that its role is under-appreciated in important situations. The rate and pattern of mutation can be influenctial variables in adaptive responses, and the role of mutation in evolution deserves to be reexamined."

³ Orr (2002) notes the absence of such models by making a far more sweeping claim that population genetics has ignored, not just new-mutations models of adaptation, but all models of adaptation, and instead has focused on neutral and deleterious alleles. That is an odd thing to say, given that the quantitative genetics of adaptation have been a topic for a long time. In any case, here is what Orr says: "Evolutionary biologists are nearly unanimous in thinking that adaptation by natural selection explains most phenotypic evolution within species as well as most morphological, physiological, and behavioral differences between species. But until recently, the mathematical theory of population genetics has had suprisingly little to say about adaptation. Instead, population genetics has, for both historical and technical resasons, focussed on the fates of neutral and deleterious alleles. The result is a curious disconnect between the verbal theory that sits at the heart of neo-Darwinism and the mathematical content of most evolutionary genetics. "

⁴ Also known as the theory of records—"record" in the sense of "pinnacle of achievement". Given a series of records, such as the world record in the long-jump, what's the interval of time to the next record, and by how much will it break the previous record? The theory of records addresses such questions. Can you see how this would be useful to make a predictive theory of adaptation?

⁵ Rokyta, et al. used a different formula for the probability of fixation, because the classic approximation only works for s << 1, whereas the phiX174 populations experience very large s, sometimes s > 1.

⁶ Formally Nu*2s_i is not a probability but a steady-state rate (e.g., for an infinite-alleles model). If we treat it as an instantaneous rate, and then compare it to all other instantaneous rates, this makes it a relative probability of choosing step i over a short interval.

⁷ For our present purposes, we don't need to explain Orr's addition to this model, which was a theory of the distribution of the favorable s values under generalized assumptions (oddly, the commentators on Rokyta, et al. did not mention that Orr's theory wasn't really needed, and that the study really was a test of the mutational landscape model itself).

⁸ Gould (2002, p. 140) is not endorsing Darwin's error about fluctuation. Darwin's followers think of that mistake as a trivial detail. Instead Gould is endorsing a more general inference. Here is what he writes. "Darwin reasoned that natural selection can only play such a role [as exclusive source of creativity and direction] if evolution obeys two crucial conditions: (1) if nothing about the provision of raw materials—that is, the sources of variation—imparts direction to evolutionary change; and (2) if change occurs by a long and insensible series of intermediary steps, each superintended by natural selection—so that "creativity" or "direction" can arise by the summation of increments.


Under these provisos, variation becomes raw material only—an isotropic sphere of potential about the modal form of a species. Natural selection, by superintending the differential preservation of a biased region from this sphere in each generation, and by summing up (over countless repetitions) the tiny changes thus produced in each episode, can manufacture substantial, directional change. What else but natural selection could be called 'creative,' or direction-giving, in such a process? As long as variation only supplies raw material; as long as change accretes in an insensibly gradual manner; and as long as the reproductive advantages of certain individuals provide the statistical source of change; then natural selection must be construed as the directional cause of evolutionary modification.


These conditions are stringent; and they cannot be construed as vague, unconstraining, or too far in the distance to matter. In fact, I would argue that the single most brilliant (and daring) stroke in Darwin's entire theory lay in his willingness to assert a set of precise and stringent requirements for variation—all in complete ignorance of the mechanics of heredity. Darwin understood that if any of these claims failed, natural selection could not be a creative force, and the theory of natural selection would collapse. "

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Credits: The Curious Disconnect is the blog of evolutionary biologist Arlin Stoltzfus, available at www.molevol.org/cdblog. An updated version of the post below will be maintained at www.molevol.org/cdblog/mutationism_myth6 (Arlin Stoltzfus, ©2010)

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Theory vs Theory

This is the third in a series of postings by guest blogger, Arlin Stoltzfus. You can read the introduction to the series at: Introduction to "The Curious Disconnect". The first part is at: The "Mutationism" Myth I. The Monk's Lost Code and the Great Confusion. Arlin is challenging the status quo in modern evolutionary theory. He's not alone in this challenge but it's important to distinguish between kooks who don't know what they're talking about and serious thinkers who have something to say. Arlin is going to explain to you why everything you thought you knew about mutationism is wrong. In this article we learn about theories.

Please pay attention.

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The Curious Disconnect

Our journey to map out the Curious Disconnect-- the gap between how we think about evolution and how we might think if we were freed from historical baggage-- began last time with part 1 of The Mutationism Myth.

Before continuing with part 2, I would like to take a detour. Issues surrounding "evolutionary theory", and evolutionary theories, are going to be coming up again and again. In fact, I can see these issues emerging already in The Mutationism Myth. So, before we get bogged down in confusion and disagreement, I would like to begin a discussion of "theory" and "theories". We'll return to the Mutationism Myth next time.

An updated version of the post below will be maintained at www.molevol.org/cdblog/theory_vs_theory (Arlin Stoltzfus, ©2010)

Theory1 vs theory2

What does it mean to invoke "evolutionary theory"? Is "neo-Darwinism" (or "Darwinism") a theory, a school of thought, or something else? What gives a theory structure and meaning (e.g., axioms, themes, formulae)? What is the relationship between mathematical formalisms and other statements of "theory" (e.g., what does it mean for a lecturer to show a key equation of quantitative evolutionary genetics and assert "this is neo-Darwinism")? Who decides how a theory is defined, or redefined (e.g., is Ohta's "nearly neutral" theory an alternative to, or a variant of, Kimura's Neutral Theory of Molecular Evolution)?

Confusion regarding "theory" and "theories" is going to be an ongoing topic of attention in The Curious Disconnect. As noted in the Introduction, we're in an enormous muddle. The way to get out of this muddle is to take some time to build common understanding, learn some useful terms, and establish ground rules.

In this post, we'll begin the process of developing a shared framework for productively discussing "theory" and "theories". We will begin by addressing an ambiguity in the use of the word "theory", partly because this particular ambiguity is important, and partly as an exercise in addressing semantics. ⁰

Definitions

Dictionaries provide definitions that can be helpful to clarify the meanings of words and the complications of their usage. Definitions can be descriptive, telling us how a word is used, or prescriptive, telling us how it ought to be used. But, as most of us don't like to be told what we ought to do, I suspect that you share my belief in studying how words are used, in order to determine their denotations (what the word says) and connotations (what the word hints or implies). The English dictionaries used in America typically agree: the definitions that they provide reflect patterns of common usage, not the decrees of authorities.

A difficulty with dictionaries arises given that, within an isolated community, e.g., a scientific discipline, words can take on special meanings. So, dictionaries can be helpful, with the proviso that we need to be sensitive to the special use of terms within a discipline.

The discipline-specific use of a term can be nailed down by looking at examples of usage. For evolutionary biology, the discipline-specific use of a term is to be found in the research literature, and also in the secondary literature of monographs, textbooks, and other disciplinary writings.

Two meanings of "theory"

A good dictionary will distinguish several different senses of the word "theory", including the following two that I believe are the most relevant for our discourse:

1) a major conjecture or systematic hypothesis to account for observed phenomena, as in "prion theory of disease" or "Lamarck's theory of evolution";

2) the body of abstract principles relevant to some discipline, methodology or problem area, as in "music theory" or "population genetics theory"

That is, a theory₁ is a grand hypothesis, a conjecture about the actual world, while a theory₂ is a collection of principles or models or other formalisms that might apply only in an imagined world. Fisher (1930) famously said that "No practical biologist interested in sexual reproduction would be led to work out the detailed consequences experienced by organisms having three or more sexes; yet what else should he do if he wishes to understand why the sexes are, in fact, always two?" Theoreticians aren't necessarily good with facts, so we'll ignore that the sexes (in the sense of mating types) are not, in fact, always two. Fisher clearly encourages us to work out formalisms for imagined or hypothetical cases. The collection of all these models or formalisms about sexes would constitute the theory₂ of sexes. A theory₁ of sexes might propose a causal explanation for the actual historic phenomenon of the origin and maintenance of sexual reproduction in animals, addressing such issues as the heterogametic basis of sex determination. ¹

These two meanings are not just recognized in dictionaries, but are established in scientific usage. Gilbert's "Exon Theory of Genes" (Gilbert 1987) is the conjecture that genes evolved from exons (i.e., large protein-coding genes emerged by joining primordial exon-minigenes). The prion theory₁ of disease clearly revolves around a conjecture that there are actual diseases caused by actual prions. By contrast, population genetics theory₂ is not the conjecture that populations have genetics; likewise, the theory₂ of stochastic processes is not a conjecture that stochastic processes occur, but consists of a body of abstract principles that might be applicable to such stochastic processes as might occur in some actual or imagined universe.

The use of the abstract noun, as in "let's talk about theory" as opposed to "let's talk about { a | the | this } theory", often signals the use of theory₂. For instance, the title of a report by the National Academy of Sciences on "The Role of Theory in Advancing 21st Century Biology" signals a likely emphasis on theory₂, and indeed, the report emphasizes the development of formalisms more than conjectures, and says that "a useful way to define theory in biology is as a collection of models", clearly a reference to theory₂. The report also mixes in some references to theories₁.

Obviously, there is a connection between scientific theories₁ and scientific theory₂. One way of thinking about the connection is that the abstract principles of theory₂, when suitably limited by measurable or observable quantities from the actual world, can provide the basis of a theory₁, and conversely, theories₁ draw on theory₂ for logical structure. Kimura's Neutral Theory (Kimura 1983) provides a clear example because the theory₁ and theory₂ were developed separately: Kimura combined pre-existing theory₂ (of stochastic population genetics) with the concrete assertion that the values of certain quantities (relating to population sizes and mutant effects) were such that, for DNA and protein sequences, neutral evolution by mutation and random fixation would be far more common than anyone had imagined previously. The definition of effectively neutral alleles (perpetually misunderstood by critics) and the probability of fixation under pure drift were known to the canonical founders of population genetics ((Wright 1931); ch. IV of (Fisher 1930); appendix of (Haldane 1932)). Another indication of the distinctness of theory₁ and theory₂ is that opponents of the Neutral Theory₁, who deny the truth of the theory₁, are nonetheless quite happy to make use of its theoretical₂ infrastructure (Kreitman 1996).

Development and application of theory₁ and theory₂

We treat the two kinds of "theory" differently, and rightly so.

A theory₁ contains a major supposition or unproved conjecture about the world. Kimura's Neutral Theory is the conjecture that most changes at the "molecular level" represent the random fixation of effectively neutral alleles. Darwin proposed, but could not prove, that all large-scale evolutionary changes were built from infinitesimal increments of change that emerged by a process of hereditary "fluctuation". A theory₁ takes risks: in Popperian terms, its subject to empirical refutation; in the words of Huxley, a beautiful theory₁ can be "killed by an ugly fact."

The relevant standard of validity for theory₂ is not verisimilitude (trueness to life), but consistency: the principles derived in the theory are consistent with its assumptions. Importantly, new principles added to a body of theory₂ are consistent with previous principles, except in the sense that a body of theory₂ may be subdivided into branches that cover non-overlapping universes. If they are not, a logical error has occurred.

While new theory₂ is consistent with existing theory₂, theories₁ often stimulate interest precisely because they conflict with previous theories₁. Of course theories₁ strive to be internally consistent, but in biology at least, theories₁ are not axiomatic, and often encompass ambiguities that make rigorous analysis difficult. A theory₁ can be brought down by a contradiction that arises internally, e.g., one part can be found to contradict another part.

While a theory₁ is about the actual world, and thus is judged by verisimilitude, principles of theory₂ need not apply to the real world. Indeed, no amount of conflicting data will cause us to discard a principle of theory₂ that is properly derived: a beautiful piece of theory₂ cannot be killed by an ugly fact. Fisher's fundamental theorem either is logically valid or is not logically valid, independent of any facts.

Digressions

The distinction between theory₁ and theory₂ is hidden in the ambiguous word "theory", but I think it comes out more clearly in specific word-derivatives and grammatical usages that seem to favor one meaning more than the other. I mentioned above that the abstract noun typically signals theory₂. I'm also convinced that when we refer to a "theoretician", we typically do not mean someone like Tom Cavalier-Smith whose scientific output consists of bold conjectures or systematic hypotheses (we might call such people "theorizers"), but instead someone like Joe Felsenstein whose work focuses on mathematical or algorithmic foundations, i.e., theory₂. Its a rare scientist, it seems to me, who is productive both as a theoretician and as a theorizer (e.g., Kimura, Hamilton).

Neither meaning of theory would cause us to relinquish the label "theory" for a proposition that lacks verisimilitude. Clearly the propositions of theory₂ do not have to apply to the real world. And a theory₁ is a conjecture, not necessarily a true conjecture. Thus, even opponents of the Neutral Theory₁, who believe that the theory does not fit the actual world, still refer to it as The Neutral Theory (Kreitman 1996).

I mention this because there is an absurd tendency in the literature of evolution advocacy, e.g., NCSE's screeds, to say that, because scientists reserve the word "theory" only for constructions that have been extensively verified and are accepted as true, the use of "theory of evolution" among scientists means that evolution is well supported.

This argument clearly is false, and the proof does not depend on the theory₁ vs. theory₂ distinction, but only on the fact that scientists habitually choose to refer to Kimura's theory or Lamarck's theory or Gilbert's theory as a "theory", even if its known to be wrong or is considered deeply suspect. This pattern holds, not just in biology, but in other disciplines. In astronomy, the geocentric theory remains a theory though it has been abandoned; in physics, the phlogiston theory, or the aether theory of light propagation (roughly, the theory that space must be substantive in order for waves to propagate in it) remain theories even though they were abandoned. So, write to the NCSE and tell them to stop using this lame argument. Really, we can do better than that.

The NCSE fallacy seems to arise from mixing together the proposed explanation of phenomena aspect of theory₁ and the accepted as valid aspect of theory₂. This is suggested from the way that NCSE's screed cites the NAS report on theory₂ (the same one that I quoted above) as though it provided a definition of theory qua "well substantiated explanation", which definitely is not the same as "collection of models".

Lets try to sort this out in terms of the distinction between theory₁ and theory₂. Evolutionists have recourse to a body of theory₂ (formalisms or models or principles), ranging from purely phenomenological models of branching and character-state change used in phylogenetics, to the breeder's equation used in quantitative genetics, to detailed formulas for population-genetics processes, and so on. We accept the validity of these abstractions in the theory₂ sense of validity, i.e., we accept that they are derived without error, so as to be logically consistent with their assumptions. This body of abstractions, principles, or formalisms (in NAS parlance, this collection of models) is evolutionary theory₂.

But saying that this theory₂ is valid is not at all the same thing as claiming that its true in the sense of verisimilitude; and claiming that it has verisimilitude is not the same as saying that its complete, in the sense of sufficiently accounting for the phenomena of evolution. For instance, the theory₂ of quantitative evolutionary genetics is based on the assumption of infinitesimal variation, but the theory₂ itself does not claim that all traits, nor even any single trait, evolved in this manner-- that would be a theory₁ issue. Kimura's diffusion equations are a part of population genetics theory₂ that provides a way to work out the probability of fixation of alleles under ideal conditions, but it doesn't assert that the results are applicable to any particular case. Got it?

Homework

The wikipedia entry on theory (http://en.wikipedia.org/wiki/Theory) has a "List of Notable Theories" that clearly mixes up theories₁ or grand conjectures (the cell theory, the phlogiston theory) with theories₂ or bodies of abstract principles (music theory, extreme value theory). What are some other clear examples of theory₁ and theory₂ in this list? Which examples are difficult to classify (and what does one learn from those)?

Who, besides Kimura and Hamilton, was productive as both a theoretician and as a theorizer?

Think of a few theories in science, ideally in life sciences. I'm going to assert that they are not axiomatic, i.e., they are not completely encompassed by precisely stated propositions. Given this, how do we really know what defines the theory? If we know a theory from the verbal statements in a body of literature (i.e., "things people say"), what is the relationship of an individual expression (e.g., a paper, a monograph, a quotation) to the theory? Is it the instantiation of a platonic form or essence? How do we get to the essence? Is the distribution of expressions of a theory its "reaction norm", representing environmental noise in the expression of an underly structure (the theory's "genotype")?

The Modern Synthesis as theory₁: into the memory hole

The folks at NCSE and wikipedia are not the only ones blurring the issues. The Modern Synthesis or modern neo-Darwinism ² was put forth originally as a falsifiable theory₁ of evolution, but evolutionists themselves don't treat it that way anymore. For instance, in Maynard Smith's defense of "neo-Darwinism" (Maynard Smith 1969), the only kinds of falsifying observations he can imagine are cases that seem to introduce supernatural forces, e.g., if the spots on a fish always appeared in prime numbers, he says this would contradict neo-Darwinism. He does not imagine variation-induced trends, discontinuous jumps based on individual mutations, or extensive neutral evolution as contradictions of "neo-Darwinism", though these ideas were rejected by the architects of modern neo-Darwinism. Maynard Smith makes the claim in regard to the Neutral Theory that "I have never seen any reason why, as a naive Darwinist, I should reject this theory" (Maynard Smith 1995). It seems that, for Maynard Smith, "neo-Darwinism" is not a theory₁ at all, but merely indicates a commitment to scientific materialism, i.e., seeking natural causes through observation and experiment.

Other authoritative sources suggest that the Modern Synthesis is no longer viewed as a falsifiable conjecture. In Hull's Encyclopedia of Evolution article on the history of evolutionary thought (Hull 2002), the Modern Synthesis is presented as an open-ended "theory" that merely assumes the principle of selection and the rules of genetics, and which has swallowed up the neutral theory along with all other useful ideas:

"Any criticism of the synthetic theory that turned out to have some substance was subsumed in a modified version of this theory. Instead of being a weakness, this ability to change is one of the chief strengths of the synthetic theory of evolution. As in the case of species, scientific theories evolve" (p. E16)

Hull's conception of the Modern Synthesis sounds more like an extensible set of principles, theory₂, than the theory₁ of Mayr, Simpson, Ayala, etc (which is extensible in some ways but closed and falsifiable in others). I'm not necessarily going to say its wrong for scientists to decide that the Modern Synthesis is no longer a theory₁, but can someone please tell me when, and on what basis, did we make this decision? Is there a citation for that? And who decided that we wouldn't tell Richard Dawkins, leaving the poor fellow stuck in a time warp defending the original Modern Synthesis? ³

But I'm getting ahead of myself. I started The Curious Disconnect with the The Mutationism Myth because 1) most evolutionists don't understand how the Modern Synthesis came into existence as a theory₁ that entails risky conjectures, and 2) the mutationist challenge provides the definitive historical proof that the Modern Synthesis is a theory₁ and not just a commitment to selection and the rules of genetics. The historical record will show clearly that the mutationists or "Mendelians" presented a workable synthesis of selection and the rules of genetics, and that their view was rejected by the architects of the Modern Synthesis. Once we find out why, we will understand what makes the Modern Synthesis a theory₁.

Literature cited

Dawkins, R. 2007. Review: The Edge of Evolution. Pp. 2. International Herald Tribune, Paris.

Fisher, R. A. 1930. The Genetical Theory of Natural Selection. Oxford University Press, London.

Gilbert, W. 1987. The exon theory of genes. Cold Spring Harbor Symp. Quant. Biol. 52:901-905.

Haldane, J. B. S. 1932. The Causes of Evolution. Longmans, Green and Co., New York.

Hull, D. L. 2002. History of Evolutionary Thought. Pp. E7-E16 in M. Pagel, ed. Encyclopedia of Evolution. Oxford University Press, New York.

Kimura, M. 1983. The Neutral Theory of Molecular Evolution. Cambridge University Press, Cambridge.

Kreitman, M. 1996. The neutral theory is dead. Long live the neutral theory. Bioessays 18:678-683.

Maynard Smith, J. 1969. The Status of Neo-Darwinism. Pp. 82-89 in C. H. Waddington, ed. Towards a Theoretical Biology 2. Sketches. Edinburgh Universeity Press, Edinburgh.

Maynard Smith, J. 1995. Life at the Edge of Chaos? Pp. 28-30. New York Review of Books, New York.

Wright, S. 1931. Evolution in Mendelian populations. Genetics 16:97.

Notes

⁰ I thank Dr. Mike Coulthart for originally drawing my attention to the importance of this distinction.

¹ If we were to propose just that the sexes are always 2 in number, simply because that is what we have seen in the past, I would call this an empirical generalization or "law". Sometimes "theory" is used for such a generalization, but that usage does not correspond to either meaning of "theory" addressed here.

² I'm using "modern neo-Darwinism" as a synonym for "Modern Synthesis". Neo-Darwinism (for our purposes, Darwinism 1.2) is the pre-Mendelian theory of Weissman and Wallace emphasizing the supreme power of selection and infinitesimal variation to build adaptation (and rejecting Darwin's reliance on Lamarckism). The Modern Synthesis (Darwinism 2.0) comes from this tradition and is often called "neo-Darwinism", though "modern neo-Darwinism" is clearer.

³ Kidding aside, its quite useful to have a scholar still defending the actual Modern Synthesis. For instance, in his attempt to rebut Behe (Dawkins 2007), Dawkins claims that mathematical geneticists "have repeatedly shown that evolutionary rates are not limited by mutation" and that Behe's critique based on the idea that evolution depends on specific mutations would mean that "the entire corpus of mathematical genetics, from 1930 to today, is flat wrong". In making this claim, Dawkins is correctly representing the Modern Synthesis view that (due to the buffering effect of the "gene pool") evolution does not depend on the rate of new mutations, a principle that he believes to be an infallible theoretical result.

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